Long-term effects of denosumab: a 10-year single-center retrospective study

Background: Denosumab produces durable BMD gains and low fracture rates in clinical trials, but long-term real-world evidence is limited, especially on the effect of prior bisphosphonate exposure and characteristics of patients who fracture during therapy. Methods: We conducted a 10-year single-center real-world retrospective study including patients receiving continuous denosumab 60 mg every 6 months. Clinical, biochemical, and densitometric data were extracted from an institutional electronic database. Longitudinal changes in BMD at total hip, lumbar spine, and femoral neck were analyzed using linear mixed-effects models adjusted for baseline BMD, age, baseline severe vertebral fractures, and glucocorticoid exposure. Bone turnover markers (CTX, ALP, PTH) were analyzed with mixed-effects models adjusted for renal function. Results: A total of 145 patients were included (mean age 70.9 years; 95.9% women). Over 10 years, BMD increased significantly at all skeletal sites: +12.9% at the total hip, + 16.3% at the lumbar spine, and +6.0% at the femoral neck. CTX and ALP showed marked and sustained reduction, whereas PTH remained stable over time. Prior bisphosphonate exposure did not modify long-term BMD trajectories at any site, and group differences in CTX converged after treatment initiation. Patients who sustained fractures showed significantly attenuated lumbar spine BMD gains, while hip sites displayed similar trajectories to non-fractured patients. Conclusions: In a real-world setting, continuous denosumab therapy for 10 years produced robust and sustained BMD gains, accompanied by a durable and stable reduction in bone turnover. Prior bisphosphonate exposure influenced only early biochemical differences and did not affect decade-long BMD responses.