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OVX Animals (ovx + animals)
Selected AbstractsLong-Term Dosing of Arzoxifene Lowers Cholesterol, Reduces Bone Turnover, and Preserves Bone Quality in Ovariectomized Rats,,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 12 2002Yanfei L. Ma M.D. Abstract Long-term effects of a new selective estrogen receptor modulator (SERM) arzoxifene were examined in ovariectomized (OVX) rats. Arzoxifene was administered postoperatively (po) at 0.1 mg/kg per day or 0.5 mg/kg per day to 4-month-old rats, starting 1 week after OVX for 12 months. At study termination, body weights for arzoxifene groups were 16,17% lower than OVX control, which was caused by mainly reduced gain of fat mass. Longitudinal analysis of the proximal tibial metaphysis (PTM) by computed tomography (CT) at 0, 2, 4, 6, 9, and 12 months showed that OVX induced a 22% reduction in bone mineral density (BMD) at 2 months, which narrowed to a 12% difference between sham-operated (sham) and OVX rats by 12 months. Both doses of arzoxifene prevented the OVX-induced decline in BMD. Histomorphometry of the PTM showed that arzoxifene prevented bone loss by reducing osteoclast number in OVX rats. Arzoxifene maintained bone formation indices at sham levels and preserved trabecular number above OVX controls. Micro-CT analysis of lumbar vertebrae showed similar preservation of BMD compared with OVX, which were not different from sham. Compression testing of the vertebra and three-point bending testing of femoral shaft showed that strength and toughness were higher for arzoxifene-treated animals compared with OVX animals. Arzoxifene reduced serum cholesterol by 44,59% compared with OVX. Uteri wet weight from arzoxifene animals was 38,40% of sham compared with OVX rats, which were 29% of sham. Histology of the uterine endometrium showed that cell heights from both doses of arzoxifene were not significantly different from OVX controls. In summary, treatment of OVX rats with arzoxifene for nearly one-half of a lifetime maintained beneficial effects on cholesterol and the skeleton. These data suggest that arzoxifene may be a useful therapeutic agent for osteoporosis in postmenopausal women. [source] Intermittently Administered Human Parathyroid Hormone(1,34) Treatment Increases Intracortical Bone Turnover and Porosity Without Reducing Bone Strength in the Humerus of Ovariectomized Cynomolgus MonkeysJOURNAL OF BONE AND MINERAL RESEARCH, Issue 1 2001David B. Burr Abstract Cortical porosity in patients with hyperparathyroidism has raised the concern that intermittent parathyroid hormone (PTH) given to treat osteoporotic patients may weaken cortical bone by increasing its porosity. We hypothesized that treatment of ovariectomized (OVX) cynomolgus monkeys for up to 18 months with recombinant human PTH(1,34) [hPTH(1,34)] LY333334 would significantly increase porosity in the midshaft of the humerus but would not have a significant effect on the strength or stiffness of the humerus. We also hypothesized that withdrawal of PTH for 6 months after a 12-month treatment period would return porosity to control OVX values. OVX female cynomolgus monkeys were given once daily subcutaneous (sc) injections of recombinant hPTH(1,34) LY333334 at 1.0 ,g/kg (PTH1), 5.0 ,g/kg (PTH5), or 0.1 ml/kg per day of phosphate-buffered saline (OVX). Sham OVX animals (sham) were also given vehicle. After 12 months, PTH treatment was withdrawn from half of the monkeys in each treatment group (PTH1-W and PTH5-W), and they were treated for the remaining 6 months with vehicle. Double calcein labels were given before death at 18 months. After death, static and dynamic histomorphometric measurements were made intracortically and on periosteal and endocortical surfaces of sections from the middiaphysis of the left humerus. Bone mechanical properties were measured in the right humeral middiaphysis. PTH dose dependently increased intracortical porosity. However, the increased porosity did not have a significant detrimental effect on the mechanical properties of the bone. Most porosity was concentrated near the endocortical surface where its mechanical effect is small. In PTH5 monkeys, cortical area (Ct.Ar) and cortical thickness (Ct.Th) increased because of a significantly increased endocortical mineralizing surface. After withdrawal of treatment, porosity in PTH1-W animals declined to sham values, but porosity in PTH5-W animals remained significantly elevated compared with OVX and sham. We conclude that intermittently administered PTH(1,34) increases intracortical porosity in a dose-dependent manner but does not reduce the strength or stiffness of cortical bone. [source] Osteointegration of titanium and hydroxyapatite rough surfaces in healthy and compromised cortical and trabecular bone: in vivo comparative study on