Skeletal disproportion in glucocorticoid-treated boys with Duchenne muscular dystrophy

Kao, Kung‐Ting; Joseph, Shuko; Capaldi, N; Brown, Sarah M.; Marco, Marina Di; Dunne, Jennifer; Horrocks, Iain; Shepherd, Sheila; Ahmed, S Faisal; Wong, Sze Choong

doi:10.1007/s00431-019-03336-5

Cited by 12 publications

(6 citation statements)

References 37 publications

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“…Height in DMD boys has been reported to be normal at birth, with a progressive slowdown in growth in the first years of life, but the underlying biological mechanism is still unknown [ 25 ]. In particular, skeletal disproportion has been noted [ 30 ]. Irrespective of the GC type, daily regimes showed the highest yearly stunting of height.…”

Section: Discussionmentioning

confidence: 99%

Growth pattern trajectories in boys with Duchenne muscular dystrophy

Stimpson

Raquq

Chesshyre

et al. 2022

Orphanet J Rare Dis

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Objectives The objective of this study is to analyse retrospective, observational, longitudinal growth (weight, height and BMI) data in ambulatory boys aged 5–12 years with Duchenne muscular dystrophy (DMD). Background We considered glucocorticoids (GC) use, dystrophin isoforms and amenability to exon 8, 44, 45, 51 and 53 skipping drug subgroups, and the impact of growth on loss of ambulation. We analysed 598 boys, with 2604 observations. This analysis considered patients from the UK NorthStar database (2003–2020) on one of five regimes: “GC naïve”, “deflazacort daily” (DD), “deflazacort intermittent” (DI), “prednisolone daily” (PD) and “prednisolone intermittent” (PI). A random slope model was used to model the weight, height and BMI SD scores (using the UK90). Results The daily regime subgroups had significant yearly height stunting compared to the GC naïve subgroup. Notably, the average height change for the DD subgroup was 0.25 SD (95% CI − 0.30, − 0.21) less than reference values. Those with affected expression of Dp427, Dp140 and Dp71 isoforms were 0.77 (95% CI 0.3, 1.24) and 0.82 (95% CI 1.28, 0.36) SD shorter than those with Dp427 and/or Dp140 expression affected respectively. Increased weight was not associated with earlier loss of ambulation, but taller boys still ambulant between the age of 10 and 11 years were more at risk of losing ambulation. Conclusion These findings may provide further guidance to clinicians when counselling and discussing GCs commencement with patients and their carers and may represent a benchmark set of data to evaluate the effects of new generations of GC.

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Section: Discussionmentioning

confidence: 99%

Growth pattern trajectories in boys with Duchenne muscular dystrophy

Stimpson

Raquq

Chesshyre

et al. 2022

Orphanet J Rare Dis

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“…The role of testosterone on bone health is well established; direct and indirect mechanisms are mainly involved (51). First, low level of androgens causes muscle weakness that reduces mechanical stimulation on bones (52). Secondly, reduced activation of bone androgen receptor by testosterone has a negative impact on the expression and function of the all three lines of bone-related cells (osteoblast, osteoclast, and osteocyte), resulting in an overall bone loss.…”

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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“…The glucocorticoids and microbial agents mentioned in many reports have good curative effects in the treatment of PMD. It can extend the patient's independent walking time to a large extent, enhance the patient's muscle function and average muscle strength, and significantly alleviate the symptoms of low weight caused by malnutrition in patients with progressive muscular dystrophy (16)(17)(18). There are some discrepancies between the results of this study and the conclusions of the above studies.…”

Section: Discussionmentioning

confidence: 55%