title: Effects of genistein aglycone in osteoporotic, ovariectomized rats: a comparison with alendronate, raloxifene and oestradiol.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  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
  The results strongly suggest that the genistein aglycone might be a new therapy for the management of postmenopausal osteoporosis in humans.
authors.affiliation: Section of Pharmacology, Department of Clinical and Experimental Medicine and 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: H
authors.initials: H
authors.lastname: Marini
authors.forename: R M
authors.initials: RM
authors.lastname: Levy
authors.forename: M A
authors.initials: MA
authors.lastname: Armbruster
authors.forename: L
authors.initials: L
authors.lastname: Minutoli
authors.forename: V
authors.initials: V
authors.lastname: Di Stefano
authors.forename: N
authors.initials: N
authors.lastname: Irrera
authors.forename: S
authors.initials: S
authors.lastname: Antoci
authors.forename: R
authors.initials: R
authors.lastname: Granese
authors.forename: F
authors.initials: F
authors.lastname: Squadrito
authors.forename: D
authors.initials: D
authors.lastname: Altavilla
mesh_terms: D019386:Alendronate / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D019833:Genistein / Q000494:pharmacology / Q000627:therapeutic use*; D010024:Osteoporosis / Q000188:drug therapy*; D010052:Ovariectomy; D048789:Phytoestrogens / Q000494:pharmacology / Q000627:therapeutic use; D020849:Raloxifene Hydrochloride / Q000494:pharmacology / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D050071:Bone Density Conservation Agents; D048789:Phytoestrogens; D020849:Raloxifene Hydrochloride; D004958:Estradiol; D019833:Genistein; D019386:Alendronate