Effects of estrogen therapy on bone marrow adipocytes in postmenopausal osteoporotic women

Summary: One-year treatment of osteoporotic postmenopausal women with transdermal estrogen resulted in significant decreases in bone marrow adipocyte volume and prevented increases in adipocyte number as compared to placebo-treated controls. Estrogen treatment also prevented increases in mean adipocyte size over 1 year. Introduction: Aging is associated not only with bone loss but also with increases in bone marrow adipocytes. Since osteoblasts and adipocytes are derived from a common precursor, it is possible that with aging, there is a preferential "switch" in commitment of this precursor to the adipocyte over the osteoblast lineage. We tested the hypothesis that the apparent "age-related" increase in marrow adipocytes is due, at least in part, to estrogen (E) deficiency. Methods: Reanalysis of bone biopsies from a randomized, placebo-controlled trial involving 56 postmenopausal osteoporotic women (mean age, 64 years) treated either with placebo (PL, n=27) or transdermal estradiol (0.1 mg/d, n=29) for 1 year. Results: Adipocyte volume/tissue volume (AV/TV) and adipocyte number (Ad#) increased (by ∼20%, P<0.05) in the PL group, but were unchanged (Ad#) or decreased (AV/TV, by -24%, P<0.001) in the E group. E treatment also prevented increases in mean adipocyte size over 1 year. Conclusions: These findings represent the first in vivo demonstration in humans that not only ongoing bone loss, but also the increase in bone marrow adipocyte number and size in postmenopausal osteoporotic women may be due, at least in part, to E deficiency.