Bone Health and Osteoporosis Leanne M. Ward, MD,a Stasia Hadjiyannakis, MD,a Hugh J. McMillan, MD, MSc,a GareyManagement Noritz, MD,b David R. Weber, MD, MSCE ofc the Patient With Duchenne Muscular Dystrophy abstract Duchenne muscular dystrophy is associated with an increased risk of bone fragility due to the adverse effects of prolonged glucocorticoid therapy and progressive muscle weakness on bone strength. Osteoporosis manifests clinically as low-trauma long-bone and vertebral fractures (VFs), with VFs frequent, particularly in those treated with glucocorticoid therapy. It is increasingly recognized that bone pain, medical complications of osteoporosis (such as fat embolism syndrome), and the potential for permanent, fracture-induced loss of ambulation can be mitigated with timely bone health surveillance and management. This includes periodic spine radiographs for VF detection because VFs can be asymptomatic in their early phases and thereby go undetected in the absence of monitoring. With this article, we provide a comprehensive review of the following 4 phases of bone health management: (1) bone health monitoring, which is used to identify early signs of compromised bone – health; (2) osteoporosis stabilization, which is aimed to mitigate back pain and interrupt the fracture refracture cycle through bone-targeted therapy; (3) bone health maintenance, which has the goal to preserve the clinical gains realized during the stabilization phase through ongoing bone-targeted therapy; and (4) osteoporosis therapy discontinuation, which places those who are eligible for discontinuation of osteoporosis treatment back on a health monitoring program. In the course of reviewing these 4 phases of management, we will discuss the criteria for diagnosing osteoporosis, along with detailed recommendations for osteoporosis intervention including specific drugs, dose, length of therapy, contraindications, and monitoring of treatment efficacy and safety.
Awareness is increasing that bone morbidity due to osteoporosis is a major complication of Duchenne muscular dystrophy (DMD) and its treatment and that it requires monitoring for early diagnosis and intervention to prevent clinically important sequelae. The 2 main risk factors for osteoporosis in this context are the progressive muscle weakness with loss of weight-bearing activity and osteotoxicity from glucocorticoid therapy. Short stature, delayed puberty, and frequent falls augment the already high risk of fractures. Vertebral fractures (VFs) can cause chronic pain
aDepartment of Pediatrics, Children’s Hospital of Eastern Ontario, University of Ottawa, Ottawa, Ontario, Canada; bNationwide Children’s Hospital, The Ohio State University, Columbus, Ohio; and cGolisano Children’s Hospital, School of Medicine and Dentistry, University of Rochester, Rochester, New York The guidelines or recommendations in this article are not American Academy of Pediatrics policy and publication herein does not imply endorsement.
Dr Ward served as chairperson for the Duchenne Muscular Dystrophy Care Considerations Endocrine and Bone Health Management Working Group, as convened by the Centers for Disease Control and Prevention, and drafted the initial manuscript; Drs Hadjiyannakis, McMillan, Noritz, and Weber served on the Duchenne Muscular Dystrophy Care Considerations Endocrine and Bone Health Management Working Group, as convened by the Centers for Disease Control and Prevention, and contributed to the development of corresponding recommendations; and all authors reviewed and revised the manuscript, approved the final manuscript as submitted, and agree to be accountable for all aspects of the work. DOI: https://doi.org/10.1542/peds.2018-0333E
Downloaded from www.aappublications.org/news by guest on September 29, 2021 SUPPLEMENT ARTICLE PEDIATRICS Volume 142, number s2, October 2018:e20180333E – and spine deformity, whereas long- individuals with DMD present with the fracture refracture cycle bone fractures have been linked low-trauma extremity fractures, often through the administration of bone- to permanent, 1premature loss at the distal femur or tibia and fibula. targeted therapy; (3) the bone health of ambulation. As such, optimal Low-trauma VFs are also frequent maintenance phase, which has the management of osteoporosis is a but often go unrecognized because – goal to preserve the clinical gains major contributor to quality of life in of their potential to be asymptomatic1,5 8 realized during the stabilization patients living with DMD. Effective (particularly in the early stages). phase; and (4) the osteoporosis management– of bone health in DMD If left untreated, VFs are associated therapy discontinuation phase, is possible2 4 and may even influence with progressive back pain, spine which places those who are eligible survival. Authors of case series deformity, and heightened risk of for discontinuation of osteoporosis have described acute respiratory sustaining a future fracture, whereas treatment