Effects of Exercise and Bisphosphonate-Therapy on Bone Mineral Density in Healthy Women - A Systematic Review and Meta-Analysis

Background Physical exercise and antiresorptive pharmacological therapy affect bone metabolism through different mechanisms. The present study addresses the question of whether bisphosphonate treatment with additional exercise training has additive effects on bone density (BMD) at the lumbar spine (LS) and/or femoral neck (SH). Methods Our systematic literature search of five electronic databases according to PRISMA included controlled trials with a duration of 6 months with at least two study arms: (a) bisphosphonates (B), (b) bisphosphonates and exercise (B + E) published up to 26 August 2021. Studies including other pharmaceutical therapies or diseases with relevant effects on bone metabolism were excluded. The analysis was conducted as a random-effects meta-analysis. Outcome measures were standardized mean differences (SMD) for BMD changes at LS and SH. Results Our search identified four eligible studies with a total of 247 participants. In summary, compared with bisphosphonate therapy alone, the combined intervention did not demonstrate significantly higher effect sizes at LS- (SMD: 0.66, 95%-CI: -0.63 to 1.94) or SH-BMD (0.49, -0.42 to 1.40). We observed very high heterogeneity among the results of the included studies for both, BMD-LWS and BMD-SH (I-2: 89 and 92 %, respectively). The evidence for a "small study" or publication bias is also quite high for both outcomes. Conclusion We could not detect a significantly superior effect of a combined intervention (B + E) compared to isolated bisphosphonate therapy on BMD at LS and/or SH. However, the eligible studies indicate a high heterogeneity, which we primarily refer to the different training protocols of the trials.