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A Novel in vivo Gene Transfer Technique and in vitro Cell Based Assays for the Study of Bone Loss in Musculoskeletal Disorders
Published on: June 8, 2014
Genistein aglycone reverses glucocorticoid-induced osteoporosis and increases bone breaking strength in rats: a
A Bitto1, B P Burnett, F Polito
1Department of Clinical and Experimental Medicine and Pharmacology, Section of Pharmacology, University of Messina, Messina, Italy.
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.
Insights
Genistein aglycone shows promise in treating glucocorticoid-induced osteoporosis (GIO), outperforming alendronate in key bone health markers. This research suggests genistein as a potential alternative therapy for secondary osteoporosis.
Area of Science:
- Endocrinology
- Bone Biology
- Pharmacology
Background:
- Glucocorticoid-induced osteoporosis (GIO) is a primary cause of secondary osteoporosis.
- Genistein aglycone's potential in treating post-menopausal osteopenia is suggested but requires comparative efficacy data.
- Current treatments for GIO lack comprehensive comparative studies.
Purpose of the Study:
- To investigate the bone-protective effects of genistein aglycone compared to alendronate in an experimental model of GIO.
- To evaluate genistein's efficacy in improving bone mineral density, content, and strength.
- To assess the impact of genistein on bone formation and resorption markers.
Main Methods:
- Glucocorticoid-induced osteoporosis (GIO) was established in 28 female Sprague-Dawley rats using methylprednisolone (MP).
- MP-treated rats were randomized to receive vehicle, genistein aglycone, or alendronate for 60 days.
- Bone mineral density, content, breaking strength, and biochemical markers (bone-alkaline phosphatase, carboxy-terminal collagen cross links) were assessed.
Main Results:
- Genistein aglycone significantly increased bone mineral density, bone mineral content, and femur breaking strength compared to alendronate.
- Genistein aglycone demonstrated a greater increase in bone-alkaline phosphatase (bone formation) and reduction in carboxy-terminal collagen cross links (bone resorption) than alendronate.
- Both genistein aglycone and alendronate treatments improved bone histology and histological scores.
Conclusions:
- Genistein aglycone exhibits superior efficacy over alendronate in improving bone health parameters in experimental GIO.
- The findings support genistein aglycone as a potential therapeutic alternative for managing secondary osteoporosis.
- Further clinical studies are warranted to confirm genistein's efficacy in human patients.
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