LOSS OF ESTROGEN UP-REGULATES OSTEOBLASTOGENESIS IN THE MURINE BONE-MARROW - EVIDENCE FOR AUTONOMY FROM FACTORS RELEASED DURING BONE-RESORPTION

Loss of sex steroids causes an increase in both the resorption and for mation of bone, with the former exceeding the latter. Based on evidenc e that the increased bone resorption after estrogen loss is due to an increase in osteoclastogenesis, we hypothesized that estrogen loss als o stimulates osteoblastogenesis. We report that the number of mesenchy mal osteoblast progenitors in the murine bone marrow was increased two - to threefold between 2 and 8 wk after ovariectomy and returned to co ntrol levels by 16 wk. Circulating osteocalcin, as well as osteoclasto genesis and the rate of bone loss, followed a very similar temporal pa ttern. Inhibition of bone resorption by administration of the bisphosp honate alendronate led to a decrease of the absolute number of osteobl ast progenitors; however, it did not influence the stimulating effect of ovariectomy on osteoblastogenesis or osteoclastogenesis. These obse rvations indicate that the increased bone formation that follows loss of estrogen can be explained, at least in part, by an increase in oste oblastogenesis. Moreover, they strongly suggest that unlike normal bon e remodeling, whereby osteoblast development is stimulated by factors released from the bone matrix during osteoclastic resorption, estrogen deficiency unleashes signals that can stimulate the differentiation o f osteoblast progenitors in a fashion that is autonomous from the need created by bone resorption, and therefore, inappropriate.