Menopause: The Journal of The North American Menopause Society Vol. 21, No. 9, pp. 1007/1016 DOI: 10.1097/gme.0000000000000201 * 2014 by The North American Menopause Society
Icariin prevents ovariectomy-induced bone loss and lowers marrow adipogenesis Guan-Wu Li, MD,1 Zheng Xu, MD,2 Shi-Xin Chang, MD,1 Hua Nian, MD,3 Xiao-Yan Wang, MD,1 and Lin-Di Qin, MD1 Abstract Objective: 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. Methods: 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 17Aestradiol 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 17A-estradiol and bone biomarker levels were measured, and marrow adipocytes were quantitatively evaluated by histopathology. Results: 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 G 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 G 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 G 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 17A-estradiol; however, icariin did not produce uterine estrogenicity. Conclusions: Early icariin treatment restores marrow adiposity in the estrogen-deficient rat model. Key Words: Icariin Y Marrow adiposity Y Bone mineral density Y Osteoporosis.
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steoporosis is the most common metabolic bone disease worldwide; it affects approximately one in two women and one in five men aged older than 50 years. Osteoporosis presents enormous social and economic challenges because of its high morbidity and mortality rates and very high associated medical costs.1,2 Received September 15, 2013; revised and accepted December 4, 2013. From the 1Department of Radiology, Yueyang Hospital affiliated with Shanghai University of Traditional Chinese Medicine, Shanghai, China; 2 Medico-technical Department, Xin-Zhuang Community Health Service Center, Shanghai, China; and 3Department of Pharmacy, Yueyang Hospital affiliated with Shanghai University of Traditional Chinese Medicine, Shanghai, China. Z.X. and G.-W.L. contributed equally to this study as coYfirst authors. Funding/support: This study was supported, in part, by grants from the National Natural Science Foundation of China (grants 81202809 and 81373856). Financial disclosure/conflicts of interest: None reported. Address correspondence to: Shi-Xin Chang, MD, Department of Radiology, Yueyang Hospital affiliated with Shanghai University of Traditional Chinese Medicine, 110 Gan-He Road, Hong-Kou District, Shanghai 200437, China. E-mail: [email protected]
Postmenopausal osteoporosis reflects an imbalance in bone remodeling in which osteoclastic bone resorption exceeds osteoblastic bone formation.3 In the past decade, advances in the prevention and treatment of osteoporosis have been made. Oral bisphosphonates are currently considered as the first-line agents for osteoporosis. However, these drugs are associated with several adverse effects, including gastrointestinal adverse effects, osteonecrosis of the jaw, and insufficiency fractures.4
Icariin prevents ovariectomy-induced bone loss and lowers marrow adipogenesis Guan-Wu Li, MD,1 Zheng Xu, MD,2 Shi-Xin Chang, MD,1 Hua Nian, MD,3 Xiao-Yan Wang, MD,1 and Lin-Di Qin, MD1 Abstract Objective: 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. Methods: 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 17Aestradiol 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 17A-estradiol and bone biomarker levels were measured, and marrow adipocytes were quantitatively evaluated by histopathology. Results: 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 G 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 G 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 G 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 17A-estradiol; however, icariin did not produce uterine estrogenicity. Conclusions: Early icariin treatment restores marrow adiposity in the estrogen-deficient rat model. Key Words: Icariin Y Marrow adiposity Y Bone mineral density Y Osteoporosis.
O
steoporosis is the most common metabolic bone disease worldwide; it affects approximately one in two women and one in five men aged older than 50 years. Osteoporosis presents enormous social and economic challenges because of its high morbidity and mortality rates and very high associated medical costs.1,2 Received September 15, 2013; revised and accepted December 4, 2013. From the 1Department of Radiology, Yueyang Hospital affiliated with Shanghai University of Traditional Chinese Medicine, Shanghai, China; 2 Medico-technical Department, Xin-Zhuang Community Health Service Center, Shanghai, China; and 3Department of Pharmacy, Yueyang Hospital affiliated with Shanghai University of Traditional Chinese Medicine, Shanghai, China. Z.X. and G.-W.L. contributed equally to this study as coYfirst authors. Funding/support: This study was supported, in part, by grants from the National Natural Science Foundation of China (grants 81202809 and 81373856). Financial disclosure/conflicts of interest: None reported. Address correspondence to: Shi-Xin Chang, MD, Department of Radiology, Yueyang Hospital affiliated with Shanghai University of Traditional Chinese Medicine, 110 Gan-He Road, Hong-Kou District, Shanghai 200437, China. E-mail: [email protected]
Postmenopausal osteoporosis reflects an imbalance in bone remodeling in which osteoclastic bone resorption exceeds osteoblastic bone formation.3 In the past decade, advances in the prevention and treatment of osteoporosis have been made. Oral bisphosphonates are currently considered as the first-line agents for osteoporosis. However, these drugs are associated with several adverse effects, including gastrointestinal adverse effects, osteonecrosis of the jaw, and insufficiency fractures.4
