Kinetics of osteoclast formation: the significance of blood monocytes as osteoclast precursors during 1 alpha-hydroxycholecalciferol-stimulated bone resorption in the mouse.

The significance of blood monocytes as a source of osteoclast precursors was investigated during 1 alpha-hydroxycholecalciferol-stimulated bone resorption in mice. Animals were given three injections of tritiated thymidine at 8 hourly intervals in order to label blood monocytes. The proportion of labelled monocytes was then compared with the proportion of labelled nuclei in osteoclasts, the formation of which was provoked by daily injections of 1 alpha-hydroxycholecalciferol, beginning 48 hours after the first injection of isotope. Although more than 60% of blood monocytes were labelled during the period of peak osteoclast formation, labelling of osteoclast nuclei in the metaphyseal endosteum of the femur never exceeded 8%. These results suggest strongly that the majority of osteoclast nuclei were derived from a source of unlabelled precursors, and that very few osteoclasts were derived directly from blood monocytes. Although few labelled osteoclasts were found, the proportion of labelled spindle shaped cells in the metaphyseal endosteum rose gradually to 16%. It is likely, therefore, that labelled mononuclear cells, possibly blood monocytes, were attracted to the endosteum where they formed a population of tissue macrophages. At this site they may participate in bone resorption, either individually or by providing a local pool of osteoclast precursors.