The Study Of Effects Of RhPTH1-34 On Osteoporotic Fracture Healing

ObjectiveTo establish the model of the right femur osteoporotic fracture in ovariectomized rats. The bone mineral density and biomechanical measure, histological observation, X-ray examination were performed to observe the effects of recombinant human parathyroid (1-34) (rhPTH1-34) on osteoporotic fracture healing in the rat, and to expect to provide an effective therapy for osteoporotic fracture. MethodEighty female six-month old SD rats were randomly divided into four groups: rhPTHl-34 group, estrogen group, osteoporosis group, sham-operated group. The three former were anesthetized by 10% Chloral Hydrate (0.3g/kg) and performed bilateral ovariectomy in abdominal route. The ovaries of sham-operated group were not resected. The months later, all rats under anesthesia underwent fracture at middle of right femur and performed internal fixation from medullary cavity using 2 mm diameter Kirscher needle. Two operations were performed on condition of sterility.After established the model of osteoporotic fracture by operation, rhPTHl-34 group was subcutaneously injected rhPTHl-34 20μg/kg three times a week, estrogen group was subcutaneously injected estrogen 0.1mg/kg three times a week, osteoporosis group and sham-operated group was subcutaneously injected physiologic saline three times a week for nine weeks.1. Measure of BMD: using HOLOGIC double-function X-ray bone intensity determinator, the BMD of lumber 3 and right femur shaft were examined at pre-ovariectomy, 12 weeks post-ovariectomy, 9 weeks after drug treatment.2. X-ray films of right femur were respectively performed at 4,8 weeks after internal fixation in order to compare the development of callus in four groups.3. Histological analysis of callus: Two rats of every group were killed at 8 weeks after internal fixation. Histological analysis of callus were observed and compared in four guoups.4. Biomechanical measure: After treatment for 9 weeks, the right femur andlumbar 3 vertebral body were respectively performed Three-point Bending test andIndentation Test by MTS-858 tape biomaterial tester.Result1. The BMD increased significantly in the rhPTHl-34 group 9 weeks after treatment (P<0.05).2. Histological examination of callus: After 8 weeks, the cartilaginous callus were gradually substituted by bone callus. In rhPTHl-34 group, the bone trabeculars were thick and compact. The ossification were normal. However, in control group, there more cartilaginous bone trabeculars which slowly transformed into bone callus. The bone trabeculas of osteoporosis group were broad, tiny, structural disorder and loose.3. X-ray examination: X-ray films of 4, 8 weeks after operation of fracture showed the callus in rhPTHl-34 group were more plentiful and maturer than in control group at the same time.4. Results of the 3th lumbar vertebral body in Indentation Test: The maximum load and indentation strength were extensively higher in rhPTHl-34 group than in control group.5. Results of the right femur in Three-point Bending Test: The maximum load was extensively higher in rhPTHl-34 group than in control group.ConclusionsrhPTHl-34 can stimulate the growth of bone in ovariectomized rats, increase the BMD, and promote the fracture healing.