Icariin prevents ovariectomy-induced bone loss and lowers marrow adipogenesis

Abstract

Icariin prevents bone loss by stimulating new bone formation and by inhibiting bone resorption. However, less is known about how icariin affects marrow adiposity. This lack of information is a vital problem, as the degree of marrow adipogenesis may be an alternative indicator of the severity of osteoporosis in relation to the degree of osteogenesis and osteoblastogenesis. To explore this question, we tested the effects of icariin on bone mineral density (BMD) and marrow fat content in a rat model of postmenopausal osteoporosis. Thirty-six 3-month-old female Sprague-Dawley rats were randomly assigned to one of the following treatment groups: sham operation, ovariectomized controls, and ovariectomized rats treated orally with either 17β-estradiol or icariin for 12 weeks. BMD and marrow fat fraction were dynamically measured on weeks 0, 6, and 12. After 12 weeks of treatment, serum 17β-estradiol and bone biomarker levels were measured, and marrow adipocytes were quantitatively evaluated by histopathology. Ovariectomized controls experienced a marked increase in fat fraction over time, with increases of 40% between weeks 0 and 6 and 69.4% between weeks 6 and 12 (P < 0.001). Marrow adiposity in ovariectomized controls was dramatically higher than that in sham rats on week 6; however, a reduction in BMD was detected in ovariectomized rats on week 12 (P < 0.001). Ovariectomized rats had levels of serum alkaline phosphatase and serum C-terminal telopeptide of type I collagen that were 49.4% and 67.2% higher, respectively, than those of sham rats (P < 0.001). The density, size, and volume of marrow adipocytes in ovariectomized controls were 57.3%, 29.5%, and 163% higher, respectively, than those in sham rats. Early icariin treatment decreased bone biomarker levels, inhibited bone degeneration, and restored marrow fat infiltration and adipocyte parameters to the levels observed in sham rats. Overall, the osteoprotective effect of icariin was comparable with that of 17β-estradiol; however, icariin did not produce uterine estrogenicity. Early icariin treatment restores marrow adiposity in the estrogen-deficient rat model.