# Enhancing Skeletal Adaptation to Exercise by Attenuating the Acute Disruption of Calcium Homeostasis During Exercise

> **NIH VA I01** · VA EASTERN COLORADO HEALTH CARE SYSTEM · 2023 · —

## Abstract

Exercise is essential for building and maintaining bone mass and strength, but our recent work has raised the
possibility that current exercise recommendations for bone health may not be appropriate. We have strong
evidence that a single bout of vigorous exercise has an acute catabolic effect in bone (i.e., increased
resorption) that lasts several hours. This is mediated by a decrease in serum calcium (Ca) during exercise,
which stimulates parathyroid hormone (PTH) secretion. PTH then activates bone resorption to mobilize Ca
from bone, presumably to prevent the decrease in serum Ca from progressing to a harmful level. This cascade
of events can be markedly attenuated by minimizing the decline in serum Ca during exercise via either
intravenous or oral Ca administration. The timing of Ca supplementation relative to exercise is likely important,
because it must be available for gut absorption during exercise. Interestingly, repeated pharmacologic
stimulation of the PTH receptor with PTH analogs (teriparatide, abaloparatide) has anabolic effects on bone,
suggesting that repeated exercise-induced increases in PTH could have a chronic anabolic skeletal effect, in
addition to the acute catabolic effect, which may be apparent only after repeated exercise sessions. If this is
the case, suppressing the PTH response with pre-exercise Ca supplementation may not be appropriate. In this
context, the proof-of-concept phase will include a short exercise intervention consisting of treadmill exercise at
70% to 80% of maximal heart rate, 60 minutes per day, 4 days per week, for 4 weeks. Serum markers of bone
formation and resorption will be measured before, during, and for 24 hours after the 1st, 8th, and 16th exercise
sessions to address two questions: 1) Does the acute catabolic response of bone to a single bout of exercise
continue to occur with repeated exercise sessions (i.e., exercise training)? 2) Does exercise training also
generate an anabolic PTH-mediated bone response, similar to the anabolic response to PTH analog therapy?
If the answers to questions 1 and 2 are YES (persistent catabolic signal) and NO (lack of anabolic signal), this
will support the need for the randomized controlled trial (RCT), which will evaluate whether taking Ca before
exercise to attenuate the acute catabolic response improves skeletal adaptations to exercise training. The RCT
will be a 36-week supervised exercise intervention, with participants randomized to take supplemental Ca
citrate plus vitamin D3 (Ca+D3) or vitamin D3 alone (D3; control) about 60 minutes before each exercise.
Primary aims are to determine 1) whether taking Ca before exercise enhances bone mineral density (BMD)
adaptations to exercise, and 2) whether this occurs by attenuating the increase in bone resorption during and
after exercise sessions. The overarching goal is to improve the currently imprecise recommendations for
exercise to improve and maintain bone health. This research is of high relevance to Vet...

## Key facts

- **NIH application ID:** 10545712
- **Project number:** 5I01CX002284-02
- **Recipient organization:** VA EASTERN COLORADO HEALTH CARE SYSTEM
- **Principal Investigator:** Wendy M Kohrt
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2023
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2021-10-01 → 2027-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10545712

## Citation

> US National Institutes of Health, RePORTER application 10545712, Enhancing Skeletal Adaptation to Exercise by Attenuating the Acute Disruption of Calcium Homeostasis During Exercise (5I01CX002284-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10545712. Licensed CC0.

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