Osteogenesis Imperfecta: A Case-Based Guide to Surgical Decision-Making and Care [1st ed.] 9783030425265, 9783030425272

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Osteogenesis Imperfecta A Case-Based Guide to Surgical Decision-Making and Care Richard W. Kruse  Editor

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Osteogenesis Imperfecta

Richard W. Kruse Editor

Osteogenesis Imperfecta A Case-Based Guide to Surgical Decision-Making and Care

Editor Richard W. Kruse Department of Orthopaedic Surgery Nemours/Alfred I. Dupont Hospital for Children Wilmington, DE USA

ISBN 978-3-030-42526-5    ISBN 978-3-030-42527-2 (eBook) https://doi.org/10.1007/978-3-030-42527-2 © Springer Nature Switzerland AG 2020 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, expressed or implied, with respect to the material contained herein or for any errors or omissions that may have been made. The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. This Springer imprint is published by the registered company Springer Nature Switzerland AG The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland

To James Richard Bowen, MD This book is respectfully dedicated to James Richard Bowen, MD, a selfless individual who has spent his life improving the lives of children through clinical care, mentoring, and research but mostly by living the example of what is good in personal character. He has an unfailing positive faith in the human spirit. Without his mentoring, guidance, and often needed prodding, this book would not exist. He, in his interactions with all humanity, has the ability to inspire and motivate one to constantly improve.

“Treat a man as he is, and he will remain as he is. Treat a man as he could be, and he will become what he should be.” —Ralph Waldo Emerson

Preface – Why This Book?

Life is the art of drawing sufficient conclusions from insufficient premises. — Samuel Butler

This book is intended to provide a detailed approach to the orthopaedic surgical care of patients with osteogenesis imperfecta (OI). Surgeons dealing with OI quickly learn the complexity of challenges in treating the extreme variability of the disease. In addition, from the care of routine fractures to the complexities of spine surgery, each patient is somewhat unique, with their own needs and abilities. The ultimate goals of surgery must be specifically tailored to improve the life of the patient as an individual. More so than in many other conditions, a successful surgical outcome depends on managing the total care of the patient, which surgeons need to understand. This is a message that permeates this book. At our current state of knowledge, we are not completely able to predict the success or utility of a specific preoperative plan in patients with OI. Procedures may not go as nicely illustrated in a technique manual. “Stuff happens.” Surgeons must be able to adapt rapidly and adopt new approaches to the surgical procedure. Each operation may become a real-time iterative event with many changes in plan “on the fly.” This book is intended to take a “deep dive” into these complexities. Nonsurgeon readers will also benefit in being able to learn the challenges faced by their surgical colleagues. So all clinicians, researchers, and ultimately patients will benefit from knowledge sharing. Caring for OI is truly a team effort. This book is not an introduction to OI, a basic surgical technique manual, an exhaustive basic science text, or a theoretical review. It is meant to be a resource for surgeons in facing the complexities of OI surgery and to learn to think about the patient as an individual with unique needs and to have options available in the surgical theater. To achieve this goal, an understanding of overall care is required. Therefore, the book is divided into three sections: 1. Medical/Non-operative Care: To guide surgeons already familiar with OI on overall care planning of the patient through the patient’s lifespan 2. Decision-Making: To understand the scientific literature and principles in the appropriate planning of surgery 3. Execution: To benefit from the experience of experts in the specifics of surgical procedures through illustrative case presentations vii

Preface – Why This Book?

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The structure of the book allows each topic to be read as a stand-alone chapter, but the overall flow of the book is general to specific. This necessarily will lead to some repetition of discussion. The reader should anticipate this. Principles guide all surgery. An effort has been made to cite the scientific literature to guide decision-making. Where the current literature often falls short is in dealing with actual surgical care. I have asked each author to be as detailed as possible in providing guiding principles and the specifics of their treatment approach in order to add clinical value to the book. My intent as editor is to also address unique challenges faced by physicians and surgeons worldwide. Each chapter is authored by a specific content expert chosen to add a global view. All authors are practicing expert clinicians and academicians. The reader will benefit from understanding their opinions and thoughts on care. It is my hope that the sharing of this knowledge is used to benefit the lives of patients with OI worldwide. Wilmington, DE, USA 

Richard W. Kruse

Acknowledgments

Without a doubt, I would like to first thank the OI community – the patients, families, and caregivers who motivated me throughout my professional career. Through adversity, we often find strength, and seeing adversity faced on a daily basis by the OI community is truly worthy of reverence. I am honored to be a part of their lives. I have been blessed with exemplary mentors and pillars in the clinical care of OI, particularly Drs. Francis Glorieux and Francois Fassier, whose guidance and friendship I value beyond measure. This book is dedicated to James Richard Bowen, MD, for inspiring me to be in pediatric orthopaedics and for being the first to expose me to caring for OI and to encourage (pushed, prodded, bugged) me to pursue it as a specialty. The intellectual journey of improving the lives of patients is the mission of all the authors of this book. Our passion is evident in our writing and in all we do. We learn from each other, and what I most enjoy is the openness of our discussions and intellectual interactions. “Never stop exploring” as the saying goes. Thanks to my mentee Jeanne Franzone, MD, who will carry the torch for OI care as a leader of the next generation of surgeons. Most of all, it is a team effort. I cannot even begin to list the value of a team in open and collaborative care of the OI patient: Steve Hines, our surgical tech, whose countless ideas have led to surgical improvements (Why don’t you try this…?). Below is a common intraoperative conversation: Me: “Steve do we have…?” Steve: “Already have it opened…” Steve has had countless technical ideas which have improved surgical care. He is always thinking outside the box. I cannot count how many times his ideas have made a difficult situation easier. Mike Bober, MD, and Tina McGreal (MSN, NP-C), whose exemplary medical care of the OI patient have made outcomes better. Renee Donohoe, DPT, whom I listen to when she speaks about therapy, activity, and patient care. Amanda Horkey, MA, my clinical right arm who has fallen in love with caring for OI patients and guides our day-to-day activity. Go Packy! ix

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Michelle Perri, my administrative assistant  – “No job too large or too small” for her thorough scrutiny and completion. She keeps us all on track. To the OI Foundation (OIF). Their compassionate care of the OI community has improved lives everywhere. In everyone’s life, there is a steadfast beacon and an unfailing rock of support if we just take time to notice. In my life, that has been my wife, Jane, whom I deeply thank for being my guiding light, sounding board, and life companion. I love you! To my daughters, Meredith, Victoria, and Amelia. Thank you for your love and support.

Acknowledgments

Contents

Part I General Considerations in Treating OI for the Surgeon 1 Introduction to Osteogenesis Imperfecta��������������������������������������   3 Peter H. Byers and Cecilie Fremstad Rustad 2 Patient Evaluation and Medical Treatment for Osteogenesis Imperfecta������������������������������������������������������������  11 Cristina McGreal and Michael B. Bober 3 Therapy, Orthotics and Assistive Devices for Osteogenesis Imperfecta������������������������������������������������������������  21 Maureen Donohoe 4 The Structure and Functioning of the Multidisciplinary Clinic in Managing and Monitoring Patients with Osteogenesis Imperfecta in the UK����������������������������������������  39 Caroline Elizabeth Ann Marr and Ali Seasman 5 Quality of Life and Functional Evaluation Measures for Osteogenesis Imperfecta������������������������������������������������������������  57 Verity Pacey and Kathleen Montpetit Part II Surgical Planning and Surgery 6 Personal Reflections on Care for Osteogenesis Imperfecta����������  73 François Fassier 7 Surgical Principles in Treating Osteogenesis Imperfecta������������  79 Richard W. Kruse and Jeanne M. Franzone 8 Anesthetic and Post-operative Pain Management������������������������ 111 Jessica K. Goeller and Leelach Rothschild Part III Surgical Cases: Hip and Extremities 9 Morphologic Features and Treatment of the Hip and Proximal Femur in OI�������������������������������������������������������������� 129 Miguel Galban, Carlos Pargas, and Adolfredo Santana

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10 Osteogenesis Imperfecta Surgical Management of the Femur and Knee������������������������������������������������������������������������ 147 Paul Esposito and Maegen J. Wallace 11 Osteogenesis Imperfecta in the Tibia and Ankle�������������������������� 183 Darko Antičević 12 Upper Extremity������������������������������������������������������������������������������ 203 Thomas Wirth 13 Osteogenesis Imperfecta in the Spine�������������������������������������������� 221 Suken A. Shah and Maegen J. Wallace 14 Unique Considerations of the Adult with Osteogenesis Imperfecta������������������������������������������������������������������ 231 Guus J. M. Janus, Anton A. M. Franken, Arjan G. J. Harsevoort, and Anne Marieke V. Dommisse 15 Extremity Surgery in Adults with Osteogenesis Imperfecta�������� 257 Tae-Joon Cho 16 Management of Osteogenesis Imperfecta in India������������������������ 265 Hitesh Shah and Benjamin Joseph

Index ���������������������������������������������������������������������������������������287

Contents

Contributors

Darko Antičević, MD, PhD  University of Osijek, Osijek, Croatia Specialty Hospital “St. Catherine”, Zabok, Croatia Michael B. Bober, MD, PhD  Division of Orthogenetics, Nemours Alfred I. Hospital for Children, Wilington, DE, USA Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, PA, USA Skeletal Dysplasia Program, Osteogenesis Imperfecta Program, Nemours Alfred I. DuPont Hospital for Children, Wilington, DE, USA Peter  H.  Byers, MD  Department of Pathology, Department of Medicine, Division of Medical Genetics, University of Washington School of Medicine, Seattle, WA, USA Tae-Joon  Cho, MD Division of Pediatric Orthopaedics, Seoul National University Children’s Hospital, Seoul, Republic of Korea Department of Orthopaedic Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea Anne Marieke V. Dommisse, MD  Department of Rehabilitation Medicine, Isala Zwolle, Zwolle, The Netherlands Maureen Donohoe, PT, DPT, PCS  Nemours/Alfred I duPont Hospital for Children, Wilmington, DE, USA Paul  Esposito, MD College of Medicine Pediatric Orthopaedic Surgeon, Orthopaedic Surgery University of Nebraska, Children’s Hospital and Medical Center, Dodge, NE, USA François  Fassier, MSC, MD, M.Sc Department of Pediatric Surgery, McGill University, Montreal, QC, Canada Shriners Hospital for Children-Canada, Montreal, QC, Canada Anton A. M. Franken, MD. PhD  Department of Internal Medicine, Isala Zwolle, Zwolle, The Netherlands

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Jeanne  M.  Franzone, MD Orthopaedic Surgery and Pediatrics, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, PA, USA Osteogenesis Imperfecta Program, Nemours Alfred I. Dupont Hospital for Children, Wilmington, DE, USA Nemours Alfred I. Dupont Hospital for Children, Wilmington, DE, USA Miguel Galban, MD  Cora Group, Medellin, Antioquia, Colombia Jessica  K.  Goeller, DO Department of Anesthesiology, University of Nebraska Medical Center, Omaha, NE, USA Division of Pediatric Anesthesiology, Children’s Hospital & Medical Center, Omaha, NE, USA Arjan G. J. Harsevoort, MSc  Department of Orthopaedics, Isala Zwolle, Zwolle, The Netherlands Guus  J.  M.  Janus, MD, PhD  Department of Orthopaedics, Isala Zwolle, Zwolle, The Netherlands Benjamin  Joseph, MS Orth, MCh Orth, FRCS Ed Consultant, Aster Medcity, Kochi, Kerala, India Richard W. Kruse, DO, MBA  Orthopaedic Surgery and Pediatrics, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, PA, USA Uniformed Services University of the Health Sciences, Bethesda, MD, USA Osteogenesis Imperfecta Program, Nemours Alfred I.  Dupont Hospital for Children, Wilmington, DE, USA Nemours Alfred I. Dupont Hospital for Children, Wilmington, DE, USA Caroline  Elizabeth  Ann  Marr, MSc, BSc (Hons) Sheffield Children’s NHS Foundation Trust, Western Bank, Sheffield, UK Cristina McGreal, MSN, NP-C  Division of Orthogenetics, Nemours Alfred I. Hospital for Children, Wilmington, DE, USA Kathleen  Montpetit, MSc, OT  Shriners Hospital for Children, Montreal, QC, Canada Verity  Pacey, PhD, PT Department of Health Professions, Macquarie University, Sydney, NSW, Australia Carlos Pargas, MD  Nemours – AIDHC, Wilmington, DE, USA Leelach Rothschild, MD  Department of Anesthesiology, Shriners Hospitals for Children, Chicago, IL, USA Department of Anesthesiology, University of Illinois Hospital and Health Sciences System, Chicago, IL, USA

Contributors

Contributors

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Cecilie  Fremstad  Rustad, MD Department of Medical Genetics, Oslo University Hospital, Oslo, Norway Adolfredo  Santana, MD  Centro Clinico Leopoldo Aguerrevere, Caracas, Venezuela Ali Seasman, BA (Hons), BSc (Hons), PGCert  Sheffield Children’s NHS Foundation Trust, Western Bank, Sheffield, UK Hitesh  Shah, MS Orth  Kasturba Medical College, Manipal Academy of Higher Education, Manipal, Karnataka, India Suken  A.  Shah, MD Spine and Scoliosis Center, Department of Orthopaedics, Nemours/Alfred I duPont Hospital for Children, Wilmington, DE, USA Department of Orthopaedic Surgery, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, PA, USA Maegen  J.  Wallace, MD College of Medicine Pediatric Orthopaedic Surgeon, Orthopaedic Surgery University of Nebraska, Children’s Hospital and Medical Center, Dodge, NE, USA Orthopaedic Surgery, University of Nebraska College of Medicine, Children’s Hospital and Medical Center, Omaha, NE, USA Thomas Wirth, MD, PhD  Department of Orthopaedics, Klinikum Stuttgart, Olgahospital, Stuttgart, Germany

Part I General Considerations in Treating OI for the Surgeon

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Introduction to Osteogenesis Imperfecta Peter H. Byers and Cecilie Fremstad Rustad

Introduction Osteogenesis imperfecta (OI) is a group of genetic bone disorders in which the major characteristic is bone fragility. The condition is uncommon, with best estimates of incidence of about 1/10,000 births and the prevalence slightly less because of perinatal mortality. The clinical picture is a continuum from severe bone deformity and fragility with death in the perinatal period to subtle increase in fracture frequency with normal life span. To help determine the natural history of fracture and other complications, clinical, radiologic and genetic studies have been used to classify affected individuals into several “types” of OI.  About 85–90% of affected individuals have mutations in the type I collagen genes (COL1A1 and COL1A2). The remainder have mutations in genes that encode proteins that control bone cell development or collagen gene expression, modify collagens, act in the collagen secretory pathway or interact in the extracellular matrix. Type I collagen is the protein “scaffold’ or framework of the bone upon which the mineral P. H. Byers Department of Pathology, Department of Medicine, Division of Medical Genetics, University of Washington School of Medicine, Seattle, WA, USA e-mail: [email protected] C. F. Rustad (*) Department of Medical Genetics, Oslo University Hospital, Oslo, Norway

content lies. Type I collagen is a ubiquitously expressed and distributed protein that assures the architectural integrity of most organs and structures. As a consequence, alterations in the genes that encode, regulate or modify the proteins put most of the body at risk for developmental alterations and abnormalities in supporting tissues. Because of the distribution of these molecules, people with OI may develop significant problems in the auditory, ocular, dental, neurological, pulmonary, cardiovascular, gastrointestinal, renal, genitourinary, skeletal and integumentary systems, some of which may require surgical intervention. From a practical point of view, skeletal integrity is at greatest risk, and the orthopaedist is generally most familiar with the surgical problems in people with OI, but most other specialists will encounter affected individuals in their practices. Thus it is helpful to have a basic knowledge of the clinical features of OI so that affected individuals can be recognized and treated appropriately. The clinical phenotype varies a great deal among the different types of OI and also to some extent within each type. Understanding the variation in OI is important as this can affect the treatment choice both for the general surgeon and for the orthopaedic surgeon. Multidisciplinary care is advised for children and adults with OI with the primary goals of managing the symptoms, minimizing fractures, relieving bone pain and promoting mobility, general health and well-being.

© Springer Nature Switzerland AG 2020 R. W. Kruse (ed.), Osteogenesis Imperfecta, https://doi.org/10.1007/978-3-030-42527-2_1

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P. H. Byers and C. F. Rustad

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Epidemiology

Classification of OI

Using data from the late 1970s to the early 1980s in Latin America, the birth prevalence of OI was found to be 0.4 per 10,000. These data reflected the more severe forms that were recognized at birth and did not include those with more subtle types of OI [1]. Folkestad et al. [2] used the Danish National Patient Register from 1997 to 2013 and found a population prevalence of 1.5 per 10,000. In Finland a population-based survey of hearing loss in Finnish adults with OI estimated a prevalence of about 0.5 per 10,000 [3]. These measures omit those with OI who died prior to the evaluation. A reasonable estimate of the incidence of OI is about 1 per 10,000 [4].

