title: Genistein aglycone reverses glucocorticoid-induced osteoporosis and increases bone breaking strength in rats: a comparative study with alendronate.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  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.
  
  
  CONCLUSIONS
  The results strongly suggest that the genistein aglycone might be an alternative therapy for the management of secondary osteoporosis.
authors.affiliation: Department of Clinical and Experimental Medicine and Pharmacology, Section of Pharmacology, University of Messina, Messina, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Bitto
authors.forename: B P
authors.initials: BP
authors.lastname: Burnett
authors.forename: F
authors.initials: F
authors.lastname: Polito
authors.forename: R M
authors.initials: RM
authors.lastname: Levy
authors.forename: H
authors.initials: H
authors.lastname: Marini
authors.forename: V
authors.initials: V
authors.lastname: Di Stefano
authors.forename: N
authors.initials: N
authors.lastname: Irrera
authors.forename: M A
authors.initials: MA
authors.lastname: Armbruster
authors.forename: L
authors.initials: L
authors.lastname: Minutoli
authors.forename: D
authors.initials: D
authors.lastname: Altavilla
authors.forename: F
authors.initials: F
authors.lastname: Squadrito
mesh_terms: D019386:Alendronate / Q000008:administration & dosage / Q000494:pharmacology*; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000494:pharmacology*; D016723:Bone Remodeling / Q000187:drug effects*; D002113:Calcification, Physiologic / Q000187:drug effects*; D024042:Collagen Type I / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005264:Femoral Fractures / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D005269:Femur / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D019833:Genistein / Q000008:administration & dosage / Q000494:pharmacology*; D007279:Injections, Subcutaneous; D008775:Methylprednisolone; D010024:Osteoporosis / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D010455:Peptides / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D015415:Biomarkers; D050071:Bone Density Conservation Agents; D024042:Collagen Type I; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; D019833:Genistein; D000469:Alkaline Phosphatase; D019386:Alendronate; D008775:Methylprednisolone