# RESTORING  BONE IN OSTEOPENIC FEMALE SKELETON

> **NIH NIH R01** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 1992 · $221,281

## Abstract

Osteoporosis is mainly a disease of elderly women, who have low cancellous
and cortical bone mass, poor bone structure, and fragility fractures.
Though osteoporosis can be prevented by maintaining "peak" bone mass,
treating it by substantially increasing bone strength is difficult.  We
propose using osteopenic, aged female rats to test a two-phase concept to
treat established osteopenia.  Since it has an anabolic phase to restore
lost bone and a maintenance phase to preserve the new bone, it is named
Activate->Restore->Maintain (A->R->M).

We propose two experiments using aged female rats with established
osteopenia originating from estrogen-depletion or chronic disuse, or a
combination of the two.  We will use either prostaglandin E2 (PGE2) or
parathyroid hormone (hPTH) as anabolic agents to restore lost bone
(+Phase).  Past experience with both shows that their discontinuation is
associated with rapid disappearance of the new bone they induce.  When we
stop +Phase, we will switch to an agent known chiefly for its ability to
block bone loss (+Phase).  We will use either 17-beta-estradiol (E2) or
risedronate, a bisphosphonate.  We will study animals at the beginning of
+Phase, at the close of +Phase, and twice during +Phase, to establish both
the permanence of the new bone and its incorporation into the adult
skeleton by modeling and remodeling processes.  A third experiment examines
the ability of co-treatment with a resorption inhibitor and an anabolic
agent, to add new bone, yet avoid an early transient phase of bone loss.
For endpoints, we plan quantitative histologic studies of bone mass,
structure, and turnover in the cancellous bone of the proximal and distal
tibial metaphyses, and cortical bone of the tibio-fibular junction.

We hypothesize that bone mass of the osteopenic skeleton improves during
treatment with an anabolic agent, and then is permanently maintained by
other routinely available agents.  We hypothesize that differences in
estrogen-depletion and disuse-related osteopenia exist, such that
risedronate can, but E2 cannot, maintain new bone in the skeleton of an
animal suffering chronic disuse osteopenia.  We hypothesize that co-
treating with a resorption inhibitor allows anabolic agents to work
normally, while blocking the consequences of any early resorption phase.
A->R->M, that limits the use of skeletal anabolic agents to the time when
they are most effective, could hasten the application of such agents for
treating osteoporosis.

## Key facts

- **NIH application ID:** 3158497
- **Project number:** 2R01AR038346-06
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **SAM.gov UEI:** LL8GLEVH6MG3
- **Principal Investigator:** WEBSTER S JEE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $221,281
- **Award type:** 2
- **Project period:** 1987-05-01 → 1996-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3158497

## Citation

> US National Institutes of Health, RePORTER application 3158497, RESTORING  BONE IN OSTEOPENIC FEMALE SKELETON (2R01AR038346-06). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3158497. Licensed CC0.

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