One of the basic problems in bone metabolism is the understanding of bone modelling and bone remodelling, and its hormonal controls. The interactions of bone with diet (intestine) and the various hormonal regulators of bone resorption and bone formation are known qualitatively but are quantitatively incomplete. Bone resorption was found to vary with animal species, age, diet, diurnally, and with physical activity. Such variations in bone resorption and their effects on the rapid and dynamic relationship between bone and diet's contribution to blood calcium will be quantified during various treatments and age. These studies will provide new insight in understanding the control of bone resorption and the dynamic conservation of calcium at a physiological and whole bone level. The experimental design is to extensively prelabel animals with 45Ca, 3H-tetracycline, and 3H-proline, and permit the animal sufficient time to reach a steady state isotopically and biologically. The isotopic variance among equally prelabeled animals will be minimized by using right and left limb comparisons, and sequential measurements of blood radioactivity for each animal as well as making group comparisons at different time intervals. Quantitative kinetics will be used in young and mature animals for acute and chronic changes in levels of bone resorption, relative contribution of bone 45Ca and dietary 40Ca to blood calcium, and the net flux of bone 45Ca. Chronic changes in the rates of bone resorption and formation are quantified directly and independently. These measurements will be made in (1) hormone deficient and treated states (parathyroid hormone, vitamin D, calcitonin), (2) mineral deficient states (Ca, P), (3) mineral treated states (calcium, strontium, fluoride), and (4) acute and chronic bone atrophy induced by immobilization.
