The SERM raloxifene improves diaphyseal fracture healing in mice

Although several studies reported that raloxifene treatment improves postmenopausal osteoporotic bone structure and reduces fracture risk, only a few animal and no human studies have examined its effects on the fracture healing process. Thus the aim of the present study was to determine, whether systemic application of the selective estrogen receptor modulator raloxifene promotes fracture healing compared to untreated control-, estrogen-deficient-, as well as estrogen-treated mice using a standardized femoral osteotomy model (n = 60 mice). Ten days after surgery, contact radiography and undecalcified histomorphometric analysis revealed that raloxifene administration significantly improved the early stage of fracture healing compared to all other groups. At day 20, raloxifene and estrogen treatment led to a significant increase in callus mineralization and trabecular thickness compared to control mice. μCT analyses revealed no evidence of complete bony bridging of the fracture site in any control-, nor estrogen-deficient mouse after 20 days, while all femoral fractures in the raloxifene and estrogen group already healed adequately at this time. These data indicate that raloxifene treatment significantly improves all phases of fracture healing at least in mice. Therefore, raloxifene could be a possible pharmaceutical to enhance fracture healing in women, without the known side effects of estrogen.