title: Positive skeletal effects of cladrin, a naturally occurring dimethoxydaidzein, in osteopenic rats that were maintained after treatment discontinuation.
abstract: Effects of cladrin treatment and withdrawal in osteopenic rats were studied. Cladrin improved trabecular microarchitecture, increased lumbar vertebral compressive strength, augmented coupled remodeling, and increased bone osteogenic genes. A significant skeletal gain was maintained 4 weeks after cladrin withdrawal. Findings suggest that cladrin has significant positive skeletal effects.
  
  
  BACKGROUND
  We showed that a standardized extract of Butea monosperma preserved trabecular bone mass in ovariectomized (OVx) rats. Cladrin, the most abundant bioactive compound of the extract, promoted peak bone mass achievement in growing rats by stimulating osteoblast function. Here, we studied the effects of cladrin treatment and withdrawal on the osteopenic bones.
  
  
  METHODS
  Adult female Sprague-Dawley rats were OVx and left untreated for 12 weeks to allow for significant estrogen deficiency-induced bone loss, at which point cladrin (1 and 10 mg/kg/day) was administered orally for another 12 weeks. Half of the rats were killed at the end of the treatments and the other half at 4 weeks after treatment withdrawal. Sham-operated rats and OVx rats treated with PTH or 17β-estradiol (E2) served as various controls. Efficacy was evaluated by bone microarchitecture using microcomputed tomographic analysis and fluorescent labeling of bone. qPCR and western blotting measured mRNA and protein levels in bone and uterus. Specific ELISA was used for measuring levels of serum PINP and urinary CTx.
  
  
  RESULTS
  In osteopenic rats, cladrin treatment dose dependently improved trabecular microarchitecture, increased lumbar vertebral compression strength, bone formation rate (BFR), cortical thickness (Cs.Th), serum PINP levels, and expression of osteogenic genes in bones; and reduced expression of bone osteoclastogenic genes and urinary CTx levels. Cladrin had no uterine estrogenicity. Cladrin at 10 mg/kg maintained acquired skeletal gains 4 weeks after withdrawal.
  
  
  CONCLUSIONS
  Cladrin had positive skeletal effects in osteopenic rats that were maintained after treatment withdrawal.
authors.affiliation: Division of Endocrinology, CSIR-Central Drug Research Institute, Chattar Manzil, P.O. Box 173, Lucknow, India.
authors.forename: K
authors.initials: K
authors.lastname: Khan
authors.forename: K
authors.initials: K
authors.lastname: Sharan
authors.forename: G
authors.initials: G
authors.lastname: Swarnkar
authors.forename: B
authors.initials: B
authors.lastname: Chakravarti
authors.forename: M
authors.initials: M
authors.lastname: Mittal
authors.forename: T K
authors.initials: TK
authors.lastname: Barbhuyan
authors.forename: S P
authors.initials: SP
authors.lastname: China
authors.forename: M P
authors.initials: MP
authors.lastname: Khan
authors.forename: G K
authors.initials: GK
authors.lastname: Nagar
authors.forename: D
authors.initials: D
authors.lastname: Yadav
authors.forename: P
authors.initials: P
authors.lastname: Dixit
authors.forename: R
authors.initials: R
authors.lastname: Maurya
authors.forename: N
authors.initials: N
authors.lastname: Chattopadhyay
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D001835:Body Weight / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001851:Bone Diseases, Metabolic / Q000188:drug therapy* / Q000503:physiopathology; D019245:Compressive Strength / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005260:Female; D005269:Femur / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D005786:Gene Expression Regulation / Q000187:drug effects; D007529:Isoflavones / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D008159:Lumbar Vertebrae / Q000187:drug effects / Q000503:physiopathology; D009929:Organ Size / Q000187:drug effects; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects / Q000235:genetics; D010052:Ovariectomy; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013977:Tibia / Q000187:drug effects / Q000503:physiopathology; D014599:Uterus / Q000187:drug effects / Q000473:pathology; D055114:X-Ray Microtomography
chemical_list: D015415:Biomarkers; D050071:Bone Density Conservation Agents; D007529:Isoflavones; D012333:RNA, Messenger; C558945:cladrin