Effect of donepezil on bone metabolism among older adults with Alzheimer's disease

North R, Liu AJ, Pieper C, Danus S, Thacker CR, Ashner M, Colón-Emeric C, Lee RH

Contemporary clinical trials, 2025

Abstract

Older adults with Alzheimer's disease (AD), in addition to significant cognitive disability, have twice the risk of fracture compared to those with normal cognition. Fractures among older adults with AD are associated with substantial morbidity, loss of physical function, and significant mortality. Prior studies have shown a decreased risk of fracture among those taking acetylcholinesterase inhibitors, such as donepezil. With both cognitive and non-cognitive benefits, donepezil would be a valuable component in a fracture prevention program for older adults with AD. Though anti-amyloid therapies are now clinically available, donepezil may still have non-cognitive benefits. However, the specific effects of donepezil on bone metabolism are unknown. We have designed this randomized, double-blind, placebo-controlled clinical trial to investigate the effect of AD treatment with donepezil on bone metabolism. The study will measure the change in bone mineral density, bone turnover markers, and bone quality related to 12-months of donepezil therapy. This will be the first known study of changes in bone metabolism among older adults with AD.

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Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design.

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