Enhancement of Experimental Fracture Healing with Parathyroid Hormone (1-34)

Objective: To determine the effect of parathyroid hormone in enhancing fracture healing in rats. Methods: 450 grams Male Sprague Dawley rats were used for this study. PTH (1-34) or aqueous vehicle was administered to the animals by daily subcutaneous injection. Three experimental groups containing N=45 each were used. Groups included: 1) Control fracture, aqueous injection; 2) 5µg/Kg PTH (1-34); 3) 30µg/Kg PTH (1-34). Each group contained 3 subgroups: a) Euthanasia day 21; b) Euthanasia day 35; c) Dosing ending day 35, and euthanasia day 84. The production of closed, transverse fracture of the femur was as developed by (Bonnarens, F., and Einhorn, T.A., 1984). At the time of euthanasia, fractured legs were harvested and cleaned to remove muscle and soft connective tissue. The bones were tested for ultimate strength by torsional testing using a custom-built torsion device. The maximum torque was determined at the point of failure. The effects of each treatment on bone callus strength was evaluated by analysis of variance (ANOVA) at p<0.05. Results: ANOVA indicated significant differences in ultimate strength (N/mm) among the means of the tested groups (P=0.0001). There was a significant difference between the means at Day 35 between the control group (350.63±15.99) and the 30µg/Kg PTH (1-34) group (547.02±48.53) (P=0.019). There were also significant differences among the means at Day 84 between the control group (606.64±22.63) and the 30µg/Kg PTH (1-34) group (810.75±23.96) (P=0.017). Conclusion: Based on this study, daily subcutaneous administration of 30µg/Kg PTH (1-34) has significant effects on increasing bone callus strength over a short period of time (Day 35). Even after cessation of treatment the increased strength of the healing bone was maintained for up to 84 days in the 30µg/Kg PTH (1-34) group.