Classification of clinical conditions is an attempt to group individuals on the basis of clinical or genetic characteristics with similar phenotypes or genotypes to facilitate diagnosis, unify treatment and be able to predict response to different therapies and provide individuals and families with prognostic information. At the beginning of the twentieth century, OI was thought of in terms of whether it was identified at birth (OI congenita) or during later development (OI tarda). In the late 1970s, on the basis of clinical presentation, radiographic features and patterns of inheritance, Sillence and his colleagues [5] proposed four major groups that for convenience became OI type I (mild dominant with blue sclerae), OI type II (perinatal lethal), OI type III (progressive deforming) and OI type IV (mild to moderate with white sclerae). OI type I and OI type IV were thought to be dominantly inherited, and OI type II and OI type III were thought to be recessively inherited because of parental consanguinity and sibling recurrence to unaffected parents in some families. Beginning in the 1980s and continuing for the next 20  years, clinical, biochemical and histological studies helped to characterize individuals and families that appeared distinct from those in the prior group, and so OI type V, OI type VI and then OI type VII were described as discrete entities. In the first decade of the current century and continuing to the present analysis of candidate genes, whole exome or genome studies in families have identified more than 20 genes, mutations in which can give rise to different forms of OI. These developments led to discussions about the best way to classify OI – should it be a classification based on clinical features alone, that is, seeing the question from the perspective of the clinician trying to assign a diagnosis, or should the classification be based strictly on the basis of the causative gene and perhaps the nature of the genetic alteration which could help to define the mode of inheritance and distinguish response to medications and other intervention? Should it be a combination of the two? Van Dijk and

Diagnosis OI is a clinically heterogeneous group of genetic disorders, which have in common bone fragility, and that result from mutations in any of more than 20 genes. Individuals with OI can be first identified at almost any time during the development, growth and ageing process. The clinical diagnosis of OI can be made in utero or in the perinatal period because of fracture(s), in childhood because of fractures that occur with no or little precipitating trauma or on the basis of family history after a proband (first affected person) is identified. In addition to family history, blue sclera, reduced hearing at a young adult age, dentinogenesis imperfecta (DI, distinctive yellowish teeth, teeth have an apparent transparency), short stature, joint laxity, cardiac valve abnormalities, reduced pulmonary function and radiographic findings are important adjuncts to the clinical diagnosis. Genetic testing (DNA sequence analysis of the known OI-related genes) is used to confirm the diagnosis, determine risk that other family members are affected and provide some guide to use of therapies. Radiographic features change with age, and major findings include fractures of different ages and stages of healing, Wormian bones, osteopenia or osteoporosis, protrusio acetabuli, platyspondyly and “codfish” vertebrae, scoliosis and basilar impression.

1  Introduction to Osteogenesis Imperfecta

Sillence [6] have championed the clinically based ­classification, OMIM has used the altered gene as the basis of classification [7], and there is growing interest in the use of a combined classification [4] (Table  1.1). We will describe the basic Sillence Classification as it is still in common use and extend the description to type V as it was the gateway to understanding the expanding variation in OI. OI type I, non-deforming OI with blue sclera, is the mildest form of OI [8] and is the most common world-wide except in some isolated unique patient populations where rare recessive forms might be more common. The fracture rate is relatively low and declines at puberty, and there are few severe bone deformi-

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ties. Stature is usually normal or slightly short for the family. It is usually associated with low bone mass, and there is a susceptibility to progressive hearing loss that may begin in adolescence and continue throughout life [6]. The inheritance pattern is autosomal dominant. OI type II, the perinatal lethal OI group, usually results from heterozygous mutations in type I collagen genes, but the phenotypic presentation is similar to some forms of OI caused by bi-­allelic mutations (recessively inherited) in non-collagen genes (CRTAP, P3H1, PPIB, TMEM38B, CREB3L1 and others). Recurrence in families may be the result of recessive inheritance or, in some, parental mosaicism for the causative dominant mutation in a type I collagen gene. The clini-

Table 1.1  Genetic classification Types of OI based on genetic classification Inheritance Clinical characteristics Mutated gene Affects the collagen synthesis or structure COL1A1 or COL1A2 I,II,III or IV AD Classical phenotype as described in text Affects the bone mineralization IFITM5 V AD Intraosseous membrane ossifications, radial head dislocation, see text SERPINF1 VI AR Moderate to severe skeletal deformity, presence of osteoid, fish-scale appearance of lamellar bone pattern. Childhood onset Abnormal collagen post-translational modification CRTAP VII AR Severe rhizomelia with white sclera P3H1 VIII AR Severe rhizomelia with white sclera PPIB IX AR Severe rhizomelia with grey sclera Compromised collagen processing and cross-linking SERPINH1 X AR Severe skeletal deformity, blue sclerae, DI, skin abnormalities, inguinal hernia FKBP10 XI AR Mild to severe skeletal deformity, congenital contractures, normal-to-grey sclerae PLOD2 No type AR Moderate to severe skeletal deformity, progressive contractures BMP1 XII AR Mild to severe skeletal deformity, umbilical hernia Altered osteoclast differentiation and function SP7 XIII AR Severe skeletal deformity, delayed tooth eruption, facial hypoplasia TMEM38 XIV AR Severe bone deformity, normal to blue sclerae WNT1 XV AR Severe skeletal abnormalities, white sclerae AD CREB3L1 XVI AR Severe bone deformities SPARC XVII AR Progressive severe bone fragility MBTPS2 XVIII XR Moderate to severe skeletal deformity, light blue sclerae, scoliosis, pectoral deformities Amended from Marini et al. (2017) [4]

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cal picture can be recognized in utero by about 16 weeks of gestation by routine screening ultrasonography and prior to that if the diagnosis is known in the family. At birth, the calvarial mineralization is markedly diminished so that the skull may feel soft, the fontanelles are large, the limbs are short and deformed and the chest is generally small, and multiple fractures are present in long bones and ribs and platyspondyly is the rule. Survival may be for hours to weeks with death usually the result of respiratory insufficiency, infection or cardiorespiratory failure. OI type III, progressively deforming OI, a severe type of OI, is recognized in utero or in newborn infants, who present with multiple fractures and striking Wormian bones in the skull and develop bone deformities. All these individuals grow poorly, and most develop progressive kyphoscoliosis during childhood and progress into adolescence [6]. The sclera can be blue at birth but becomes less so with age [9]. DI is usually present and reduced hearing is common as is the development of basilar impression. Lifespan is shortened because of pulmonary compromise. Inheritance is usually autosomal dominant as a result of mutations in type I collagen genes, but some individuals whose initial clinical classification was in this group have proved to have bi-­allelic mutations in non-collagen genes (recessive inheritance). OI type IV, “variable OI with normal sclera”, is moderate in severity with fractures in childhood, osteoporosis and variable degrees of long bone and spine deformity. Height ranges from near normal to about 130 cm. Some have reduced hearing and almost all have DI.  The frequency of basilar impression is increased in OI type IV [10]. Severity may vary considerably within a family and among individuals. The inheritance is autosomal dominant and is a consequence of mutations in the type I collagen genes (COL1A1 and COL1A2). OI type V [11] is not in the original Sillence classification. It is a dominantly inherited condition that is characterized by hyperplastic callus, progressive calcification of the interosseous membranes and coarse mesh-like lamellation of the bone in bone biopsies [6, 11, 12]. Sclerae

are white and dentinogenesis is absent. OI type V results from a recurrent mutation that leads to addition of five amino acids at the amino terminal end of the protein that interferes with function. Genetic studies in individuals with similar phenotypes in whom type I collagen mutations could not be identified led to the identification of mutations in other genes characterized by autosomal recessive or X-linked inheritance.

Differential Diagnosis Child Abuse and OI When a child is admitted to hospital with fractures of unknown cause, medical professionals have the difficult task of evaluating whether the fractures are due to non-accidental injury (NAI) or whether the child has an underlying predisposition to fractures. The prevalence of NAI is 24 per 10,000 children under 3 years of age, in the United States, whereas the prevalence of OI is about 1 per 10,000 [13]. In two studies conducted in a group of children thought to have NAI but evaluated for OI, about 4% had biochemical evidence consistent with OI [13]; this suggests that it is difficult to identify the children who have OI without using biochemical or genetic testing. A more recent study [14] came to similar conclusions after studying the effectiveness of genetic screening. In the clinical diagnostic work-up, recognition of a family history of OI or diagnostic features of OI like blue sclera, Wormian bones and dentinogenesis imperfecta will help in the evaluation. Some of these clinical features may not be present in some forms of OI or not yet apparent in very young children. Because the recognition of the mild forms of OI in this setting at young ages may be difficult, molecular genetic testing for mutations in COL1A1, COL1A2 and IFITM5 that includes deletion/duplication testing should be considered, if not routine [15]. Often the known OI genes are tested together in a large panel which could eliminate the need for unnecessary cascade testing. Recessive forms are more likely to be identified in infants and children of consan-

1  Introduction to Osteogenesis Imperfecta

guineous parents or in some small populations that have an increased frequency of the recessive alleles. If a variant of unknown significance (VUS) is identified during the genetic testing, analysis of parental samples could determine if it is consistent with a clinical picture of fractures. However, parental studies could show that the variant does not explain the fractures and

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so may compromise the right of the parent to self-protection.

Other Differential Diagnosis See Table 1.2 for other differential diagnosis

Table 1.2  Differential diagnosis

Perinatal hypophosphatasia Neonatal lethal short-limbed thanatophoric dysplasia Campomelic dysplasia

Achondrogenesis Type 1B Bruck syndrome

Hajdu-Cheney osteolysis

Osteoporosis pseudoglioma syndrome

Cole-Carpenter

Idiopathic juvenile osteoporosis

Time of diagnosis In utero

Clinical features Short, bowed and angled long bones. Polyhydramnios Respiratory distress Can in utero be Limbs are very short and fingers and toes are short as well. Narrow thorax difficult to differentiate from OI Can in utero be The long bones are short and bowed difficult to Pierre Robin sequence and club feet differentiate can be present. Respiratory from OI insufficiency Can in utero be Micromelia can be detected early in pregnancy Hydropic appearance difficult to Short trunk Prominent abdomen differentiate from OI Birth Also termed OI with congenital joint contractions Characterized by bone fragility, club feet, blue or white sclera and Wormian bones Infancy/ Acroosteolysis of distal phalanges, childhood generalized osteoporosis, Wormian bones, short stature, hearing loss, dysmorphic features, pathological fractures, kyphoscoliosis, joint laxity, basilar impression and short, broad digits Bone fragility, fractures, secondary Infancy (reduced vision deformities of long bones after fractures, short stature, hypotonia and from birth) pseudoglioma which can cause reduced visual acuity from birth Birth Bone fragility, craniosynostosis, ocular proptosis, blue sclerae, hydrocephalus and distinctive facial features Pre-adolescent Pre-adolescent fractures and osteoporosis

Genes ALPL

Inheritance AR

FGFR3

AD

SOX9

AD

SLC26A2

AR

FKBP10 and PLOD2

AR

NOTCH2

AD

LRP5

AR

P4HB or SEC24D

AD, type 1 AR, type 2

AD A small percentage have been described to have mutations in LRP5 and classified as a primary genetic osteoporosis [16]

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 hen Is Genetic Testing Done, What W Tests Should Be Done and What Is Its Value Best practice guidelines for laboratory testing were published by the European Molecular Genetics Quality Network working group in 2012, which stated that individuals with suspected OI should have genomic DNA sequence analysis and deletion/duplication analysis of COL1A1 and COL1A2 [17], the two genes which, in most populations, account for about 90% of all people with OI.  If no pathological variants are found and the clinical diagnosis of OI is confirmed after clinical re-evaluation, analysis of the recessive OI genes is recommended. This was written after the transition of testing for OI by analysis of collagens synthesized by cultured dermal fibroblasts but before the widespread use of massively parallel genetic sequence analysis. With the introduction of new techniques for genetic analysis such as next-generation sequencing, it is possible to analyse many genes (or all) at once relatively inexpensively and has become the preferred method to confirm the diagnosis OI and characterize natural history and risks. Of note is that various laboratories doing gene testing may have differences in which genes are sequenced in panel testing for OI.

Summary OI is a clinically heterogeneous set of genetic conditions that are characterized principally by bone fragility and fractures that can be accompanied by abnormalities in bone growth, tooth formation and structure, significant skeletal deformity, hearing loss and blue sclerae that are helpful in leading to the clinical diagnosis. About 90% of individuals with OI (including those with lethal forms) have mutations in the type I collagen genes (COL1A1 and COL1A2) that encode the major protein in the bone and are inherited in a dominant fashion. Nearly 20 additional genes can have mutations that result in forms of OI that are often clinically similar to those that result from mutations in type I collagen genes and can

be distinguished on the basis of clinical findings (in some) and, definitively, by identification of the alterations in target genes. OI can be the reason for surgery (fractures, scoliosis, basilar impression, hearing loss) and involves surgeons from many disciplines or be the context in which surgery is for a non-OI-­ related condition. If surgery is done because of immediate need, the genetic basis of the condition may not be known, and consultation with a geneticist or other clinician familiar with the clinical heterogeneity of the condition is often a valuable adjunct to pre-surgical evaluation. If time permits, then genetic testing to confirm the diagnosis and to generate factors to consider prior to and during surgery (respiratory status, complications with anaesthesia, known response to surgery of specific kinds (e.g. scoliosis) and any concerns about prior or ongoing treatment with bisphosphonates would be essential elements in management.

References 1. Orioli IM, Castilla EE, Barbosa-Neto JG.  The birth prevalence rates for the skeletal dysplasias. J Med Genet. 1986;23:328–32. 2. Folkestad L, Hald JD, Canudas-Romo V, Gram J, Hermann AP, Langdahl B, Abrahamsen B, Brixen K.  Mortality and causes of death in patients with osteogenesis imperfecta. A register-based nationwide cohort study. J Bone Miner Res. 2016;31(12):2159–66. 3. Kuurila K, Kaitila I, Johansson R, Grénman R.  Hearing loss in Finnish adults with osteogenesis imperfecta: a nationwide survey. Ann Otol Rhinol Laryngol. 2002;111:939–46. 4. Marini JC, Forlino A, Bächinger HP, Bishop NJ, Byers PH, De Paepe A, Fassier F, Fratzl-Zelman N, Kozloff KM, Krakow D, Montpetit K, Semler O. Osteogenesis imperfecta. Nat Rev Dis Primers. 2017;3:17052. 5. Sillence DO, Senn A, Danks DM.  Genetic heterogeneity in osteogenesis imperfecta. J Med Genet. 1979;16(2):101–16. 6. Van Dijk FS, Sillence DO.  Osteogenesis imperfecta: clinical diagnosis, nomenclature and severity assessment. Am J Med Genet A. 2014;164A(6):1470–81. 7. https://omim.org/phenotypisSeries/PS166200. 8. Steiner RD, Adsit J, Basel D. COL1A1/2-related osteogenesis imperfecta. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong CT, Stephens K, editors. GeneReviews. University of Washington, Seattle (last updated 2013). https://www.ncbi.nlm.nih.gov/books/NBK1295/.

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COL1A1 and COL1A2 sequencing results in 9. Sillence DO, Barlow KK, Cole WG, Dietrich S, cohort of patients undergoing evaluation for potenGarber AP, Rimoin DL. Osteogenesis imperfecta tial child abuse. Am J Med Genet A. 2016;170(7): type III. Delineation of the phenotype with refer1858–62. ence to genetic heterogeneity. Am J Med Genet. 1 5. Pepin MG, Byers PH. What every clinical geneticist 1986;23:821–32. should know about testing for osteogenesis imper 10. Sillence DO.  Craniocervical abnormalities in osteofecta in suspected child abuse cases. Am J Med Genet genesis imperfect: genetic and molecular correlation. C Semin Med Genet. 2015;169(4):307–13. Pediatr Radiol. 1994;24:247–430. 11. Glorieux FH, Rauch F, Plotkin H, Ward L, Travers 16. Hartikka H, Ma ̈kitie O, Ma ̈nnikko ̈ M, Doria AS, Daneman A, Cole WG, Ala-Kokko L, Sochett R, Roughley P, Lalic L, Glorieux DF, Fassier F, EB.  Heterozygous mutations in the LDL receptor-­ Bishop NJ.  Type V osteogenesis imperfecta: a new related protein 5 (LRP5) gene are associated with form of brittle bone disease. J Bone Miner Res. primary osteoporosis in children. J Bone Miner Res. 2000;15:1650–8. 2005;20:783–9. 12. Forlino A, Marini JC.  Osteogenesis imperfecta. 17. Van Dijk FS, Byers PH, Dalgleish R, Malfait F, Lancet. 2016;387(10028):1657–71. Maugeri A, Rohrbach M, Symoens S, Sistermans EA, 13. Marlowe A, Pepin MG, Byers PH.  Testing for Pals G. EMQN best practice guidelines for the laboraosteogenesis imperfecta in cases of suspected non-­ tory diagnosis of osteogenesis imperfecta. Eur J Hum accidental injury. J Med Genet. 2002;39(6):382–6. Genet. 2012;20:11–9. 14. Zarate YA, Clingenpeel R, Sellars EA, Tang X, Kaylor JA, Bosanko K, Linam LE, Byers PH.

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Patient Evaluation and Medical Treatment for Osteogenesis Imperfecta Cristina McGreal and Michael B. Bober

Introduction Chapter 1 served as an overview of osteogenesis imperfecta. This chapter outlines the nonsurgical treatment approach to OI from the authors’ perspective. The course of treatment as outlined is primarily for the patient diagnosed with osteogenesis imperfecta from birth though the early years of adulthood.

