Prevention of Atrophic Nonunion by the Systemic Administration of Parathyroid Hormone (PTH 1–34) in an Experimental Animal Model

Objectives: 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.