Ovariectomy-induced bone loss

J p (2000) Daidzein is more efficient than genistein in preventing ovariectomy-induced bone loss in rats. J Nutr. 130 1675-81. 

Lasofoxifene is a SERM that also protects from bone loss, reduces cholesterol levels, and exerts a positive effect on bone strength in rats, specifically in male models (Ma et al. 2002). This compound is in the final stages of clinical development. Two other SERMs also in advanced phase III trials are bazedoxifene and arzoxifene, both with protective effects against ovariectomy-induced bone loss. Arzoxifene has shown both bone remodeling reduction with positive effects on bone quality as well as a reduction in cholesterol levels in oophorectomized rats (Biskobing2003). 

Chen HK, Ke E1Z, Jee WS, Ma YZ, Pirie CM, Simmons HA, et al. (1995) Droloxifene prevents ovariectomy-induced bone loss in tibiae and femora of aged female rats a dual absorptiometric and histomorphometric study. J Bone Miner Res 10 1256-1262... 

These compounds, however, do not possess cell or tissue specificity and show antiestrogenic activity in all the tissues tested. For example, ICI 164,384 and ICI 182,780 do not lower serum cholesterol levels and do not prevent ovariectomy-induced bone loss (Dodds et al., 1993 Jordan, 1992 Wakeling, 1993), thus limiting our interest in them when there are other compounds that also exert pure antiestrogenic activity in the breast and uterus, while at the same time preventing bone loss and decreasing serum cholesterol (Labrie et al., 1999). 

Shirke, S.S., S.R. Jadhav, and A.G. Jagtap. 2008. MethanoUc extract of Cuminum cyminum inhibits ovariectomy-induced bone loss in rats. Exp. Biol. Med. 233(11) 1403-1410. 

In rats, the compound 8-PN was shown to have estrogenic activity in reproductive tissue about 20,000-fold weaker compared to 17P-estradiol (Schaefer et al. 2003). Doses of 0.67 to 18 mg/kg of 8-PN daily administered subcutaneously to mice for 28 days completely inhibited ovariectomy-induced bone loss while exhibiting minimal, dose-independent, trophic effects on uterus and endometrium (Humpel et al. 2005). 

Humpel, M., P. Isaksson, O. Schaefer, et aL 2005. Tissue sp>ecificity of 8-prenylnaringenin Protection from ovariectomy induced bone loss with minimal trophic effects on the uterus. /. Steroid Biochem. Mol. Biol. 97(3) 299-305. 

Nielsen, K.L. et al (2003) Biglycan deficiency interferes with ovariectomy-induced bone loss. /. Bone Miner. Res., 18 (12), 2152 -2158. 

Similar to the human studies, the animal studies are not entirely consistent, due to the different study designs (source and dose of soy protein/isoflavones time, method and length of administration age of rats, etc.). Nevertheless, a certain number of conclusions may be drawn. Overall, soy extracts or pure isoflavones show an osteoprotective effect in the ovariectomized rat model of menopausal bone loss. The time of administration is important and they must be given at the time of ovariectomy which allows prevention but not reversal of bone loss. Although the OVX-induced bone loss in the rat is a... 

Interleukin 1 (IL-1) is produced mainly by activated monocytes-macropha-ges, and its principal action is to stimulate thymocytes. A pleiotropic cytokine, IL-1 induces the expression of a large diversity of cytokines such as IL-6, leukaemia inhibitory factor (LIF), and other proinflammatory molecules (Di-marello 1994). IL-1 and TNF-a carry out as part of their function increasing the expression of NF-/cB and JNK (c-Jun N-terminal kinase). The importance of IL-1 in OCS is demonstrated because the IL-1-receptor-deficient mouse is resistant to ovariectomy (OVX)-induced bone loss (Lorenzo et al. 1998). The importance in pathological bone loss is also illustrated by the fact that treatment with IL-1 receptor antagonist slows down bone erosion for patients affected with rheumatoid arthritis (Kwan et al. 2004). IL-1 increases osteoclast differentiation rather than mature osteoclast activity, and infusion of IL-1 into mice induces hypercalcemia and bone resorption. Finally, IL-1 and TNF-a... 

In a model of murine collagen-induced arthritis, CORM-3 inhibited the levels of TNF-a, interleukin (IL)-ip, IL-2, IL-6, IL-10, and prostaglandin E in the Joint tissues, suppressing the manifestation of disease and inflammation [69]. In a model of postmenopausal arthritis, ovariectomy followed by collagen administration in mice, CORM-3 was also able to protect systemic bone loss, with a decrease of serum levels of COMP, IL-6, alkaline phosphatase, osteocalcin, and TNF-a [70]. 

Das, A.S., Mukherjee, M., Das, D., et al 2009. Protective action of aqueous black tea (Camellia sinensis) extract (BTE) against ovariectomy-induced oxidative stress of mononuclear cells and its associated progression of bone loss . Phytotherapy Research., 25 1287-1294. 

As RJ contains testosterone [24] and possesses steroid hormone-type activities [54—57], it was hypothesized that it may have beneficial effects on osteoporosis. In a recent study, both an ovariectomized rat model and a tissue culture model were used. The results of the study indicated that RJ was almost as effective as 17p-estradiol in preventing the development of bone loss induced by ovariectomy in rats. In tissue culture models, RJ increased calcium contents in femoral-diaphyseal and femoral-metaphyseal tissue cultures obtained from normal male rats however, in a mouse marrow culture model, it neither inhibited the parathyroid hormone (PTH)-induced calcium loss nor affected the formation of osteoclast-like cells induced by PTH. Therefore, these results suggested that RJ may prevent osteoporosis by enhancing intestinal calcium absorption, but not by directly antagonizing the action of PTH [60]. In a comparable study, it was investigated whether RJ and bee pollen reduce the bone loss due to osteoporosis in oophorectomized female rats model. It was concluded that RJ and bee pollen after a 12-week treatment decrease the bone loss due to osteoporosis, proposing that these results may contribute to the clinical practice [61]. 

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