Evaluation of Patient History and Physical Overview As in any medical condition, patient evaluation begins with a thorough history and physical examination. Patients present with a variety of chief complaints whether it be multiple fractures, bone pain, deformity, or for general counC. McGreal (*) Division of Orthogenetics, Nemours Alfred I. Hospital for Children, Wilmington, DE, USA e-mail: [email protected] M. B. Bober Division of Orthogenetics, Nemours Alfred I. Hospital for Children, Wilmington, DE, USA Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, PA, USA Skeletal Dysplasia Program, Osteogenesis Imperfecta Program, Nemours Alfred I. DuPont Hospital for Children, Wilington, DE, USA e-mail: [email protected]

seling. To facilitate care an attempt is made to obtain all existing medical records and imaging studies. A detailed family and patient history focuses on fracture history along with the mode of injury for previous fractures. Family history focuses on fractures, hypermobility, short stature, hearing loss, and dental problems suggesting dentinogenesis imperfecta. Prior to the initial visit, available imaging studies are reviewed. A determination of frequency, location, pattern, and healing of fractures helps guide later treatment. Spinal compression fractures and presence or progression of deformity of spine and extremities are also indicative of disease severity. Availability of previous studies can help place the patient into the appropriate type OI, which in turn will drive the treatment plan. A detailed analysis of comorbidities is also required to plan care.

 atient Presenting with Known P Diagnosis In a patient presenting with an established diagnosis, we first evaluate the patient and family’s existing level of understanding of OI. Past treatments and interventions are thoroughly reviewed and outcomes of treatments. In this patient group, it is beneficial to understand previous treatments with bisphosphonates or other agents to include dosages, frequency of administration, and documented patient response.

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History and Physical-Specific Findings In evaluating the patient with OI, pay close attention to the patient as a whole and not just for their OI. Having OI does not exclude them from having other changes in their body. Routine health screening by their primary care physician must be continued. OI mainly plays a role in bone fragility and fractures; however, the changes in collagen can affect other areas in the body as well. People with OI may also have dysmorphic triangular shaped facies, ligamentous laxity, hypermobility, and easy bruising or complain of constipation. In one study, it was found that in a study of 47 patients with OI, 70% of them had joint hypermobility. Joint hypermobility was found to be independent of the severity of OI [6].

Extra-skeletal Features Blue or gray discoloration of sclera. Blue sclerae are commonly seen in OI.  While having blue sclera does not affect vision, ophthalmology screening should be performed to have a baseline assessment. Discoloration and brittleness of teeth (dentinogenesis imperfecta, DI) can be associated. Dentinogenesis imperfecta is very common and variable in the pediatric patient with OI. Routine dental examination is mandatory. DI may lead to the need for tooth extractions, caps, and dental cleanings under anesthesia. Hearing loss can be associated with OI; it is typically not found until the second or third decade of life. In our practice we perform a baseline hearing assessment before the child enters school. We may do this sooner if there is a concern for hearing loss or speech delay. Cardiac assessment must be undertaken with attention for murmur or rhythm abnormalities. Heart sounds may have regular rate and rhythm on exam, and a normal physical examination does not exclude cardiac involvement. Cardiac manifestations of OI include mitral valve prolapse or aortic regurgitation. If available obtain an electrocardiogram (ECG) and echocardiogram to assess

C. McGreal and M. B. Bober

for valve disease. We recommend an ECG and echocardiogram on all adult patients at presentation. Follow-up testing is on an as-­needed basis depending on findings. There is no current literature on the frequency of testing for cardiac surveillance in OI patients. It is this author’s practice to have every adult patient with OI, have a baseline ECG and echo cardiogram, and repeat every 12–18 months, unless more frequent surveillance or involvement by cardiology is recommended. Pulmonary evaluation is necessary as chest deformity may affect pulmonary function. Respiratory status is thoroughly assessed, paying close attention to the work of breathing. Pulmonary problems in OI may be associated with underlying chest wall deformity or scoliosis. In any type of OI, it is always important to assess for scoliosis and vertebral fractures. This may change the course of treatment. We assess for possible vertebral fractures by assessing pain and/or tenderness over the vertebral bodies. Spinal deformity is often present in OI [6]. Scoliosis and some type of cranial base anomalies (including basilar impression, basilar invagination, or platybasia) were found in 26%. Scoliosis and cranial anomalies are more common in the moderate and severe types. We suggest pulmonary function testing (PFTs) for any patient with moderate to severe scoliosis or abnormally shaped chest or rib cage deformity. Sleep apnea may also be present in OI. PFTs and sleep studies are appropriate for a patient that snores, is obese, and/or has daytime sleepiness. Gastrointestinal status is also important to asses. A history of constipation should be sought. Assess the abdomen for distention which may be a sign of constipation. Umbilical hernia may also be present on examination.

Comprehensive Studies to Obtain X-Rays  As a baseline we obtain anteroposterior and lateral spine, upper and lower extremity, and skull X-rays. More specific films are ordered as necessary to evaluate bony deformity, fracture healing, limb length inequality, and chest or

2  Patient Evaluation and Medical Treatment for Osteogenesis Imperfecta

p­elvic deformity. Specific attention is paid to checking for bone deformity, fractures that have healed with deformity, appearance of a thin cortex, and bowing of long bones. Check skull X-rays for the presence of Wormian bones. Bone Density Testing  It is our practice to obtain DEXA (dual-energy X-ray absorptiometry) scan on all patients with OI. Our standard of practice is to obtain a DEXA scan prior to the start of bisphosphonate therapy. DEXA Z-scores can help guide the dosing regime for bisphosphonate therapy. We repeat DEXA scans annually. People with OI may have lower than average z-score on DEXA scan. The American Academy of Pediatrics (AAP) and International Society for Clinical Densitometry (ISCD) define osteoporosis as the presence of both clinically significant fracture history and low bone mineral content or density showed by dual-energy X-ray absorptiometry (DEXA) with z-scores less than or equal to −2.0 [7]. pQCT Scanning  More centers are using peripheral quantitative computerized tomography (pQCT) scanners to analyze trabecular and cortical bone compartments. This test is more helpful in analyzing not only bone mineral density but also bone geometrical parameters [16]. Laboratory Testing  We obtain laboratory evaluation to include 25-OH vitamin D.  Vitamin D functions as a chaperone for the ingested calcium to improve absorption and also to enter the bone. We will obtain a urinary hCG prior to initiation of bisphosphonate therapy or before each dose in postmenarchal females due to the limited evidence on the safety of the drug during pregnancy. Additional laboratory tests are checked prior to monitoring renal function once a patient begins bisphosphonate therapy, such as a complete metabolic panel (CMP), phosphorus assay, UA, urinary calcium, and urinary creatinine. Bisphosphonates are excreted through the kidneys. In patients with renal disease, bisphosphonates may accumulate and contribute to

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acute renal toxicity. Bisphosphonates may also decrease serum calcium on initiation of therapy. This is usually short lasting and causes no symptoms. However in patients with known or suspected hypoparathyroidism, hypocalcemia may become symptomatic. Some centers will evaluate osteocalcin levels, collagen cross-linking studies, procollagen type 1 intact N-terminal propeptide (PINP), and deoxypyridinoline; however, these are mostly research tools and have varying reference ranges for pediatric patients [12]. These labs are not routinely checked in our facility. Audiology  We recommend audiologic evalua­ tion to test for hearing loss prior to children ­starting school. Hearing loss in OI has a higher incidence in adults, rather than children. We recommend having a baseline exam prior to the start of school, so that the issue can be addressed before problems at school can occur due to hearing loss. Gait Analysis  We obtain gait analysis (video at minimum) on ambulatory patients to further clarify abnormalities seen during the clinical analysis. This facilitates planning of any physical therapy or planning surgical intervention. We also use the 6-min walk test in ambulatory patients as a baseline to identify the effect of any deformity or muscular weakness on ambulation and to guide physical therapy interventions. Advanced Imaging  MRI of the brain and cervical spine is obtained to evaluate for basilar invagination in moderate to severely affected patients with spinal deformity at approximately the age of 7 or sooner if any neurologic signs or deficits such as hyperreflexia are present on examination. Symptoms of basilar invagination may include headache, dizziness, swallowing difficulties, visual disturbance, or gait disturbance. Other symptoms of basilar invagination may include behavioral changes or loss of ability to concentration that is otherwise unexplained.

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The Diagnosis of OI: Genetic Testing Based on history, physical examination, imaging, and basic laboratory evaluation, a clinical diagnosis of OI can often be made. Classification of disease type and severity is then used for beginning counseling and treatment. The options of further genetic testing are discussed. Ninety percent of OI cases come from mutations in the COL1A1 gene and the COL1A2 gene. Most mutations are autosomal dominant so our first line of testing would be to obtain a dominant OI panel. Most testing centers include the COL1A1, COL1A2, and IFITM5 (the gene which has been described in OI type V) genes in their dominant OI panel.

 atient Without Known Diagnosis: P Prenatal/Perinatal Clinical diagnosis can begin as early as in utero. Findings on ultrasound may consist of shortened limbs and fractures. A thorough discussion of the in utero diagnosis of OI is beyond the scope of this chapter. We recommend genetic testing once the baby is born using an umbilical cord blood sample. It is also our practice that the type of OI is not be determined until the child is born. Clinical diagnosis can also be made after birth, and it may be consistent with a history of fractures, blue sclera, joint laxity, and dentinogenesis imperfecta. Genetic diagnosis can also be made at any stage of life. Molecular testing can be done in utero through amniocentesis or immediately after birth with a cord blood sample. After delivery, blood may be drawn for DNA analysis if needed to assist in diagnosis. As a side note in our country, due to the high costs of testing, it is our practice to communicate the need for molecular testing with the health insurance carrier to determine if the testing will be covered by their plan.

Classifications David Sillence originally described four basic types  – mild, moderate, severe, and lethal  – which were discussed in Chap. 1. As noted, today there are over 15 types and some may consider

OI as more likely a continuum of disease. While some experts have proposed expanding the original Sillence classification with each causative gene, other experts continue to utilize the clinically based approach and decouple the Sillence classification. The 2015 Nosology and Classification of Genetic Skeletal Disorders established a revised nomenclature to categorize OI by phenotype: type 1, non-deforming; type 2, perinatal lethal; type 3, progressively deforming; type 4, moderate severity; and type V with interosseous membrane calcification or hypertrophic callus [4]. This author (Michael B. Bober) continues to use the Sillence classification and adds only OI type V to the classifications, because it is clinically distinguishable with hyperplastic callus formation. We clinically categorize most if not all of our OI patients into the mild, moderate, severe, or type V OI.

Initial Treatment Planning Initial treatment depends on disease classification in severity and OI type. A treatment plan is developed through a multidisciplinary team. All patients have a baseline audiologic and ophthalmologic evaluation. A dental evaluation is performed if there is dentinogenesis imperfecta. Nutritional counseling is done. Adult patients are recommended to have a baseline echocardiogram

Nutrition Nutritional counseling with attention to calcium and vitamin D is done. We currently use the following guidelines (Table 2.1) for advising on calcium and vitamin D intake [22–24]. We check serum vitamin D level (25 hydroxy) in all of our OI patients. We accept vitamin D levels within normal ranges >30 ng/mL. If serum levels are below normal, the patient must take a supplement, as they are not getting enough through food or sunlight exposure. It is important to recheck a low vitamin D level after 8  weeks after supplementation has begun to make sure the

2  Patient Evaluation and Medical Treatment for Osteogenesis Imperfecta Table 2.1  Calcium and vitamin D: important at every age Age 0–6 months 6–12 months 1–3 years 4–8 years 9–18 years 19–70 years

Vitamin D (IU)/ Calcium mg/day day 200 400 260 400 700 400–600 1000 400–600 1300 400–600 1000 males, 1200 females 600 (600–800 > 50 year)

dose is appropriate. After that levels are checked annually. If a patient is currently on bisphosphonate therapy, then a vitamin D level is checked with each infusion, to decrease the risk for hypocalcemia. Weight is also measured with each patient and is plotted on our OI growth grids. We prefer that all of our patients maintain a lean body mass, to help prevent greater orthopaedic problems in the future. We refer patients who have difficulty maintaining a healthy weight to a weight management clinic.

Splinting and Home Fracture Care All patients receive education on home fracture care and splinting, and pain control with oral medications is discussed.

Pain Control Nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen for acute fracture pain and diazepam for acute fracture spasm are commonly prescribed. All patients receive education on home fracture care and splinting as the primary modality for controlling fracture pain. Judicious use of oral medications is discussed and prolonged administration after acute fracture is discouraged. Use of narcotic medication is minimized; however, in select situations, families may require a prescription to have medications available at home. This may include dose-­appropriate antispasmodics such as diazepam for the patient prone to femoral fracture. It is emphasized that

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splinting is the basis of fracture care and pain relief. A plan for the patient to have timely medical and surgical follow-up is developed depending on specific patient need to minimize the necessity of home medications.

Therapy/Mobility/Activity A multidisciplinary team helps plan patient therapy, mobility, and activity based on patients’ disease severity and developmental status. In the young patient with severe disease, transitioning to sitting or upright posture is not forced if the patient is not developmentally ready for this transition. If able, weight-bearing exercises and core strengthening exercises are important to promote gross motor development and to maximize functional independence and therefore quality of life [2]. Our preferred choice of exercise for all patients with OI is swimming or supervised aquatic exercise. Swimming and aquatics offer opportunities for flexion and extension strengthening exercises. If weight-bearing is prescribed, aquatic therapy can be used to control and adjust resistance to muscular effort and thus limit forces across the bone and joint. This is also an excellent cardiovascular activity for children and adults who are unable to bear any weight on land. We also have a discussion on activities such as contact sports, trampolines, or slides to avoid vertebral fractures.

Developmental Stages Developmental stages in OI may be delayed. This author’s approach is to let each child meet milestones on their own timeline (especially sitting or anything that would cause increased stress on the spine). Pushing an infant or child to sit or stand when not ready can cause added stress on the spine and, with brittle bones, may lead to vertebral compression fractures. Our practice has been to allow a child to sit completely upright, only when they can achieve and maintain this position on their

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own with any assistance or assisted devices. We have tailored infant seats to remain at an angle. We allow patients to stand also when they are ready. Our recommendation is to first stand in the pool, supported underwater to minimize gravity, and then gradually work up to standing-assist devices.

Medical Treatment Decision to Treat In our practice, the indications for using bisphosphonate therapy are any child who has been classified as having moderate or severe OI. Criteria to begin bisphosphonate treatment are based on repetitive fracture, progressive bony deformity, and one or more vertebral compression fractures.

Controversy on Whom to Treat Bisphosphonates remain bound to the bone for years after administration. Bisphosphonates are retained in the skeleton with evidence of renal excretion 8 years after the cessation of pamidronate in young people [13]. Although long-term studies do not suggest adverse effects, there still remains some uncertainty as there is no published long-term data. With unknown data, it does seem prudent to limit the exposure as much as possible to these drugs. Some centers are now decreasing the bisphosphonate dose by half once their bone mineral density z-scores by DXA have improved to >−2.0. Our center chooses this approach as long as the patient is clinically stable. We will repeat a DXA scan roughly 6 months after the dose has been decreased to make sure bone density does not rapidly decline. A systematic review confirmed improvement in bone density in growing children with OI who were treated with bisphosphonates. It also enables improvement of vertebral compression fractures by bone remodeling. There is also described improvement in mobility and functional outcome [4, 5].

Our Approach This author’s approach is to treat with bisphosphonate, pamidronate, for moderate and severe OI until skeletal maturity is reached. Skeletal maturity is assessed by radiographic review of the growth plates. If growth plates remain open, bisphosphonate therapy is continued. Criteria to begin bisphosphonate treatment in mild OI cases are based on repetitive fracture, progressive bony deformity, and/or one or more vertebral compression fractures.

Bisphosphonates The last two decades have seen an increasing use of bisphosphonates in the treatment of OI which is now routinely used for moderate and severe forms of OI. Bisphosphonates are analogs of pyrophosphate that bind to bone mineral and inhibit osteoclast function, reducing bone resorption. Glorieaux and his team published updated reports on the use of pamidronate, a bisphosphonate given by IV in an OI-controlled study and noted a decrease in fracture frequency, improvement in bone mineral density, and improvement of chronic bone pain [2, 21]. Bisphosphonates are inhibitors of osteoclastic bone resorption and bone resorption is also critical to tooth eruption. This means there is potential for dental complications in children receiving bisphosphonates: (1) the potential risk for bisphosphonate-related osteonecrosis of the jaw and (2) delayed tooth eruption and the development of dentition. To date, there have been no reported cases of bisphosphonate-related osteonecrosis of the jaw. There is very limited data to make recommendations about the dental ­management in children treated with bisphosphonates [8]. Histomorphometric studies have been done in children which have shown that bisphosphonates significantly reduce bone remodeling. They do not however reduce bone growth, trabecular bone formation, or periosteal bone formation. Reduced bone resorption and ongoing bone growth result in the significant bone increase in bone mass and

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strength observed when bisphosphonates are administered to the growing child [12]. The two most commonly used bisphosphonates are pamidronate and zoledronic acid. To date there is no data to indicate that one form of bisphosphonate is superior to the other.

