Dose-dependent enhancement of spinal fusion in rats with teriparatide (PTH[1-34]).

Abstract

Controlled animal experiments. To test the dose and efficacy of teriparatide in a rat spinal fusion model. 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. 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. 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. 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.