# Bone Water and Mineralization Measured by Nuclear Magnetic Resonance

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2020 · $414,872

## Abstract

Project Summary
Given that many of the most common fracture sites, such as those of the distal radius and vertebrae, are
predominantly trabecular, the prevailing view is that osteoporotic fractures primarily result from decreased
density and impaired structural integrity of trabecular bone. However, 80% of the skeleton consists of cortical
bone and some of the most devastating fractures, such as those of the femoral neck, occur at a location where
the stresses are shared by the two types of bone. Hormonal loss following menopause causes enhanced
cortical remodeling leading to increased pore volume fraction caused by expansion of Haversian and Volkman
canals and formation of composite osteons. Paralleling these processes is a decrease in mineralization,
referred to as degree of mineralization of bone (DMB), due to the bone's failure of undergoing secondary
mineralization. Both effects have previously been shown to be modifiable and partially reversible by treatment
with antiresorptive drugs as assessed with measurements in iliac bone biopsy specimens. In preliminary
studies leading up to this project, we conceived new quantitative solid-state 1H and 31P MRI methods based
on zero-echo-time (ZTE) PETRA encoding and new non-iterative reconstruction techniques for evaluating
measures of cortical porosity and mineral density, thereby delineating a path toward noninvasive assessment
of cortical bone ultrastructure and chemistry. The approach chosen makes use of T2-selective suppression
pulses providing pore and collagen-bound water. The latter is shown to represent a surrogate for bone tissue
matrix density yielding, along with 31P density, DMB. In this competing renewal application we propose to
reduce to practice, validate, and translate these methods to patient studies. Our primary hypothesis is that
postmenopausal women with osteoporosis (OP) have greater cortical porosity as assessed by 1H MRI
surrogate markers than their healthy peers; and further that porosity in these patients decreases upon
antiresorptive treatment. Our secondary hypothesis is that OP subjects have lower DMB as measured by 31P
MRI surrogate markers, and that antiresorptive treatment increases DMB. We propose to evaluate these
hypotheses with an integrated MRI protocol in a cohort of OP women in comparison to matched healthy
controls, both at baseline and after 12 and 24 months of alendronate treatment. We expect the outcome to
show that the proposed technology can quantify and distinguish inter-group differences of the parameters
measured, both at baseline and in response to intervention.
 The proposed comprehensive quantitative MR imaging protocol, which can readily be implemented on
standard clinical MRI equipment, should yield new insight into microstructure and mineral properties of cortical
bone, and provide new ways to evaluate the response to antiresorptive treatment in patients.

## Key facts

- **NIH application ID:** 9606059
- **Project number:** 5R01AR050068-11
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Felix W Wehrli
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $414,872
- **Award type:** 5
- **Project period:** 2003-09-09 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9606059

## Citation

> US National Institutes of Health, RePORTER application 9606059, Bone Water and Mineralization Measured by Nuclear Magnetic Resonance (5R01AR050068-11). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9606059. Licensed CC0.

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