Concentration of bisphosphonate (incadronate) in callus area and its effects on fracture healing in rats

The aim of the present study was to investigate effects of incadronate on e arly stages of fracture healing and to detect its concentration in callus a rea (Ca.Ar), Rats were injected three times per week with either two doses of incadronate (10 mu g/kg and 100 mu g/kg) or vehicle for 2 weeks. Femora were then fractured and fixed and animals were divided into pretreatment (P -10 and P-100) and continuous treatment (C-10 and C-100) groups, Incadronat e treatment was stopped in P-10 and P-100 groups but continued in C-10 and C-100 groups. Animals were killed at 2 weeks and 4 weeks after fracture. Re sults showed significantly large callus, compared with the control, only in C-100 group at 4 weeks but not at 2 weeks. Both linear labeled surface (LS ) and eroded surface (ES) decreased significantly in C-10 and C-100 groups at 2 weeks and 4 weeks. Osteoclast number (N.Oc) decreased significantly in C-10 and C-100 groups at 2 weeks but increased slightly at 4 weeks. Howeve r, there was no significant difference in the above parameters in P-10 and P-100 groups at 4 weeks. Apoptotic osteoclasts were observed only in the C- 100 group at 4 weeks. A time-course decrease in incadronate concentration w as detected in P-10 and P-100 groups whereas an increase was observed in C- 10 and C-100 groups. These findings suggest that larger callus under incadr onate treatment may result from the inhibition of bone resorption, histolog ical characteristics of callus may be correlated with incadronate concentra tion, and metabolism of incadronate in bone may be related to the rate of b one turnover.