Denosumab in Patients with Osteogenesis Imperfecta and A Historical Control Study with Alendronate

Yazhao Mei¹Shiya Cai^1,2Yunyi Jiang¹Yuan Tian¹Li Shen³Jie Mei Gu¹Chun Wang^1*ZhenLin Zhang^1*Hao Zhang^1*

• ¹Other, Shanghai, China
• ²Department of Endocrinology, Punan Hospital of Pudong New District, Shanghai, China
• ³Clinical Research Center, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China

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.Results: Pediatric denosumab recipients exhibited significant LS-BMD (+30.3%, P<0.001) and FN-BMD gains (+38.7%, P=0.001) versus baseline, whereas adults showed non-significant increases (LS: +2.6%, P=0.10; FN: +4.4%, P=0.051).Sensitivity analyses revealed attenuated BTMs suppression in adults after excluding peri-/post-menopausal women (only ALP decreased by 27.9%, P=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 (P>0.05) but superior pediatric height gain (+5.8% vs. +2.5%, P=0.004).Vertebral area loss decreased significantly with denosumab (-14.6%, P=0.029), unlike alendronate (-8.8%, P=0.296). Adverse events were more frequent with denosumab in children (hypercalcemia: 62.5% vs. 0%, P=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.