# Bone microarchitecture and bone strength relationships to muscle quantity, quality and function in older adults

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2020 · $397,899

## Abstract

The long-term goal of the project is to substantially improve our understanding of the interaction between bone
and muscle. The “mechanostat theory” proposes that bone adapts its morphology and strength to long-term
loads exerted by muscle contraction (1). However, the bidirectional signaling between muscle and bone that
has emerged broadens the relationship beyond that of a purely mechanical perspective (2). We propose to
examine the association between maximal capacity of muscle to generate ATP (ATP-max) by 31P-Magnetic
Resonance Spectroscopy (31P –MRS), quadriceps contractile volume by MRI, total muscle mass (TMM) by D3
creatine dilution (D3Cr), and functional muscle power and bone microarchitecture and strength. The
underlying scientific premise is that age related declines in the capacity to generate ATP in muscle, muscle
volume, TMM and functional power lead to decreases in bone strength and poor bone microarchitecture. This
proposal builds on the Study of Muscle, Mobility and Aging (SOMMA), the first prospective study of muscle
aging aimed to study the contributions of skeletal muscle biology and function to major mobility disability. We
propose to extend SOMMA to include important skeletal measures of bone strength using high-resolution
peripheral quantitative computed tomography (HRpQCT). To our knowledge, no studies have linked ATP-max
and quadriceps contractile volume to volumetric BMD, microarchitecture and strength (failure load as assessed
by finite element analysis). We will examine these characteristics globally and separately in the trabecular and
cortical compartments and in a weight bearing (tibia) and non-weight bearing (radius) bone site. The D3Cr
method of measuring TMM is limited to men enrolled in the Osteoporotic Fractures in Men study (MrOS; mean
age 84 yrs). In SOMMA we will be able to study the D3Cr TMM associations with the HRpQCT parameters on
a wider age group of both men and women. Establishing HRpQCT relationships to TMM and functional power
from the stair climb may identify target outcomes for interventions that can improve both tissues (2). We will
recruit 400 of the 438 SOMMA subjects in Pittsburgh. Our proposal offers a cost-efficient opportunity to
investigate the bone-muscle interaction in older adults using state-of-the-art measurements. We propose the
following specific aims: Aim 1: To determine the association of bone microarchitecture, volumetric BMD, and
bone strength (failure load) globally and in the trabecular and cortical compartments separately to in-vivo ATP-
max, contractile muscle volume and total skeletal muscle mass. Aim 2: To determine the association
between functional muscle power as measured by the stair climb to HRpQCT parameters of volumetric
density, microarchitecture and strength. Aim 3, Exploratory: To explore sex differences in the associations
studied in Aims 1 and 2. OVERALL IMPACT: This SOMMA ancillary study will be the first to study novel
properties of muscle biology, volume, an...

## Key facts

- **NIH application ID:** 10019331
- **Project number:** 5R01AR076752-02
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** JANE Ann CAULEY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $397,899
- **Award type:** 5
- **Project period:** 2019-09-18 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10019331

## Citation

> US National Institutes of Health, RePORTER application 10019331, Bone microarchitecture and bone strength relationships to muscle quantity, quality and function in older adults (5R01AR076752-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10019331. Licensed CC0.

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