back on a skeletal health distress leading to death as a femur fractures have been linked monitoring program. In the course result of fat embolism syndrome to permanent,5 premature loss of of reviewing these 4 phases, we will occurring after long-bone fractures2,3 ambulation. That osteoporosis discuss the criteria for diagnosing or injuries in patients with DMD ; treatment with bisphosphonates osteoporosis, along with detailed authors of another study suggested has been linked to survival provides recommendations for osteoporosis that bisphosphonate therapy for further rationale for effective intervention including specific osteoporosis4 may be linked to osteoporosis diagnosis, surveillance,4 drugs, dose, length of therapy, longevity. and prevention strategies. contraindications,Skeletal Health Monitoring and monitoring. Phase This review is targeted for primary Although the frequency of fractures care providers, neurologists, is high in DMD, no published studies endocrinologists, and bone health in this setting or in any other at-risk The extent of bone morbidity specialists involved in the care of pediatric condition have been used in pediatric DMD, including the patients with DMD by providing to evaluate the safety and efficacy potential for fractures before specific recommendations to guide of drug therapy to prevent the first and in the years immediately clinical practice. With appropriate fracture. The current approach is after diagnosis, has prompted prevention and treatment of to diagnose and treat the earliest the recommendation to initiate glucocorticoid-related bone signs of fractures, including VFs, monitoring at the time of diagnosis morbidity, it is anticipated that in those with limited potential for or no later than the time at which serious sequelae of osteoporosis and spontaneous (drug-unassisted) glucocorticoid therapy is initiated. the need to withdraw glucocorticoid recovery. This is in line with a Because VFs are more common 5in therapy because of bone health secondary prevention strategy, boys on glucocorticoid therapy, complications will be mitigated. which is to interrupt the progression lateral thoracolumbar spine The goals of optimal bone health of osteoporosis and facilitate radiographs should be conducted management, therefore, are twofold. recovery in patients with not only at least every 2 years, compared The first is to improve quality of early evidence of bone fragility but with radiographs every few years life by reducing bone pain and also less potential for medication- in those who are not receiving preventing loss of ambulation due unassisted recovery because of glucocorticoid therapy. Radiographs for VF detection should be conducted to fractures. The second goal is to persistent risk factors. ≥ provide skeletal protection in a sooner in the presence of back pain An overview of the rationale for the z timely manner so as to allow the or a 0.5 decline in spine bone recommended approach to bone patient to remain on glucocorticoid mineral density (BMD) score on health management is provided therapy for as long as desired and serial BMD measurements over a in the 2018 Updated DMD Care indeed necessary. 12-month period or more. A baseline Considerations, sponsored by the lateral spine radiograph around the OSTEOPOROSIS IN DMD Centers for Disease Control and 9 time of diagnosis is recommended to Prevention. In the present article, we facilitate the detection of the earliest delve more deeply into the 4 phases signs of collapse on subsequent films. Fractures due to osteoporosis5 are of bone health care, as follows: (1) frequent in DMD, arising from the the bone health monitoring phase, A lumbar spine BMD by dual- toxic effects of glucocorticoid therapy which is used to identify early signs energy x-ray absorptiometry is on bone metabolism along with the of compromised bone health in this recommended annually in all patients progressive dystrophinopathy, both high-risk group; (2) the osteoporosis to determine the overall bone health of which are negative regulators stabilization phase, which is aimed trajectory on serial measurements. of bone strength. Up to 60% of to mitigate back pain and interrupt In the event that dual-energy x-ray Downloaded from www.aappublications.org/news by guest on September 29, 2021 PEDIATRICS Volume 142, number s2, October 2018 S35 absorptiometry is challenging for 25-hydroxyvitamin D (25OHD) approach, with pain assessed either – cost or logistical reasons, a lateral should be verified annually (ideally according to a standardized tool such21 thoracolumbar spine radiograph at the end of winter in seasonal as the Faces of Pain Scale Revised should be prioritized for VF countries, recognizing that this is not or by routine history taking. Back or ’ detection. Although the lumbar spine always feasible). In keeping with the17 bone pain that is reported between is a frequent site 10for ascertaining Institute of Medicine s guidelines, clinic visits should be assessed by BMD