Pamidronate This author uses the protocol reported by the work of Francis Glorieux and his group: namely, pamidronate diluted in normal saline, infused over 4  h each day for three consecutive days, cycled every 8–16 weeks depending on age [17]. We begin treatment as early as possible. The decision to delay treatment after osteotomies remains controversial. This author delays infusions after osteotomies until good callous formation is radiographically evident. Infusions are not delayed after fractures. Infusions are generally well tolerated. The primary adverse effect is a febrile acute phase reaction that is common with the first dose. Therefore on the first day of the very first dose, we decrease the dose to one-fourth of the typical dose and one-half of the typical dose on days 2 and 3. We also premedicate with acetaminophen each day. This will hopefully decrease the acute phase reaction. Transient hypocalcemia after an infusion is also seen on occasion, but has rarely been reported of clinical significance with pamidronate. We perform pretreatment assessment and normalization of vitamin D status and calcium intake to lessen this potential effect. We may also check an ionized calcium prior to infusion if there is heightened concern. Atypical femur fractures [1, 3] have been associated with prolonged pamidronate treatment. There are case reports of children on long-­ term, cyclic pamidronate treatment who develop fractures without trauma or with minimal trauma in the subtrochanteric or diaphyseal regions of the femur over preexisting intramedullary rods. This raises concern about the role of prolonged remodeling suppression [3]. More recent publications, however [18, 20], in children with OI

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suggest that these fractures may more closely relate to the severity of the OI than to the history of bisphosphonate exposure. Treatment with pamidronate therapy has been found to improve bone mineral density, improve mobility, decrease fracture rates, prevent further severe deformities, and improve patient quality of life [7].

Zoledronic Acid The advantage of zoledronic acid over pamidronate is that the infusion is given over 30 min compared to that of the 4 h of pamidronate for a single infusion. Small randomized studies have shown results are comparable for both drugs although larger, long-term studies have not been published [9]. This author’s experience is that zoledronic acid more frequently causes significant hypocalcemia and acute phase reactions when compared to pamidronate. At the time of this writing, long-­term data is not available. Until more long-term data is available, we will continue to use pamidronate.

Other Bisphosphonates Alendronate  One study compared the use of alendronate to zoledronic acid. This study concluded that both medicines had similar effects on increasing BMD in children and adolescents; however, zoledronic acid was superior in reducing the clinical fracture rates [9]. Risedronate  One study done in 2009 examined the use of oral risedronate in pediatric patients with mild osteogenesis imperfecta. This was a single-center randomized double-blind placebo-­ controlled trial done over 2  years. This study showed lumbar spine BMD z-scores by 0.65 although no significant differences in bone mass were found at the radial metaphysis and diaphysis, hip, and total body. There was also no detectable effect on vertebral morphometry, second metacarpal cortical width, grip force, bone pain, or fracture rate [11].

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Other Treatments

Patient Monitoring and Follow-Up

Growth Hormone

For patients under 1 year, we maintain follow-up every 6 months At this 6-month visit, we assess fractures: rates, modes of injury and treatment, growth, diet, and nutrition. For patients over 1  year, we follow annually and obtain fracture history, medical history, and surgical history. We obtain images of AP/Lat spine, bilateral lower extremities, gait analysis, DEXA scan, and 25-OH vitamin D level.

Growth hormone has been used as a treatment for OI.  Currently there is no published data suggesting that their use has any longterm benefits to growth or effect on fracture rates. One study published by Antoniazzi et al. [19] suggested synergy between growth hormone and bisphosphonates; however, further research is needed [10].

Annual Echocardiograms for Adults Monoclonal Antibodies Denosumab is a RANK ligand antibody that prevents RANK ligand-RANK interaction and inhibits osteoclast formation, thus reducing bone resorption. Denosumab has been approved for the treatment of postmenopausal osteoporosis. There is very little research available about the effectiveness of denosumab in children with OI.  A brief report was done by the Acta Paediatrica on denosumab in 2018, describing that the quality of evidence on the treatment effects of denosumab was “sparse, limited and inconclusive” [14].

Combination Therapies Combination therapies are ongoing and are lacking published data. One such study combines scl-­Ab (anti-sclerostin monoclonal antibodies) along with zoledronic acid treatment in relevant mouse models. After 9 weeks of treatment with combination therapy, there were significant increases in bone mineral density in the tibia in OI mice and even greater increases in bone mineral density of the spine in OI mice. Further studies using alternate types of OI mice would need to be completed to validate the efficacy of anti-sclerostin antibodies/zoledronic acid treatment [15].

We recommend that each patient has routine dental visits every 6 months, annual ophthalmology screening, and audiological screenings as needed. Annual visits are tailored to the need of each unique individual patient. Every patient has annual DEXA scans, two-view standing spine X-rays, and two-view hip through ankle X-rays. They also have annual vitamin D levels checked and dietary intake of daily calcium assessed. Other X-rays are obtained on an as-needed basis. If a patient is on bisphosphonate therapy, we obtain a CMP, 25-OH vitamin D level, and phosphorus assay with every infusion. We also obtain a urinalysis and urine and calcium and creatinine ratio, with every infusion. We also check a urine HCG for any postmenarchal female, prior to each bisphosphonate treatment. Outcome Measurements: The use of patient reported outcome measurements is important to monitor effectiveness of care. The use of PROMIS or Patient-Reported Outcomes Measurement Information System (PROMIS®), which is the patient-reported outcome platform funded by the National Institutes of Health, has also been particularly advantageous. There is ongoing discussion in the medical community on which specific outcome measurement tools are most useful, but monitoring is critical to optimizing care. PROMIS® harnesses a set of measurement tools that use computer adaptive technology and person-centered measurements to evaluate and monitor physical, mental, and social health in adults and children.

2  Patient Evaluation and Medical Treatment for Osteogenesis Imperfecta

One other way we address the functional status on individuals with OI is by performing a 6 min walk test or video gait analysis in ambulatory patients. This helps us measure progression or deterioration of endurance and ambulation.

References 1. Etxebarria- Foronda I, Carpintero P. An atypical fracture in male patient with osteogenesis imperfecta. Clin Cases Miner Bone Metab. 2015;12(3):278–81. 2. Zeitlin L, Fassier F, Glorieux FH. Modern approach to children with osteogenesis imperfecta. J Pediatr Orthop. 2003;10:77–87. 3. Hegazy A, et  al. Unusual femur stress fractures in children with osteogenesis imperfecta and intramedullary rods, long term intravenous pamidronate therapy. J Pediatr Orthop. 2016;36:757–61. 4. Biggin A, Munns CF. Long-term bisphosphonate therapy in osteogenesis imperfecta. Curr Osteoporos Rep. 2017;15:412–8. 5. Rauch F, Glorieux FH.  Osteogenesis imperfecta. Lancet. 2004;363:1377. 6. Arponen H, Makitie O, Walimo-Siren J. Association between joint hypermobility, scoliosis, and cranial base anomalies in paediatric osteogenesis imperfecta patients: a retrospective cross-sectional study. BMC Musculoskelet Disord. 2014;15:428. 7. Marginean O, Tamasanu RC, Mang N, Mozos I, Brad GF. Therapy with pamidronate in children with osteogenesis imperfecta. Drug Design Dev Ther. 2017;11:2507–15. 8. Bhatt RN, Halbert SA, Munns CF.  The use of bisphoshonates in children: review of the literature and guidelines in dental management. Aust Dent J. 2014;59:9–19. 9. Lv F, Liu Y, et  al. Zoledronic acid versus alendronate in the treatment of children with osteogenesis imperfecta: a 2- year clinical study. Endocr Pract. 2018;24(2):179–88. 10. Thomas IH, DiMeglio LA. Advances in the classification and treatment of osteogenesis imperfecta. Curr Osteoporos Rep. 2016;14:1–9. 11. Rauch F, et  al. Risedronate in the treatment of mild pediatric osteogenesis imperfecta: a randomized placebo- controlled study. J Bone Miner Res. 2009;24:1282.

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12. Simm PJ, Biggin A, et al. Consensus guidelines on the use of bisphosphonate therapy in children and adolescents. J Paediatr Child Health. 2018;54:223–33. 13. Papapouls SE, Cremers SC.  Prolonged bisphosphonate release after treatment in children. New Engl J Med. 2007;356:1075–6. 14. Li G, Jin Y, MAH L, Hoyer-Kuhn H, Ward L, Adachi JD. Systematic review of the effect of denosumab on children with osteogenesis imperfecta showed inconsistent finding. Found Acta Paediatr. 2018;107:534–7. 15. Little DG, Peacock L, et  al. Combination sclerostin antibody and zoledronic acid treatment outperforms either treatment alone in a mouse model of osteogenesis imperfecta. Bone. 2017;101:96–103. 16. Stagi S, Cavalli L, et al. Peripheral quantitative computed tomography (pQCT) for the assessment of bone strength in most of bone affecting conditions in developmental age: a review. Ital J Pediatr. 2016;42:88. 17. Munns C, Rauch F, et al. Effects of pamidronate treatment in infants with osteogenesis imperfecta: clinical and histomorphometric outcomes. J Bone Min Res. 2005;20:1235–43. 18. Trejo P, Rauch F. Osteogenesis imperfecta in children and adolescents – new developments in diagnosis and treatment. Osteoporos Int. 2016;27:3427. https://doi. org/10.1007/s00198-016-3723-3. 19. Antoniazzi F, Monti E, Venturi G, Franceschi R, Doro F, Gatti D, et  al. GH in combination with bisphosphonate treatment in osteogenesis imperfecta. Eur J Endocrinol. 2010;163(3):479–87. 20. Trejo P, Fassier F, Glorieux FH, Rauch F. Diaphyseal femur fractures in osteogenesis imperfecta: characteristics and relationship with bisphosphonate treatment. J Bone Min Res. 2017;32(5):1034–9. 21. Glorieux FH.  Experience with bisphosphonates in osteogenesis imperfecta. Pediatrics. 2007;119(Suppl 2):S163–5. 22. Wagner CL, Greer FR. Prevention of rickets and vitamin D deficiency in infants, children, and adolescents. Pediatrics. 2008;122(5):1142–52. 23. Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96(7):1911–30. 24. National Institutes of Health. NIH osteoporosis and related bone diseases National Resource Center. Calcium and vitamin D: important at every age. 2013. https://www.bones.nih.gov/health-info/bone/ osteoporosis/overview.

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Therapy, Orthotics and Assistive Devices for Osteogenesis Imperfecta Maureen Donohoe

Introduction

Newborn Nursery

It is well documented that physical therapy and occupational therapy are important to the care of individuals who have osteogenesis imperfecta (OI). Those who have bone fragility often have gross motor and fine motor delays. Even those with the mildest forms of OI may have motor delays related to fractures and hypermobility [1]. That does not mean that every gross motor delay should be addressed aggressively, as natural gains in muscle strength are often seen over time. There are key places where therapy is an important component in care. These include in the newborn nursery, during postfracture or postsurgical care, in the school environment, and as a part of conditioning for lifelong activity and fitness opportunities. Measurement to assess current level of function, to qualify for service, and to track efficacy of treatment is an important component of therapeutic intervention. Although all do not need them, assistive devices and orthotics may be used to enhance mobility.

In the new born nursery and the neonatal intensive care unit (NICU), the physical therapist complements the nursing team in training the family in safe handling techniques. Families need to learn handling strategies for positioning, bathing, dressing, and feeding [2]. In the face of fracture-­ related pain, the early handling techniques are important to gain caregiver comfort and bonding with the child. As the child’s caregiver learns to hold the baby and manage the day-­ to-­day baby care issues, the caregiver also learns strategies to calm the baby as well as differences in the baby’s cry, which could signal a fracture. When the child is medically ready to go home, it is important to establish safe transportation for the baby. Handling techniques include lifting the child with hands spread wide and support given through the trunk and head. One should avoid lifting through arms or legs, as this distal pull puts fragile extremities at risk of fracture. When

M. Donohoe (*) Nemours/Alfred I duPont Hospital for Children, Wilmington, DE, USA e-mail: [email protected] © Springer Nature Switzerland AG 2020 R. W. Kruse (ed.), Osteogenesis Imperfecta, https://doi.org/10.1007/978-3-030-42527-2_3

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diapering a newborn, rolling the baby from side to side while cleaning the diaper area is better than lifting through the legs to support the diaper change. Although handling a fragile baby can be frightening to caregivers, the benefits of holding a baby and having the baby bond through touching are important [3]. Teaching caregivers strategies to hold the baby is important. Even the most fragile baby can be held, but it may take two people working together to initially position the baby so everyone can relax and enjoy the experience. Although having the baby lifted and carried on a pillow is often easier for the parent, the child will naturally get stronger and more comfortable with movement, if the caregivers learn how to hold the baby in their arms. Initially, if the baby is on a receiving blanket in the crib, it gives a total contact support to help lift the child. If a parent is nursing, it is often helpful in the first few days for the mother to be positioned well and then have another caregiver lift the baby and hand off to the mother, helping to gain an optimal ­position for feeding, for both the mother and the baby. Positioning strategies are important as the newborn needs to feel comfortable in a wide variety of positions. Those with very soft bones, left lying only on their back, will develop plagiocephaly. Careful positioning on the head and neck allows the child to scan the environment and not be limited by the rotational bias caused by a flat spot on the back of the head. Sleeping in a supine position is always preferred, but when the child is awake and well monitored by adults, the baby can be positioned in side lying and even prone. If the baby has much larger head in proportion to the body, positioning in prone (tummy time) may be difficult. This does not mean it

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should be avoided, but rather using caregivers to prop the baby chest to chest helps gain a comfort in prone that can be developed further over the next few months. Bathing activities often begin with sponge baths, but once the umbilicus has dropped off, the baby can be submerged in a baby bathtub. Typically, the baby does not go in a tub in the newborn nursery, but educating families as to soft-sided infant tubs and reclined supports to allow the baby to be submerged but keeping the head out of the water. It is also helpful to let the water out of the tub and dry the infant first rather than trying to manage a slippery, wet baby who is fragile. A newborn with OI presents with many clothing challenges. Clothing needs to be able to accommodate splinting for fracture management. It should allow easy access for diaper changes and, yet, not too much material that the child gets caught up in the garments. Clothing that opens wide from the front or the back is easier to manage than items that pull overhead. Clothing that allows both legs to be exposed such as snap open bottoms of stretch material pants that pull off makes diaper access easier when rolling the baby for diaper changes. Before leaving the hospital, the infant should undergo what we call an Infant Car Seat Challenge. This determines if the child can safely ride in a semi-reclined position. If the baby is not able to be positioned well in a typical infant car seat, with straps tightened to safety standards and maintaining a safe level for heart rate, respiration rate, and oxygen saturation for 90–120 min, the baby should be tested in a car bed [4]. Please refer to Table  3.1 for checklist of important care considerations before discharge from the NICU.

3  Therapy, Orthotics and Assistive Devices for Osteogenesis Imperfecta Table 3.1  Care consideration checklist prior to discharge from newborn nursery Caregivers have strategies for positioning at home for sleep including times of fracture Caregivers educated on the importance of recumbent positioning of the child until the baby is naturally seeking more upright alignment, independently Caregiver competent in diapering, dressing, and bathing the newborn Caregivers have strategies for positioning for feeding at home without support staff orchestrating the care Caregivers have splinting strategy for new fractures, until they can seek medical support Infant has been assessed for car seat safety and a plan for safe transportation in an automobile has been determined Referral has been made to community-based services such as home nursing or early intervention services, if needed

Infant Case Study

The baby was born at 37  weeks gestation via caesarian section and with fractures of two ribs, left femur, and right humerus. The baby spent 8 days in NICU, mostly to help with family training and to address some feeding issues. The baby is ready to go home and has been referred to PT for a car seat checkout and support in positioning strategies. Formal developmental testing was not performed due to the fractures. Handling was kept to a minimum, but family was taught to move and lift with support through the head and trunk. Family was educated to support interactive play but to not push upright alignment at this time. When car seat testing was done, it was found that the baby could not be positioned comfortably in a traditional infant car seat as heart rate was high and the baby’s saturation rates dropped over less than 5 min of sitting. It was felt a car bed was the safest means of transporting the baby at this time. The baby was able to be safely positioned

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in the car bed for over 30  min with no changes in heart rate or saturation rates, deeming this positioning to be safe for transport to home. Family was instructed on how to secure the baby in the car bed as well as how the car bed is installed in the car. The car bed’s owner’s manual was given to the family for reference when installing in the car.

Early Intervention Children born with documented diagnosis of OI are often referred to early intervention (EI) services. EI supplies family support services for the child between birth and 3 years of age including early childhood education, occupational therapy, physical therapy, and speech therapy. The EI team tests the child using standardized tools in order to identify needs. The child may test below age-matched peers for gross motor skills, qualifying the child for service. Despite the measured delay, facilitating gross motor skills is not always appropriate. Natural development of strength and mobility against gravity with attention to positioning to enhance natural development should be the emphasis of care. Many of the standardized testing tools looking at developmental skills include skills involving jumping, hopping, and ball play, which may put a child at risk of fracture. Although the tools are not contraindicated for all individuals who have OI, the therapist should proceed with great caution and make safe choices when testing children. Children who are mildly affected may be delayed in hopping and jumping skills, but this deficit should not be an area of focus for therapy as the risk of fracture while working on the skills is higher than the benefit from gaining the skill. Please refer to Table 3.2 to identify testing tools helpful in this age range.

