The preventive and therapeutic roles of phytoestrogen α-Zearalanol on osteoporetic rats due to ovariectomization

Document Type : Original Article


1 School of Basic Medical Sciences, Hebei University, Baoding 071002, China

2 Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China

3 School of Life Science, Beijing Institute of Technology, Beijing 10081, China


Objective(s): The aim of this study was to observe the influence of phytoestrogen α-Zearalanol on ovariectomy-induced postmenopausal osteoporosis in rats.
Materials and Methods:40 SD female rats were randomly divided into four groups: Sham group, OVX group (ovariectomized and fed estrogen), α-Zearalanol group (ovariectomized and fed α-Zearalanol) and untreated group (ovariectomized). Three weeks later after surgery, α-Zearalanol and estradiol valerate were administered by oral gavage for 12 weeks to the α-Zearalanol group and the OVX group, respectively. In contrast, the sham and untreated controls were treated with distilled water in a                   daily basis. After the treatments, uterus histomorphometry, bone mechanical strength, bone histomorphometry, bone mineral density (BMD) of femur, and serum biochemical indicators, such as serum E2, CT and PTH, as well as the levels of TNF and IL-1 were examined.
Results: The BMD was overall declined rigorously in the OVX rats, and that could be mitigated through feeding on either estrogen or α-Zearalanol. Estrogen or α-Zearalanol was found to decrease the levels of serum ALP and BGP in OVX rats, while, α-Zearalanol was found to increase the levels of serum E2 and CT, the thickness of the endometrium, and decrease the levels of PTH, TNF and IL-1 in serum in OVX rats. Feeding the OVX rats on α-Zearalanol improved the bone histomorphometric parameters impaired due to estrogen deficiency and enhanced the bone mechanical properties in the ovariectomized rats.
Conclusion: α-Zearalanol treated rats reduced the resorption of bone, and showed a preventive and therapeutic effect of α-Zearalanol on postmenopausal osteoporosis.


