Feeding and drinking patterns of ovariectomized old female rats

Circadian rhythms and patterns of feeding and drinking behavior of ovariectomized old female rats (23 to 34 months of age) were studied and the changes due to the aging process were analyzed. In order to assess sex difference in these patterns in old age, the data were also compared with the previous studies in old male rats. There was significant increase in daily feeding events but not in licking events in old female rats. Circadian rhythms disappeared in 2 out of 7 old female rats in feeding events and 1 out of 8 old female rats in licking events. The remaining old rats which still showed circadian rhythmicity in feeding events and licking events, had smaller meal number/day, larger mean intermeal interval, quicker feeding events/min/meal, larger draft number/day, shorter mean draft duration, longer mean interdraft interval and quicker licking events/min/draft than young female rats. Drinking/feeding ratio was higher in the dark period than the light period in young as well as old female rats. These changes resemble those in old male rats and in ventromedial hypothalamic lesioned rats in the obese stage, but to less extent.     

Simvastatin did not prevent nor restore ovariectomy-induced bone loss in adult rats

Current published results on whether statins have beneficial effects on bone metabolism have been conflicting so far. In order to further investigate if statins were promising candidates for the treatment for osteoporosis, we conducted a study in which rats were ovariectomized (OVX) at 6 months of age, allowed to lose bone for 60 days and followed by oral administration of simvastatin at the dose levels of 0.3-10 mg/kg/d for 60 days. PGE2 (6 mg/kg) was used as a positive control. Study endpoints included bone histomorphometry on the proximal tibial metaphysis (PTM) and the tibial diaphysis (TX), dual-energy X-ray absorptiometry on the right femur and micro computed tomography (ICT) on the 5th lumbar vertebra (LV). After 120 days of OVX, cancellous bone lost by 80% in the PTM and 18% in the LV accompanied by increased bone formation and resorption. Simvastatin at all dose levels did not affect bone volume, bone formation rate and bone erosion surface when compared to 120 day ovariectomized animals at all bone sites studied. By contrast, PGE2 restored cancellous and cortical bone area to sham control levels. In conclusion, this study demonstrated that unlike PGE2, oral administration of simvastatin did not have effects on cancellous or cortical bone formation and resorption; and consequently was not able to prevent further bone loss or restore bone mass in the osteopenic, OVX rats.     

Effects of misoprostol on bone loss in ovariectomized rats.

This study was performed to investigate whether misoprostol (prostaglandin E1 analogue) (Cytotec, Searle, England) is effective for restoration of bone loss. Four-month-old parous female Sprague-Dawley rats (n = 30) were subjected either to bilateral ovariectomy (OVX, 24 rats) or to sham surgery (sham, 6 rats). The OVX rats were divided into four groups 60 days after the surgery. Six of them were killed, and dual-energy X-ray absorption (Norland xr-36, Norland Corporation, Fort Atkinson, WI, USA) measurements were performed, called pretreatment OVX group. The remaining groups (each had 6 rats) treated orally with 0 (control), 100, 200 micrograms/kg/day misoprostol for 60 days. All rats were killed 60 days after having treatment, and bone loss of the lumbar spine was measured by dual-energy X-ray absorption. The bone mineral density was decreased by 25.4% in control group and 23.6% in pretreatment group compared to sham group, but restored by 86% and 96% in groups treated with 100 and 200 micrograms/kg/day misoprostol, respectively. These results suggest that misoprostol restores bone loss in the lumbar spine of OVX rats in a dose-dependent manner.     

Feeding blueberry diets inhibits angiotensin II-converting enzyme (ACE) activity in spontaneously hypertensive stroke-prone rats

Feeding flavonoid-rich blueberries to spontaneously hypertensive stroke-prone rats (SHRSP) lowers blood pressure. To determine whether this is due to inhibition of angiotensin-converting enzyme (ACE) activity, as seen with other flavanoid-rich foods, we fed blueberries to SHRSP and normotensive rats and analyzed ACE activity in blood and tissues. After 2 weeks on a control diet, the hypertensive rats showed 56% higher levels of ACE activity in blood as compared with the normotensive rats (p < 0.05). Feeding a 3% blueberry diet for 2 weeks lowered ACE activity in the SHRSP (p < 0.05) but not the normotensive rats. ACE activity in plasma of SHRSP was no longer elevated at weeks 4 and 6, but blueberry feeding inhibited ACE in SHRSP after 6 weeks. Blueberry diets had no effect on ACE activity in lung, testis, kidney, or aorta. Our results suggest that dietary blueberries may be effective in managing early stages of hypertension, partially due to an inhibition of soluble ACE activity.     

