Eel calcitonin (elcatonin) suppressed callus remodeling but did not interfere with fracture healing in the femoral fracture model of cynomolgus monkeys

Abstract

We investigated the effect of eel calcitonin (elcatonin) on the process of fracture repair in the osteotomized femur of cynomolgus monkeys, since they possess a Haversian remodeling system similar to that of humans. Alendronate was used for comparison. Twenty female cynomolgus monkeys (Macaca fascicularis), aged 18-22 years, were allocated into five groups: control (CNT, n = 4), low-dose elcatonin group (0.5 U/kg; ELL, n = 4), high-dose elcatonin group (5 U/kg; ELH, n = 4), low-dose alendronate group (10 microg/kg; ALL, n = 4) and high-dose alendronate group (100 microg/kg; ALH, n = 4). All animals were given subcutaneous injections twice a week for 3 weeks. Then fracture was produced surgically by transversely cutting the midshaft of the right femur and fixing with stainless steel plate. After fracture, treatments were continued until sacrifice at 26 weeks after surgery. The femora were assessed by micro CT, contact microradiograph, three-point bending mechanical test and histomorphometry. Micro CT showed that callus sizes in elcatonin-treated groups were similar to CNT, whereas alendronate-treated groups had larger calluses than those in the CNT and elcatonin-treated groups. Fracture lines almost disappeared in the CNT and elcatonin-treated groups but remained clear in the alendronate-treated groups. Total area did not differ significantly between the elcatonin-treated groups and the CNT but was significantly greater in the ALH compared to the CNT and elcatonin-treated groups, due to increased callus area in the ALH group. Callus remodeling was less suppressed in the elcatonin-treated groups than in the alendronate-treated groups when compared with callus remodeling in the CNT. Although no significant differences in structural mechanical properties such as ultimate load, stiffness and work to failure were found among all groups, ultimate stress was significantly reduced in the ALH group compared with CNT and ELL groups. In conclusion, mild suppression of callus remodeling by elcatonin did not impair overall fracture healing process. In contrast, alendronate delayed structural fracture healing process by strongly suppressing callus remodeling.