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24 Table 3.2  Evaluation tools Multitask tests BAMF,: Brief Assessment of Motor Function: sets baseline skill Bayley Scales of Infant and Toddler Development

Bruininks-­ Oseretsky Test of Motor Proficiency (BOT-2)

GMFM, Gross Motor Function Measure

Movement Assessment Battery for Children 2nd edition

Peabody Developmental Motor Scales 2nd edition (PDMS-2)

Age range

Tasks

Positives

Negatives

5 months to 18 years

Assesses  Gross motor  Fine motor  Oral motor

Tool specifically for OI Quick to administer and identify baseline skills for OI Norm referenced Observational multidimension skills compared to typically developing peers

Cintas et al. Screening tool therefore it does not [13] help plan for treatment

Norm referenced compared to typically developing peers Diagnoses motor impairments

Higher-level gross Deitz et al. motor tasks involve [15] high impact activities potentially putting the individual at risk of fracture

1–43 months

Five domains  Adaptive behavior  Cognitive  Language  Motor  Social Emotional 4 to 21 + Eight subtests 11 years  Fine motor precision  Fine motor integration  Manual dexterity  Bilateral coordination  Balance  Running speed and agility  Upper limb coordination  Strength 5 months to Five dimensions 16 years  Lying and rolling  Sitting  Crawling and kneeling  Standing  Walking, running and jumping 3 years to Assesses 16 + 11 years  Manual dexterity  Ball skills  Dynamic balance  Static balance

Birth to 6 years

Six subtests  Reflexes  Stationary  Locomotion  Object manipulation  Grasping  Visual motor Integration

Tracks individual against oneself

Screening tool to determine if more testing is needed Does not qualify individual for service

Tool does not compare individual to general population therefore may not qualify for educational services Observation of motor Higher level gross tasks motor tasks involve high impact Takes into account activities emotional and potentially putting motivational difficulties for tasks the individual at risk of fracture Compared individual Higher-level gross motor tasks involve against typically high impact developing activities individuals. Useful potentially putting for qualifying for the individual at therapy services risk of fracture

Reference

Bayley [14]

Ruck-Gibis et al. [16]

Engelbert et al. [17]

Wuang et al. [18]

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Table 3.2 (continued) School Function Assessment (SFA)

Age range 6–12 years

Tasks School-related tasks assessed in terms of  Participation  Task support  Activity performance

Patient-recorded outcome measures 4–18 years Assistance for travel Functional distances Mobility Scale  5 m (FMS)  50 m  500 m 6–18 years Themes OI Qual:  Being safe and OI-specific quality careful of life scale  Reduced function  Pain  Fear  Isolation  Independence 0–8 years Assesses Pediatric  Activities of daily Evaluation of living Disability  Behavior Inventory (PEDI):  Cognition assesses ADL  Communication  Eating  Functional mobility  Infant and child development  Language  Life participation  Reasoning and problem solving  Social relationships 0–21 years Assesses Pediatric  Activities of daily Evaluation of living Disability  Cognition inventory-­  Communication Computer Adaptive  Developmental Test (PEDI-CAT):  Functional assesses ADL mobility  Language  Life participation  Social relationship  Upper extremity function

Positives Tool designed to look at specific school-based tasks. Helpful in establishing school-related functional goals

Negatives Reference Based on judgment Davies et al. [19] of teacher and/or therapist

Self-report of assistance needed over various distances

Kerr et al. Tool has not been validated for the OI [20] population

Diagnosis-specific quality of life survey Useful for diagnosis-­ specific research

Does not predict quality of life compared to the general population

Looks at functional skills including caregiver assistance and modifications needed for the tasks

Haley et al. Paper-based tool [22] requiring 30–60 minutes to complete. Limited age range compared the computer-based version

Cohen and Biesecker [21]

Compares to individuals who do not have disabilities

Computer access Gives comparable required for use data to PEDI, but CAT version requires less than 10 minutes to administer

Haley et al. [23]

(continued)

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26 Table 3.2 (continued) Age range 5–17 years Participation and Environment Measure for Children and Youth (PEM-CY)

Tasks Measures participation in home, school, and community  Participation frequency  Involvement  Environmental barriers  Participation support Pediatric Outcomes Parent report Assesses  Upper extremity ages 2–10 Data Collection function Child report Instrument  Transfers and ages 11–18 (PODCI) mobility  Physical function and sports  Comfort (lack of pain)  Happiness  Satisfaction  Expectations Parent report: Assess Patient-Reported  Physical health 5–17 Outcomes Child report:  Mental health Measurement  Social health 8–17 Information System (PROMIS) Adult: 18+

Timed tasks 2 min walk test

3 years– elderly adult

Distance travelled in 2 min Allows for use of assistive devices

Positives Negatives Parent or child report Not validated for the OI population on ability to participate Includes report on the child’s health condition and functional issues

Reference Anaby et al. [24]

Parent or child report Tool does not have a comparable adult tool designed for measure musculoskeletal disorders Compares individual against age-based norms

Daltroy et al. [25] Sousa et al. [26]

Health measure to identify functions, symptoms, behaviors, and feelings Compares individual to the general population Available in paper version (long and short forms) and Computer Adaptive Tests (CAT) Tests have been translated to >40 languages Tools grow with the individual, allowing tracking similar dimensions across the life span

Not validated for the OI population Need to administer the same dimensions over time to track change Not every test has been translated CAT versions need a repository to hold the information such as an electronic health record or REDCap Paper versions may be perceived as lengthy to perform

PROMIS [27] Tosi et al. [28]

Endurance measure high correlation to the 6 min walk test Tracks individual against oneself Useful in a situation where multiple tests are performed in a short period of time Allows retest with different assistive devices

Not validated for the OI population

Bohonnan et al. [29] Bohonnan et al. [30]

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Table 3.2 (continued) 6-min walk test

Age range 2 years– elderly adult

10-m shuttle ride

Not established

Gait speed

Not established

Jebsen Hand Function Test

6 years– elderly adult

Timed Unipedal Stance

4 years– elderly adult

Timed “Floor to Stand” (TFTS)

5–14 years

Tasks Distance travelled in 6 min Allows for use of assistive devices

Positives Tracks individual against oneself Norm referenced with the general population as well as with a variety of diagnoses Useful for establishing endurance-based goals, especially in the school environment Validated test for Test of youth who have OI cardiorespiratory and use a manual fitness wheelchair part of the day. Tracks individual against oneself Tracks individual Ability to travel against oneself for across defined defined distance distance Able to use assistive devices as needed Able to compare assistive device versus no assistive device Able to test speed on stairs Assesses hand skills Able to track individual against  Writing oneself  Card turning  Picking up small Able to compare sides objects Helpful pre- and  Stacking postsurgical  Simulated intervention to feeding document change  Moving light Normed against the objects general population  Moving heavy objects Able to track Assesses individual against  Balance oneself  Strength Able to compare sides Normed against the general population Useful tool for Tests balance, functional mobility, school-age children who may need to get and gait Involves transferring up and down off the floor as part of to and from the classroom activities floor

Negatives Tendency to fatigue the individual during the task therefore retest looking at with and without an assistive device may not give consistent data Not validated for the OI population

Reference Klepper and Muir [31] Lammers et al. [32]

Only those who use Bongers et al. [33] a manual wheelchair on a regular basis

Must define task for No reference distance and supports needed to be able to track change over time

Not validated for the OI population Assesses speed not quality of performance

Sears and Chung [34]

Proceed with caution for those with lower extremity fracture risk

Condon and Cremin [35]

Weingarten Tool has not been validated for the OI et al. [36] population

(continued)

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28 Table 3.2 (continued) Timed transfers

Age range Not established

Tasks Transfer tasks specific to the individual

Timed “Up and Go” (TUG)

5 years – elderly adult

Tests balance, functional mobility, and gait

Case Study: A Tale of Two Toddlers

Two children were diagnosed with the same gene mutation and presented in clinic at 3 months with very similar presentation. Both families were encouraged to keep the child in a recumbent position until actively pursuing more upright mobility. This means rolling and reaching as well as prone time is encouraged, but positioning with head against gravity above the pelvis should be discouraged. One family went home and focused on supine play and rolling activities. Emphasis was on floor play. Around 7 months of age, this family started to work on sitting skills but noticed the child’s back was starting to become more kyphotic. Their physician warned of the potential for microfractures in the spine caused by the facilitated upright positioning. Due to the fear of this, the family went back to recumbent positioning and play with emphasis on rolling. They had occupational therapy services support them in age-appropriate play activities, adapted for the alignment. They had a physical therapy consult working on aquatic strengthening and took the child

Positives Tracks individual against oneself Compare speed based on transfer height, transfer type, and equipment used Helpful in defining energy efficiency and level of support needed Quick to administer Normed to general population and validated to some specialty populations

Negatives Reference Defined assistance, No heights, materials, reference and surfaces necessary for reproducibility Consistency in variables necessary for information to show change Williams Tool has not been validated for the OI et al. [37] Itzkowitz population et al. [38] Podsiadlo and Richardson [39]

swimming in their oversized bathtub two to three times a week. At the age of 18 months, the child started to push up to sit. At that time, sitting skill was supported for short periods of time. At age of 2 years, X-rays showed no bony changes in the spine (see Fig. 3.1). The other family used infant seats and carried the child consistently upright of the parent’s shoulder. They felt their child was happier upright and able to interact better when sitting. Although they had the same warning of risk of microfractures in the spine, they felt upright was best. Therapy facility sitting skills eventually developed around 18 months of age. They pursued a wheelchair in the first 2 years. PT and OT worked on skills in sitting and upright alignment as tolerated. Rolling skills were not the emphasis, as the family was fearful of the child fracturing with rolling activities. Around 2  years of age, the X-rays revealed multilevel anterior compression fractures of the vertebral spine, resulting in bony changes into kyphotic alignment (see Fig. 3.2). Please refer to Table 3.2 to identify testing tools helpful in this age range.

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School-Based Therapy Services

Fig. 3.1  2-year-old’s spine after unfacilitated upright activities

Fig. 3.2  2-year-old’s spine after facilitated upright activities during the 1st year of life

Although there is no research to support the bias toward using natural development of sitting in the OI population, there is research that matches in the achondroplasia population. The take-home message is that making an attempt to prevent compression fractures of the spine protects the spine early on from lifelong spinerelated issues [5–7].

A child who has fine motor, gross motor, and/or language-related delays that could interfere with the educational process at a deficit of 25% delay when compared to typically developing peers can qualify for therapy services in a public school environment. In the United States, public schools develop an individual education plan (IEP) including goals the therapists and teachers plan to achieve with the child throughout the school year. In this plan, the educational team identifies with the family strategies and equipment to create success on a day-to-day basis as well as in the case of an emergency. Often a child who qualifies for service has direct service in the classroom (push-in service) or, during the school day, outside of the classroom (pull-out service). Where the service occurs is based on the child’s needs. Sometimes therapy services are provided on a consultative basis to support the educators, when the child does not get direct services. This helps with strategies to enhance positioning in the classroom, to educate for transfers in the bathroom, to support safe playground activities, and to identify any equipment adaptations that may be needed for success in the classroom. Therapist support may be more intensive around times of fractures or postoperative periods. When restriction for participation in physical education is in place, therapy may be helpful in identifying fitness activities the child can perform safely to support gaining strategies for lifelong fitness from an early age. The American Academy of Pediatrics recommends children have a daily physical activity goal of 60  min. Creating opportunities for the significantly involved child helps gain strength and fitness and helps combat obesity [8–10]. Physical therapy should not be a replacement for physical education but rather a support to help the child gain skills addressed in the physical education class. The therapist often supports the physical education teacher in identifying safe adaptations to keep the child safe and physically active. In the United States, if a child does not have a 25% delay in skills, what is known as a “504 plan” is sometimes put into place. This will give

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the child time, space, and materials to enhance educational access. Although the 504 plan does not give direct therapy services, physical therapist (PT) and occupational therapist (OT) participate in the 504 plan to help determine what is needed in terms of time to complete tasks, what special environmental supports are needs, and the specific materials the child may need including seating, desk adaptations, storage for personal items, extra sets of books, computer access, and any other adaptive equipment needed for success in school. Please refer to Table  3.2 to identify testing tools helpful in this age range.

Nonambulatory Middle School Student

A 12-year-old attends seventh grade and uses a motorized wheelchair for mobility. There is a classroom aide to support management of materials and to assist with toilet transfers during the day. The child has school-based physical and occupational therapy to support the educational process with the hope of reducing reliance on a personal assistant with greater management of materials. Although there has not been a fracture or a surgery in 3  years, the child and family have not been eager to work on better independence. Using the School Function Assessment, it was found that the child required assistance for all gross motor tasks including playground activities, transfers, and mobility through the classroom and hallways in the motorized wheelchair. For computer use, there was not a wheelchair accessible computer nor was there an appropriate desk to use a laptop. There was an emergency exit plan for when the child was on the first floor, but when traveling to higher floors using an elevator, there was no exit plan. The IEP did include an emergency plan if a fracture should occur at school. The PT and OT worked together with the teacher and the aide to identify daily needs and how to adjust the environment to help gain better independence. Desks were

rearranged to allow better access to various areas in the classroom, without added assistance. Materials were set up for easy access. A mount was purchased for the laptop computer so books and written work were easily accessible via the computer. Strategies were designed for managing the cafeteria, including how to drive and carry the cafeteria tray. The child learned how to do level scooting transfers from wheelchair to another chair, in preparation to use an evacuation chair down the stairs in the event of an emergency in the building when on the second floor. This transfer skill later was useful in gaining transfer skill to a transfer bench next to the toilet, reducing the need to be lifted throughout the day. A key component to success on this skill was learning clothing management which occurred during medically based occupational therapy. Strengthening and cardiovascular endurance became a focus for the rest of the school year. A manual wheelchair was available for use during gym classes. Use of this chair for timed activities became goals for the school year. A 6-min roll in the manual chair was performed at the start of the school year and monthly. This documented distance travelled in 6  min. Transfers were timed at the start of the school year, documenting height of transfer surface, setup needed, and amount of time to complete task. On the playground, the child had the opportunity to learn power hockey, with the stick attached to the wheelchair. Badminton and tether ball with a beach ball were added to activity options. These overhead reaching activities helped with scapular strengthening and translated to better access to writing on the white board in the classroom. At the end of school year, the classroom aide was assisting as needed, but there was a 75% reduction in one-on-one support throughout the classroom day. Speed

3  Therapy, Orthotics and Assistive Devices for Osteogenesis Imperfecta

increased when using the manual chair and distance travel improved by 200%. Transfers improved to allow a standby assist scooting transfer to an evacuation chair, allowing safe egress, in the case of an emergency. Also, in the case of an emergency where the motorized wheelchair was left on the second floor, the child had ability to use a manual chair for school distances.

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Table 3.3  Care consideration checklist for discharge after surgical intervention or major fracture with spica cast Caregivers able to manage transfer status Strategy for bowel and bladder management Vehicle transportation worked out via car seat, seat belt system, or medical transportation There is a pain management strategy The individual has several position options to limit potential for skin breakdown

The Ambulatory Child After Fracture

 ostfracture Medically Based P Service In the acute care environment, postfracture and postsurgical therapy intervention’s focus is on strategies to get the individual home. This includes caregiver education for transfers. The individual may require a car seat, a seat belt system, or medical transport to leave the hospital. Please refer to Table  3.3 for care consideration checklist for discharge after surgical intervention or major fracture with spica cast. The need for therapy following a fracture tends to be on a case-by-case basis. Often after a few episodes of care following fractures, families become well versed on strategies to get the individual back to baseline function. Those who have been immobilized for a prolonged period or have lost a significant amount of function benefit from strengthening and training to regain skills. A baseline evaluation of present skills and an assessment of prior function helps to plan treatment, with the goal of getting back to prior function or better. In growing children with progressive bowing of the long bones along with fractures, surgical intervention is often considered to rod the bones in a straight alignment. While waiting for the correct timing of surgery, sometimes clamshell bracing is used to hold the limb circumferentially and to reduce the deforming forces of gravity and weight-bearing. Please refer to Table 3.2 to identify testing tools helpful in identifying functional measures when evaluating an individual after fracture in order to establish therapy goals and to track progress.

A 7-year-old was playing on the playground running with friends and fell, fracturing midshaft tibia, radius, and ulna on the same side. The family splinted the extremities in advance of the physician appointment. Two days later the child was casted for arm and leg. They were given a wheelchair and a forward walker with a forearm attachment, allowing weight-­ bearing through the upper arm. The family investigated a knee scooter, as it would allow modified weight-bearing and better speed, but they found that the device does not come small enough for the child. Six weeks after the fractures, casts were removed. The child who had not been walking consistently was referred to physical therapy to get moving again. The following tests were performed: range of motion, timed floor to stand, GMFM, PEDI-CAT, and 2-min walk test. Significant limitations were noted in skills. On the GMFM, limitations were noted on the standing, walking, running, and jumping dimensions. The child and family were fearful of reinjury. It was decided to work on skills in an aquatic environment. Working on strengthening, endurance, and mobility in a gravity-reduced environment quickly allowed improvement and comfort in skills. Once there was a comfort level performing higher-level balance skills in waist deep water, the emphasis of therapy was moved to a land-based program with emphasis on regaining skills but also in

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symmetry of strength. Focus ended up being on hip strength as it had gotten very weak from the 6 weeks being immobilized. By the end of the 6  weeks of therapy including three visits in the pool and three visits on land, the family had a home program they could manage, and the child had returned to running and walking on the playground.