Oral administration of phytocomponent p-hydroxycinnamic acid prevents bone loss in ovariectomized rats

The preventive effect of phytocomponent p-hydroxycinnamic acid (HCA) on ovariectomy (OVX)-induced bone loss was investigated. HCA (250 or 500 μg/100 g body weight) was orally administered once daily for 30 days to OVX rats. The analysis using a peripheral quantitative computed tomography (pQCT) showed that OVX caused bone loss in the femoral-metaphyseal tissues. This change was significantly restored after the administration of HCA (250 or 500 μg/100 g body weight) to OVX rats. Mineral content, mineral density, and polar strength strain index in the femoral-metaphyseal tissues were significantly decreased in OVX rats. These decreases were significantly restored after the administration of HCA (500 μg/100 g) to OVX rats. Moreover, OVX caused a significant decrease in calcium content or alkaline phosphatase activity in the femoral-diaphyseal and -metaphyseal tissues. These decreases were significantly restored after the administration of HCA (250 or 500 μg/100 g) to OVX rats. Deoxyribonucleic acid (DNA) content in the diaphyseal or metaphyseal tissues was significantly increased in OVX rats. These increases were significantly restored after oral administration of HCA (500 μg/100 g). This study demonstrates that HCA has preventive effects on OVX-induced bone loss of rats in vivo.     

Inhibitory effect of Galgeun-tang on RANKL-induced osteoclast differentiation and bone loss in ovariectomized rats

Galgeun-tang (GGT) is a traditional Korean medication known to have a diaphoretic effect and to improve cerebral circulation. The aim of this study was to investigate the effects of GGT on osteoclast differentiation and bone loss in ovariectomized (OVX) rats compared to Galgeun-tang fermented by Bifidobacterium breve (designated as GFT). GGT significantly and dose-dependently inhibited the receptor activator for nuclear factor κB ligand (RANKL)-induced tartrate-resistant acid phosphatase (TRAP) activity and the formation of multinucleated osteoclasts in RAW264.7 cells. In addition, GGT significantly reduced RANKL-induced mRNA expression levels of TRAP, c-Src, and Cathepsin K. To examine the effect of GGT or GFT in OVX rats, we administered GGT or GFT (15 mL/kg/day) orally to OVX rats for 12 weeks. GGT administration significantly reduced body weight gain in OVX rats. GGT administration also significantly reduced total serum cholesterol, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, and triglyceride levels in OVX rats. GFT administration significantly reduced serum LDL-cholesterol and triglyceride levels in OVX rats. Moreover, administration of GGT, but not GFT, significantly increased bone mineral density of the femur, which is normally decreased in OVX rats. In conclusion, these results suggest that GGT could have the potential to decrease ovariectomy-induced increases in body weight and lipid content and could prevent bone loss through its inhibitory effect on osteoclast differentiation.     

Protective effect of polysaccharides from morinda officinalis on bone loss in ovariectomized rats

In order to examine the effect of polysaccharides from morinda officinalis (MOP) on bone quality of osteoporosis rats. The osteoporosis in rats was induced by ovariectomy, and MOP (100 or 300mg/kg) was orally administrated once daily. The animals were assessed 30 days after the operation for bone mineral density, serum cytokines level and mineral element concentration. MOP administration in rats resulted in an increase in bone mineral density and mineral element concentration, a decrease in serum cytokines level, which indicated that MOP administration may play an important role in the development of osteoporosis.     

Green tea polyphenols mitigate bone loss of female rats in a chronic inflammation-induced bone loss model

