title: Strontium fructose 1,6-diphosphate prevents bone loss in a rat model of postmenopausal osteoporosis via the OPG/RANKL/RANK pathway.
abstract: OBJECTIVE
  To evaluate the protective effects of strontium fructose 1,6-diphosphate (FDP-Sr), a novel strontium salt that combined fructose 1,6-diphosphate (FDP) with strontium, on bone in an ovariectomy-induced model of bone loss.
  
  
  METHODS
  Eighty female Sprague-Dawley rats were ovariectomized (OVX) or sham-operated. Three months later, the rats were assigned to six groups (10 for each): sham-operated, OVX control, OVX+FDP-Sr (110, 220, or 440 mg/kg), or OVX+strontium ranelate (SR, 180 mg/kg). Drugs were administered orally for 3 months. When the treatment was terminated, the following parameters were assessed: bone mineral density (BMD), the biomechanical properties of the femur and lumbar vertebrae, trabecular histomorphology, serum phosphorus, calcium, bone-specific alkaline phosphatase (B-ALP), tartrate-resistant acid phosphatase 5b (TRACP5b), N-telopeptide of type I collagen (NTx) and a series of markers for oxidative stress. Receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG) levels in serum were measured using ELISA and their gene expression levels in the bone were measured using R-T PCR.
  
  
  RESULTS
  Treatment with FDP-Sr (220 or 440 mg/kg) or SR (180 mg/kg) significantly increased the BMD and improved the bone microarchitecture and bone strength in OVX rats. The treatments also decreased in the levels of H(2)O(2) and MDA, restored the CAT level in serum and bone marrow, increased the serum B-ALP and decreased NTx and TRACP 5b in OVX rats. Treatment with FDP-Sr decreased the RANKL level, and increased the OPG level in serum in a dose-dependent manner. It also significantly down-regulated the RANKL expression and up-regulated OPG expression in bone marrow.
  
  
  CONCLUSIONS
  FDP-Sr may be an effectve treatment for postmenopausal osteoporosis that acts, in part, via a decrease in osteoclastogenesis through the OPG\RANKL\RANK pathway.
authors.affiliation: School of Pharmaceutical Sciences, Nanjing University of Technology, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Ma
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.forename: Di
authors.initials: D
authors.lastname: Wu
authors.forename: Yong-lu
authors.initials: YL
authors.lastname: Wang
authors.forename: Ying-ying
authors.initials: YY
authors.lastname: Hu
authors.forename: Yan-ping
authors.initials: YP
authors.lastname: Cheng
authors.forename: Zhen-dong
authors.initials: ZD
authors.lastname: Yang
authors.forename: Ya-ya
authors.initials: YY
authors.lastname: Zheng
authors.forename: Han-Jie
authors.initials: HJ
authors.lastname: Ying
mesh_terms: D000818:Animals; D015519:Bone Density / Q000187:drug effects; D001842:Bone and Bones / Q000187:drug effects / Q000473:pathology; D005260:Female; D005635:Fructosediphosphates / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology / Q000627:therapeutic use*; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D015663:Osteoporosis, Postmenopausal / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D053244:Osteoprotegerin / Q000097:blood; D018384:Oxidative Stress / Q000187:drug effects; D053245:RANK Ligand / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000097:blood; D015398:Signal Transduction
chemical_list: D005635:Fructosediphosphates; D007155:Immunologic Factors; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D007334:Insulin-Like Growth Factor I; C029063:fructose-1,6-diphosphate