The multidisciplinary approach to the treatment of children and young people living with OI seeks to provide well-coordinated, comprehensive assessments and interventions that place the child and family at the very center of their care. The coordinated efforts of a multidisciplinary team can support children with OI to fulfill their potential, maximizing function, independence, and well-being [11].

Case Study: Nonambulatory Adult

Multidisciplinary Clinic Multidisciplinary clinics for OI often include geneticist, orthopaedic surgeon, physiatry, orthotists, physical therapists, occupational therapists, and clinical nurse practitioners to come up with an organized plan of care for the individual [1]. Consultation with the therapist in the clinic is often an opportunity to collect data on how the person is doing and to identify if referrals for more intervention are needed. Annual data collection is helpful to insure the individual is making gains and if there is a problem, to address it. If there is surgical intervention planned, recording skills prior to surgery is helpful to know baseline and move toward baseline and beyond after surgery. Looking at testing in the clinic, it needs to be relatively quick to administer and provide information that is useful as it will grow the child into adulthood. Patient-recorded outcome measures help tease out areas of strength and need as perceived by the parent and the child. Please refer to Table 3.2 for a variety of patient-recorded outcome measures. Range of motion and strength are often addressed especially if there are self-care and mobility deficits related to alignment and strength [12]. An endurance measure such as the 2- or 6-min walk helps track cardiovascular fitness over time. For those who do not walk, a roll test can be performed if the individual has a manual wheelchair.

A 28-year-old comes into the clinic. The individual’s height versus weight puts the body mass index (BMI) into the obese range. The referral to physical therapy is to increase activity to help with weight loss. On examination, the family reports they perform all transfers to avoid the risk of fracture. There is complete dependency for self-care activities for the individual in order to save time during the day. A motorized wheelchair is the only means of mobility. PROMIS scores report that there is no skill on the physical mobility and upper extremity function dimensions, based on self-report. Despite the significant physical limitations, the dimensions looking at social interactions, pain, and fatigue rank within normal limits for the general population. There is no interest in exercise. In the past swimming was the preferred exercise, but as the parents have aged, and transfers have become more challenging for them, they have not gone swimming in over 10  years. Conversation leads to personal responsibility of energy expenditure matched with monitoring intake of calories. Encourage participation in dressing activities including donning and doffing upper body clothing each day and self-­ brushing of teeth. Although these seem like small tasks, the body movements needed to participate translate to exercise in the severely deconditioned individual. Adding

3  Therapy, Orthotics and Assistive Devices for Osteogenesis Imperfecta

in ball play with the family dog several days a week adds the opportunity to use upper body outside the normal tasks of using a joystick and a keyboard. Having the individual track calorie intake via a phone app and track calorie expenditure through a fitness tracking device helps establish baselines in order to build a program in the future. The key is to start a program based on functional tasks that fit in the person’s life. Knowing a baseline helps all parties become more involved with enhancing activities and decreasing unintentional excessive calorie intake. Once there is buy into establishing baselines, the key is to progressively increase daily activity expectations for ADL prior to adding in exercise. Work on rolling and scooting in bed in advance of transfers or as a part of assisting caregivers in lower body dressing is a natural way to work on increasing activity that will eventually use some of those skills.

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Orthotic Management The use of lower extremity orthotics is based on individual need. Not everyone needs orthotics, and the amount of bracing is truly based on overall alignment. Before the consistent use of bisphosphonates in treatment of OI, bracing was one of the few treatments to help mobilize children. With stronger bones, the child’s risk of fracture is higher off the top of the brace, than it is with no brace. The bias is to use less bracing if possible. One caveat is when there is a progressive bow in a long bone and the individual is not ready for surgical intervention, use of a circumferential brace or a clamshell-type brace that supports the bone may help reduce fracture frequency while waiting for intervention. Those with OI tend to have hypermobility of joints and often have pronated feet that limit ambulation comfort. Adding support to the longitudinal arch often is helpful. This can be with custom-molded orthotics or with off-the-shelf orthotics if the foot corrects easily. Please refer to Table 3.4 Lower Extremity Orthotics for the wide range of orthotic options.

Table 3.4  Lower extremity orthotics Supportive insoles

Supramalleolar orthotics

Ankle foot orthosis

Rationale Orthotic designed to support the longitudinal arch of the foot Best for a pronated foot with no contributory issues up the chain such as angular alignment or bowing impacting on foot alignment Orthotic designed to not only support the arch but also to give added support through the ankle; best for a weaker foot that struggles with holding neutral alignment of the hindfoot but corrects easily to neutral, when passively positioned

Solid ankle orthotic designed to hold the foot and ankle in best possible alignment without allowing movement

Positives Fits inside shoe Many off-the-shelf options prior to investigating custom-molded orthotics May allow for better shock absorption during gait Gives added support for hypermobile feet, protecting longitudinal arch Often helpful for stability for children who are learning to walk

Negatives Will only support the foot but does not correct rotational or angular issues above the ankle joint

Risk of fracture off the top of the brace Will not stabilize for angular deformity For those with anterior bow of the tibia, will not control the bias into plantarflexion when standing Holds the limb in alignment Holds lower limb stiff May need shoe while healing from fractures. Anterior shell can adaptations to allow flatfoot alignment when be added to protect a limb in the brace that has a progressing Risk of fracture off the anterior bow top of the brace (continued)

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34 Table 3.4 (continued) Articulating ankle foot orthosis

Rationale Ankle foot orthosis which allows movement into dorsiflexion or plantarflexion

Knee ankle foot orthosis

Often has free moving hinges, allowing control of the knee joint alignment

Hip knee ankle foot orthosis

Bracing involving hips, knees, and ankles May allow movement in one plane, reducing rotational forces May be used to lock the limb in best alignment while healing from a fracture or a surgery

Positives Holds the limb in alignment while healing from fractures. Anterior shell can be added to protect a limb that has a progressing anterior bow Allows dorsiflexion and/or plantarflexion but prevents inversion and eversion of the ankle Helps prevent genu recurvatum For those who have knee flexion contractures, helps to hold limb on comfortable end range stretch May be used after fracture to mobilize while keeping the fracture alignment stable

Negatives May need shoe adaptations to allow flatfoot alignment when in the brace Risk of fracture off the top of the brace

Heavy Risk of fracture off the top of the brace Difficult to transfer in

Heavy Risk of fracture as a result of moving with the brace Difficult to transfer in Uncomfortable to sit on all day

Assistive Devices

Conclusion

Many OI patients have a variety of assistive devices used as needed. For energy conservation one may use a cane or crutches, while others may use a wheelchair for long distances, despite being able to walk in the home. Please refer to Table 3.5 for information on many of the assistive devices used to enhance mobility.

Osteogenesis imperfecta presents from very mild to extremely involved. Therapy needs to be specific to the individual needs. Testing is important to identify needs and track change. Work on physical activity from an early age supports enhancing independence for a lifetime. Fractures will impact on therapy needs with the individual often requiring more support to return to baseline function. Orthotics help control alignment issues. Assistive devices for mobility help to conserve energy, off weight fractures, and enhance access to home and the community.

3  Therapy, Orthotics and Assistive Devices for Osteogenesis Imperfecta

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Table 3.5  Assistive devices Cane

Crutches

Knee scooter/ walker

Anterior walker

Posterior walker

Manual wheelchair

Motorized scooter

Motorized wheelchair

Rationale Ambulation device for an individual who needs a device for balance or to partially off weight an uncomfortable lower extremity Ambulation device for individual who has two arms with relatively symmetrical alignment

Positives Gives wider base of support when walking on unpredictable terrain Lightweight and easy to manage

Several different designs include axillary, forearm, and European style

Negatives Requires one to always hold on the device, as it does not easily attach to or rest against the body

Difficult to use if significant bowing of the upper extremity Forearm and European-­ style crutches may be difficult to use with a non-weight-bearing status on one lower extremity Not always readily Ambulation device when Allows reduced weight-bearing on involved area but more stability for walking than using available and does not weight-bearing is come in small sizes restricted to distal end of crutches Heavy to get in and out of the body such as a foot a car or ankle injury May be difficult to use if Best for those who can maintain upright Ambulation device for an individual who needs alignment while moving forward and stepping upper body fractures are present upper extremity support Lightweight compared to other types of walkers to step and potentially For individuals who are typically independent off weight a lower ambulators, may be useful postoperatively extremity Many cost-effective options available Encourages upright trunk over hips and lower Some may find it difficult Ambulation device for to stand up and turn an individual who needs extremities around to get into the Gives posterior touch point to allow better support for hip walker upright control extension. Allows Open front of walker allows individual to pull Tends to be larger than an posterolateral weight shift and balance during up to a work surface and stand, without having anterior walker, resulting in a larger turning radius the walker in the way stepping Requires good upper body Lightweight mobility device that is easily Seated mobility device strength to manage chair allows the individual to transported community distances and Gives opportunity for upper body work self-propel or for an over unpredictable terrain exercise assistant to push the Allows ambulatory individual to use energy chair conservation over long distances Mobility device allowing access to community Smaller-based devices Power mobility with a may have greater risk of while supporting energy conservation steering mechanism tipping over when Adjunct to mobility for those who are requiring two hands to negotiating turns and ambulatory steer uneven terrain Easy to transfer in and out of for those who Some scooters are not able can perform standing transfers to be used on public transportation Mobility device allowing access to home and Chair tends to be heavy Power mobility which therefore an adaptive van community, more frequently used by those relies on a joystick to or public transportation who have limited ability to ambulate steer the device tie-downs are needed to Adaptations to chair such as tilt in space, move the chair height adjustment, and transfer arms help to Without elevator access, aid access to environment and support safe transfer status for those with limited ability to the chair can only be used on one floor weight-bear Able to support addition of computers and environmental control devices when necessary

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References 1. Marr C, Seasmon A, Bishop N. Managing the patient with osteogenesis imperfecta: a multidisciplinary approach. J Multidiscip Healthc. 2017;10:145–55. 2. Neonatal and Nursery Care: Osteogenesis Imperfecta Foundation. http://www.oif.org/site/DocServer/ Neonatal_and_Nursery_Care__Pdf_for_page_12.0_. pdf?docID=7362. 3. Aagaard H, Uhrenfeldt L, Spliid M, Fegran L. Parents’ experiences of transition when their infants are discharged from the Neonatal Intensive Care Unit: a systematic review protocol. JBI Database System Rev Implement Rep. 2015;13:123–32. https://doi. org/10.11124/jbisrir-2015-2287. 4. Bass JL.  The infant car seat challenge: determining and managing an “abnormal” result. Pediatrics. 2010;125:597. 5. Ireland PJ, Donachey S, McGill J, Zankl A, Ware RS, Pacey V, Ault J, Savarirayan R, Sillence D, Thompson E, Townshed S, Johnston LM. Development in children with achondroplasia: a prospective clinical cohort study. Dev Med Child Neurol. 2012;54:532–7. 6. Pauli RM, Breed AM, Horton VK, Glinski LP, Reiser CA. Prevention of fixed, angular kyphosis in achondroplasia. J Pediatr Orthop. 1997;17:726–33. 7. Shirley ED, Ain MC.  Achondroplasia: manifestations and treatment. J Am Acad Orthop Surg. 2009;17:231–41. 8. Takken T, Terlingen HC, Helders PJ, Pruijs H, van Der Ent CK, Engelbert RH. Cardiopulmonary fitness and muscle strength in patients with osteogenesis imperfecta type I. J Pediatr. 2004;145:813–8. 9. Brizola E, Staub AL, Felix TM. Muscle strength, joint range of motion, and gait in children and adolescents with osteogenesis imperfecta. Pediatr Phys Ther. 2014;26:245–52. 10. Van Brussel M, Takken T, Uiterwaal CS, et  al. Physical training in children with osteogenesis imperfecta. J Pediatr. 2008;152:111–6. 11. Mueller B, et  al. Consensus statement on physical rehabilitation in children and adolescents with osteogenesis imperfecta. Orphanet J Rare Dis. 2018;13:158. https://doi.org/10.1186/s13023-018-0905-4. 12. Dahan-Oliel N, Oliel S, Tsmicalis A, et al. Quality of life in osteogenesis imperfecta: a mixed-methods systemic review. Am J Med Genet A. 2016;170A:62–76. 13. Cintas HL, Siegel KL, Furst GP, Gerber LH.  Brief assessment of motor function: reliability and concurrent validity of the gross motor scale. Am J Phys Med Rehabil. 2003;82:33–41. 14. Bayley N. Bayley scales of infant and toddler development. 3rd ed. Pearson Education Limited: San Antonio; 2005. 15. Deitz JC, Kartin D, Kopp K. Review of the Bruininks-­ Oseretsky test of motor proficiency, second edition (BOT-2). J Phys Occup Ther Pediatr. 2009;27:87–102.

M. Donohoe 16. Ruck-Gibis J, Plotkin H, Hanley J, Wood-Dauphinee S. Reliability of the gross motor function measure for children with osteogenesis imperfecta. Pediatr Phys Ther. 2001;13:10–7. 17. Engelbert RH, Kooijmans FT, van Riet AM, Feitsma TM, Uiterwaal CS, Helders PJ. Relationship between generalized joint hypermobility and motor development. Pediatr Phys Ther. 2005;17:258–63. 18. Wuang YP, Su CY, Huang MH.  Psychometric comparisons of three measures for assessing motor functions in preschoolers with intellectual disabilities. J Intellect Disabil Res. 2012;56:567–78. 19. Davies PL, Soon PL, Young M, Clausen-Yamaki A.  Validity and reliability of the school function assessment in elementary school students with disabilities. Phys Occup Ther Pediatr. 2004;24:23–43. 20. Kerr GH, Harvey A, et  al. The functional mobility scale (FMS). J Pediatr Orthop. 2004;24(5):514–20. 21. Cohen JS, Biesecker B. Quality of life in rare genetic conditions: a systematic review of the literature. Am J Med Genet. 2010;152A:1136–56. 22. Haley SM, Coster WJ, Ludlow LH, et  al. Pediatric evaluation of disability inventory (PEDI): development, standardization and administration manual. Boston: New England Medical Centre Hospitals; 1992. 23. Haley SM, Coster WJ, Dumas HM, et  al. Accuracy and precision of the pediatric evaluation or disability inventory computer adaptive tests (PEDI-CAT). Dev Med Child Neurol. 2011;53(12):100–6. 24. Anaby D, Law M, Coster W, et  al. The mediating role of the environment in explaining participation of children and youth with and without disabilities across home, school, and community. Arch Phys Med Rehabil. 2014;95:908–17. 25. Daltroy LH, Liang MH, Fossel AH, Goldberg MJ.  The POSNA pediatric musculoskeletal functional health questionnaire: report on reliability, validity, and sensitivity to change. Pediatric outcomes instrument ­ development group. Pediatric orthopaedic society of North America. J Pediatr Orthop. 1998;18(5):561–71. 26. Sousa T, Bompadre V, White K.  Musculoskeletal functional outcomes in children with osteogenesis imperfecta: associations with disease severity and pamidronate therapy. J Ped Orthop. 2014;34(1):118–22. 27. PROMIS: http://www.healthmeasures.net/index. php?option=com_content&view=category&layout=b log&id=147&Itemid=806. 28. Tosi L, Floor MK, Dollar CM, Gillies AP, et  al. Assessing disease experience across the life span for individuals with osteogenesis imperfecta: challenges and opportunities for patient-reported outcomes (PROs) measurement: a pilot study. Orphanet J Rare Dis. 2019;14(1):23. https://doi.org/10.1186/ s13023-019-1004-x.

3  Therapy, Orthotics and Assistive Devices for Osteogenesis Imperfecta 29. Bohonnan RW, Bubela D, Magasi S, et  al. Comparison of walking performance over the first 2 minutes and the full 6 minutes of the six- minute walk test. BMC Res Notes. 2014;25(7):269. https://doi. org/10.1186/1756-0500-7-269. 30. Bohonnan RW, Wang YC, Bubela D, Gershon RC.  Normative two-minute walk test distances for boys and girls 3 to 17 years of age. Phys Occup Ther Pediar. 2018;38(1):39–45. 31. Klepper SE, Muir N.  Reference values on the 6-­minute walk test for children living in the United States. Pediatr Phys Ther. 2011;23(1):32–40. 32. Lammers AE, Hislop AA, et al. The 6- minute walk test: normal values for children 4–11 years of age. Arch Dis Child. 2007;93(6):464–8. 33. Bongers BC, Rijks EB, Harsevoort AG, Takken T, van Brussel M. 10-m shuttle ride test in youth with osteogenesis imperfecta who use wheelchairs: feasibility, reproducibility, and physiological responses. Phys Ther. 2016;96(5):679–86.

