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.