1. Hohenhaus MH, McGarry KA, Col NF. Hormone therapy for the prevention of bone loss in menopausal women with osteopenia: is it a viable option? Drugs 2007; 67:2311–2321.
2. Lorraine AF. Estrogen therapy for postmenopausal osteoporosis. Arq Bras Endocrinol Metabol 2006; 50: 705-719.
3. Landete JM, Arqués J, Medina M, Gaya P, de Las Rivas B, Muñoz R.Bioactivation of Phytoestrogens: Intestinal bacteria and health. Crit Rev Food Sci Nutr 2015; 56:1826-1843.
4. Liu T, Hou DD, Zhao Q, Liu W, Zhen PP, Xu JP. Phyto-estrogen α-Zearalanol Attenuates Homocysteine-Induced Apoptosis in Human Umbilical Vein Endothelial Cells. BioMed Res Int 2013; 2013:813450.
5. Dai S, Duan J, Lu Y, Cheng J, Ren J, Deng W, et al. α-Zearalanol inhibits the progression of atherosclerosis and improves lipid profile in ovariectomized cholesterol-fed rabbits. Endocrine 2004; 25:121–130.
6. Celotto AC, Fukada SY, Laurindo FR, Haddad R, Eberlin MN, De Oliveira AM et al. Chronic hyperhomocysteinemia impairs vascular function in ovariectomized rat carotid arteries. Amino Acids2010; 38:1515-1522.
7. Peng Z, Tuukkanen J, Zhang H. The mechanical strength of bone in different rat models of experimental osteoporosis. Bone 1994;15:523–532.
8. Stellon AJ, Webb, A, Compston JE. Bone histomorphometry and structure in corticosteroid treated chronic active hepatitis. Gut 1988; 29:378-384.
9. Lee, Il Jae, Lee, Jong Joo, Bae, Joon-Ho, et al. Significance of Osteoporosis in Facial Bone Density Using Computed Tomography. J Craniofac Surg 2013; 24:428-431.
10. Routh RH, Rumancik S, Pathak RD, Burshell AL, Nauman EA, et al. The relationship between bone mineral density and biomechanics in patients with osteoporosis and scoliosis. Osteoporos Int 2005; 16:1857-1863.
11. Weitzmann MN, Pacifici R. Estrogen deficiency and bone loss: an inflammatory tale. J Clin Invest 2006; 116:1186–1194.
12. Dai S, Duan J, Lu Y, Cheng J, Ren J, Deng W, et al.  α-zearalanol, a phytoestrogen for cardiovascular therapy. Endocrine 2004; 25:117-119.
13. Takeuchi Y. Treatment of osteoporosis with PTH. Clin Calcium 2014; 24:893-902.
14. McNeilly T, McNally C, Finch M, Beringer T. Effects of PTH (1-84) on bone quality in a validated model of osteoporosis due to androgenic deprivation. Aging Male 2014; 17:42-50.
15. Martín-Fernández M, Martínez E, Díaz-Curiel M, Guede D, Caeiro JR, De la Piedra C, et al. Effects of PTH (1-84) on bone quality in a validated model of osteoporosis due to androgenic deprivation. Aging Male 2014; 17:42-50.
16. Kuo YJ, Tsuang FY, Sun JS, Lin CH, Chen CH, Li JY, et al. Calcitonin Inhibits SDCP-Induced Osteoclast Apoptosis and Increases Its Efficacy in a Rat Model of Osteoporosis. PLoS One 2012; 7:e40272.
17. Rodríguez Rodríguez LP. Etidronate and calcitonin to PTH (1-84) in postmenopausal osteoporosis. An R Acad Nac Med (Madr) 2011; 128:169-198.
18. Ophoff VK, Callewaert F, Boonen S, Bouillon R, Vanderschueren D. Sex steroids during bone growth: a comparative study between mouse models for hypogonadal and senile osteoporosis. Osteoporos Int 2009; 20:1749-1757.
19. Pacifici R, Rifas L, McCracken R, Vered I, McMurtry C, Avioli LV, et al. Ovarian steroid treatment blocks a postmenopausal increase in blood monocyte interleukin 1 release. Proc Natl Acad Sci USA 1989; 86:2398-2402.
20. Jilka RL, Hangoc G, Girasole G, Passeri G, Williams DC, Abrams JS, et al. Increased osteoclast development after estrogen loss: mediation by interleukin-6. Science 1992; 257:88-91.
21. Weitzmann MN, Roggia C, Toraldo G, Weitzmann L, Pacifici R. Increased production of IL-7 uncouples bone formation from bone resorption during estrogen deficiency. J Clin Invest 2002; 110:1643-1650.
22. Pacifici R, Brown C, Puscheck E, Friedrich E, Slatopolsky E, Maggio D, et al. Effect of surgical menopause and estrogen replacement on cytokine release from human blood mononuclear cells. Proc Natl Acad Sci USA 1991; 88:5134-5138.
23. Dai S, Duan J,Lu Y, Dai S, Wu Y, Sun R, et al. Phytoestrogen alpha-zearalanol inhibits atherogenesis and improves lipid profile in ovariectomized cholesterol-fed rabbits. Endocrine 2004; 25:121-129.
24. Duan J, Xu H, Dai S, Wang X, Wu Y, Zhang Y, et al. Phytoestrogen alpha-zearalanol inhibits homocysteine-induced endothelin-1 expression and oxidative stress in human umbilical vein endothelial cells. Atherosclerosis 2008; 197:549-555.
25. Xu H, Duan J, Sun R, Wang X, Xu X, Wu Y, et al. Effect and mechanism of phytoestrogen α-Zearalanol on No and ET-1 secretion induced by oxLDL in human umbilical vein endothelial cells. Zhongguo Yao Li Xue Tong Bao 2005; 21:692-697.