# Genetic Factors of Bone Loss in Older Adults Taking Antidepressants

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2020 · $393,061

## Abstract

One in six older adults takes an antidepressant, usually serotonin reuptake inhibitors (SRIs)  such 
as Prozac and Zoloft. Both preclinical and epidemiological studies suggest that SRIs accelerate 
bone loss, a major public health concern given the high human and economic burden of osteoporosis. 
Despite the public health significance, the relationship between SRIs and accelerated bone loss 
remains poorly understood and unproven. Serotonin is a prominent signaling molecule in many tissues 
outside of the brain including platelets, intestines, and bone. This, combined with the marked 
serotonergic effects of SRIs, suggests SRIs might elicit  changes in cell signaling in non-neural 
tissues leading to accelerated bone loss. Our preliminary data suggest that genetic variation may 
contribute to susceptibility to SRI-mediated bone loss, and herein we propose a definitive study of 
bone turnover with SRI use to address this. We take advantage of a large, ongoing randomized 
controlled trial testing antidepressant treatment strategies in older adults. This trial provides 
an ideal parent trial to test the long-term effects of SRI exposure on bone health and to identify 
both common and rare genetic variants that modify risk for SRI-mediated bone loss. We will then 
rapidly validate the functional impact of candidate genes and variants using a CRISPRi-based screen 
in cells. This project leverages both an ongoing large-scale clinical trial of antidepressants and 
novel molecular techniques to demonstrate the effects of SRI-mediated bone loss and their genetic 
modifiers. It will clarify whether, why, and in whom SRIs lead to osteoporosis, improve patient 
care and health outcomes for older adults, and identify novel treatment targets for bone health.

## Key facts

- **NIH application ID:** 9952320
- **Project number:** 5R01AR073017-03
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Timothy R Peterson
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $393,061
- **Award type:** 5
- **Project period:** 2018-09-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9952320

## Citation

> US National Institutes of Health, RePORTER application 9952320, Genetic Factors of Bone Loss in Older Adults Taking Antidepressants (5R01AR073017-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9952320. Licensed CC0.

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