Denosumab Versus Bisphosphonates in Glucocorticoid-Induced Osteoporosis: A Systematic Review

Glucocorticoid-induced osteoporosis (GIOP) is a major cause of secondary bone loss characterized by rapid trabecular deterioration and increased fracture risk, and while bisphosphonates are widely used as first-line therapy, the comparative effectiveness of denosumab remains clinically relevant. This systematic review synthesized evidence from randomized trials, imaging studies, and observational cohorts evaluating denosumab versus bisphosphonates in adults receiving glucocorticoids, focusing on bone mineral density, bone turnover, microarchitecture, fractures, and safety. Denosumab consistently produced greater increases in lumbar spine bone mineral density, with modest but generally favorable effects at the hip and variable advantages at the femoral neck. High-resolution imaging suggested superior preservation of cortical thickness, trabecular density, and estimated bone strength with denosumab, accompanied by deeper suppression of bone turnover markers across studies. Fracture outcomes did not demonstrate meaningful differences between treatments, likely due to limited power and relatively short follow-up. Safety profiles were broadly comparable, without significant variation in adverse events or serious complications. Overall, denosumab appears to offer stronger densitometric and mechanistic benefits than bisphosphonates in GIOP, supporting its use in patients who are inadequately responsive to alternative therapies or require long-term glucocorticoid treatment, although larger and longer trials with fracture endpoints are still needed.