Estrogen action on bone marrow osteoclast lineage cells of postmenopausal women in vivo

In bone marrow aspirates from postmenopausal women, systemic estrogen treatment decreased differentiation of mononuclear progenitor cells toward a more mature osteoclast phenotype. This was not associated with changes in surface receptor for proresorptive cytokines. Although mechanisms by which estrogen (E) decreases bone resorption have been extensively studied in rodents, little information is available in humans. In bone marrow aspirates from 34 early postmenopausal women randomly assigned to receive 4 weeks of treatment (100 mu g/day of transdermal 17 beta-estradiol) or no treatment, we assessed osteoclast differentiation and surface receptors using flow cytometry with fluorescent-labeled specific antibodies. E treatment decreased (P < 0.05) the proportion of bone marrow mononuclear cells (BMMNCs) expressing the calcitonin receptor (CTR), a late osteoclast phenotype marker. There was an increase in c-Fms concentration in osteoclast lineage cells (P < 0.05) and in the proportion of BMMNCs expressing TNFR2 (P < 0.05), but there were no significant effects on other surface receptors for proresorptive factors (RANK, TNFR1, TREM2, or OSCAR). Changes in serum CTx and TRAP 5b, markers for bone resorption, correlated directly (P < 0.05) with the proportion of BMMNCs expressing CTR and, for TRAP 5b only, TNFR2 and inversely with c-Fms concentration (all P < 0.05). E reduces bone resorption, in part, by decreasing differentiation of BMMNCs into mature osteoclasts. This action cannot be explained by decreased concentrations of surface receptors for proresorptive factors. The roles of increases in c-Fms concentration and the proportion of TNFR2((+)) cells are unclear.