title: Prevention of atrophic nonunion by the systemic administration of parathyroid hormone (PTH 1-34) in an experimental animal model.
abstract: OBJECTIVE
  Recombinant human parathyroid hormone (PTH 1-34) has been previously shown to enhance fracture healing in animal models. Here, we sought to determine whether the systemic administration of PTH 1-34 is effective in preventing atrophic fracture nonunion in a murine, surgical nonunion model.
  
  
  METHODS
  We used an established reproducible long-bone murine fracture nonunion model by generating a midshaft femur fracture, followed by fracture distraction using an intramedullary pin and custom metallic clip to maintain a fracture gap of 1.7 mm. Mice were randomized to receive either daily intraperitoneal injections of 30 μg/kg PTH 1-34 for 14 days or saline injections. At 6 weeks after the procedure, radiographic and histologic assessment of fracture healing was performed.
  
  
  RESULTS
  At 6 weeks after surgery, the group treated with PTH showed higher rates of bony union (50% vs 8%; P < 0.05) as assessed by radiographic analysis. Mean gap size was also significantly lower in the PTH group (1.42 vs 0.36 mm in the control group; P < 0.05). Histologic analysis of atrophic nonunions in the control group revealed a persistent fracture gap with intervening fibrous tissue. In contrast, healed subjects in the PTH-treated group had cortical bridging with mature bone and relatively little callus, which is consistent with primary intramembranous ossification.
  
  
  CONCLUSIONS
  Daily systemic administration of recombinant PTH 1-34 increased the rate of union in a mouse atrophic nonunion model. This may have important implications for the potential clinical role of PTH 1-34 in the treatment of atrophic fracture nonunions.
authors.affiliation: Department of Orthopaedic Surgery, New York University School of Medicine, New York, NY, USA.
authors.forename: Edward A
authors.initials: EA
authors.lastname: Lin
authors.forename: Chuan-Ju
authors.initials: CJ
authors.lastname: Liu
authors.forename: Alexa
authors.initials: A
authors.lastname: Monroy
authors.forename: Sonya
authors.initials: S
authors.lastname: Khurana
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Egol
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005264:Femoral Fractures / Q000188:drug therapy* / Q000473:pathology*; D017102:Fracture Healing / Q000187:drug effects*; D017759:Fractures, Malunited / Q000188:drug therapy* / Q000473:pathology*; D006801:Humans; D007274:Injections, Intraperitoneal; D051379:Mice; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000008:administration & dosage*; D019379:Teriparatide / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016896:Treatment Outcome
chemical_list: D010446:Peptide Fragments; D019379:Teriparatide; C035748:parathyroid hormone (1-34)amide