Comparative efficacy and safety of antiresorptive and anabolic therapies for male osteoporosis: an updated Bayesian network meta-analysis

Background: Osteoporosis in men is an increasingly recognized health issue associated with reduced bone mineral density (BMD) and elevated fracture risk. While both antiresorptive and anabolic therapies are recommended in clinical practice, evidence directly comparing these drug classes in male populations remains limited. Methods: We performed a systematic review and Bayesian network meta-analysis (NMA), registered on PROSPERO (CRD420251151177), to assess the efficacy and safety of pharmacological interventions for male osteoporosis. Randomized controlled trials (RCTs) evaluating alendronate, risedronate, zoledronic acid, denosumab, teriparatide, or abaloparatide were identified from PubMed, Web of Science, and the Cochrane Library through 2025. Primary outcomes included percent change in lumbar spine, femoral neck, and total hip BMD at 12 months. Safety outcomes were all adverse events (AEs) and serious adverse events (SAEs). Category-level meta-analyses were further conducted to compare pooled effects of antiresorptive versus anabolic agents. Results: Eighteen RCTs comprising 19-1199 participants each were included. At the drug level, abaloparatide and teriparatide ranked highest for lumbar spine BMD, while alendronate and abaloparatide demonstrated the most favorable effects for femoral neck and total hip BMD, respectively. Safety profiles were broadly similar, with teriparatide and alendronate showing relatively lower risks of AEs and SAEs. At the class level, anabolic therapies significantly outperformed antiresorptives in improving lumbar spine (MD 6.62, 95% CI 5.01-8.23 vs. 3.58, 95% CI 2.52-4.64) and total hip BMD (3.53, 95% CI 2.18-4.89 vs. 1.98, 95% CI -1.10-5.06), whereas antiresorptives showed modest advantages at the femoral neck (1.66, 95% CI 0.57-2.75 vs. 1.43, 95% CI -0.03-2.86). No significant differences were observed between classes in AEs or SAEs. Conclusions: This study provides the first comprehensive drug- and class-level synthesis of treatments for male osteoporosis. Anabolic agents confer greater efficacy at the lumbar spine and total hip, while antiresorptives may offer modest benefits at the femoral neck. Safety outcomes were comparable across drug classes, suggesting that treatment choice should primarily be guided by efficacy considerations. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD420251151177.