Effects of Dietary Calcium and Fasting on Osteoclast Recession and Recruitment in Calcium Deficient Rats

The osteoclast, a multinucleated giant cell, has as its role the resorption of bone matrix with consequent release of calcium. The osteoclast is thought to derive from a pluripotent stem cell which also gives rise to monocytes and macrophages. The development, activation, and inhibition of osteoclasts are influenced by a number of systemic and local factors. The release of these factors is influenced by changes in the dietary status of the animal. Calcium deficiency is known to stimulate the recruitment and activity of large numbers of osteoclasts. These osteoclasts can subsequently be inhibited by increasing dietary calcium intake. Disappearance of osteoclasts from the endosteum of long bones is complete after three days, but it is not known whether this phenomenon is gradual or whether there is a dietary calcium threshold that must be reached to cause complete osteoclast inhibition. This study examines changes in osteoclast morphology in calcium deficient rats following calcium supplementation and fasting. In rats which had been given a calcium-deficient diet 7 days, 12 hours of ad libitum calcium supplementation caused changes in osteoclast morphology indicating a reduction in osteoclast activation. These morphological changes were reversed when calcium supplementation was followed by a 12-hour fast. In another experiment, generalized nutritional deficiency (i.e. fasting) was compared with calcium deficiency. Forty-eight hours of fasting in normal rats caused a decrease in the osteoblast area fraction and an increase in the restingcell area fraction; the osteoclast area fraction was unaffected. Forty-eight hours of calcium deficiency, however, increased the osteoclast area fraction and decreased the resting area fraction, while the osteoblast area fraction did not change. These results suggest that whereas fasting conserves plasma calcium by reducing the osteoblast area fraction and thus bone formation, calcium deficiency maintains plasma calcium by increasing osteoclastic bone resorption. A final experiment showed that osteoclasts that have been inhibited by 48 hours of calcium supplementation did not return to pre-inhibition levels of activity after 48 hours of calcium deficiency. It was concluded that osteoclasts are under dynamic control and that their responses to changes in dietary status are graded