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34. Sears ED, Chung KC.  Validity and responsiveness of the Jebsen-Taylor hand function test. J Hand Surg Am. 2010;35(1):30–7. 35. Condon C, Cremin K.  Static balance norms in children. Physiother Res Int. 2014;19(1):1. https://doi. org/10.1002/pri.1549. 36. Weingarten G, Lieberstein M, Itzkowitz A, Vialu C, Doyle M, Kaplan SL.  Timed floor to stand-natural: reference data for school age children. Pediatr Phys Ther. 2016;28(1):71–6. 37. Williams EN, Carroll SG, et  al. Investigation of the timed “Up & Go” test in children. Dev Med Child Neurol. 2005;47(8):518–24. 38. Itzkowitz A, Kaplan S, Doyle M, Weingarten G, Lieberstein M, Covino F, Vialu C.  Timed up and go: reference data for children who are school age. Pediatr Phys Ther. 2016;28(2):239–46. 39. Podsiadlo D, Richardson S.  The timed Up & Go: a test of basic functional mobility for frail elderly persons. J Am Geriatr Soc. 1991;39(2):142–8.

4

The Structure and Functioning of the Multidisciplinary Clinic in Managing and Monitoring Patients with Osteogenesis Imperfecta in the UK Caroline Elizabeth Ann Marr and Ali Seasman The MDT approach to the management of osteogenesis imperfecta (OI) was established with the Metabolic Bone Disease Service at Sheffield Children’s NHS Foundation Trust (SCH) in 1999, following its initial conception in 1998. At this time the team consisted of a consultant, a clinical nurse specialist  (CNS), a half-time physiotherapist and a full-time occupational therapist. Twelve years later Sheffield is one of four centres designated by NHS England to deliver a highly specialized service (HSS) for severe, complex and atypical paediatric OI. At the time of this writing, there are 280 patients within this designated service, 110 of whom are considered to have highly complex forms of OI. Consequently the MDT has increased steadily to include psychology, social work, dentistry and dietetics to the core services (now two consultants, three occupational thera-

pists, three physiotherapist and three CNS). In addition to the weekly MDT meetings of core services, there are monthly, extended MDT meetings to include orthopaedic, spine  and neurosurgery, specialized skeletal radiology and genetics consultant input. As such Sheffield offers a team approach with core disciplines providing a range of therapeutic options and access to other specialties as required. This approach enables effective communication and collaboration between medical, surgical and allied health professionals; equal consideration is thus given to all treatment options to develop individual treatment plans (Table 4.1). We present three case studies to highlight the important role played by the MDT in the orthopaedic management of children under the auspices of the HSS for severe, complex and atypical OI.

Table 4.1  Summary of key team members in the UK multidisciplinary service Core team members Physician

Clinical nurse specialist

Key role Diagnosis of osteogenesis imperfecta excluding other metabolic bone diseases. Development of a medical management plan including the decision regarding bisphosphonate therapy. Co-ordinate patient care, facilitate the admission processes. Provide handling support in the early years. Source of education for families/schools/other health professionals. Drive the transition process.

(continued) C. E. A. Marr (*) · A. Seasman Sheffield Children’s NHS Foundation Trust, Western Bank, Sheffield, UK e-mail: [email protected]; [email protected]

© Springer Nature Switzerland AG 2020 R. W. Kruse (ed.), Osteogenesis Imperfecta, https://doi.org/10.1007/978-3-030-42527-2_4

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C. E. A. Marr and A. Seasman

40 Table 4.1 (continued) Core team members Physiotherapist/ occupational therapist

Clinical psychologist

Social worker Speech and language therapist/dietician Orthopaedic surgeon Spinal surgeon Neurosurgeon

Key role Provide handling and positioning advice from birth to discharge. Promote development. Facilitate the acquisition of gross and fine motor skills through strengthening; prevention of joint contractures, prevention of malalignment, provision of equipment and promotion of adaptations. Support optimal functioning and participation in home, school and community life. Assess and monitor development. Help to support individuals and their families with the social and emotional demands of having a chronic health condition. Work with other team members to ensure that interventions take into consideration the social and emotional impact of osteogenesis imperfecta. Provide support for housing, education and charitable funding. Ensure that families and individuals gain the benefits they are entitled to. Provide advice regarding dietary modifications and develop nutritional care plans, ensuring a healthy balanced diet. Reducing the risk of obesity. Provide strategies to improve feeding. Provide both elective and nonelective surgery for the upper and lower limbs in order to manage fractures and/or correct deformities. Management of spondylosis, spondylolisthesis, kyphosis and scoliosis. Management of hydrocephalus and basilar invagination.

Case One: Katrina

Katrina was the third child born of non-­ consanguineous parents. She was diagnosed clinically with type three OI at birth, commencing bisphosphate therapy at 2 weeks of age. She remains on treatment. Katrina first became known to the OI team at SCH at the age of 6 years. At her initial review, it was noted that she had bowing in all four limbs, was of short stature and had a scoliosis: Cobb angle 30° (Fig.  4.1a). This case study focuses upon the management of Katrina’s scoliosis. This case illustrates the impact that scoliosis and its treatment can have on quality of life. Scoliosis in OI: Therapist’s Role. An international consensus meeting of therapists specializing in OI was convened in 2017 [1]. A key theme was the management and care of scoliosis in the OI population; a persistent feature of the condition which has been, and continues to be, difficult to manage. There is a paucity of quality literature supporting the use of bracing for the management of scoliosis; hence, bracing remains controversial. It is clinically

acknowledged that scoliotic curves may continue to progress despite bracing. The brace can also cause rib fractures and rib cage deformity owing to the poor bone quality associated with OI.  As such bracing to prevent and control scoliosis progression is not standard practice at SCH. Rather consultants and clinicians hold the view that scoliosis is best managed from a multidisciplinary team perspective, including muscle strengthening, postural management and surgical intervention as required for progressive curvature. At SCH we offer care to children from a wide geographical area, with care often shared with the child’s local hospital. Katrina’s case is typical in this sense, with the initial treatment for her scoliosis provided by her local team who had little experience of working with children with OI. Katrina’s case provides an example of lessons learnt in regard to bracing a child with OI. At the age of 8 years (Fig. 4.1b) due to progression of her scoliosis, a decision was made to place Katrina in a nonremovable spinal cast brace.

4  The Structure and Functioning of the Multidisciplinary Clinic in Managing and Monitoring Patients…

The brace impacted every aspect of Katrina’s life. She could no longer participate in sporting activities such as swimming as the brace was nonremovable. Her ambulation was reduced as she could not manage the additional weight of the brace; moreover she often felt unsteady due to its impact on her proprioception making transfers more challenging. Self-cares such as brushing her hair became problematic as she could no longer achieve full glenohumeral joint flexion or abduction due to the position of the brace. She could no longer wash independently as specific care was needed in order to keep the brace dry. Despite these difficulties the family persevered with the brace. The only time Katrina was out of the brace was following rodding surgery of her lower and upper limb, completed at two separate time points. It was at these times that Katrina’s reliance on the brace was noted. Without the brace Katrina lost the ability to sit independently. Though atrophy of the para spinous muscles was apparent, it was not significant enough to cause this regression in motor skills. It transpired that Katrina had convinced herself of negative consequences to her spine should she sit without the brace. She conceded that the brace had actually become a comfort and reassurance to her and without it Katrina felt increasingly anxious. The loss of her ability to sit independently had become psychological rather than physical. To help Katrina regain her sitting balance, a loose bandage was applied to her trunk. Though providing no physical support, the bandage provided sensory feedback and supported Katrina psychologically by containing her worries and fears, enabling her to sit once again independently. Interestingly there are no documented rib fractures prior to the brace fitting, though a number of these were identified during the time she wore the brace.

After a year of wearing the nonremovable brace, Katrina was reviewed in clinic. Katrina had developed significant paramuscular weakness and atrophy. Her dualenergy X-ray absorptiometry (DEXA) showed a loss of lumbar bone mineral density (0.519 BMD in 2015, 0.422 BMD in 2016). A healing rib fracture was noted possibly due to stress shielding, and her scoliosis had increased with a Cobb angle of 62° (Fig. 4.1c). When Katrina was aged 10  years, the family gained a second opinion from an consultant orthopaedic spinal surgeon at another specialist centre for OI in the UK. It was at this point that Katrina’s nonremoval brace was exchanged for a removal brace (Fig.  4.2). There was no therapy involvement at this time, and after the initial assessment  at the secondary centre, Katrina was referred back to her local hospital. During a review by the therapist at SCH, concerns were raised about Katrina’s reliance on the brace, owing to the negative impact it seemed to have on her independence, mobility and participation in activities. Consequently her case was discussed at SCH’s orthopaedic MDT. This meeting is attended by the medical consultants, orthopaedic consultants, spinal consultant, neurologist, geneticist, physiotherapist, occupational therapist and psychologist. All patients with severe, complex and atypical OI are reviewed at least annually in this meeting. As each team member is able  to share their involvement with the patient, voicing any concerns/management plans/ goals, there is an opportunity to consider the patient care and formulate unified holistic prospective plans. As the plain radiograph shows (Fig. 4.3) despite the brace, Katrina’s curve continued to progress. The consultant orthopaedic spinal surgeon alongside other members of the MDT concluded that surgical inter-

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C. E. A. Marr and A. Seasman

42

vention would be required within the next 12–18  months. He reasoned that waiting for Katrina’s growth to finish would not be in the best interests of the child as the curve would continue to progress within the brace due to the Cobb angle. Moreover, over time surgery would become more challenging due to the rotational component of the spine/ribs making access and instrumentation difficult. As the identified key team member, with a close working relationship with the family, the physiotherapist discussed the outcome of the MDT with Katrina and her parents. The importance of the therapeutic relationship should not be underestimated in these cases. A relationship based on mutual trust and respect facilitates open and honest communication. The family agreed to a clinic appointment with the SCH spinal consultant. The therapist attended this appointment to offer support and clarification as needed. Therapists are often skilled in offering medical information to families in language which is clear and easy to understand. The outcome of this consultation was that Katrina herself decided to proceed with the surgery. T2 pelvis instrumented fusion was completed when Katrina was 12  years old (Fig. 4.4). The MDT worked together to prepare Katrina for her surgery. Katrina was advised that as a consequence of the surgery, she would lose range of movement in her spine and that because of this her movement patterns would alter, potentially making ambulation more difficult. As part of the pre-op plan, the physiotherapist, working in partnership with Katrina and her mother, created a graded programme that sought to reduce Katrina’s dependency on her spinal brace. In line with infection control policies at SCH the brace had to be removed 2 weeks prior to

surgery. As such the programme began with Katrina removing the brace for a short period at night over a weekend, followed by a short period at night during the week, increasing this steadily until she was able to sleep without the brace in situ. Once this was achieved, she removed the brace for brief periods throughout the school day until she felt confident to remove it entirely. This process took approximately 5 weeks. Concurrently the physiotherapist provided exercises to strengthen Katrina’s spinal muscles and abdominals. All exercises were low impact, taking into consideration the mechanical strains and muscle forces acting upon the bone. Practice of moving supine to sit (log roll technique) was also encouraged. Prior to her surgery Katrina moved into a seated position by rolling onto her front and utilizing lumber, thoracic and hip flexion. Katrina would be unable to do this post-surgery. In children with OI, fear of the unknown and fear of fracture are common and can impede progress especially after orthopaedic intervention. By practising the movement, first with the physiotherapist then at home, Katrina could build her confidence and strength with this new technique prior to her surgery. The physiotherapist and occupational therapist worked with the family to identify equipment needed to facilitate Katrina’s recovery and promote her function and independence in light of her altered movement patterns. A high-low profiling bed was purchased with consideration given to the design of the bed as Katrina was keen to avoid having ‘medical’ equipment at home. The high-low feature enabled independent sideway transfers with use of the banana board into both her manual and electrical wheelchair; it would also allow transfers to the floor and facilitate sit to stand practice if indicated at a later date. In addition a profil-

4  The Structure and Functioning of the Multidisciplinary Clinic in Managing and Monitoring Patients…

ing back rest would aid the log roll transfer. Completing the transfer from an angle of 60 degrees is easier than attempting it from a horizontal side lying position. By allowing the incline initially, Katrina could build her confidence and independence. Moreover if she was to fracture her arm, a potential risk with the log roll since it requires substantial force through the upper limbs, transfers would still be possible; a log roll from an incline of 60° can be completed with assistance of one arm only. Whilst other specialist equipment was available for bathing and toileting, Katrina was keen to avoid the use of this unless it was deemed a health and safety risk not to do so; this could only be assessed post-surgery. Katrina’s surgery was not without complications. During the surgery there was a loss of sensory spinal cord monitoring, unstable blood pressure and clotting dysfunction. Katrina required overnight ventilation post-surgery and was initially not able to sit past 20° to allow for spinal cord perfusion. Katrina was noted to have clonus in the left lower limb. Pain was also a significant problem for Katrina, with muscular spasms present. The patient and her family were understandably distressed post-surgery; however due to the preoperative work of each team member, progression could be made in reasonable time. Katrina was discharged home after 10 days without the need for additional bathing and toileting equipment. The social and emotional demands of the surgery were addressed by the clinical psychologist who worked closely with the family throughout the process. The clinical psychologist had already established a relationship with the family; it is routine at SCH for patients to be reviewed by the psychologist when they enter the highly spe-

cialized service. Following the surgery the clinical psychologist supported the family in applying strategies to normalize the traumatic event, a psychological process described as containment. At her 8-week follow-up, Katrina reported she no longer had pain in her back. She stated that she could move independently from prone to supine and supine to sit, using the log roll technique. Self-cares such as toileting and dressing were also independent. Katrina was back in full-­time education and felt very positive about the future. Learning Points: • There is a lack of consensus surrounding the management of scoliosis in this patient group. An MDT approach is essential with recognition given to  the physical, social and emotional demands placed on patients and their families. • When planning an intervention for children, it is important to view them holistically. Consider how interventions impact upon the child’s ability to participate, complete self-­ cares and mobilize. • Listen to the family and keep open and honest communication. This will ensure that you work together to achieve the best outcome. • Planning is key. Ensure all appropriate MDT members are involved from the start as this will impact the outcome. • Surgical procedures are life changing for children and their families. The time allowed and support needed for families and patients to come to terms with the surgery should not be underestimated. • MDT meetings provide opportunities to discuss and coordinate patient care, facilitating the best outcome for patients.

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a

b

c

Fig. 4.1 (a) Plain radiograph of the spine aged 5 years. (b) Plain radiograph of the spine aged 8 years, shortly after the brace was applied. (c) Plain radiograph of the spine aged 9 years showing the progression of the curve over a 1-year period of which the brace was worn continually

Fig. 4.2  Katrina in removal brace aged 10 years; anterior and posterior views

4  The Structure and Functioning of the Multidisciplinary Clinic in Managing and Monitoring Patients…

Fig. 4.3  Spine film age 10 (removable brace in situ) showing further progression of the curve

Fig. 4.4  Plain radiographs showing spinal instrumentation

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Case Two: Michelle

Michelle first became known to our service at the age of 18  months. She was referred following investigations for nonaccidental injury after sustaining a left tibial and right humeral fracture. At the initial clinic assessment, Michelle was found to have typical OI features: blue/ grey sclera, a delay in the attainment of gross motor milestones, hypermobility and a slim build. No bowing of the long bones was noted. A clinical diagnosis of mild osteogenesis imperfecta was given. Medical treatment was deemed unnecessary. Specialist occupational and physiotherapy was provided to facilitate Michelle’s gross and fine motor development. This included educating the parents and the local therapy team about OI. Early education about the disorder is key in reducing anxiety and facilitating working relationships between all parties involved in the child’s care. In toddlers with OI, it is important to promote milestone acquisition in a gradual manner so as to protect against fracture [2]. Children, even with the milder forms of the condition, often require exercises to promote their strength and stamina owing to their hypermobility and fatigue levels. At SCH we promote acquisition of motor skills through play, of which table top activities are key. By utilizing a small table and chair, a therapist can tailor activities so as to promote proprioception, improve confidence and facilitate weight bearing through the lower limbs in a relatively safe manner (Fig. 4.5). For Michelle table top activates were a precursor in gaining sit to stand and ultimately ambulation. Her ambulation was also facilitated by use of a specialist walker and provision of insoles (Fig. 4.6).

Michelle obtained the ability to mobilize independently at 29 months. At the age of 6  years after sustaining two appendicular fractures: right metatarsal and left tibia; and four axial fractures of the thoracic spine, Michelle was started on the bisphosphonate therapy, zoledronic acid. At 8 years of age Michelle sustained bilateral tibial fractures (Fig.  4.7). Both fractures were treated conservatively by Michelle’s local team. The MDT at SCH did not become involved until Michelle’s routine clinical review, 5  months after the fractures occurred. At the review Michelle’s parents voiced concerns about the shape of the right lower limb and commented that Michelle had continued to report persistent pain in her right leg. The local physiotherapist had seen Michelle regularly, providing a standard strengthening programme which Michelle had completed daily. With their support she had regained her mobility though continued to need the use of a walking stick, despite being independently mobile prior to her injury. Michelle’s parents had been informed by the local orthopaedic surgeon that the bowing within the right lower limb would remodel in time and that this was a typical presentation following the type of injury Michelle had sustained. All clinic appointments at SCH are multidisciplinary with a consultant, CNS, physiotherapist and occupational therapist present. During the MDT review, Michelle was assessed as having significant bowing deformity within the shaft of the right tibia. Leg length was reduced by 2  cm on the right side, and Michelle had tenderness on palpation along the anterior shaft. Her gait was altered with hip circumduction and reduced stance phase on the right.