The purpose of this study was to explore the bioavailability, efficacy and molecular mechanisms of green tea polyphenols (GTP) related to preventing bone loss in rats with chronic inflammation. A 2 [placebo vs. lipopolysaccharide (LPS)]×2 (no GTP vs. 0.5% GTP in drinking water) factorial design enabled the evaluation of effects of LPS administration, GTP levels, and LPS×GTP interaction. Urinary GTP components and 8-hydroxy-2′-deoxyguanosine (8-OHdG) levels were determined by high-pressure liquid chromatography for bioavailability and molecular mechanism, respectively. Efficacy was evaluated by examining changes in femoral mineral content (BMC) and density (BMD) using dual-energy X-ray absorptiometry, and bone turnover biomarkers [osteocalcin (OC) and tartrate-resistant acid phosphatase (TRAP)] using respective ELISA kits. The mRNA expression of tumor necrosis factor-α (TNF-α) and cyclooxygenase-2 (COX-2) in spleen was determined by real-time RT-PCR. Neither LPS administration nor GTP levels affected body weight and femoral bone area throughout the study period. Only GTP supplementation resulted in increased urinary epigallocatechin and epicatechin concentrations. LPS administration led to a decrease in femur BMC and BMD, and serum OC levels, but an increase in serum TRAP, urinary 8-OHdG and spleen mRNA expression of TNF-α and COX-2 levels. GTP supplementation resulted in higher values for femur BMC, BMD and serum OC, but lower values for serum TRAP, urinary 8-OHdG and spleen mRNA expression of TNF-α and COX-2 levels. We conclude that GTP mitigates bone loss in a chronic inflammation-induced bone loss model by reducing oxidative stress-induced damage and inflammation.     

Evaluation of the preventive effect of isoflavone extract on bone loss in ovariectomized rats

To examine a potential role for soybean phytoestrogens in postmenopausal bone loss, twenty-four 12-week-old Sprague-Dawley rats were divided randomly into 4 groups and given controlled diets for 16 weeks. The treatment groups were as followed: sham operated, ovariectomized (OVX) control, OVX + isoflavone extract (6.25 g/kg), and OVX + 17beta-estradiol (4 mg/kg). OVX treatments reduced femoral and fourth lumbar vertebral bone density and mineral content (p<0.01), decreased uterine weight (p<0.01), accelerated body weight increases (p<0.05), and increased the activities (p<0.01) of both serum alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRAP). Supplementation with isoflavone prevented the losses of bone density and mineral content caused by OVX (p<0.01). Although both isoflavone and 17beta-estradiol exhibited similar bone-sparing ability on the OVX-induced bone loss, the effect of isoflavone was not the same as that of 17beta-estradiol on the serum ALP and TRAP, body weight increase, and uterine weight change. We concluded that dietary supplementation with soybean isoflavone can prevent postmenopausal bone loss via a different mechanism of estrogen in OVX rats.     

Suppressive effects of genistein dosage and resistance exercise on bone loss in ovariectomized rats.

This study was designed to determine whether combined treatments with genistein dosage and moderate resistance exercise would exhibit synergistically preventive effects on bone loss following the onset of menopause. Forty-one 12 wk-old female SD rats were assigned to five groups: 1) Sham operated (Sham); 2) ovariectomized (OVX-Cont); 3) OVX received genistein (OVX-GEN); 4) OVX exercised (OVX-EXE); and 5) OVX treated with both genistein and exercise (OVX-GEN-EXE). All rats were fed a low Ca (0.1%) diet ad libitum. Daily genistein dosage was 12 mg/kg body weight. Exercising rats took 40 sets of 1-min run interspersed with 1-min rest with a 100 g weight on the back on an uphill treadmill at 20 m/min. The experimental duration consisted of the adaptation and treatment periods of 4 weeks each. Uterine weight in OVX-Cont, OVX-GEN, OVX-EXE and OVX-GEN-EXE decreased to about 15% of that in Sham (p < 0.001). The femoral BMD (mg/cm2; mean +/- SE), assessed by DEXA (Lunar), of OVX-Cont was significantly lowered to 206 +/- 5 by -9%, as compared to 226 +/- 2 of Sham (p < 0.001). The BMD of OVX-GEN, OVX-EXE and OVX-GEN-EXE were 217 +/- 2, 217 +/- 2 and 222 +/- 2, respectively, and genistein dosage and resistance exercise equally increased the BMD of OVX rats by 5% (p < 0.01). Combined treatment of genistein and exercise more successfully recovered their decreased BMD by 8% (p < 0.001). BMD of the fourth lumbar vertebrae in OVX-Cont was declined to 191 +/- 7 by -15%, as compared to 225 +/- 4 in Sham (p < 0.001). OVX-EXE and OVX-GEN-EXE gained the BMD by 6% to 205 +/- 4 and 203 +/- 3, respectively, as compared to that of OVX-Cont (p < 0.01). These results suggest the possibility that the combined treatment of genistein dosage and resistance exercise have more beneficial effects by acting rather independently than their separate trials on the prevention of ovx-induced bone loss in femurs.     

