Estrogen and raloxifene improve metaphyseal fracture healing in the early phase of osteoporosis. A new fracture-healing model at the tibia in rat

Abstract

BackgroundFracture healing in osteoporosis is delayed. Quality and speed of fracture healing in osteoporotic fractures are crucial with regard to the outcome of patients. The question arises whether established antiosteoporotic drugs can further improve fracture healing.Materials and methodsOsteoporosis manifests predominantly in the metaphyseal bone. Nevertheless, an established metaphyseal fracture model is lacking. A standardized metaphyseal fracture-healing model with stable plate fixation was developed for rat tibiae. The healing process was analyzed by biomechanical, gene expression, and histomorphometric methods in ovariectomized (OVX) and sham-operated rats (SHAM), compared to standardized estrogen (E)- and raloxifene (R)-supplemented diets.ResultsEstrogen and raloxifene improved the biomechanical properties of bone healing compared to OVX (Yield load: , , , ). Estrogen vs OVX was significant based on a denser trabecular network. Raloxifene greatly induced total callus formation (, , ,), whereas estrogen mainly enhanced new endosteal bone formation. There was no correlation between the gene expression (osteocalcin, collagen1α1, IGF-1, tartrate-resistant phosphatase) in the callus and the morphology and quality of callus formation.ConclusionRaloxifene and estrogen improve fracture healing in osteoporotic bone significantly with regard to callus formation, resistance, and elasticity. The biomechanically stable metaphyseal osteotomy model with T-plate fixation presented here has proven to be appropriate to investigate fracture healing in osteoporosis.

Effect of daidzein, 4-methylbenzylidene camphor or estrogen on gastrocnemius muscle of osteoporotic rats undergoing tibia healing period

“…We tried to mimic clinical situation the best, when a typical patient (female) with osteoporotic fracture, before being traumatized, suffers for years from post-menopausal changes in muscle and bone and receives no fracture preventive treatment (Haeussler et al 2007). Therefore, a metaphyseal osteotomy of tibia was performed after severe osteoporosis had been established (Wronski et al 1985, Stuermer et al 2008 and the animals received the substances orally to facilitate bone healing. Finally, the comparisons were made with osteoporotic rats either untreated serving as an osteoporotic control or properly treated with estrogen to meet the goal of the present experiment.…”

“…Soy proteins were substituted by potato proteins to eliminate an estrogenic effect of isoflavones presented in soy. After 8 weeks, when osteoporosis was established (Kalu 1991), a metaphyseal osteotomy and T-plate fixation of the tibiae was done under ketamine/xylazine anesthesia as described previously (Stuermer et al 2008). Along with anesthesia, rats received s.c. 5 mg Decentan (Merck) and 4 mg Rimadyl (Pfizer, Karlsruhe, Germany) per kg of BW respectively.…”

Sex and Gender Considerations in Male Patients With Osteoporosis

“…Furthermore, animal studies suggest the presence of estrogen will enhance fracture healing [31,51,55]. Both men and women experience lower estrogen levels as aging occurs [21], but the effects on bone quality may be more profound in men because of the lower likelihood of early diagnosis and primary prevention.…”

BMP-7 in Combination with Estrogen Enhances Bone Formation in a Fracture Callus Explant Culture

“…Whilst estrogen treatment alone could induce dose dependent stimulation of both AP and NO production, tissue mineralization occurred only on the periphery of the callus explant without BMP-7 and cell proliferation was not as elevated. A previous report has shown that estrogen administration improved fracture healing in an ovarectomised rat model, where new tissue resembled healthy (non osteoporotic) bone and investigations showed that the estrogen suppressed genes associated with osteoblast and osteoclast activity (Stuermer et al 2010).…”