Three-year longitudinal assessment of denosumab's efficacy and safety in postmenopausal osteoporosis: a 36-month real-world cohort study.

BACKGROUND

Denosumab is an effective antiresorptive therapy for postmenopausal osteoporosis; however, long-term real-world data regarding sustained efficacy, treatment adherence, safety, and biochemical outcomes remain limited. This study evaluated the 36-month effectiveness and safety of denosumab in postmenopausal women with osteoporosis receiving routine clinical care.

METHODS

This retrospective analysis included a prospectively followed real-world clinical cohort of 130 postmenopausal women with osteoporosis treated with denosumab (60 mg subcutaneously every 6 months) plus calcium and vitamin D supplementation. Participants were followed for 36 months with assessments at baseline, 12, 24, and 36 months. Outcomes included bone mineral density (BMD), T-scores, bone turnover markers, renal function, adherence patterns, prior treatment history, fracture occurrence, and adverse events. Changes over time were analyzed using paired longitudinal comparisons and linear mixed-effects models, with significance defined as p < 0.05.

RESULTS

Lumbar spine (L1-L4) BMD increased from 0.674 ± 0.120 to 0.741 ± 0.102 g/cm2, while femoral neck BMD increased from 0.526 ± 0.086 to 0.562 ± 0.079 g/cm2 over 36 months (both p < 0.001). BMD improvements were accompanied by reductions in bone turnover markers, including β-CTX and PINP, indicating sustained suppression of bone resorption. No clinically meaningful renal deterioration was observed during follow-up. Twenty-one participants had prior osteoporosis treatment history, whereas all included patients completed seven denosumab injections. Delayed injections occurred in 29 patients, although most delays were <30 days. No new fragility fractures occurred during follow-up. No cases of osteonecrosis of the jaw, atypical femoral fracture, or injection-related serious adverse events were observed. Mild hypocalcemia occurred in several patients and resolved with monitoring and supplementation adjustment.

CONCLUSION

Thirty-six months of denosumab treatment was associated with sustained improvement in BMD, suppression of bone turnover, acceptable adherence, and a favorable safety profile in postmenopausal women with osteoporosis who completed the planned 36-month treatment course. Because only patients completing all seven injections with complete follow-up data were included, adherence, persistence, and safety outcomes may be overestimated compared with an intention-to-treat population. These findings support the effectiveness of denosumab under routine clinical practice while emphasizing the importance of continued monitoring and adherence management.