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.

Grant Number: 5R01AG074979-04
NIH Institute/Center: NIH
Principal Investigator: Kristen Beavers