Potential Role of Local Estrogen in Enhancement of Fracture Healing: Preclinical Study in Rabbits

Background: Effects of estrogen on bone metabolism and its protective role on prevention of osteoporosis are well   documented. However, the efficacy of estrogen treatment on bone healing is not well investigated. The drug can be delivered both systemically or locally to the bone with differences in concentrations and side effects. The aim of this study was to investigate the effect of local and systemic administration of estrogen on the fracture healing process.       Methods: Standardized tibial fractures with 4 millimeter gaps were created in twenty four adult male Dutch rabbits. Fractures were fixed using intramedullary wires and long leg casts. Rabbits were randomly divided into three groups. Group A was treated with twice a week administration of long acting systemic estrogen; group B was treated with a similar regimen given locally at the fracture gap; and group C received sham normal saline injections (control). Fracture healing was assessed at six weeks post fracture by gross examination, radiographic and histomorphometric analysis. Results: Group B had significantly higher gross stability, radiographic union and gap reduction than the two other groups. Histomorphometric analysis showed higher cartilaginous proportion of periosteal callus area in the control group. Conclusions: Our results showed that estrogen may enhance fracture healing of long bone in rabbits. Furthermore, local estrogen treatment might have better effect than systemic treatment.