# Age Differences and Mechanisms of Ketogenic Diet Induced Bone Loss

> **NIH NIH K99** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2023 · $85,918

## Abstract

Project Summary
Ketogenic diet (KD), a high fat low carbohydrate diet is used to treat intractable epilepsy, is becoming increasingly
popular for weight management, and it can potentially slow cognitive ageing and alleviate symptoms of
neurological disorders such as stroke, Parkinsons disease, and Alzheimers. However, KD also causes bone loss
and increases fracture risk in children. It is not known if KD causes bone loss in adults. Based on prior studies,
it is also possible that KD may reduce the ability for exercise to increase bone strength. The mechanisms
responsible for KD bone loss have not been identified. Determining if β-hydroxybutyrate (BHB), the most
abundant ketone body is linked to bone loss is important, because this molecule is thought to lay a large role in
the neurological benefits of KD. This project will use a mouse model to evaluate age differences in ketogenic
diet induced bone loss, determine if KD decreases the ability of exercise to make bone stronger, and investigate
if BHB causes bone loss.
 Aim 1 will determine how age and diet duration affect the magnitude of KD induced bone loss and
decrease in bone strength. Aim 2 will evaluate if KD reduces the ability of exercise to increase bone strength
and if this is mediated by muscle and tendon. Aim 3 will focus specifically on defining the role of BHB in bone
loss. In the long term, this project will help clarify how KD affects bone, and it can contribute to the use of KD or
BHB supplementation to deliver neurological benefits without increasing fracture risk.
 As a clinical researcher, I strive to develop therapies to improve skeletal health, and as a biological
anthropologist, I use skeletal remains to reconstruct the behavior and health of past people. Through the
K99/R00 career development award, I seek to combine the anthropological and biomedical strands of my
research career by examining the combined effect of ketogenic diet and exercise on bone health throughout life.
During the fellowship, I will receive training in molecular biology and laboratory skills essential for the study of
cellular responses to diet and exercise. I will also expand my knowledge of muscle and tendon, gaining the ability
to conduct innovative interdisciplinary research that achieves new perspectives on how exercise and diet affect
bone strength. UC Davis is an unparalleled location for conducting the proposed project and training. I will have
access to cutting edge facilities and equipment. Through numerous seminars, workshops, and training
opportunities I will interact with faculty, students, and staff, broadening my understanding of skeletal health.
Through the K99/ R00 I will develop an innovative interdisciplinary research career that explores the relationship
between diet, behavior, and health in past human populations and contributes to the development of therapies
that use diet and exercise to decrease fracture risk.

## Key facts

- **NIH application ID:** 10740305
- **Project number:** 1K99AR081401-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Benjamin Osipov
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $85,918
- **Award type:** 1
- **Project period:** 2023-08-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10740305

## Citation

> US National Institutes of Health, RePORTER application 10740305, Age Differences and Mechanisms of Ketogenic Diet Induced Bone Loss (1K99AR081401-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10740305. Licensed CC0.

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