Increases in number and size of osteoclasts in response to calcium or phosphorus deficiency in the rat.

Abstract

In this study, the two determinants of the rate of osteoclastic bone resorption, cell number and cell activity, were evaluated to characterize the response to two chronic resorptive stimuli, a calcium-deficient diet and a phosphorus-deficient diet, fed to rats for 8 days. The number of osteoclast nuclei was determined directly and the resorptive activity of osteoclasts indirectly from cell size. In our sampling site in the tibial diaphysis, there were marked increases in osteoclast layer width (i.e., cell size) and in the number of osteoclasts and osteoclast nuclei in both test groups. Also, in both test groups the increase in the number of osteoclast nuclei was greater than the increase in osteoclast width, emphasizing the importance of osteoclast stem cell activity in the resorptive response. When the data on the control and test animals were pooled, there was a strong correlation between the width of the osteoclast layer and the number of osteoclast nuclei (r = 0.87, P less than 0.001). Thus, these two resoprtive stimuli produced proportional changes in osteoclast cell number and probably activity, raising the possibility that the resorptive response is sterotyped. These results also suggest the existence of a control mechanism which coupled the proliferative activity of osteoclast stem cells and the resorptive activity of osteoclasts. Despite the fact that the rats were subjected to chronic resorptive stimuli, forming surface and the total number of osteoblasts were also increased. Moreover, in data pooled from control and test rats, there was a strong correlation between the number of osteoclast nuclei and the number of osteoblasts (r = 0.92, P less than 0.001). This implies that chronic resorptive stimuli directly or indirectly stimulate osteogenic stem cells to increase production of osteoblasts as well as osteoclasts. The observed coupling of differentiated cell number probably contributes to the established phenomenon of coupling between the rates of bone accretion and resorption.