Department of Pediatrics, School of Medicine, Johns Hopkins University, Baltimore, MD, 21205, USA.
Department of International Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, 21205, USA.
Osteoporos Int. 2024 Feb;35(2):327-338. doi: 10.1007/s00198-023-06951-z. Epub 2023 Oct 23.
Glucocorticoid use in Duchenne and Becker muscular dystrophy prolongs ambulation but cause significant skeletal toxicity. Our analysis has immediate clinical implications, suggesting that growth hormone and testosterone have a stronger effect prior to first and subsequent vertebral fracture, respectively, relative to bisphosphonates alone in children with dystrophinopathies on chronic glucocorticoids.
Glucocorticoids prolong ambulation in boys with Duchenne muscular dystrophy; however, they have significant endocrine side effects. We assessed the impact of growth hormone (GH), testosterone, and/or zoledronic acid (ZA) on vertebral fracture (VF) incidence in patients with dystrophinopathies on chronic glucocorticoids.
We conducted a longitudinal retrospective review of 27 males with muscular dystrophy. Accelerated failure time (AFT) models were used to estimate the relative time to VF while on GH, testosterone, and/or ZA compared to ZA alone. Results are reported as failure time ratio, where >1 indicates prolonged time versus <1 indicates shorter time to next VF.
The prevalence of growth impairment was 96% (52% utilized GH), pubertal delay was 86% (72% utilized testosterone), and low trauma fractures were 87% (72% utilized ZA). Multivariable analysis of the AFT models showed that participants on either GH or testosterone treatment relative to ZA alone experienced prolonged time to next VF (1.253, P<0.001), with GH being the significant contributor when analyzed independently from testosterone (1.229, P<0.001). Use of ZA with GH or testosterone relative to ZA alone resulted in prolonged time to next VF (1.171, P<0.001), with testosterone being a significant contributor (1.130, P=0.033).
GH and testosterone each decreased VF risk in patients independent of or in combination with ZA, respectively.
糖皮质激素可延长杜兴氏肌营养不良症男孩的活动能力；然而，它们具有显著的内分泌副作用。我们评估了生长激素（GH）、睾酮和/或唑来膦酸（ZA）对慢性糖皮质激素治疗的肌营养不良症患者椎骨骨折（VF）发生率的影响。
我们进行了一项 27 名男性肌营养不良症患者的纵向回顾性研究。使用加速失效时间（AFT）模型来估计在使用 GH、睾酮和/或 ZA 与单独使用 ZA 相比，发生 VF 的相对时间。结果以失效时间比报告，大于 1 表示相对于<1 表示下一次 VF 的时间延长。
生长障碍的患病率为 96%（52%使用 GH），青春期延迟为 86%（72%使用睾酮），低创伤性骨折为 87%（72%使用 ZA）。多变量 AFT 模型分析表明，与单独使用 ZA 相比，接受 GH 或睾酮治疗的参与者下一次 VF 的时间延长（1.253，P<0.001），当与睾酮独立分析时，GH 是显著的贡献者（1.229，P<0.001）。与单独使用 ZA 相比，使用 ZA 联合 GH 或睾酮可延长下一次 VF 的时间（1.171，P<0.001），其中睾酮是一个显著的贡献者（1.130，P=0.033）。
GH 和睾酮分别独立于或与 ZA 联合使用时均可降低患者的 VF 风险。
