Genistein aglycone reverses glucocorticoid-induced osteoporosis and increases bone breaking strength in rats: a comparative study with alendronate.

BACKGROUND AND PURPOSE: Glucocorticoid-induced osteoporosis (GIO) is the leading cause of secondary osteoporosis. Clinical evidence suggests a role for genistein aglycone in the treatment of post-menopausal osteopenia although proof of efficacy in comparison with currently available treatments is still lacking. To clarify this issue, we investigated the effects of genistein on bone compared with alendronate in experimental GIO. EXPERIMENTAL APPROACH: A total of 28 female Sprague-Dawley rats were used. GIO was induced by daily injections of methylprednisolone (MP; 30 mg x kg(-1) s.c.) for 60 days. Sham GIO animals (Sham-MP) were injected daily with the MP vehicle. At the end of the osteoporosis development period, MP rats were randomized to receive: vehicle (n= 7), genistein aglycone (5 mg x kg(-1) s.c.; n= 7) or alendronate (0.03 mg x kg(-1) s.c.; n= 7). Treatment lasted 60 days. Sham-MP animals were treated with vehicle for an additional 60 days. At the beginning and at the end of treatments, animals were examined for bone mineral density and bone mineral content. Bone-alkaline phosphatase and carboxy-terminal collagen cross links were determined; femurs were removed and tested for breaking strength and histology. KEY RESULTS: Genistein aglycone showed a greater increase in bone mineral density, bone mineral content and in breaking strength than alendronate and significantly increased bone-alkaline phosphatase (bone formation marker), reduced carboxy-terminal collagen cross links (bone resorption marker), compared with alendronate. Both treatments improved bone histology and the histological score. CONCLUSION AND IMPLICATIONS: The results strongly suggest that the genistein aglycone might be an alternative therapy for the management of secondary osteoporosis.

Effects of genistein aglycone in osteoporotic, ovariectomized rats: a comparison with alendronate, raloxifene and oestradiol.

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-alpha-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-kappaB 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.