Eighty-four pediatric patients with Osteogenesis Imperfecta (OI) were randomized to receive denosumab (n=42) or zoledronic acid (ZOL) (n=42) for 12 months. The primary outcome of interest was the change in BMD at the lumbar spine, femoral neck, and total hip. Secondary outcomes included serum calcium levels, bone turnover biomarkers, incidence of new fractures, and spinal morphometry changes. After 12 months, both denosumab and ZOL significantly increased BMD at all measured sites, though ZOL led to greater increases at the femoral neck and total hip. Vertebral height and projection area improved in both groups. However, denosumab was associated with rebound hypercalcemia in 31.0% of patients, with 14.3% experiencing hypercalcemic crises. Switching to ZOL alleviated hypercalcemia. Overall, denosumab and ZOL were effective in improving BMD and spinal morphometry in pediatric OI patients, but the risk of severe hypercalcemia suggests that denosumab should be used with caution.