| Objective To investigate the effect of zoledronic acid combined with insulin on the early stage fracture healing in type 2 diabetic rats with estrogen deficiency. Methods Thirty-two female SD rats were randomly divided into the CF, DOF, DOFI, and DOFIZ group. Except for CF group, rats in the other 3 groups were induced to develop type 2 diabetes and estrogen deficiency animal model. The rats in DOFI and DOFIZ groups received insulin alone or combined with zoledronic acid, respectively. All rats were killed at 3 weeks post-fracture. X-ray, micro-CT, safranine O-fast green staining, TRAP-positive cell density, OCN, and Caspase-3 expression in the callus were analyzed to evaluate the effect of insulin alone or combined with zoledronic acid on the early stage of fracture healing in rats. Results The radiographic healing score, Tb.N, BV/TV, mineralized area per periosteal callus area, and OCN expression in the DOF group were significantly lower than those in CF group (P<0.05), and Th.Sp, TRAP-positive cell density, and the expression of Caspase-3 in the callus were significantly higher than those in CF group (P<0.05). After insulin intervention, all the above parameters in DOFI group were significantly improved except Th.Sp (P<0.05). After insulin combined with zoledronic acid intervention, the callus area, Tb.N, BV/TV, and mineralized area per periosteal callus area in DOFIZ group were significantly higher than those in DOFI group (P<0.05), and the Th.Sp and TRAP-positive cell density were significantly lower than those in the DOFI group (P<0.05). Conclusion Insulin combined with early single dose of zoledronic acid promotes early fracture healing in type 2 diabetic rats with estrogen deficiency. |