young, aged, and estrogen-deficient sheepJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 9 2007Veronica Borsari Abstract The osteointegration rate of titanium (Ti; TI01) and duplex Ti plus HA (HT01) coating systems with high surface roughness was investigated in healthy, aged, and oestrogen-deficient sheep. After having evaluated the bone quality, TI01 and HT01 rods were implanted in the tibial diaphyses (two implants for each tibia) and epiphyses (1 implant for each tibia) of five young (YOUNG), five aged (AGED), and five aged and ovariectomized (OVX) sheep. The iliac crest trabecular bone volume (BV/TV) and number (Tb.N) in OVX sheep were respectively 33.5% and 28.5% lower than in YOUNG sheep (p,<,0.005) and lower than in the AGED group (BV/TV, ,17%; Tb.N, ,13.5%; not significant); in the OVX group the trabecular separation was 77.9% higher than in YOUNG (p,<,0.05) and 30.9% higher than in AGED animals. Lumbar vertebrae L5 bone mineral density was significantly lower in AGED (8.9%, p,<,0.05) and OVX sheep (19.3%, p,<,0.0005) when compared with YOUNG animals. Five samples of five sheep from each group were analyzed for each observation. At 3 months, in cortical bone both affinity index and pushout test results showed no significant differences between the two materials in each group of animals. In trabecular bone, the affinity index of HT01 was significantly higher than that of TI01 in each group of animals (YOUNG, 90.7%; AGED, 76.9%; OVX, 49.9%) with no significant differences between groups. In conclusion, the performance of TI01 and HT01 surfaces was high not only in YOUNG, but also in OVX animals and, therefore, they might be useful for aged and osteoporotic patients. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 25:1250,1260, 2007 [source] Ovariectomy stimulates and bisphosphonates inhibit intracortical remodeling in the mouse mandibleORTHODONTICS & CRANIOFACIAL RESEARCH, Issue 4 2010DJ Kubek To cite this article: Kubek DJ, Burr DB, Allen MR: Ovariectomy stimulates and bisphosphonates inhibit intracortical remodeling in the mouse mandible Orthod Craniofac Res 2010;13:214,222 Structured Abstract Authors,,, Kubek DJ, Burr DB, Allen MR Objective,,, The pathophysiology of osteonecrosis of the jaw (ONJ) is thought to be linked to suppression of intracortical remodeling. The aim of this study was to determine whether mice, which normally do not undergo appreciable amounts of intracortical remodeling, could be stimulated by ovariectomy to remodel within the cortex of the mandible and if bisphosphonates (BPs) would suppress this intracortical remodeling. Material and Methods,,, Skeletally mature female C3H mice were either ovariectomized (OVX) or SHAM operated and treated with two intravenous doses of zoledronic acid (ZOL, 0.06 mg/kg body weight) or vehicle (VEH). This ZOL dose corresponds to the dose given to patients with cancer on a mg/kg basis, adjusted for body weight. Calcein was administered prior to sacrifice to label active formation sites. Dynamic histomorphometry of the mandible and femur was performed. Results,,, Vehicle-treated OVX animals had significantly higher (eightfold) intracortical remodeling of the alveolar portion of the mandible compared to sham , this was significantly suppressed by ZOL treatment. At all skeletal sites, overall bone formation rate was lower with ZOL treatment compared to the corresponding VEH group. Conclusions,,, Under normal conditions, the level of intracortical remodeling in the mouse mandible is minimal but in C3H mice it can be stimulated to appreciable levels with ovariectomy. Based on this, if the suppression of intracortical remodeling is found to be part of the pathophysiology of ONJ, the ovariectomized C3H mouse could serve as a useful tool for studying this condition. [source] Osseointegration of titanium alloy and HA-coated implants in healthy and ovariectomized animals: a histomorphometric studyCLINICAL ORAL IMPLANTS RESEARCH, Issue 11 2009Guaracilei Maciel Vidigal Jr Abstract Objectives: The objective of the present study is to evaluate the response to dental implants in healthy and osteoporotic bone. Materials and methods: Ten ovariectomized (OVX) New Zealand rabbits submitted to a hypocalcic diet and 10 sham-aged rabbits were used. All animals were submitted to bone mineral density (BMD) measurements before ovariectomy, and also 4 months afterwards, using dual energy X-ray absorptiometry. The BMD measurements showed a significant loss of bone mass, between the first and second examinations, only in the experimental group (P<0.05). After the bone mass loss induction period, three different implants were installed in the proximal tibia metaphisis of each animal: a titanium alloy implant (Ti), a plasma-spray hydroxyapatite-coated implant (HA-PS), and another implant coated with hydroxyapatite with