Objectives: Denosumab (Dmab) is a monoclonal antibody targeting RANKL administered by sub-cutaneous injection. Given its convenient mode of administration, our goal was to assess the safety and efficacy of Dmab compared to intravenous zoledronic acid (ZA) in pediatric osteoporosis.
Methods: In this one-year pilot study (NCT02632916), children 416 years with low-trauma fractures due to osteoporosis were randomized 1:1 to receive ZA 0.025 mg/kg or Dmab 1 mg/kg every 6 months (total of 3 doses), followed by calcium supplementation for at least 10 days following each dose. The primary outcome was the proportion of children with at least one episode of hypocalcemia at 48-hours post-dosing. 12-month changes in bone mineral density Z-scores (BMDZ), Spinal Deformity Index (SDI), and the incidence of long bone fractures were assessed with blinding to treatment. Adverse events (AEs) were reported. As a pilot study, all measures but the primary outcome were reported descriptively.
Results: Ten children were enrolled in and completed the study (4 with Duchenne muscular dystrophy and 1 with juvenile osteoporosis in each group, all boys). 80% on ZA had at least one episode of asymptomatic hypocalcemia vs none on Dmab (P=0.01). The mean ± standard deviation (SD) changes in BMDZ in the ZA versus Dmab groups were: lumbar spine (areal) +1.1±0.7 vs +0.4±0.4; hip (areal) +0.7±0.5 vs +0.02±0.2; tibia (volumetric) −0.2±1.7 vs −0.05±0.5). At baseline, the median SDI on ZA was 2 (range 0, 6) vs 0 (range 0, 1) on Dmab, and remained unchanged in both groups at 12 months. Two children sustained low-trauma non-VF (1 radius, 2 femur) on ZA compared to none on Dmab. AEs deemed related to the study drug occurred in 100% on ZA versus 40% on Dmab, none of which were serious. First exposure AEs occurred in 100% of patients on ZA compared to none on Dmab.
Conclusion: In this pilot study, hypocalcemic episodes and side effects were fewer on Dmab compared to ZA, and vertebral fractures stabilized in both groups. These data support further study of Dmab in children with osteoporosis.
Disclosure: Leanne Ward has been a consultant to and participated in clinical trials with Novartis Pharmaceuticals and Amgen Inc.