Graduation Date

Spring 5-7-2022

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Programs

Medical Sciences Interdepartmental Area

First Advisor

Laura D. Bilek, P.T., Ph.D.

Second Advisor

Kristen Beavers, Ph.D., R.D., MPH

Third Advisor

Karsten Koehler, Ph.D.

Fourth Advisor

Vishal Kothari, M.D.

Abstract

Loss of bone and muscle mass often occurs in tandem, increasing the risk of fragility fractures. Whereas many drugs are approved for the treatment of bone loss, there are few treatments available for the concomitant loss of bone and muscle. Identification of a treatment to mitigate pathologic bone and muscle atrophy has the potential to impact countless populations and influence approaches for healthy aging. Bisphosphonates have emerged as a potential treatment for both bone and muscle loss in cellular, murine, and observational human studies. Our findings of modest weight maintenance in postmenopausal women treated with 12-months of risedronate, relative to control, corroborates this evidence, suggesting oral bisphosphonates have the potential to mitigate menopause-related bone and body composition changes. Likewise, our analysis of participants randomized to 6 months of oral bisphosphonate or placebo following sleeve gastrectomy, demonstrated lean mass sparing, particularly at the appendicular sites. These results support the potential use of the medication for populations at high risk of concurrent bone and lean mass loss due to rapid weight loss. We hypothesize our ongoing clinical trial investigating an intravenous bisphosphonate, zoledronic acid, for prevention of bone and muscle loss following sleeve gastrectomy will substantiate our findings and offer an effective therapy for coexistent bone and muscle loss in high-risk groups.

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