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Abstract
Background and purpose:Genistein aglycone positively affects bone loss in postmenopausal women, but bone quality data are still lacking. To clarify this, we investigated the effects of genistein compared with alendronate, raloxifene and oestradiol in an animal model of established osteoporosis.Experimental approach:Six months after ovariectomy, 96 ovariectomized (OVX) rats were divided into 8 equal groups, randomized to treatments (genistein aglycone (1 and 10 mg kg−1 s.c.); alendronate (0.003 and 0.03 mg kg−1 s.c.); raloxifene hydrochloride (0.05 and 0.5 mg kg−1 s.c.); 17-α-ethinyl oestradiol (0.003 and 0.03 mg kg−1 s.c.)) for 12 weeks. Untreated OVX (n=12) and sham OVX (n=12) were used as controls. At the beginning and end of treatment, bone mineral density (BMD) and bone mineral content (BMC) were assessed. At the end of the experiment, calcium, phosphorus, bone-alkaline phosphatase (b-ALP), collagen C-telopeptide (CTX), osteoprotegerin (OPG) and soluble receptor activator of nuclear factor-κB ligand (sRANKL) were assayed. Femurs were removed and tested for breaking strength and histology.Key results:Genistein (10 mg kg−1) showed a greater increase in both BMD (P<0.0001 vs OVX) and BMC than all the other treatments. Moreover, genistein significantly increased breaking strength, bone quality, b-ALP (P<0.0001 vs OVX) and OPG, and reduced CTX and sRANKL compared with the other treatments at all dose levels.Conclusions and implications:The results strongly suggest that the genistein aglycone might be a new therapy for the management of postmenopausal osteoporosis in humans.
Highlights
Osteoporosis is a systemic disease, characterized by reduced bone mass and structural deterioration of bone tissue
We have previously shown that treatment with pure genistein aglycone increased bone mineral density (BMD) at the lumbar spine and femoral neck in postmenopausal women with no clinically significant adverse effects on the breast and uterus (Morabito et al, 2002; Marini et al, 2007)
In the light of these results, we investigated whether genistein aglycone might be a useful alternative treatment for postmenopausal osteoporosis compared with other commonly used therapies such as alendronate, raloxifene and oestradiol in an OVX animal model of established osteoporosis
Summary
Osteoporosis is a systemic disease, characterized by reduced bone mass and structural deterioration of bone tissue. It is considered a public health issue threatening a large part of the population above 50 years of age (Hohenhaus et al, 2007; Levine, 2007). Several experimental studies compared the effects of currently used therapies for osteoporosis in ovariectomized (OVX) animals (Frolik et al, 1996; Sato et al, 1996; Bourrin et al, 2002; Helvering et al, 2005), but the results were variable and different doses were used. Genistein significantly increased breaking strength, bone quality, b-ALP (Po0.0001 vs OVX) and OPG, and reduced CTX and sRANKL compared with the other treatments at all dose levels. British Journal of Pharmacology (2008) 155, 896–905; doi:10.1038/bjp.2008.305; published online 11 August 2008
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