title: The effects of combined human parathyroid hormone (1-34) and zoledronic acid treatment on fracture healing in osteoporotic rats.
abstract: Ovariectomized (OVX) rats with tibial fracture received vehicle, ZA, PTH, or ZA plus PTH treatment for 4 and 8 weeks. Bone metabolism, callus formation, and the mass of undisturbed bone tissue were evaluated by serum analysis, histology, immunohistochemistry, radiography, micro-computerized tomography, and biomechanical test.
  
  
  BACKGROUND
  Previous studies have demonstrated the effect of ZA or PTH on osteoporotic fracture healing. However, reports about effects of ZA plus PTH on callus formation of osteoporotic fracture were limited. This study was designed to investigate the impact of combined treatment with ZA and PTH on fracture healing in OVX rats.
  
  
  METHODS
  Twelve weeks after bilateral ovariectomy, all rats underwent unilateral transverse osteotomy on tibiae. Animals then randomly received vehicle, ZA (1.5 μg/kg weekly), PTH (60 μg/kg, three times a week), or ZA plus PTH until death at 4 and 8 weeks. The blood and bilateral tibiae of rats were harvested for evaluation.
  
  
  RESULTS
  All treatments increased callus formation and strength other than the control; ZA + PTH showed the strongest effects on percent bone volume (BV/TV), trabecular thickness, total fluorescence-marked callus area, and biomechanical strength. Additionally, inhibited RANKL and enhanced osteoprotegerin expression were observed in the ZA + PTH group. But no difference in bone mineral density and BV/TV of the contralateral tibiae was observed between treated groups.
  
  
  CONCLUSIONS
  Findings in this study suggested an additive effect of ZA and PTH on fracture healing in OVX rats, and this additive effect was specific to callus formation, not to undisturbed bone tissue.
authors: The State Key Laboratory of Oral Diseases and Center of Orthognathic Surgery, West China College of Stomatology, Sichuan University, Chengdu 610041, China.
authors: Y F
authors: YF
authors: Li
authors: C C
authors: CC
authors: Zhou
authors: J H
authors: JH
authors: Li
authors: E
authors: E
authors: Luo
authors: S S
authors: SS
authors: Zhu
authors: G
authors: G
authors: Feng
authors: J
authors: J
authors: Hu
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002146:Bony Callus / Q000000981:diagnostic imaging / Q000187:drug effects; D004164:Diphosphonates / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004359:Drug Therapy, Combination; D005260:Female; D017102:Fracture Healing / Q000187:drug effects*; D007093:Imidazoles / Q000494:pharmacology / Q000627:therapeutic use*; D058866:Osteoporotic Fractures / Q000188:drug therapy* / Q000503:physiopathology; D053244:Osteoprotegerin / Q000097:blood; D010281:Parathyroid Hormone / Q000494:pharmacology / Q000627:therapeutic use*; D053245:RANK Ligand / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D013978:Tibial Fractures / Q000188:drug therapy / Q000503:physiopathology; D055114:X-Ray Microtomography / Q000379:methods; D000077211:Zoledronic Acid
chemical_list: D015415:Biomarkers; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D053244:Osteoprotegerin; D010281:Parathyroid Hormone; D053245:RANK Ligand; C506032:Tnfrsf11b protein, rat; D000077211:Zoledronic Acid