# ERT AND FOCAL BALANCE BETWEEN RESORPTION AND FORMATION

> **NIH NIH R01** · HENRY FORD HEALTH SYSTEM · 1993 · $138,181

## Abstract

The main effect of estrogen is to reduce the rate of bone remodeling
activation and so to reduce the whole body rates of resorption, formation
and the rate of bone loss.  There is both clinical and (in vivo and in
vitro) evidence for an additional effect of estrogen to increase the
recruitment and function of osteoblasts.  Such an effect could increase the
completeness with which resorption cavities are refilled, despite a
reduction in whole body bone formation rate.  We will test the efficacy of
estrogen replacement therapy in correcting the age-related worsening of
focal remodeling imbalance between resorption and formation in iliac
cancellous bone, manifested principally as a decline in wall thickness.
The subjects will be recruited from among 200 expected to participate in a
companion proposal        to test the efficacy of estrogen replacement
therapy in reducing the rate of bone loss from the upper femur.  All
subjects will already have undergone prospective measurement of the rate of
bone loss for two years prior to randomization into active and placebo-
treated groups.  We hope to recruit subjects in each arm who will have had
bone biopsy 2-24 months before randomization and are willing to have a
second bone biopsy on the opposite side after completion of the two-year
intervention trial period.  We will compare all methods that have been
proposed, both by other investigators and ourselves, for measuring wall
thickness and erosion depth and select the most appropriate methods after
 validation.  We will also apply established stereologic methods for
counting the number of cells in three-dimensional tissue volume, and
express formation and resorption rates per osteoblast or osteoclast nuclei,
and per aggregate osteoblast or osteoclast volume.  A panel of putative
indirect mediators of estrogen effect on bone, including parathyroid
hormone, basal and calcium stimulated calcitonin, calcitriol, growth
hormone, insulin-like growth factor I and its binding proteins, will be
measured in each subject before and after the conclusion of the
intervention trial.  If we confirm a beneficial effect of estrogen
replacement therapy on osteoblast recruitment or function, this will have
important therapeutic implications, since estrogen replacement therapy will
no longer need to be restricted to patients within the first few years
after menopause, or with high bone turnover, but could be useful in
preventing bone loss and fractures in older women, regardless of how long
ago they underwent menopause, and whatever their level of bone turnover.

## Key facts

- **NIH application ID:** 3122309
- **Project number:** 5R01AG010381-03
- **Recipient organization:** HENRY FORD HEALTH SYSTEM
- **SAM.gov UEI:** R9NXPE2GTCN9
- **Principal Investigator:** A MICHAEL PARFITT
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $138,181
- **Award type:** 5
- **Project period:** 1991-09-30 → 1996-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3122309

## Citation

> US National Institutes of Health, RePORTER application 3122309, ERT AND FOCAL BALANCE BETWEEN RESORPTION AND FORMATION (5R01AG010381-03). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3122309. Licensed CC0.

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