in children, lateral distal the lowest acceptable vitamin D plain radiographs to assess the z 5 ≥ femur, hip, and total-body BMD level is 20 ng/mL (50 nmol/L), with possibility of fracture. scores are also useful in children the ideal target being 30 ng/mL 11,12 18 ’ with neuromuscular disorders, (75 nmol/L). Intakes beyond the The Genant22 semiquantitative including8 those with declining muscle Institute of Medicine s recommended method for VF assessment is now zfunction. BMD raw values are 600 IU per day are often required accepted as a valid tool in children, converted to age- and sex-specific to achieve these target levels, given given observations that Genant- scores and require additional the paucity of vitamin D in the defined fractures are associated interpretation in view of body size, most commonly consumed foods, with biologicallyz logical23 predictors ethnicity, and pubertal staging or compounded by the lack of sunlight including back pain, low16,23 and/or skeletal maturity13 (the latter, by or sun exposure in many countries. declining BMD scores, 16, 23 bone age). Because BMD can be As a fat-soluble vitamin, vitamin D glucocorticoid exposure, 16, and23 an underestimated in patients with can be given daily or intermittently increased risk of future VF. The Genant method defines VF according DMD because of their short stature, at higher doses (ie, weekly, monthly). ≤ bone size should be adjusted by using In the absence of rickets, typical to the following reduction in height a technique such as bone mineral vitamin D doses used to achieve these ratios: grade 0 (normal) 20%; → apparent density (an estimation levels are as follows: 25OHD = 20 grade 1 fracture (mild) >20% to 25%; z → of volumetric BMD, in gram per to 30 ng/mL 1000 IU per day; grade 2 fracture (moderate) >25% – 14 z → cubic centimeter) or height 25OHD <20 ng/mL 2000 IU per to 40%; grade 3 fracture (severe) ≥ z 15 score corrected BMD score. A day; and 25OHD <10 ng/mL 4000 >40%. The scoring should be done 0.5 decline in spine BMD score is IU per day. Higher doses may be by a radiologist, because it requires considered clinically significant 16on required in some patients (those expertise in distinguishing24 VF from the basis of recent observations ; overweight or obese, with darker normal pediatric variants. Treatment: Osteoporosis such a decline on serial BMD skin, less sun exposure, diets low Stabilization Phase measurements over a 12-month in vitamin D, malabsorption, or period provides the rationale in medical therapy that interferes with a given patient to conduct spine vitamin D metabolism including radiographs sooner rather than later, glucocorticoids). After vitamin D Osteoporosis is present once a child as outlined in the 2018 Updated9 Care supplementation for a low 25OHD with risk factors for low-trauma Considerations algorithm. level has been initiated, the bone fragility demonstrates at least measurement should be repeated 1 clinically significant fracture (ie, During the monitoring phase, 25 3 months later to document the a long-bone fracture or VF; Fig 1). conservative steps can be taken adequacy of dosing and compliance. The patient should be referred at to maintain overall bone health, Although vitamin D2 and D3 have the time of a low-trauma fracture to including discussion around 19 similar efficacy with daily dosing, a clinician with specific expertise in strategies to prevent falls and other vitamin D2 has rapid decay with managing pediatric osteoporosis if accidents. Calcium intake should intermittent therapy, whereas the this has not already been done. As be assessed at least annually, with 20 ’ decay is less rapid with vitamin D3. shown in the algorithm (Fig 2), in recommendations to achieve the Thus, vitamin D3 is recommended in the presence of a mild (grade 1) VF, Institute of Medicine s updated 17 any patient undergoing intermittent treatment is recommended at the age-related intake through diet therapy. latest once the mild VF is associated and/or supplementation. Calcium with symptomatology, with back pain supplementation is recommended At each monitoring visit, the relief providing an important index only if daily intake is inadequate, practitioner should take a fracture of treatment efficacy in this setting. out of concern for exacerbating history and advise patients to report When an asymptomatic or minimally the hypercalciuria that is a known to their health care provider any symptomatic grade 1 VF is identified, feature of DMD. fractures that occur in between visits. the patient should have a follow-up In addition to at least an annual Bone and back pain assessments are lateral spine radiograph 6 to 12 assessment of calcium intake, serum also part of the annual monitoring months later, or sooner if back pain Downloaded from www.aappublications.org/news by guest on September 29, 2021 S36 WARD et al bisphosphonate therapy during or other means of communication is the pediatric years is not advised recommended. because of