# EFFECTS OF IMMOBILIZATION OF BONE & MINERAL HOMEOSTASIS

> **NIH NIH R01** · MAYO CLINIC ROCHESTER · 1992 · $138,448

## Abstract

Disuse causes osteolysis of the skeleton, with attendant hypercalcemia,
hypercalciuria and osteoporosis.  Immobilization with a cast and stress
shielding by an orthopedic implant result in localized bone loss.  Although
these problems have been recognized for decades, there has been limited
progress towards identifying the underlying cellular and biochemical
changes.  Consequently, at present, there is no effective treatment to
prevent bone wasting associated with disuse.  Previous studies in man and
animals have emphasized the role of increased bone resorption in
development of disuse osteopenia.  However, the results of studies that we
carried out in the previous grant period indicate that decreased bone
formation may account for most of the deficit.  These findings suggest to
us that osteoblast activity is modulated by gravitational loading and
muscle loading.  The hypothesis of this proposal that osteoblasts are under
direct regulation of mechanical loading at the level of gene expression
will be tested in rats subjected to the near weightlessness of orbital
spaceflight and unweighting due to hind limb suspension.  We postulate that
weight bearing modulates the elaboration of specific signaling molecules
(growth factors) by osteoblasts and, in turn, these signaling molecules
promote normal coupling of bone formation and bone resorption.  Normal
coupling is essential to maintenance of bone volume: it is the pronounced
uncoupling that occurs during disuse which leads to potentially
catastrophic bone loss in humans.  Although several signaling molecules may
be involved, the weight of evidence favors transforming growth factor-beta
(TGF-beta) as having an important role in this process.  TGF-beta is
produced by osteoblasts, acts on osteoblasts and osteoclasts, is
incorporated into bone matrix and its secretion may be altered by weight
bearing.  The proposed studies will challenge this postulated role of
TGF-beta in modulating the skeletal effects of weight bearing by 1)
determining the magnitude of changes in bone resorption following disuse
and reloading, 2) determining the effects of disuse and reloading on
TGF-beta expression in bone cells, 3) determining the effects of disuse and
reloading on mRNA levels for bone matrix proteins, 4) localizing TGF-beta
mRNA and peptide in skeletal tissues at the cellular level, and 5)
establishing whether locally administered TGF-P counteracts the effects of
disuse on bone matrix synthesis and bone resorption.  If the proposed
hypothesis is correct, it may be possible to prevent disuse osteopenia by
manipulating the levels of specific signaling molecules in the unweighted
skeleton.

## Key facts

- **NIH application ID:** 3157313
- **Project number:** 2R01AR035651-06A1
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **SAM.gov UEI:** Y2K4F9RPRRG7
- **Principal Investigator:** RUSSELL Thomas TURNER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $138,448
- **Award type:** 2
- **Project period:** 1984-12-01 → 1996-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3157313

## Citation

> US National Institutes of Health, RePORTER application 3157313, EFFECTS OF IMMOBILIZATION OF BONE & MINERAL HOMEOSTASIS (2R01AR035651-06A1). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3157313. Licensed CC0.

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