Endocrine Abstracts

JOINT1042

Context: Osteogenesis Imperfecta (OI) is a rare genetic condition, primarily caused by mutations in the COL1A1 and COL1A2 genes. Denosumab, a monoclonal antibody inhibiting the receptor activator of nuclear factor kappa-B ligand (RANKL), reduces osteoclast activity and bone resorption. Although it has demonstrated efficacy as an anti-resorptive treatment, its clinical utility is constrained by concerns regarding rebound hypercalcemia. This study was conducted as part of the multicenter trial NCT02352753, which was prematurely terminated due to calcium-related adverse events. At our center, we implemented a sub-study to monitor the dynamics of bone resorption markers and calcium levels during denosumab treatment in pediatric OI patients to prevent rebound-associated complications in this population.

Methods: A total of 40 children and adolescents aged 2 to 17 years with moderate to severe OI were treated with subcutaneous denosumab at a dose of 1 mg/kg body weight every six months. Urinary bone resorption markers (NTX and DPD) and calcium levels were measured at weeks 2, 8, 12, 16, 18, 20, and 22 post-injection. Calcium supplementation was individually adjusted based on age-specific thresholds.

Results: Bone resorption was effectively suppressed during the first two months following denosumab administration. However, levels of uNTX and DPD began to rise already after eight weeks, returning to baseline after three months, with a mild rebound observed at four months. No serious calcium-related adverse effects occurred in these patients.

Conclusion: Individualized monitoring of urinary calcium levels, along with timely adjustments to calcium supplementation, successfully prevented rebound hypercalcemia in children treated with denosumab for OI, without causing hypocalcemia shortly after administration.