title: Dose-dependent enhancement of spinal fusion in rats with teriparatide (PTH[1-34]).
abstract: METHODS
  Controlled animal experiments.
  
  
  OBJECTIVE
  To test the dose and efficacy of teriparatide in a rat spinal fusion model.
  
  
  BACKGROUND
  Teriparatide was shown to enhance spinal fusion in rats and rabbits previously, but the dose-dependent effect of teriparatide in spinal fusion in rats was not well characterized.
  
  
  METHODS
  A 0.5 × 0.5 cm trabecular bone graft was taken and implanted onto the L5 and L6 transverse processes of the same rat. Rats were randomly assigned into 3 groups: saline vehicle control (Vehicle), teriparatide 4 μg/kg per day (PTH4), and teriparatide 23 μg/kg per day (PTH23) subcutaneous injections for 4 weeks (5 d per wk). The L5-L6 spinal segments were harvested at week 4, and assessments included radiography, micro-computed tomography, manual palpation, and histomorphometry. L3 vertebra, femurs, and serum bone markers were examined.
  
  
  RESULTS
  The average radiographical score of L5-L6 fusion in Vehicle, PTH4, and PTH23 groups was 1.53, 2.87, and 4.11, respectively, with the PTH23 being significantly higher (P = 0.001 vs. Vehicle). The average micro-computed tomographic score of L5-L6 fusion in Vehicle, PTH4, and PTH23 groups was 1.53, 2.40, and 3.74, respectively (P = 0.001, PTH23 vs. Vehicle and PTH4). Manual palpation showed that fusion rate was 20%, 50%, and 67.7% in Vehicle, PTH4, and PTH23 groups, respectively. The bone mineralization apposition rate at the fusion site was significantly increased in a dose-dependent manner among the groups. Teriparatide significantly increased vertebral and femoral bone mineral density, bone mineral content, and trabecular area in a dose-dependent manner relative to Vehicle. No difference was found between the circulating Procollagen type I N-terminal propeptide and intact osteocalcin levels in the serum at 4 weeks after treatments.
  
  
  CONCLUSIONS
  Teriparatide at 23 μg/kg per day for 4 weeks showed anabolic skeletal effects and significantly enhanced spinal fusion rate in rats, whereas teriparatide at 4 μg/kg per day had also anabolic effects but did not significantly enhance spinal fusion rate. Higher doses of teriparatide may be needed to promote spinal fusion in short-term application.
authors.affiliation: Department of Orthopaedics, the General Hospital of Chinese People's Liberation Army, Beijing, PR China.
authors.forename: Ni
authors.initials: N
authors.lastname: Ming
authors.forename: Jimmy Tin-Yan
authors.initials: JT
authors.lastname: Cheng
authors.forename: Yun-Feng
authors.initials: YF
authors.lastname: Rui
authors.forename: Kai-Ming
authors.initials: KM
authors.lastname: Chan
authors.forename: Stuart
authors.initials: S
authors.lastname: Kuhstoss
authors.forename: Yanfei L
authors.initials: YL
authors.lastname: Ma
authors.forename: Masahiko
authors.initials: M
authors.lastname: Sato
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Gang
authors.initials: G
authors.lastname: Li
mesh_terms: D000818:Animals; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000494:pharmacology; D016025:Bone Transplantation / Q000379:methods; D004305:Dose-Response Relationship, Drug; D007279:Injections, Subcutaneous; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000601:surgery*; D008297:Male; D015675:Osteocalcin / Q000097:blood; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013123:Spinal Fusion / Q000379:methods*; D019379:Teriparatide / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D055114:X-Ray Microtomography
chemical_list: D050071:Bone Density Conservation Agents; D015675:Osteocalcin; D019379:Teriparatide