Acute reduction in osteoclast number during bone repletion

Growing rats were fed a calcium-deficient diet for 12 days to induce bone loss and were subsequently placed on a calcium-replacement diet for 1 to 3 days to evoke bone repletion. Control animals were fed the calcium-replacement diet continuously. Twelve days of calcium deprivation resulted in a 21-fold increase in the number of endosteal osteoclasts in the tibial diaphysis as compared with controls. These osteoclasts, however, rapidly disappeared from the endosteum after restoration of dietary calcium. Only 14% of these endosteal osteoclasts remained after 1 day, and no osteoclasts were present after 3 days of calcium replenishment. During this time, plump osteoblasts replaced osteoclasts on the endosteal surface. The number of osteoclasts in the marrow space also changed strikingly. An 11-fold increase in the number of osteoclasts in the marrow space occurred during the calcium-deprivation phase. However, the greatest increase (39-fold) was observed during the first day of calcium replenishment. Thereafter, the number of osteoclasts in the marrow space declined and, after 3 days of calcium replenishment, returned to the control level. During calcium replenishment, acid phosphatase-positive fragments in the marrow space appeared concomitantly with osteoclast disintegration and fragmentation. The kinetic changes and acid phosphatase staining of these fragments suggest that the fragments are the products of disintegrating osteoclasts, a finding consistent with the hypothesis that the fate of some osteoclasts in vivo is cell death. At the end of calcium deprivation, serum iPTH levels and the production of 1,25-dihydroxyvitamin D3 from 25-hydroxyvitamin D3 were significantly increased compared to controls. After 3 days of calcium replenishment, serum iPTH had decreased to control levels, but the production of 1,25-dihydroxyvitamin D3 was still elevated. Changes in serum iPTH and the production of 1,25-dihydroxyvitamin D3 cannot, therefore, be totally responsible for the observed decrease in osteoclast number during bone repletion. Bone repair after calcium deprivation may be a locally controlled phenomenon.