data arising from Bisphosphonates are contraindicated controlled trials in osteogenesis in patients with poor renal function imperfecta; the published controlled (estimated glomerular filtration rate trials in which authors quantified <35 mL per minute). Recently, the vertebral body height clearly US Food and Drug Administration revealed increased vertebral updated the label for zoledronic acid, heights in youth with osteogenesis – stating it is also contraindicated in imperfecta who were treated with 27 29 patients with acute renal impairment IV bisphosphonate therapy. and that patients should be screened In contrast, none of the controlled for renal insufficiency before studies of oral bisphosphonate – initiating treatment. To this end, studies revealed a positive 30 32 serum creatinine is not a reliable effect on vertebral height. marker of renal function in patients In addition, it is well known that with DMD, creating the need for the oral bioavailability of oral 33,34 other measures such as cystatin C bisphosphonates is low. These to ensure adequate renal function data are particularly relevant to before each bisphosphonate infusion. DMD in1 which the frequency of VF Monitoring for other side effects is high and support the use of IV reported in adults on long-term instead of oral bisphosphonates as bisphosphonate therapy (including first-line therapy wherever possible osteonecrosis of the jaw and atypical in children despite its less convenient femur fractures) is also necessary mode of administration. and underscores the importance of bisphosphonate therapy in IV therapy should be given at the hands of an osteoporosis
standard, published25,27, doses,35, 36 as treatment expert. A full discussion outlined in Fig 2. A clinician of appropriate doses, potential side with relevant expertise should effects, and steps to ensure patient administer these agents to ensure the safety on bisphosphonate therapy appropriate side effect management is beyond the scope of these core and that contraindications, such as recommendations, but these issues
renal disease, are respected. In some are comprehensively9,26, 38 discussed in centers, bisphosphonate therapy recentTreatment: reviews Osteoporosis. FIGURE 1 is administered on an in-patient Examples of VFs on a lateral thoracolumbar spine Maintenance Phase and radiograph in a patient with DMD. This figure basis. However, the treatment Discontinuation of Osteoporosis reveals the spine of a patient, age 10 years, can also be safely delivered in Therapy with DMD who presented with back pain after outpatient settings provided an 18 months of glucocorticoid therapy, in the absence of a previous history of routine spine on-call physician is available to health monitoring. Multiple VFs were identified the patient in the week after each Risk factors for ongoing bone fragility ± on a lateral thoracolumbar spine radiograph, infusion. Given the possibility of are inherently persistent in DMD many in advanced stages of collapse. T10, thoracic fever and vomiting with the first vertebra 10; L5, lumbar vertebra 5. (ie, the myopathy glucocorticoid infusion, glucocorticoid stress-dosing therapy). Therefore, once the patient recommendations must be provided is clinically stable (see Fig 2 for the (as discussed in the article on obesity definition of clinically stable in the emerges in the interim, to evaluate and endocrine37 management in this osteoporosis setting), consideration In centers where the status of the VF. supplement). should be given to continuing39 IV access to a clinician with expertise in therapy but at a lower dose. The The current standard of care for osteoporosis medical management goal of this approach is to preserve treating osteoporosis in childhood is not available yet, and a patient is the clinical gains achieved during the is intravenous (IV) bisphosphonate in need of treatment, liaison with stabilization phase while avoiding therapy (pamidronate,25, zoledronic26 an osteoporosis expert (usually an overtreatment. Vertebral body acid, or neridronate). Using oral endocrinologist) through telehealth reshaping after VF is a frequently Downloaded from www.aappublications.org/news by guest on September 29, 2021 PEDIATRICS Volume 142, number s2, October 2018 S37 FIGURE 2 Osteoporosis monitoring, diagnosis, and treatment algorithm for patients with DMD. DXA, dual-energy x-ray absorptiometry. *Signs of clinically significant bone fragility are low-trauma fractures of long bones or vertebra. †Clinical stability refers to the absence of nonvertebal fractures, stable healed VFs, absence of new VFs in previously normal vertebral bodies, absence of bone and back pain, and a BMD z score appropriate for height z score or >−2 SDs. (Reproduced with permission from Birnkrant DJ, Bushby K, Bann CM, et al; DMD Care Considerations Working Group. Diagnosis and management of Duchenne muscular dystrophy, part 2: respiratory, cardiac, bone health, and orthopaedic management. Lancet Neurol. 2018;17[4]:353.)
