Increased Osteoclast Development After Estrogen Loss: Mediation by Interleukin-6

TLDR

Osteoclasts arise from bone marrow hematopoietic precursors and are promoted by the cytokine interleukin‑6, which drives both hematopoiesis and osteoclastogenesis. Estrogen loss elevates interleukin‑6 production, enhancing osteoclast development and bone resorption, but these effects are blocked by 17β‑estradiol or IL‑6 antibody, indicating an IL‑6–mediated mechanism underlying postmenopausal osteoporosis.

Abstract

Osteoclasts, the cells that resorb bone, develop from hematopoietic precursors of the bone marrow under the control of factors produced in their microenvironment. The cytokine interleukin-6 can promote hematopoiesis and osteoclastogenesis. Interleukin-6 production by bone and marrow stromal cells is suppressed by 17β-estradiol in vitro. In mice, estrogen loss (ovariectomy) increased the number of colony-forming units for granulocytes and macrophages, enhanced osteoclast development in ex vivo cultures of marrow, and increased the number of osteoclasts in trabecular bone. These changes were prevented by 17β-estradiol or an antibody to interleukin-6. Thus, estrogen loss results in an interleukin-6-mediated stimulation of osteoclastogenesis, which suggests a mechanism for the increased bone resorption in postmenopausal osteoporosis.