Murdoch Children's Research Institute, Royal Children's Hospital, Parkville 3052, Victoria, Australia.
Department of Pediatrics, University of Melbourne, Parkville 3052, Victoria, Australia.
J Clin Endocrinol Metab. 2021 Jul 13;106(8):2328-2342. doi: 10.1210/clinem/dgab302.
Patients with glucocorticoid-dependent Duchenne muscular dystrophy (DMD) have increased fracture risk and reduced bone mineral density (BMD), often precipitating mobility loss.
To investigate use of zoledronic acid (ZA) in DMD in improving BMD.
Two arm, parallel, randomized controlled trial, set in pediatric hospitals across Australia and New Zealand. Sixty-two (31 per arm) boys with glucocorticoid-dependent DMD between 6 and 16 years were included. Five ZA infusions (0.025 mg/kg at months 0, and 3, and 0.05 mg/kg at months 6, 12, and 18), plus calcium and vitamin D, were compared with calcium and vitamin D alone. The main outcome measures were change in lumbar spine (LS) BMD raw and Z-score by dual energy absorptiometry x-ray (DXA) at 12 and 24 months, secondary outcomes assessing mobility, fracture incidence, bone turnover, peripheral quantitative computerized (pQCT) and pain scores.
At 12 and 24 months, mean difference in changes of LS BMD Z-score from baseline was 1.2 SD (95% CI 0.9-1.5), higher by 19.3% (14.6-24.0) and 1.4 SD (0.9-1.9), higher by 26.0% (17.4-34.5) in ZA than control arms respectively (both P < .001). Five controls developed Genant 3 vertebral fractures, 0 in the ZA arm. Mobility, pain, and bone turnover markers were similar between arms at 12 and 24 months. Trabecular BMC and vBMD pQCT at radius and tibia were greater at 12 months in the ZA cohort than control; the evidence for this difference remained at 24 months for radius but not tibia.
ZA improved BMD in glucocorticoid-dependent DMD boys. Although the small cohort precluded demonstrable fracture benefit, improved BMD might reduce incident vertebral fracture.
患有糖皮质激素依赖性杜氏肌营养不良症（DMD）的患者骨折风险增加，骨密度（BMD）降低，常常导致活动能力丧失。
研究唑来膦酸（ZA）在改善 DMD 患者 BMD 中的作用。
这是一项在澳大利亚和新西兰的儿科医院进行的双臂、平行、随机对照试验。共纳入 62 名（每组 31 名）年龄在 6 至 16 岁之间的依赖糖皮质激素的 DMD 男孩。将 5 次 ZA 输注（0.025mg/kg，分别在第 0 个月、第 3 个月和第 3 个月，0.05mg/kg，分别在第 6 个月、第 12 个月和第 18 个月）联合钙和维生素 D 与单纯钙和维生素 D 进行比较。主要观察指标是双能 X 线吸收法（DXA）检测的腰椎（LS）BMD 原始值和 Z 评分在 12 个月和 24 个月时的变化，次要观察指标评估移动能力、骨折发生率、骨转换、外周定量计算机断层扫描（pQCT）和疼痛评分。
在 12 个月和 24 个月时，与对照组相比，LS BMD Z 评分从基线的平均变化差值分别高出 1.2 个标准差（95%CI 0.9-1.5），高出 19.3%（14.6-24.0）和 1.4 个标准差（0.9-1.9），高出 26.0%（17.4-34.5）（均 P<0.001）。对照组中有 5 名患者发生了 Genant 3 型椎体骨折，而 ZA 组无 1 例。在 12 个月和 24 个月时，两组之间的移动能力、疼痛和骨转换标志物相似。ZA 队列的桡骨和胫骨的小梁骨矿物质含量和体积骨密度 pQCT 在 12 个月时均高于对照组；这种差异在 24 个月时仍存在于桡骨，但不存在于胫骨。
ZA 改善了依赖糖皮质激素的 DMD 男孩的 BMD。尽管小样本队列无法证明骨折获益，但改善 BMD 可能会减少椎体骨折的发生。
