Exercise and Bisphosphonate Use to Minimize Weight Loss Associated Bone Loss among Older Adults

PROJECT SUMMARY Despite adverse metabolic and functional consequences of obesity, dietary weight loss (WL) recommendation remains controversial for older adults due to WL associated reduction in bone mineral density (BMD) and increased risk of osteoporotic fracture. Several studies show a positive effect of exercise on BMD in weight- stable, older adults; however, literature examining the ability of exercise to preserve bone during dietary WL is surprisingly equivocal. Discordant findings may be due to varying exercise prescriptions, with recent data from our group suggestive of a superior ability of progressive resistance training (RT) to minimize bone loss during dietary WL, as compared to aerobic training. Nevertheless, some bone loss still occurs with RT, prompting the consideration of alternate or adjuvant osteoprotective strategies. Pharmacotherapy represents another countermeasure strategy, and several medications are FDA-approved to prevent and treat osteoporosis. Bisphosphonates, in particular, are a promising choice as they decrease bone resorption (which is upregulated during WL) and also appear to blunt the catabolic effect of acute exercise on bone, thereby signaling the potential for additive effects during WL — though these hypotheses have not been formally tested. To address these knowledge gaps, the proposed 12 month, 2x2 factorial randomized controlled trial will compare the independent and combined effects of RT plus bone loading exercise and bisphosphonate use on dietary WL associated bone loss among 392 older (60+ years) adults with obesity (BMI=30-40 kg/m2) who are also at risk for low BMD (total hip T-score: 0 to -2.2) at Wake Forest University and The University of Colorado-Anschutz Medical Campus. All participants will receive the same group-mediated dietary WL intervention and be randomized to one of four groups: no RT and placebo capsules (NoRT+PL); progressive RT plus bone-loading exercises and placebo capsules (RT++PL); no RT and bisphosphonate capsules (70 mg weekly oral alendronate; NoRT+BIS); or progressive RT plus bone-loading exercises and bisphosphonate capsules (RT++BIS). Due to its robust change following dietary WL and clinical utility in predicting fracture, our primary outcome is change in total hip aBMD measured via dual x-ray absorptiometry (DXA). This will be complemented by DXA assessment at other skeletal sites, as well as high resolution peripheral quantitative computed tomography (HR-pQCT) derived compartmental volumetric (v)BMD, trabecular bone microarchitecture, cortical thickness/porosity, and strength at the distal radius and tibia — allowing for assessment of intervention effectiveness on novel measures of bone quality. Finally, assessment of biomarkers of bone turnover and metabolism will provide insight into the roles of RT+ and BIS on the bone remodeling unit during dietary WL.