overlooked treatment goal, one that bisphosphonates following severe led to the general recommendation occurs only when bisphosphonate vertebral collapse after years of in children that bisphosphonate therapy is administered to patients glucocorticoid therapy; highlighted therapy should be continued at least during the growth phase (Fig 3). in this observation is the importance until the end of final height in those
This phenomenon underscores the of early rather than late identification with persistent or permanent41 risk critical importance of treating signs and treatment of VF. factors for osteoporosis (including of vertebral collapse earlier rather glucocorticoid therapy and myopathy ’ than later, so that treatment can be The duration of maintenance as in DMD) and, as a minimum, administered as far in advance of therapy depends on the patient s even beyond final adult height if the epiphyseal closure as possible. On bone health status (whether patient is not yet clinically stable. the other hand, patients with DMD clinically stable or not) and whether With Fig 2, we outline the definition often manifest growth deceleration glucocorticoid therapy is ongoing. of clinically stable in patients and even growth arrest because of When bisphosphonate therapy is undergoing osteoporosis treatment. the toxic effects of glucocorticoids discontinued during the growth on the growth plate. In such cases, phase, the newly formed bone No studies have been used to the potential for vertebral body adjacent to the growth plate (ie, the address which BMD increment or reshaping is limited, and the goals treatment-naive bone) is once again cutoff is associated with a clinically of therapy then become prevention low density, creating a stress riser acceptable decrease in fracture rates of new VF and associated back between the treated and treatment- that would categorize the patient pain, because reshaping of existing naive bone. Metaphyseal fractures as stable once achieving final adult VF may not be realistic depending have been observed at the interface zheight. In the absence of such data, it on the magnitude of the growth between the treated and untreated is recommended that the areal BMD failure. In our experience, new VFs bone in children40 after treatment is score should stabilize (if previously are more likely in those who start discontinued. This observation has on the decline) or increase beyond Downloaded from www.aappublications.org/news by guest on September 29, 2021 S38 WARD et al VF in44 DMD patients increases with age. Further research is required to determine the optimal efficacy and safety with these long-term bisphosphonate approaches in DMD. FUTURE DIRECTIONS IN OSTEOPOROSIS MANAGEMENT FOR DMD
The most pressing need is for a large- scale, well-designed osteoporosis prevention trial in which medical therapy is started around the time of diagnosis or glucocorticoid FIGURE 3 initiation to prevent the first fracture. The evolution of spine morphology in a patient with DMD treated with glucocorticoid followed by IV The challenge with such a trial is bisphosphosphonate therapy for painful VFs. This figure is used to illustrate changes in vertebral morphology during glucocorticoid and IV bisphosphonate therapy. A, Early asymptomatic signs of T7 achieving an adequate sample size and T8 VFs on glucocorticoid therapy. B, Progressive vertebral collapse with an emergence of back to assess differences between the pain triggering IV pamidronate therapy. C and D, Vertebral body reshaping on IV pamidronate therapy. treated and control groups for VF Vertebral body reshaping is a growth-dependent process that is facilitated by bone strengthening and non-VF outcomes; assessing therapy. The extent to which vertebral bodies can undergo reshaping on bisphosphonate therapy is determined by a number of clinical factors, including the degree of collapse, growth velocity, only surrogates for bone strength severity of ongoing risk factors for osteoporosis, and the magnitude of residual growth potential (bone biomarkers and BMD) does not (before epiphyseal fusion). Patients with poor growth velocity have less potential for reshaping, as address the clinical end points that do patients who start therapy with more severe collapse and who are closer to attaining their final are most relevant to the patient. In adult height. T7, Thoracic vertebra 7; T8, Thoracic vertebra 8. the context of such a trial, patients will receive therapy before a fracture would have occurred naturally, so the safety of such an approach zthe precision of the measurement, with a low risk of first-ever fractures and furthermore, the areal BMD warrants rigorous scrutiny. Secondly, ’ z and for those with a moderate risk score should approximate the who are clinically well after 3 to 5 more convenient antiresorptive 25 43 agents (such as denosumab) merit zpatient s height score. Another years of therapy. High-risk adult − ≤− further study. Because patients approach is to aim for a BMD patients (those with a history of 42 may experience some degree of score > 2.0. bone fragility or a T score 2) are