1alpha-Hydroxyvitamin D3 suppresses trabecular bone resorption by inhibiting osteoclastogenic potential in bone marrow cells after ovariectomy in mice.

ABSTRACT

To test the hypothesis that 1alpha-hydroxyvitamin D3 (1alpha(OH)D3) suppresses bone resorption after ovariectomy (ovx) by inhibiting osteoclastogenic potential in bone marrow cells, the bilateral tibiae of ddY mice, 8 weeks of age, subjected to ovx were obtained. 1alpha(OH)D3, at doses of 0, 0.2 (low dose), or 0.4 microg/kg body weight (high dose), was administered orally by canula three times a week for 2 or 6 weeks. Histomorphometric analysis of the proximal tibiae revealed that 1alpha(OH)D3 administration had no significant effect on trabecular bone volume of ovx limbs, which was reduced after ovx. The bone formation rate, increased by ovx, was significantly decreased by the administration of high-dose 1alpha(OH)D3. The ovx-induced increases in osteoclast number and surface at 2 weeks postsurgery were suppressed by the administration of high-dose 1alpha(OH)D3. With regard to bone marrow cells, the number of nonadherent cells per tibia obtained from ovx limbs increased, and this increase was suppressed by the administration of low- and high-dose 1alpha(OH)D3. The formation of mineralized nodules in marrow cultures obtained from ovx limbs was increased after surgery and unaltered by 1alpha(OH)D3 administration. The number of osteoclast-like multinucleated cells obtained from ovx limbs was reduced by low- and high-dose 1alpha(OH)D3 administration alike. The number of colony forming units-fibroblast and the number of colony forming units for granulocytes and macrophages was unaltered by ovx or the administration of 1alpha(OH)D3. The present study clearly demonstrates that high-dose 1alpha(OH)D3 suppresses osteoclast numbers and surface after ovx. The inhibitory effects of low- and high-dose 1alpha(OH)D3 on bone marrow cells after ovx were marked in the differentiation from osteoclast precursors to mature osteoclasts. Administration of 1alpha(OH)D3 suppressed ovx-promoted trabecular bone resorption by inhibiting osteoclastogenic potential in bone marrow cells.