BACKGROUND: The menopause transition is marked by hormonal shifts leading to body composition changes, such as fat mass gain and lean mass loss. Weight-bearing and resistance exercise can help maintain lean mass during the menopause transition; however, uptake is low. Pre-clinical research points to bisphosphonates as also being effective in preventing loss of lean mass. Thus, we sought to investigate whether bisphosphonate therapy can mitigate loss of lean mass and outperform weight-bearing exercise in the years immediately following menopause. METHODS: Data come from the Heartland Osteoporosis Prevention Study (NCT02186600), where osteopenic, postmenopausal women were randomized to bisphosphonate (n = 91), weight-bearing/resistance exercise (n = 92), or control (n = 93) conditions over a one-year period. Dual energy X-ray absorptiometry (DXA)-derived body composition measures (including total lean mass, total fat mass, lean mass index, and lean mass-to-fat mass ratio) were ascertained at baseline, six, and 12 months. Adherence to risedronate and weight-bearing exercise was defined as the percentage of dosages taken and exercise sessions attended. Intent-to-treat analysis using linear modeling was used to generate treatment effects on body composition. Secondary analysis utilized per-protocol analysis and included adjustment for weight change. RESULTS: 276 women (age 54.5 years; 83.3% Caucasian; BMI 25.7 kg/m2) were included in the analyses. 12 month adherence to the risedronate and exercise interventions was 89% and 64%, respectively. Group-by-time interactions were observed for lean mass, revealing exercise (0.43 +/- 1.49kg) and risedronate groups (0.31 +/- 1.68 kg) gained significantly more lean mass than control (-0.15 +/- 1.27 kg) over 12 months. However, after controlling for weight change in secondary analysis, the difference in lean mass change between control and risedronate became non-significant (p = 0.059). CONCLUSIONS: Results suggest both 12 months of oral risedronate and 12 months of weight-bearing exercise may diminish lean mass loss experienced during the menopause transition as compared to control. The lean mass sparing effect for risedronate may be driven by overall weight change.

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