Effect of bisphosphonate (incadronate) on fracture healing of long bones in rats

This study was designed to test whether bisphosphonates disturb the process of fracture healing. Female Sprague-Dawley rats were injected with either two doses of bisphosphonate (incadronate) (10 mu g/kg and 100 mu g/kg) or v ehicle three times a week for 2 weeks. Right femora were then fractured and fixed with intramedullary wires. Incadronate treatment was stopped in pret reatment groups (P-10 and P-100 groups), while the treatment was continued in continuous treatment groups (C-10 and C-100 groups). Animals were sacrif iced at 6 and 16 weeks after surgery. Soft X-ray of all fractured femora wa s taken. After mechanical testing, fractured femora were stained in Villanu eva bone stain and embedded in methyl methacrylate, Grass-sections near fra cture line were analyzed by microradiography and histomorphometry. Radiogra phic study showed that bony callus was present in all the fractures and inc adronate treatment led to a larger callus, especially in C-100 group at bot h 6 and 16 weeks. Histologic study showed that the process of fracture heal ing in pretreatment groups was delayed at 6 weeks, but reached control leve l thereafter and showed same characteristics as in control at 16 weeks. Wov en bony callus could still be seen in continuous treatment groups at 16 wee ks. Mechanical study indicated that the ultimate load of C-100 group was sl ightly higher than the other treatment groups and control. The results sugg est that pretreatment with incadronate did not affect fracture healing at 1 6 weeks after fracture. However, continuous incadronate treatment could lea d to larger callus, but it delayed remodeling process during fracture heali ng, especially with high-dose treatment.