Immobilization caused by paraplegia and quadriplegia produced by spinal cord injury results in demineralization of the skeleton and causes increased release of calcium into the peripheral circulation. This is turn leads to the development of kidney stones, kidney damage and kidney infection as well as to softening of the skeleton or osteoporosis. Renal damage and infection cause much of the morbidity and mortality related to immobilization. In addition, demineralization of the skeleton occurs in astronauts as a consequence of weightlessness and poses a potential limitation on the duration of space travel. The cause for demineralization of the skeleton after immobilization and weightlessness is unknown. The objective of this study is to clarify the mechanism(s) by which immobilization alters bone and mineral metabolism. Increased bone resorption plays a major role in the development of immobilization osteoporosis. We will use animal models to test the possibility that as yet unidentified factor(s) accounts for the enhanced bone resorption during the development of immobilization osteoporosis. Suspension is a model in which the limbs are mechanically unloaded but not immobilized. We plan to compare the effects of immobilization and suspension on calcium metabolism and bone formation and resorption in normal rats and in t1/t1 mutant rats with defective osteoclasts and impaired bone resorption. These investigations will be useful for clarifying the contributions of reduced mechanical stress and of osteoclasts in the development of immobilization osteoporosis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR035651-04
Application #
3157315
Study Section
Orthopedics and Musculoskeletal Study Section (ORTH)
Project Start
1984-12-01
Project End
1992-02-29
Budget Start
1990-03-01
Budget End
1991-02-28
Support Year
4
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Mayo Clinic, Rochester
Department
Type
DUNS #
City
Rochester
State
MN
Country
United States
Zip Code
55905
Gill, R K; Turner, R T; Wronski, T J et al. (1998) Orchiectomy markedly reduces the concentration of the three isoforms of transforming growth factor beta in rat bone, and reduction is prevented by testosterone. Endocrinology 139:546-50
Evans, G L; Morey-Holton, E; Turner, R T (1998) Spaceflight has compartment- and gene-specific effects on mRNA levels for bone matrix proteins in rat femur. J Appl Physiol 84:2132-7
Zhang, M; Turner, R T (1998) The effects of spaceflight on mRNA levels for cytokines in proximal tibia of ovariectomized rats. Aviat Space Environ Med 69:626-9
Turner, R T; Evans, G L; Cavolina, J M et al. (1998) Programmed administration of parathyroid hormone increases bone formation and reduces bone loss in hindlimb-unloaded ovariectomized rats. Endocrinology 139:4086-91
Westerlind, K C; Fluckey, J D; Gordon, S E et al. (1998) Effect of resistance exercise training on cortical and cancellous bone in mature male rats. J Appl Physiol 84:459-64
Sibonga, J D; Bell, N H; Turner, R T (1998) Evidence that ibuprofen antagonizes selective actions of estrogen and tamoxifen on rat bone. J Bone Miner Res 13:863-70
Westerlind, K C; Wronski, T J; Ritman, E L et al. (1997) Estrogen regulates the rate of bone turnover but bone balance in ovariectomized rats is modulated by prevailing mechanical strain. Proc Natl Acad Sci U S A 94:4199-204
Jimenez, M A; Magee, D E; Bryant, H U et al. (1997) Clomiphene prevents cancellous bone loss from tibia of ovariectomized rats. Endocrinology 138:1794-800
Firling, C E; Evans, G L; Wakley, G K et al. (1996) Lack of an effect of sodium zeolite A on rat tibia histomorphometry. J Bone Miner Res 11:254-63
Turner, R T (1995) Effects of short-term spaceflight and recombinant human growth hormone (rhGH) on bone growth in young rats. Aviat Space Environ Med 66:763-9

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