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Comparative Study
. 2009 Apr;156(8):1287-95.
doi: 10.1111/j.1476-5381.2008.00100.x. Epub 2009 Mar 19.

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

A Bitto  1 , B P Burnett, F Polito, R M Levy, H Marini, V Di Stefano, N Irrera, M A Armbruster, L Minutoli, D Altavilla, F Squadrito
Affiliations
Comparative Study

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

A Bitto et al. Br J Pharmacol. 2009 Apr.

Abstract

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.

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Figures

Figure 1
Figure 1
Flow chart of the experimental protocol. BMC, bone mineral content; BMD, bone mineral density; MP, methylprednisolone.
Figure 2
Figure 2
(A) Effects of alendronate (ALN) and genistein aglycone (GEN) on femoral bone mineral density (BMD) and (B) bone mineral content (BMC) in rats with glucocorticoid-induced osteoporosis (methylprednisolone, MP). Data are shown as the mean ± SD of seven animals. *P < 0.01 versus Sham-MP; #P < 0.005 versus MP + VEH (vehicle).
Figure 3
Figure 3
(A) Effects of alendronate (ALN) and genistein aglycone (GEN) on serum bone-alkaline phosphatase (b-ALP), (B) collagen C-telopeptides (CTX), (C) femur breaking strength and (D) histological score in rats with glucocorticoid-induced osteoporosis (methylprednisolone, MP). Data are shown as the mean ± SD of seven animals. b-ALP: §P < 0.05 versus MP + VEH (vehicle), #P < 0.001 versus MP + ALN. CTX: §P < 0.001 versus MP + VEH, *P < 0.05 versus MP + ALN. Femur breaking strength: §P < 0.001 versus MP + VEH, #P < 0.05 versus MP + VEH, *P < 0.05 versus MP + ALN. Histological score: §P < 0.001 versus MP + VEH.
Figure 4
Figure 4
Light microscopy of the bone structure of the femur head taken from the different treatment groups. (haematoxylin and eosin stain; original magnification 5×). ALN, alendronate; GEN, genistein aglycone; MP, methylprednisolone; VEH, vehicle.
See this image and copyright information in PMC

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