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

Background Fracture 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 methods Osteoporosis 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. Results Estrogen and raloxifene improved the biomechanical properties of bone healing compared to OVX (Yield load: SHAM = 63.1 +/- 20.8N, E = 60.8 +/- 17.9 N, R = 44.7 +/- 17.5 N, OVX = 32.5 +/- 22.0 N). Estrogen vs OVX was significant based on a denser trabecular network. Raloxifenegreatly induced total callus formation (R = 5.3 +/- 0.9 mm(2), E = 4.7 +/- 0.5 mm(2), SHAM = 4.51 +/- 0.61 mm(2), OVX = 4.1 +/- 0.6 mm(2)), whereas estrogen mainly enhanced new endosteal bone formation. There was no correlation between the gene expression (osteocalcin, collagen1 alpha 1, IGF-1, tartrate-resistant phosphatase) in the callus and the morphology and quality of callus formation. Conclusion Raloxifene 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

Immunohistochemical analysis of estrogen receptors in the urethra of sexually intact, ovariectomized, and estrogen-substituted ovariectomized sheep

INTRODUCTION AND HYPOTHESIS: Urinary incontinence is prevalent in postmenopausal women and spayed dogs and is associated with decreased estrogen plasma concentrations. The objective of the study was to investigate the expression of estrogen receptors (ER) in the urethra of sexually intact, ovariectomized, and estrogen-substituted ovariectomized ewes. METHODS: Paraffin cross-sections from each urethral quarter were immunohistochemically analyzed. The reactivity of ER was semiquantitatively assessed employing an immunoreactive score (IRS). RESULTS: In contrast to ERβ, ERα was identified in all urethral compartments; the highest IRS was detected in the epithelium of the distal urethra. The immunoreactivity and distribution of ERα did not differ among groups. Highly significant differences in ERα concentrations were observed between consecutive urethral quarters in each group. CONCLUSIONS: Neither ovariectomy nor ovariectomy and estrogen substitution seem to have a significant effect on overall urethral ERα concentration. The results demonstrate that the precise location of the investigated urethral part is crucial to the reliable evaluation or possible comparison of ERα concentrations