Fractures and bone health monitoring in boys with Duchenne muscular dystrophy managed within the Scottish Muscle Network

Joseph, Shuko; Wang, Cunyi; Marco, Marina Di; Horrocks, Iain; Abu‐Arafeh, Ishaq; Baxter, Alex; Cordeiro, Nuno; McLellan, Linda; McWilliam, Kenneth; Naismith, Karen; Stephen, Elma; Ahmed, S Faisal; Wong, Sze Choong

doi:10.1016/j.nmd.2018.09.005

Cited by 30 publications

(20 citation statements)

References 45 publications

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“…Joseph et al showed a mean latency of 2.3 years to incur in symptomatic VFs after the beginning of the treatment (48). However, painful VFs are present in less than half of DMD patients, with these lesions frequently detected as asymptomatic incidental findings.…”

Section: Nmds Involving Skeletal Muscle Structurementioning

confidence: 99%

Neuromuscular Diseases and Bone

et al. 2019

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Neuromuscular diseases (NMDs) are inherited or acquired conditions affecting skeletal muscles, motor nerves, or neuromuscular junctions. Most of them are characterized by a progressive damage of muscle fibers with reduced muscle strength, disability, and poor health-related quality of life of affected patients. In this scenario, skeletal health is usually compromised as a consequence of modified bone–muscle cross-talk including biomechanical and bio-humoral issues, resulting in increased risk of bone fragility and fractures. In addition, NMD patients frequently face nutritional issues, including malnutrition due to feeding disorders and swallowing problems that might affect bone health. Moreover, in these patients, low levels of physical activity or immobility are common and might lead to overweight or obesity that can also interfere with bone strength features. Also, vitamin D deficiency could play a critical role both in the pathogenesis and in the clinical scenario of many NMDs, suggesting that its correction could be useful in maintaining or enhancing bone health, especially in the early phases of NMDs. Last but not least, specific disease-modifying drugs, available for some NMDs, are frequently burdened with adverse effects on bone tissue. For example, glucocorticoid therapy, standard of care for many muscular dystrophies, prolongs long-term survival in treated patients; nevertheless, high dose and/or chronic use of these drugs are a common cause of secondary osteoporosis. This review addresses the current state of knowledge about the factors that play a role in determining bone alterations reported in NMDs, how these factors can modify the biological pathways underlying bone health, and which are the available interventions to manage bone involvement in patients affected by NMDs. Considering the complexity of care of these patients, an interdisciplinary and multimodal management strategy based on both pharmacological and non-pharmacological interventions is recommended, particularly targeting musculoskeletal issues that are closely related to functional independence as well as social implications.

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Section: Nmds Involving Skeletal Muscle Structurementioning

confidence: 99%

Neuromuscular Diseases and Bone

et al. 2019

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“…While effective in reflecting the musculoskeletal changes that occur with complete immobilization or unloading, these models are limited in their ability to assess musculoskeletal changes due to partial reductions in mechanical loading that occur in many situations. For example, there is an increased risk of fracture associated with muscular dystrophy, cerebral palsy, and stroke [11][12][13] , where patients are partially loaded. Furthermore, an animal model that could mimic the musculoskeletal effects of fractional gravity, such as that experienced on the Moon or Mars, could provide insights useful for planning future space missions.…”

Section: Introductionmentioning

confidence: 99%

Dose-dependent skeletal deficits due to varied reductions in mechanical loading in rats

Mortreux

Riveros

et al. 2020

npj Microgravity

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Reduced skeletal loading leads to marked bone loss. Animal models of hindlimb suspension are widely used to assess alterations in skeleton during the course of complete unloading. More recently, the effects of partial unloading on the musculoskeletal system have been interrogated in mice and rats, revealing dose-dependent effects of partial weight bearing (PWB) on the skeleton and skeletal muscle. Here, we extended these studies to determine the structural and functional skeletal alterations in 14-week-old male Wister rats exposed to 20%, 40%, 70%, or 100% of body weight for 1, 2, or 4 weeks (n = 11-12/group). Using in vivo pQCT, we found that trabecular bone density at the proximal tibia declined in proportion to the degree of unloading and continued progressively with time, without evidence of a plateau by 4 weeks. Ex vivo measurements of trabecular microarchitecture in the distal femur by microcomputed tomography revealed deficits in bone volume fraction, 2 and 4 weeks after unloading. Histologic analyses of trabecular bone in the distal femur revealed the decreased osteoblast number and mineralizing surface in unloaded rats. Three-point bending of the femoral diaphysis indicated modest or no reductions in femoral stiffness and estimated modulus due to PWB. Our results suggest that this rat model of PWB leads to trabecular bone deterioration that is progressive and generally proportional to the degree of PWB, with minimal effects on cortical bone.

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“…In childhood, especially glucocorticoids play a major role in secondary osteoporosis. Studies on patients receiving systemic steroids for acute lymphoblastic leukemia (4), juvenile idiopathic arthritis (5, 6), Duchenne muscular dystrophy (7) or asthma (8) all indicate increased peripheral and vertebral fracture rates.…”

Section: Introductionmentioning

confidence: 99%

New Insights Into Monogenic Causes of Osteoporosis

et al. 2019

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Osteoporosis, characterized by deteriorated bone microarchitecture and low bone mineral density, is a chronic skeletal disease with high worldwide prevalence. Osteoporosis related to aging is the most common form and causes significant morbidity and mortality. Rare, monogenic forms of osteoporosis have their onset usually in childhood or young adulthood and have specific phenotypic features and clinical course depending on the underlying cause. The most common form is osteogenesis imperfecta linked to mutations in COL1A1 and COL1A2 , the two genes encoding type I collagen. However, in the past years, remarkable advancements in bone research have expanded our understanding of the intricacies behind bone metabolism and identified novel molecular mechanisms contributing to skeletal health and disease. Especially high-throughput sequencing techniques have made family-based studies an efficient way to identify single genes causative of rare monogenic forms of osteoporosis and these have yielded several novel genes that encode proteins partaking in type I collagen modification or regulating bone cell function directly. New forms of monogenic osteoporosis, such as autosomal dominant osteoporosis caused by WNT1 mutations or X-linked osteoporosis due to PLS3 mutations, have revealed previously unidentified bone-regulating proteins and clarified specific roles of bone cells, expanded our understanding of possible inheritance mechanisms and paces of disease progression, and highlighted the potential of monogenic bone diseases to extend beyond the skeletal tissue. The novel gene discoveries have introduced new challenges to the classification and diagnosis of monogenic osteoporosis, but also provided promising new molecular targets for development of pharmacotherapies. In this article we give an overview of the recent discoveries in the area of monogenic forms of osteoporosis, describing the key cellular mechanisms leading to skeletal fragility, the major recent research findings and the essential challenges and avenues in future diagnostics and treatments.

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Fractures and bone health monitoring in boys with Duchenne muscular dystrophy managed within the Scottish Muscle Network

Cited by 30 publications

References 45 publications

Neuromuscular Diseases and Bone

Neuromuscular Diseases and Bone

Dose-dependent skeletal deficits due to varied reductions in mechanical loading in rats

New Insights Into Monogenic Causes of Osteoporosis

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