Mei Yazhao, Cai Shiya, Jiang Yunyi, Tian Yuan, Shen Li, Gu Jiemei, Wang Chun, Zhang Zhenlin, Zhang Hao
Shanghai Clinical Research Center of Bone Disease, Department of Osteoporosis and Bone Diseases, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Endocrinology, Punan Hospital of Pudong New District, Shanghai, China.
Front Endocrinol (Lausanne). 2025 May 27;16:1445093. doi: 10.3389/fendo.2025.1445093. eCollection 2025.
Optimal dosing of denosumab in osteogenesis imperfecta (OI) remains undefined. This prospective cohort study evaluated the 12-month efficacy and safety of denosumab in OI patients, with a historical control study with alendronate.
Eight pediatric patients (1 mg/kg every 3 months; ≤60 mg/dose) and ten adults (60 mg every 6 months) received denosumab. Outcomes included lumbar spine (LS) and femoral neck (FN) bone mineral density (BMD), bone turnover markers (BTMs), vertebral compression fractures (assessed via AI-assisted Genant grading [AI_OVF_SH system]), fracture incidence, height velocity and adverse events. Historical controls (n=25 alendronate-treated OI patients) were analyzed for comparative efficacy. Sensitivity analyses excluded female pediatric participants (n=4) and peri-/post-menopausal adults (n=4) to assess hormonal confounding.
Pediatric denosumab recipients exhibited significant LS-BMD (+30.3%, <0.001) and FN-BMD gains (+38.7%, =0.001) versus baseline, whereas adults showed non-significant increases (LS: +2.6%, =0.100; FN: +4.4%, =0.051). Sensitivity analyses revealed attenuated BTMs suppression in adults after excluding peri-/post-menopausal women (only ALP decreased by 27.9%, =0.028). Rebound hypercalcemia occurred in 62.5% (5/8) of children, peaking at 2.93 mmol/L. Compared to alendronate, denosumab demonstrated comparable BMD improvements and fracture reduction (>0.050) but superior pediatric height gain (+5.8% . +2.5%, =0.004). Vertebral area loss decreased significantly with denosumab (-14.6%, =0.029), unlike alendronate (-8.8%, =0.296). Adverse events were more frequent with denosumab in children (hypercalcemia: 62.5% . 0%, =0.002).
Denosumab demonstrates non-inferior efficacy to alendronate for BMD improvement in OI, with heightened vertebral remodeling and pediatric height gains. However, its overshoot phenomenon in children (rebound hypercalcemia) and hormone-dependent efficacy in adults necessitate risk-stratified use. Age and menopausal status considerations are critical for optimizing denosumab therapy in OI.
https://www.chictr.org.cn/bin/project/edit?pid=184231, identifier ChiCTR2300074207.
地诺单抗在成骨不全（OI）中的最佳剂量仍未明确。这项前瞻性队列研究评估了地诺单抗在OI患者中的12个月疗效和安全性，并与阿仑膦酸钠进行了历史性对照研究。
8名儿科患者（每3个月1mg/kg；每次剂量≤60mg）和10名成人（每6个月60mg）接受了地诺单抗治疗。结果包括腰椎（LS）和股骨颈（FN）骨密度（BMD）、骨转换标志物（BTMs）、椎体压缩骨折（通过人工智能辅助的Genant分级[AI_OVF_SH系统]评估）、骨折发生率、身高增长速度和不良事件。对历史性对照（n=25例接受阿仑膦酸钠治疗的OI患者）进行了比较疗效分析。敏感性分析排除了女性儿科参与者（n=4）和围绝经期/绝经后成人（n=4），以评估激素混杂因素。
与基线相比，接受地诺单抗治疗的儿科患者LS-BMD显著增加（+30.3%，<0.001），FN-BMD增加（+38.7%，=0.001），而成人患者的增加不显著（LS：+2.6%，=0.100；FN：+4.4%，=0.051）。敏感性分析显示，排除围绝经期/绝经后妇女后，成人患者的BTMs抑制作用减弱（仅碱性磷酸酶降低27.9%，=0.028）。62.5%（5/8）的儿童出现反弹性高钙血症，峰值为2.93mmol/L。与阿仑膦酸钠相比，地诺单抗在改善BMD和减少骨折方面表现相当（>0.050），但儿科患者的身高增长更显著（+5.8%对+2.5%，=0.004）。与阿仑膦酸钠（-8.8%，=0.296）不同，地诺单抗治疗后椎体面积损失显著减少（-14.6%，=0.029）。儿童使用地诺单抗的不良事件更频繁（高钙血症：62.5%对0%，=0.002）。
在改善OI患者的BMD方面，地诺单抗显示出与阿仑膦酸钠相当的疗效，椎体重塑增强，儿科患者身高增加。然而，其在儿童中的过冲现象（反弹性高钙血症）和在成人中的激素依赖性疗效需要进行风险分层使用。年龄和绝经状态的考虑对于优化OI患者的地诺单抗治疗至关重要。
https://www.chictr.org.cn/bin/project/edit?pid=184231，标识符ChiCTR2300074207。