progressive vertebral height loss not considered candidates for drug If a patient deteriorates after 43 even on IV bisphosphonate therapy holidays. In practical terms, our treatment is discontinued (ie, if therapy is started once VFs are in current recommendations are to 45 presents with a new VF, worsening more advanced stages of collapse, treat the pediatric patient with DMD of existing VF, or a low-trauma the question is whether treatment according to the IV bisphosphonate extremity fracture after adult height before the first-ever VF will be even attainment and after bisphosphonate initiation guidelines outlined here more successful in maintaining the cessation), then reinitiation of and then continue until final adult height of vertebral bodies rather treatment is indicated. At present, height is attained. After final adult than starting treatment once collapse the benefits and risks of drug height is attained, the course of is evident and the VF cascade holidays (periods of bisphosphonate action is less clear. One approach is to is in motion. Thirdly, it remains discontinuation) in pediatric or adult discontinue therapy if the patient is unanswered whether bone anabolic clinically stable (as defined in Fig 2). patients with DMD (all of whom have agents will improve efficacy given the45 permanent bone heath threats and Monitoring should then be continued, low bone turnover in DMD patients. thereby at least the theoretical need and if fractures recur, treatment can Antisclerostin antibody is one such “ for ongoing bone protection) remain be reinitiated. The other approach promising agent. Another anabolic ” uncertain. Although rare, atypical is to adopt the adult criteria for agent, teriparatide, has an FDA black femur fractures on bisphosphonate deciding to institute drug holidays. box label for patients with open therapy have led care providers for In this case, patients should not epiphyses but is a logical agent for adult postmenopausal osteoporosis take drug holidays based on current study in DMD once final adult height to consider drug holidays for those adult guidelines because the risk of is attained. Downloaded from www.aappublications.org/news by guest on September 29, 2021 PEDIATRICS Volume 142, number s2, October 2018 S39 ACKNOWLEDGMENTS ABBREVIATIONS ’ Canadian Child Health Clinician Scientist Program, the Children s We thank Victor Konji for his 25OHD: 25-hydroxyvitamin D assistance in the preparation of Hospital of Eastern Ontario Research BMD: bone mineral density references and figures for the Institute, the University of Ottawa ’ DMD: Duchenne muscular manuscript. Dr Leanne M. Ward Research Chair Program, and the dystrophy was supported by the Canadian Children s Hospital of Eastern IV: intravenous Institutions for Health Research Ontario Departments of Pediatrics VF: vertebral fracture Operating Grants Program, the and Surgery. Accepted for publication Jul 26, 2018 Address correspondence to Leanne M. Ward, MD, Children’s Hospital of Eastern Ontario, University of Ottawa, 401 Smyth Rd, Ottawa, ON, K1H 8L1, Canada. E-mail: [email protected] PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275). Copyright © 2018 by the American Academy of Pediatrics FINANCIAL DISCLOSURE: Other than those listed under Potential Conflict of Interest, the other authors have indicated they have no financial relationships relevant to this article to disclose. FUNDING: Dr Ward is supported by a research chair from the University of Ottawa. This publication was supported in part by the cooperative agreement, NU38OT000167, funded by the Centers for Disease Control and Prevention. POTENTIAL CONFLICT OF INTEREST: Dr Ward was a consultant to and participated in clinical trials with Novartis; Dr Weber was a paid consultant for Marathon Pharmaceuticals; and Drs Hadjiyannakis, McMillan, and Noritz have indicated they have no potential conflicts of interest to disclose.
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Downloaded from www.aappublications.org/news by guest on September 29, 2021 S42 WARD et al Bone Health and Osteoporosis Management of the Patient With Duchenne Muscular Dystrophy Leanne M. Ward, Stasia Hadjiyannakis, Hugh J. McMillan, Garey Noritz and David R. Weber Pediatrics 2018;142;S34 DOI: 10.1542/peds.2018-0333E
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Downloaded from www.aappublications.org/news by guest on September 29, 2021 Bone Health and Osteoporosis Management of the Patient With Duchenne Muscular Dystrophy Leanne M. Ward, Stasia Hadjiyannakis, Hugh J. McMillan, Garey Noritz and David R. Weber Pediatrics 2018;142;S34 DOI: 10.1542/peds.2018-0333E
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Pediatrics is the official journal of the American Academy of Pediatrics. A monthly publication, it has been published continuously since 1948. Pediatrics is owned, published, and trademarked by the American Academy of Pediatrics, 345 Park Avenue, Itasca, Illinois, 60143. Copyright © 2018 by the American Academy of Pediatrics. All rights reserved. Print ISSN: 1073-0397.
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