Fracture callus under anti-resorptive agent treatment evaluated by pQCT

Abstract

Effects of estrogen, raloxifene, and alendronate on fracture healing were evaluated by a peripheral quantitative computed tomography (pQCT) in an osteoporotic fracture rat model. Three-month-old ovariectomized (OVX; except sham-operated controls) Sprague-Dawley rats were pretreated with vehicle (sham and OVX controls), 0.1 mg/kg day-1 estrogen (17α-ethynyl estradiol), 1 mg/kg day-1 raloxifene, or 0.01 mg/kg day-1 alendronate for 4 weeks before fracture induction. At this point, the pre-fracture groups were killed while transverse osteotomy was performed at the midshaft of both femora in the remaining animals and kept for 6 weeks with drug treatment, and then killed 16 weeks after fracture induction. Excised femora and fracture calluses were analyzed by high-resolution pQCT. At 6 weeks after fracture, the alendronate and OVX groups showed larger calluses at a larger cross-sectional moment of inertia (CSMI) than that of other groups. At 6 weeks after fracture, the calluses in OVX rats were significantly smaller than those observed at 6 weeks, whereas the calluses treated with alendronate did not change in size; therefore, calluses in OVX rats without drug treatment remodeled towards the original geometry in the femoral midshaft faster than drug-treated rats, and on the contrary, the fracture calluses in rats treated with alendronate were the slowest. In conclusion, OVX-induced higher bone turnover and resulted in the fastest remodeling of fracture callus, which was, however, delayed under alendronate treatment. Estrogen and raloxifene treatment showed intermediate callus remodeling between OVX and sham. © 2007 Springer-Verlag Berlin Heidelberg.