# RESTORATION OF LOST BONE MASS AFTER OVARIECTOMY

> **NIH NIH R01** · UNIVERSITY OF FLORIDA · 1993 · $139,081

## Abstract

Various inhibitors of bone resorption (estrogen, diphosphonate
compounds, and calcitonin) have been used for treatment of
postmenopausal osteoporosis.  The effectiveness of these therapeutic
agents has been limited by their inhibition of bone formation as well as
bone resorption or, in the case of calcitonin, a lack of a stimulatory
effect on bone formation.  As a result, bone balance after treatment
with these agents is only marginally positive, The proposed research
will evaluate combined treatments with endocrine or pharmacologic
inhibitors of bone resorption and stimulators of bone formation to
induce a greater positive bone balance for more effective restoration of
lost bone mass in the estrogen-deficient state.  The anabolic effects of
such combined treatments will be compared to those of treatments with a
single therapeutic agent.  Development of treatment protocols for
restoration of lost bone mass would alleviate orthopedic problems by
reducing the incidence of vertebral, wrist, and hip fractures in the
elderly female population.

Ovariectomized rats will be untreated for the first month after surgery
to allow sufficient time for the development of moderate osteopenia.
These animals will then be treated with inhibitors of bone resorption
(estrogen, the diphosphonate compound EHDP, or calcitonin) and a
stimulator of bone formation (parathyroid hormone), singly or in
combination, for periods of 30, 60, 90, or 180 days.  The skeletal
effects of the various treatments will be studied in cancellous bone
tissue of the proximal tibial metaphysis by standard bone
histomorphometric techniques.  Changes in cancellous bone mass and
histologic indices of bone formation, resorption, and mineralization
will be measured.  It is hypothesized that combined treatment with
inhibitors of bone resorption and stimulators of bone formation will
restore lost bone mass in the estrogen-deficient state.  It is further
hypothesized that such combined treatments will have a greater positive
bone balance and, conse4uently, a greater anabolic effect on the
skeleton than treatment with a single therapeutic agent.  Validation of
these hypotheses will provide a rationale for improved therapies to
restore lost bone mass in, osteoporotic patients.  Such a finding would
mitigate the pain and suffering associated with the orthopedic
complications of,osteoporosis in numerous postmenopausal women.

## Key facts

- **NIH application ID:** 3121046
- **Project number:** 5R01AG009241-03
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **SAM.gov UEI:** NNFQH1JAPEP3
- **Principal Investigator:** THOMAS J WRONSKI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $139,081
- **Award type:** 5
- **Project period:** 1991-07-01 → 1995-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3121046

## Citation

> US National Institutes of Health, RePORTER application 3121046, RESTORATION OF LOST BONE MASS AFTER OVARIECTOMY (5R01AG009241-03). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3121046. Licensed CC0.

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