Journal of aging and physical activity · 2026
Synergistic Effects of Bisphosphonates and Physical Exercises and Modalities on Osteoporosis Management: A Systematic Review and Meta-Analysis.
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Jin Jun, Ma Haile
Аннотация
BACKGROUND: Osteoporosis is a major global health concern associated with increased fracture risk, reduced functional capacity, and impaired quality of life (QoL). Although bisphosphonates improve bone mineral density (BMD), adjunctive physical interventions may provide additional synergistic benefits. This systematic review and meta-analysis evaluated whether combining bisphosphonates with physical interventions provides greater improvements in BMD and QoL compared with bisphosphonate therapy alone.
METHODS: A systematic search of PubMed and the Cochrane Library was conducted from inception to April 2025. Randomized controlled trials comparing bisphosphonates alone versus bisphosphonates combined with physical interventions were included. Outcomes assessed were percentage changes in femoral neck, lumbar spine, total hip, and total body BMD as well as QoL scores. Risk of bias was evaluated using the RoB2 tool. Heterogeneity was assessed using the I2 statistic. Random-effects models were applied.
RESULTS: Seven trials involving 314 participants were included, involving bisphosphonates and various physical interventions. Interventions included various physical exercises and multimodal physical therapies. Combined therapy resulted in a statistically significant improvement in femoral BMD (mean difference [MD] = 5.27; 95% confidence interval [CI]: [2.23, 8.32]; p = .0007) and QoL (MD = 30.16; 95% CI: [22.16, 38.16]; p < .00001) compared with bisphosphonates alone. No statistically significant differences were observed for lumbar spine BMD (MD = 2.56; 95% CI: [-0.20, 5.32]; p = .07), total hip BMD (MD = 2.77; 95% CI: [-0.69, 6.23]; p = .12), or total body BMD (MD = -0.35; 95% CI: [-0.96, 0.26]; p = .25). Substantial heterogeneity was observed across most outcomes (I2 = 88%-100%), except for total body BMD (I2 = 0%).
CONCLUSIONS: Combining bisphosphonates with physical interventions may improve femoral BMD and QoL; however, no significant benefits were observed for other BMD outcomes. The substantial heterogeneity and clinical diversity among studies limit the generalizability of pooled estimates. Significance/Implications: These findings suggest that adjunctive physical interventions may offer site-specific skeletal and functional benefits, but standardized protocols and larger, high-quality trials are needed to establish consistent clinical recommendations.
METHODS: A systematic search of PubMed and the Cochrane Library was conducted from inception to April 2025. Randomized controlled trials comparing bisphosphonates alone versus bisphosphonates combined with physical interventions were included. Outcomes assessed were percentage changes in femoral neck, lumbar spine, total hip, and total body BMD as well as QoL scores. Risk of bias was evaluated using the RoB2 tool. Heterogeneity was assessed using the I2 statistic. Random-effects models were applied.
RESULTS: Seven trials involving 314 participants were included, involving bisphosphonates and various physical interventions. Interventions included various physical exercises and multimodal physical therapies. Combined therapy resulted in a statistically significant improvement in femoral BMD (mean difference [MD] = 5.27; 95% confidence interval [CI]: [2.23, 8.32]; p = .0007) and QoL (MD = 30.16; 95% CI: [22.16, 38.16]; p < .00001) compared with bisphosphonates alone. No statistically significant differences were observed for lumbar spine BMD (MD = 2.56; 95% CI: [-0.20, 5.32]; p = .07), total hip BMD (MD = 2.77; 95% CI: [-0.69, 6.23]; p = .12), or total body BMD (MD = -0.35; 95% CI: [-0.96, 0.26]; p = .25). Substantial heterogeneity was observed across most outcomes (I2 = 88%-100%), except for total body BMD (I2 = 0%).
CONCLUSIONS: Combining bisphosphonates with physical interventions may improve femoral BMD and QoL; however, no significant benefits were observed for other BMD outcomes. The substantial heterogeneity and clinical diversity among studies limit the generalizability of pooled estimates. Significance/Implications: These findings suggest that adjunctive physical interventions may offer site-specific skeletal and functional benefits, but standardized protocols and larger, high-quality trials are needed to establish consistent clinical recommendations.