The fracture of bone plays a key role in osteoporosis. BMD measurement, however, is only an indirect parameter of this phenomenon. We therefore developed a highly sensitive three-point bending test for the metaphyseal tibias in rats to evaluate stiffness and strength. This was validated in a right-left comparison and a bioassay with soy-free food, estradiol, raloxifene, and testosterone in orchidectomized rats.Introduction: Osteoporosis becomes manifest predominantly in the metaphyseal rat tibia. The antiosteoporotic character of substances should, therefore, be tested (mechanically) in this bone area. Materials and Methods:We evaluated a new three-point bending test for the metaphyseal tibia in rats in a right-left trial. In an animal experiment, we studied the change of bone quality under estradiol (E)-, raloxifene (R)-, and testosterone (T)-supplemented food and compared it with trabecular BMD (qCT). Results: In the right-left comparison, the mean difference between the metaphyseal loads of both tibias in 37 rats was 8.43% for the maximum load (F max ) and 6.46% for the failure load (fL). These results show the high reproducibility of the test, because they are close to the usual intraindividual difference of the two extremities. In a second experiment, four groups of 11 3-month-old male orchidectomized rats were fed with soy-free food only (C) or with the additives E, T, or R for 12 weeks. E and R were similar for F max and fL. There were significant differences in the stiffness (E ‫ס‬ 406.92 N/mm versus R ‫ס‬ 332.08 N/mm), the yield load (yL; E ‫ס‬ 99.17 N versus R ‫ס‬ 83.33 N), and the ratio between yL and F max (E ‫ס‬ 86.33% versus R ‫ס‬ 76.37%). T was similar to the controls concerning F max , fL, and stiffness. There were significant differences in yL (T ‫ס‬ 49.00N versus C ‫ס‬ 39.5N) and the ratio between yL and F max (T ‫ס‬ 64.28% versus C ‫ס‬ 51.28%). Conclusions: Estradiol is superior to raloxifene concerning stiffness and yield load, and both are superior to testosterone. We conclude that the described three-point bending test for the metaphyseal tibia is a highly sensitive method to study hormones and substances with regard to their osteoprotective character. The precision and the low SD of the presented results are superior to the data from qCT and the calculated index of stiffness (SSI).

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.

The treatment and prevention of osteoporosis involve great challenges. Nonpharmacological and supportive therapy procedures, sport, and physical exercises seem to prevent bone loss and improve bone mass. In the present study, we examined the effect of whole-body vertical vibration (WBVV) on femoral intertrochanteric bone quality in the rat osteoporosis model. Sixty female Sprague–Dawley rats, 3-month old, were ovariectomized (OVX) or sham-operated. After 3 months, each group was divided into two subgroups. In one of the subgroups, rats were treated with WBVV at 90 Hz (3.9 g) for 35 days; the second subgroup remained untreated. After killing the animals, biomechanical strength and trabecular bone architecture of the proximal region of femurs were analyzed. New cortical bone appositions and mineral density of femurs were additionally measured. Treatment with WBVV resulted in improved biomechanical properties. Maximal load and stiffness of the intertrochanteric region of femurs after WBVV were significantly enhanced. Maximal load and stiffness in treated OVX animals reached the levels observed in untreated sham rats. WBVV significantly improved all measured histomorphometric parameters in the trabecular area. Treated rats showed significantly improved mineral content in ashed femurs compared to untreated animals. A comparison of widths of fluorescence bands in cortical bone of subtrochanteric cross sections did not show any significant differences between the groups after WBVV. Low-magnitude, high-frequency mechanical stimulation improves bone strength in the proximal femur and may be a possible nonpharmacologic treatment option for postmenopausal osteoporosis.

Introduction Currently, osteoporosis research is rarely undertaken in males but an increase in male life expectancy in the company of hypogonadism suggests the necessity for potential therapeutic options. Materials and methods In this study, the changes in bone structure under standardized testosterone-(T), raloxifene-(R) and estrogen (E)-supplemented diets were analyzed in osteoporotic castrated male rats. Results Unexpected biomechanical results could be only explained by the histomorphometry, but not by BMD measurements obtained from the qCT. All tested substances showed a signiWcant improvement in the trabecular network (trabecular bone area for C: 2.55 mm 2 , T: 4.25 mm 2 , R: 4.22 mm 2 and E: 4.28 mm 2 ), and suggests that the bone structure was preserved. For the metaphyseal cortical bone, a signiWcant loss was detected in T (CBP: 18.7%) compared to R (CBP: 30.0%), E (CBP: 26.8%) and even to the osteoporotic control (CBP: 28.6%). This explains the observed early mechanical Wnal failure after T supplementation. However, due to the preserved trabecular bone in T, the occurrence of the Wrst microfractures (yL: 49 § 21.4 N) was signiWcantly later than in the osteoporotic control (yL: 39.5 § 15.5 N). Raloxifene performed well in hindering the bone loss associated with osteoporosis. However, its eVect (yL: 83.3 § 16.5 N) did not approach the protective eVect of E (yL: 99.2 § 21.1 N). Conclusion Testosterone only preserved the deterioration of the trabecular bone but not of the cortical bone. Raloxifene prevented the bone loss associated with osteoporosis at all bony structures. This eVect did not approach the protective eVect of estrogen on trabecular bone, but it is more suitable for male individuals because it has no feminizing eVects on the subject.

Osteoporosis is accompanied by predominantly metaphyseal fractures with a delayed and qualitatively reduced healing process. This study addressed the question of whether fracture healing in the context of osteoporosis prophylaxis is improved with estrogen (E) or alendronate (ALN). Thirty-six ovariectomized and 12 sham-operated 12-week-old rats received soy-free (osteoporotic C, sham), E-, or ALN-supplemented diets. After 10 weeks, a metaphyseal tibia osteotomy and standardized T-plate fixation were performed. After a 5-week healing process, the fracture callus was evaluated qualitatively by biomechanical bending test and quantitatively in microradiographic sections. The time course of callus formation was examined using fluorochrome-labeled histological sections. 3.44 ± 0.42, E: 3.69 ± 0.58, ALN: 3.06 ± 0.56). Osteoporotic metaphyseal fracture healing was qualitatively and quantitatively improved by E prophylaxis. The process of fracture healing occurred nearly physiologically (shamlike). Notably, ALN hardly improved metaphyseal callus properties when assessed as osteoporosis prophylaxis, but to a lesser extent than E.Keywords Alendronate Á Bisphosphonate Á Estrogen Á Metaphyseal fracture healing Á Osteoporosis Life expectancy has recently increased, resulting in changing population demographics. As the population ages, osteoporosis is becoming one of the most prominent worldwide health problems. Menopause involves hormonal changes that increase bone turnover and distort the balance between bone formation and bone resorption [1]. Hormone deficiency impairs cancellous metaphyseal bone, which reduces bone mineral density (BMD) in humans and animals [2][3][4]. Within the metaphysis, the trabecular structure degrades. Bone loss occurs in the diaphyseal bone as well, but to a lesser extent [5]. The mechanical strength of cortical bone is preserved as a result of periosteal apposition [4]. Therefore, long bones are more often predisposed to osteoporotic fractures at the