Triweekly administration of parathyroid hormone (1-34) accelerates bone healing in a rat refractory fracture model

Abstract

Background: Some reports have shown that intermittent parathyroid hormone (PTH) (1-34) treatment for patients with delayed union or nonunion have led to successful healing. In this study, we investigated whether systemic intermittent administration of PTH (1-34) has a beneficial effect on bone healing in a rat refractory fracture model. Methods: We created a refractory femoral fracture model in 32 rats with periosteal cauterization that leads to atrophic nonunion at 8 weeks after surgery. Half the rats received subcutaneous intermittent human PTH (1-34) injections at a dosage of 100 μg/kg, thrice a week for 8 weeks. The other half received the vehicle only. At 8 weeks after fracture, radiographic, histological and mechanical assessments were performed. Results: Radiographic assessments showed that the union rate was significantly higher in the PTH group than in the control group (P < 0.05). The degree of fracture repair as scored using the Allen grading system in histological assessment was significantly greater in the PTH group than in the control group (P < 0.05). The ultimate stress and stiffness measurements were significantly greater in the PTH group than in the control group (p < 0.05). Conclusions: We demonstrated that triweekly administration of PTH (1-34) increased union rate and accelerated bone healing in a rat refractory fracture model, suggesting that systemic administration of PTH (1-34) could become a novel and useful therapy for accelerating fracture healing in patients at high risk of delayed union or nonunion.