the biomimetic process (HA-B). Results: After 3 months, histomorphometry showed a bone-to-implant contact (BIC) for Ti implants of 73.09±13.74% in healthy and 66.09±30.01% in OVX animals. The BIC for the HA-PS was 64.83±15.65% and 90.17±8.14% for healthy and OVX animals, respectively, and 88.66±5.30% and 87.96±10.71% for the HA-B implants placed in the same conditions. The differences between the implants in healthy and OVX conditions were not statistically significant (P>0.05). The only significant difference within groups was observed in the healthy animals between HA-B and Ti implants (P<0.06). Conclusion: Within the parameters used in this animal model it was not possible to observe BIC differences between osteoporotic and healthy animals. [source] Uterine blood flow responses to ICI 182 780 in ovariectomized oestradiol-17,-treated, intact follicular and pregnant sheepTHE JOURNAL OF PHYSIOLOGY, Issue 1 2005Ronald R. Magness Oestrogen dramatically increases uterine blood flow (UBF) in ovariectomized (Ovx) ewes. Both the follicular phase and pregnancy are normal physiological states with elevated levels of circulating oestrogen. ICI 182 780 is a pure steroidal oestrogen receptor (ER) antagonist that blocks oestrogenic actions in oestrogen-responsive tissue. We hypothesized that an ER-mediated mechanism is responsible for in vivo rises in UBF in physiological states of high oestrogen. The purpose of the study was to examine the effect of an ER antagonist on exogenous and endogenous oestradiol-17, (E2,)-mediated elevations in UBF. Sheep were surgically instrumented with bilateral uterine artery blood flow transducers, and uterine and femoral artery catheters. Ovx animals (n= 8) were infused with vehicle (35% ethanol) or ICI 182 780 (0.1,3.0 ,g min,1) into one uterine artery for 10 min before and 50 min after E2, was given (1 ,g kg,1i.v. bolus) and UBF was recorded for an additional hour. Intact, cycling sheep were synchronized to the follicular phase using progesterone, prostaglandin F2,(PGF2,) and pregnant mare serum gonadotrophin (PMSG). When peri-ovulatory rises in UBF reached near peak levels, ICI 182 780 (1 or 2 ,g (ml uterine blood flow),1) was infused unilaterally (n= 4 sheep). Ewes in the last stages of pregnancy (late pregnant ewes) were also given ICI 182 780 (0.23,2.0 ,g (ml uterine blood flow),1; 60 min infusion) into one uterine artery (n= 8 sheep). In Ovx sheep, local infusion of ICI 182 780 did not alter systemic cardiovascular parameters, such as mean arterial blood pressure or heart rate; however, it maximally decreased ipsilateral, but not contralateral, UBF vasodilatory responses to exogenous E2, by ,55,60% (P < 0.01). In two models of elevated endogenous E2,, local ICI 182 780 infusion inhibited the elevated UBF seen in follicular phase and late pregnant ewes in a time-dependent manner by ,60% and 37%, respectively; ipsilateral , contralateral effects (P < 0.01). In late pregnant sheep ICI 182 780 also mildly and acutely (for 5,30 min) elevated mean arterial pressure and heart rate (P < 0.05). We conclude that exogenous E2,-induced increases in UBF in the Ovx animal and endogenous E2,-mediated elevations of UBF during the follicular phase and late pregnancy are partially mediated by ER-dependent mechanisms. [source] Maintenance of pregnancy in ovariectomized Mongolian gerbils (Meriones unguiculatus)ANIMAL SCIENCE JOURNAL, Issue 5 2002Osamu KAI ABSTRACT Bilateral ovariectomy (Ovx) was carried out on day 20 of pregnancy in Mongolian gerbils (Meriones unguiculatus). The body weights of all groups tended to decrease on the day after the operation, and the decrease was significant in the group that was ovariectomized and given vehicle (Ovx + vehicle group). The body weight in this group never recovered until autopsy on day 24, which is normally 1 day before parturition. No fetuses survived to the time of autopsy in any of the animals of the Ovx + vehicle group. Daily administration of 4 mg of progesterone (P4) prevented the termination of pregnancy in Ovx animals, but 1 mg did not. Treatment with estradiol 17, (E2) in addition to 4 mg of P4 tended to result in a lower rate of fetal survival than that of the Ovx group treated with 4 mg of P4 alone. With regard to fetal weight, treatment with 4 mg of P4 resulted in the same weight as in the sham-operated controls, but the addition of 0.2 or 1 ,g of E2 to the 4 mg of P4 resulted in a significantly lower weight than that of fetuses in the 4 mg of P4 group. The present study suggests that adequate maintenance of pregnancy in ovariectomized gerbils can be achieved by daily treatment with 4 mg of P4 alone. Moreover, treatment with 0.2 or 1 ,g of E2 in addition to 4 mg of P4 caused a deterioration in the maintenance of gestation, in contrast to the effects in rats, mice and hamsters. [source] | |||||||||||||