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An X-ray was completed during the clinic appointment (Fig.  4.8) which showed nonunion and bowing deformity within the right tibia. Due to the non-union, pain, potential worsening deformity and risk of further fractures, an orthopaedic review at SCH  was instigated. Due to the close links between the medical and orthopaedic teams at SCH, this was completed on the same day, which was of benefit to the family who had to travel a long distance for the review at Sheffield. Rodding surgery was completed 4 weeks later at SCH (Fig.  4.9). Within 3  months Michelle was pain-free, had equal limb length and was mobilizing independently. In the clinic appointment, the medical consultant’s main role is to ensure the correct medical management of a patient, for example, the need for bisphosphonate treatment. However by having the MDT in the clinic, each member can support the other. This case highlights the benefits of a specialist MDT therapy review. By utilizing the close links with the wider MDT, a surgical plan could be conceived quickly and the family’s anxieties addressed. For optimal care all providers involved should have experience in treating OI. All treatment plans should consider the individual child’s OI.  OI bone should not be regarded in the same way as non-OI bone. The risk of refracture, especially after prolonged immobilization, is high. Non-union is a significant risk especially within the tibia and humeri due to the muscle action and position of the limb. Discrepancies in limb length and alignment are often overlooked, though they have significant implications in terms of gait and spinal alignment.

It is important to consider the physical, social and emotional impact of fractures and consequent rehabilitation on the family unit. In this case the fractures and the 5  months of rehabilitation that followed placed an enormous strain on the family. Improved communication between the team at Sheffield and the local service may have led to earlier surgical intervention, potentially reducing Michelle’s time in cast and the length of her rehabilitation, ultimately ameliorating the strain on the family. Learning Points: • An MDT clinic allows for a holistic review of patients establishing an excellent standard of care. • OI bone is different to non-OI bone and will not react in the same way to stresses and strains. Significant bowing deformities are likely to cause recurrent fractures rather than remodel. The rate of non-union is high within the humeri and tibia. • Medical and surgical teams should not underestimate the impact that fractures have on the family unit. Effort should be made to alleviate the family’s anxieties, with local teams liaising with specialist units. • Rehabilitation should commence as soon as is possible following the fracture/surgical intervention. This limits long periods of ­immobilization whilst supporting function and participation. • Limb length should be assessed postfracture of the lower limb, with surgical or orthotic management offered as appropriate.

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Fig. 4.5  Photo of Michelle using her table and chair

Fig. 4.6  Photo of Michelle using her walker

Fig. 4.7  X-rays showing lower limb fractures. Fractures sustained from a low impact fall

4  The Structure and Functioning of the Multidisciplinary Clinic in Managing and Monitoring Patients…

Fig. 4.8  X-rays showing non-union and bowing in the right tibia 5 months after initial injury

Fig. 4.9  X-rays 4 months after insertion of TST rod. Note correction of bowing deformity

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Case Three: Jack

Jack is a 10-year-old boy diagnosed clinically with type III OI at birth. He was born with more than 20 fractures and commenced pamidronate treatment at 2  days old. He was transferred to zoledronic acid  when he was 4 years. Jack’s  intial treatment was provided by non-specialist services outside of NHS England. Jack became known to the Sheffield Metabolic Bone Team in 2014 after his parents requested a second opinion from specialist services. At this time Jack remained on zoledronic acid. He had recently been found to have multiple crush fractured vertebrae and had begun to complain of back pain. At his initial assessment Jack was noted to have short stature and a large head in relation to his body size. This is common in severe OI and often contributes to difficulties with transitioning and movement. He had anterolateral bowing of the femurs, 70° anterior bowing of the tibias and 80–90° bowing deformity of the forearms. Jack had significant hypermobility in his hands and feet, poor muscle length in the Achilles tendon and hip flexors and reduced muscle strength surrounding his hips, pelvis and within his abdominals. Functionally Jack was able to sit independently but could only achieve sitting with support from an angle of 70°. He was able to independently roll left and right into side lying. He was able to roll to prone with support. Jack was lifted for all transfers. He was unable to bear weight through his upper or lower limbs; Jack could not reach the floor in sitting owing to bowing deformity and shortening of the upper limbs impacting upon his ability to bottom shuffle. Jack struggled with upper body dressing owing to reduced strength and stamina in the upper limbs and

restricted range of movement. Jack was wheelchair dependent, electing to use a power chair as the mainstay of his mobility. Jack and his family received specialist advice and therapy input, albeit from a distance, through liaison with local therapists and consultants. In 2015 Jack attended Sheffield Children’s Hospital for a week of intensive therapy. This involves a fournight stay at the hospital for those children who have reached a plateau in function. Children are seen two to three times per day by both an occupational therapist and a physiotherapist. The aim of intensive therapy is not only to develop range of movement, muscle strength, functional ability and independent skills but also to encourage determination and help develop the confidence required from the children to move forward and progress. Goals are established collaboratively at the start of the week and reviewed at the close. Activities combine to include practical self-care skills such as toileting, dressing, baking, arts and crafts, games (including technology such as the Wii/switch adapted) and muscle strengthening/stretching activities. Dependent on the activity children are often challenged to complete these tasks from a variety of positions, for example, prone or perch. During his intensive therapy week, Jack achieved his goals of improving his selfcare skills such as dressing and feeding and his ability to bottom shuffle. Following the success of the intensive therapy week, parents began to consider orthopaedic intervention in the form of rodding surgery of the lower limbs as they appreciated how it would be of benefit for Jack. However the local orthopaedic consultant advised the parents that rodding of Jack’s limbs would have no functional benefit and the risk of surgery would outweigh any posi-

4  The Structure and Functioning of the Multidisciplinary Clinic in Managing and Monitoring Patients…

tive gains. Consequently in early 2017 parents requested an orthopaedic assessment for Jack at SCH.  This assessment was attended by the orthopaedic consultant, metabolic bone consultant, specialist occupational therapist and specialist physiotherapist. It was agreed rodding would improve lower limb alignment effecting postural stability in sitting and reducing the strain on the lower back. Longer term, weight bearing through the feet would facilitate bottom shuffling and standing transfers. The joint clinic embraces a biopsychosocial approach which seeks to broaden the scope with which health, illness and disability are examined in clinical practice. As such the patient is viewed as an individual with a particular lifestyle and not simply as a child with a disability which has resulted in impaired functioning. Following open and honest discussions between consultants, therapists, Jack and his family, all agreed Jack should be listed for rodding surgery in the summer of 2017, to include rodding of both the right femur and tibia, followed 3 weeks later with rodding of the left femur and tibia (Figs. 4.10 and 4.11). The plan considered the family’s needs: the distance they would have to travel to Sheffield, length of time for postoperative rehabilitation, equipment needs (toileting, hoisting) and modifications to equipment already in situ (broomstick cast following phase 2 of the surgery therefore wheelchair adaptations likely), and the psychological implications of this type of surgery. As school was viewed as a protective factor to Jack’s social and emotional well-being, here he was able to engage and socialize with peers and perform to a high academic standard, it was agreed that surgery should be undertaken at the beginning of the

6 week summer break. Time absent from school would therefore be limited, and Jack could plan to return at the start of the new term. Though lower limb surgery was successful, Jack was unable to progress with sit to stand owing to upper limb deformity of both the forearm and humerus. Whilst long bone rodding in the lower extremities has become standard treatment in OI, upper limb deformities historically are less commonly treated surgically due to lack of clear indications, limited surgical experience and the view that the upper extremities are non-­weight bearing. Significantly as children like Jack have become more mobile due to improved medical and surgical treatment, they often require the use of their upper limbs to push through from supine to sitting, initiate standing and maintain walking, as well as for activities of daily living. As such, upper limb deformities and fractures have become a more significant problem and can impact on function and quality of life in patients such as Jack [3]. Occupational therapy and physiotherapy play an important role in the assessment of functional difficulties that underpin sound clinical reasoning for surgery. Upper extremity deformities in OI are surgically more challenging to treat due to the size of the bones and the extent of the deformities. The proximal humerus is more commonly addressed surgically as these are typically easier to correct than those in the distal third of the bone. A common complication of osteotomies in the distal third of the humerus is non-union with development of a pseudarthrosis. There is also a risk of radial nerve palsy. With a predominance of poor bone quality in the severe OI population, another frequent cause for concern is rod migration and rod

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prominence which requires further surgery for revision [4]. Following the success of the lower limb surgery, and despite the complications associated with upper limb surgery, parents were keen to pursue upper limb rodding. However, given the technical difficulty of realigning a 90° deformity and obtaining fixation, it was agreed at the monthly orthopaedic MDT that Jack would return to Sheffield for a further week of intensive therapy before a final decision was made. The joint goals of the therapy week included the following: • To assess upper limb strength for weight bearing (to support standing skills) • To develop acquisition of sideways bottom shuffle skill • To secure independent transfers using a transfer board from plinth to wheelchair • To sit from supine without assistance • To progress independent dressing skills • To review manual wheelchair provision The admission included an orthopaedic review and X-rays (Fig. 4.12) at the start of the week and an orthopaedic review at the close of the week to discuss functional gains and decisions regarding upper limb rodding. All key members of the MDT were present at these meetings. By the close of the intensive therapy week, Jack had made significant gains in his functional ability to weight bear through his feet. Though not yet able to sit from fully supine, he was able to achieve sitting from an incline of 60° independently. Jack was able to bottom shuffle along a plinth and transfer independently into his wheelchair with the use of a transfer board. Importantly, his

confidence to move forwards with activities to support standing, for example, pulling to stand from a perch position with the support of a therapist/carer, had improved. The intensive therapy week highlighted other issues which were to impact on the clinical decision to rod the upper limbs. Therapists raised concerns about Jack’s posture; on observation he appeared to have developed a scoliosis of which parents had not been aware. This had not been assessed locally and so a management plan was not in place. In addition to identifying a scoliosis, therapists established through their therapeutic alliance with Jack that he was an accomplished drummer. In view of the complications associated with upper limb rodding, for example, radial nerve palsy, it was decided surgery could affect his drumming skills and ultimately impact on his well-being and quality of life; Jack the drummer was integral to his identity. In addition Jack was continuing to make functional gains with both mobility and selfcares. It was therefore agreed amongst family, therapists and consultants that upper limb surgery should be postponed and reviewed again 1  year later with the current focus on the management of Jack’s scoliosis. Prior to discharge spinal X-rays were completed and a referral made to his local spinal team. SCH therapists liaised with local therapists with regard to postural review for seating and wheelchairs to ensure optimal support, function and comfort. Learning Points: • Early MDT assessment is fundamental in the management and care of children and young people living with OI.  Children and young people should

4  The Structure and Functioning of the Multidisciplinary Clinic in Managing and Monitoring Patients…

have access to a specialist MDT at the point of diagnosis, to facilitate optimal care planning and  establish best health outcomes. • Lower limb rodding may not always result in significant functional gains such as ambulation but should be considered from a broader perspective to

Fig. 4.10  Jack’s lower limbs prior to rodding surgery

include the determinants of health and well-being. • Rodding of the upper limbs is difficult; clinical decisions should be based on assessment from the wider MDT which embrace a biopsychosocial approach. • Children with OI should be monitored regularly for postural changes.

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Fig. 4.11  Jack’s lower limbs post-TST and Sheffield rodding

Fig. 4.12  X-rays of Jack’s upper limbs

Conclusion Creativity and flexibility are key determinants in the provision of multiprofessional care and management of children and young people living with OI. Whilst management can often be challenging owing to the heterogeneity both across and within different types, the MDT should foster clear understanding of the contribution,

responsibilities and accountabilities of individual team members to maximize their impact. This implies a shared learning experience with, from and about each other. Whilst achievements in terms of collaborative working can be dependent upon time pressures and resources, this can often be mediated by the enthusiasm of a multidisciplinary team who share the goal of improving the lives of children with OI.

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At Sheffield Children’s Hospital, best practice is achieved through MDT working delivered in a specialist paediatric bone team. There is no single intervention or plan that can meet the needs of all children and young people presenting with OI; hence focus of care must be on the broader determinants of health. Only by working together can medical, surgical and therapeutic interventions improve function and quality of life in children and young adults with OI.

References 1. Mueller B, Engelbert R, Baratta-Ziska F, Bartels B, Blanc N, Brizola E, et  al. Consensus statement on physical rehabilitation in children and adoles-

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cents with osteogenesis imperfecta. Orphanet J Rare Dis. 2018;13(1):158. https://doi.org/10.1186/ s13023-018-0905-4. 2. Marr C, Seasman A, Bishop N. Managing the patient with osteogenesis imperfecta: a multidisciplinary approach. J Multidiscip Healthc. 2017;10:145. 3. Ashby E, Montpetit K, Hamdy RC, Fassier F.  Functional outcome of forearm rodding in children with osteogenesis imperfecta. J Pediatr Orthop. 2018;38(1):54–9. Available from: http://www.ncbi. nlm.nih.gov/pubmed/26840274 4. Franzone JM, Bober MB, Rogers KJ, Mcgreal CM, Kruse RW. Re-alignment and intramedullary rodding of the humerus and forearm in children with osteogenesis imperfecta: revision rate and effect on fracture rate. J Child Orthop. 2017;11:185–90. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/ PMC5548033/pdf/jco-11-185.pdf

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Quality of Life and Functional Evaluation Measures for Osteogenesis Imperfecta Verity Pacey and Kathleen Montpetit

Introduction The success of any surgical treatment must focus on an individual’s goals and the importance of meaningful participation in everyday life. Everyday life poses multiple challenges to individuals with OI.  Recurrent fractures, pain, and fatigue create barriers to an individual’s participation in daily activities at home, school, or work and when interacting with peers. Impairments such as weakness, leg length discrepancy, and altered skeletal alignment are often the focus of health professionals when making treatment decisions and recommendations. However, prioritization of an individual’s goals, their functional abilities, and their self-perceived overall quality of life is required during surgical decision-­ making. Health professionals, working together in multidisciplinary teams, must aim to empower and enable their patients to achieve the optimal participation and well-being that is considered important to each individual. When managing children with OI, the broader role of the family and their goals must also be considered.

V. Pacey (*) Department of Health Professions, Macquarie University, Sydney, NSW, Australia e-mail: [email protected] K. Montpetit Shriners Hospital for Children, Montreal, QC, Canada e-mail: [email protected]

Therefore, this chapter aims to provide surgeons with an overview of functional performance and quality of life of individuals with OI, to assist in surgical goal setting. Strategies to incorporate appropriate and timely assessment of these constructs into clinical decisionmaking when planning and measuring the success of surgical interventions for an individual with OI will also be discussed and case studies provided.

Goal Setting Aligning health professionals and individual or family’s goals has always been a challenge in orthopaedics. Customarily, the surgeon identifies goals based on a limited clinical picture of radiological and physical findings and primarily focuses on preventing or addressing deformity or a fracture. Theoretically, the patient’s objectives are included during this surgical decision-making process. However, often the biomedical thinking of “diagnose, treat, and try to fix” may override a patient’s own goal when their individual context is not adequately considered. Individuals with OI have reported that many health professionals are not aware of the daily reality of living with OI and hence underestimate the functional challenges it presents during clinical decision-­ making [33]. Current best practice medical management, including the use of bisphospho-

© Springer Nature Switzerland AG 2020 R. W. Kruse (ed.), Osteogenesis Imperfecta, https://doi.org/10.1007/978-3-030-42527-2_5

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nates, does not provide a cure. Advances in surgical techniques provide orthopaedists with greater opportunities to address many deformities characteristic of OI that previously could not be managed without significant risks of adverse events. However, having the skills and equipment to do so does not always mean it should be done. Fortunately, in the context of individuals with OI, family and physician goals are more closely aligned than with individuals with neurological conditions. For individuals with OI, parents and orthopaedists want to reduce pain and/or deformity to promote mobility and independence in daily life. Nevertheless, the huge variation in manifestations and functioning within the spectrum of OI underlines the need to engage the individual and their family in goal

setting. To date, no studies have been performed assessing the effectiveness of patient-centered goal setting for clinical decision-making in individuals with OI.  Informing patients of options and engaging in critical discussion with patients regarding their preferences, including the decision to not have surgery, has demonstrated improved patient satisfaction and improved quality of life outcomes in the orthopaedic management of adults with other chronic conditions [32]. Goal setting with patients and families is a specific skill that health professionals must consciously undertake during their daily practice. Standardized tools are available to assist in patient goal setting and the measurement of success in meeting set goals, in terms of attainment and satisfaction (Table 5.1). These tools are typi-

Table 5.1  Useful standardized assessments to assist in surgical planning and to measure outcome success Domain of measurement GOALS Canadian Occupational Performance Measure (COPM) [35] Goal Attainment Scale (GAS) [21]

Type of measure

Age of use

Comments

Interview with patient and family

All

Interview with patient and family

All

Cost to purchase, used by therapists, takes 15–60 min to administer Cost to purchase, used by therapists, takes 15–60 min to administer

4–8-item self- or proxyreport questions regarding the impact of pain of function in the last 7 days

Ages 8–17 years and Nil cost, simple questions and scoring, takes 5 years

Timed Up and Go [27]

Objective performance measure

>5 years

Gait self-efficacy questionnaire [25]

Patient-reported questionnaire

>8 years

Functional Mobility Scale [15]

Patient-reported questionnaire

4–18 years

Pain PROMIS Pain Interference Scale [9]; Pediatric [38] FUNCTION Mobility Six-minute walk test [2]

Nil cost, follow standardized instructions, requires hazard-free walkway (20–30 m), takes