Along with the technical difficulties presented by spaceflight are the biological problems that will be encountered during prolonged periods of weightlessness. Zero gravity poses a great threat to, amongst many things, skeletal strength and microarchitectural integrity. Bone loss, as result of the mechanical unloading of the skeleton under these conditions, is a potentially serious health problem to current and future astronauts. We propose to study this issue using an animal model of stimulated weightlessness induces bone loss, the immobilized rat. We have set forth the following specific aims for this study. 1) To understand the cellular and structural mechanisms for immobilization- induced cancellous bone loss. 2) To study the interactions of estrogen or dietary calcium deficiency and immobilization-induced bone loss. 3) To test the efficacy and the mechanism of action of a combined anti- resorptive and anabolic agent treatment in immobilization-induced bone loss. 4) To assess the relative contribution of changes in trabecular bone thinning and/or microarchitecture to the changes in bone mechanical strength which occur during immobilization. These proposed studies are not only of vital interest to those who must endure zero gravity, but are of great relevance to more terrestrial health concerns. Immobilization occurs in many disease states, e.g. multiple sclerosis, stroke, spinal injury and spine and hip fractures. The problem of immobilization may be even worse in postmenopausal women - when estrogen deficiency might accentuate the rate of bone loss or alter the "set point" to a lower absolute level of mass. These issues we are preparing to evaluate using an animal model. The knowledge gained in our study of this insidious skeletal disorder will be useful to meet the national objectives set forth in "Healthy People 2000" of improving the quality of living of the general population.