Daidzein but not other phytoestrogens preserves bone architecture in ovariectomized female rats in vivo

Ovariectomy of immature female rats, results in significant decrease of trabecular bone volume and in cortical bone thickness. Previously, we found that estradiol-17beta (E(2)) restored bone structure of ovariectomized (Ovx) female rats to values obtained in intact sham-operated female rats. E(2) also selectively stimulated creatine kinase (CK) specific activity a hormonal-genomic activity marker. In the present study, we compared the effects of E(2) and the phytoestrogens: daidzein (D), biochainin A (BA), genistein (G), carboxy-derivative of BA (cBA), and the SERM raloxifene (Ral) in Ovx, on both histological changes of bones and CK, when administered in multiple daily injections for 2.5 months. Bone from Ovx rats, showed significant disrupted architecture of the growth plate, with fewer proliferative cells and less chondroblasts. The metaphysis underneath the growth plate, contained less trabeculae but a significant increased number of adipocytes in the bone marrow. D like E(2) and Ral but not G, BA, or cBA, restored the morphology of the tibiae, similar to that of control sham-operated animals; the bony trabeculeae observed in the primary spongiosa was thicker, with almost no adipocytes in bone marrow. Ovariectomy resulted also in reduced CK, which in both epiphysis and diaphysis was stimulated by all estrogenic compounds tested. In summary, only D stimulated skeletal tissues growth and differentiation as effectively as E(2) or Ral, suggesting that under our experimental conditions, D is more effective in reversing menopausal changes than any of the other isolated phytoestrogens which cannot be considered as one entity.     

The fitness costs of senescence: The evolutionary importance of events in early adult life

Summary The increased mortality caused by ageing represents a fitness cost to organisms. This paper develops techniques for determining the proportions of that cost that accrue at each age. A variety of analyses using several different sources of data on human ageing—palaeodemographic life tables and life tables from more recent societies with high mortality rates—all suggest that the fitness cost of ageing was high during most of our evolutionary history, and was largely due to physiological changes occurring early in adult life. These results imply that predictions about the nature of senescence based on evolutionary theory should be tested using data from middle-aged individuals. They also have implications about the relative importances for human evolution of the pleiotropy and mutation-accumulation theories of the evolution of senescence, and for the validity of Gompertz Law' for the shape of the relationship between mortality and age. An analysis of a life table of the African buffalo suggests that the costs of ageing early in adult life are relatively high in at least one non-human species in its natural environment.     

Metformin stimulates osteoprotegerin and reduces RANKL expression in osteoblasts and ovariectomized rats

Anti-diabetic drug metformin has been shown to enhance osteoblasts differentiation and inhibit osteoclast differentiation in vitro and prevent bone loss in ovariectomized (OVX) rats. But the mechanisms through which metformin regulates osteoclastogensis are not known. Osteoprotegerin (OPG) and receptor activator of nuclear factor κB ligand (RANKL) are cytokines predominantly secreted by osteoblasts and play critical roles in the differentiation and function of osteoclasts. In this study, we demonstrated that metformin dose-dependently stimulated OPG and reduced RANKL mRNA and protein expression in mouse calvarial osteoblasts and osteoblastic cell line MC3T3-E1. Inhibition of AMP-activated protein kinase (AMPK) and CaM kinase kinase (CaMKK), two targets of metformin, suppressed endogenous and metformin-induced OPG secretion in osteoblasts. Moreover, supernatant of osteoblasts treated with metformin reduced formation of tartrate resistant acid phosphatase (TRAP)-positive multi-nucleated cells in Raw264.7 cells. Most importantly, metformin significantly increased total body bone mineral density, prevented bone loss and decreased TRAP-positive cells in OVX rats proximal tibiae, accompanied with an increase of OPG and decrease of RANKL expression. These in vivo and in vitro studies suggest that metformin reduces RANKL and stimulates OPG expression in osteoblasts, further inhibits osteoclast differentiation and prevents bone loss in OVX rats.     

Rolipram, a phosphodiesterase 4 inhibitor, prevented cancellous and cortical bone loss by inhibiting endosteal bone resorption and maintaining the elevated periosteal bone formation in adult ovariectomized rats

Cyclic AMP (cAMP) is a continually produced nucleotide inactivated by hydrolysis to 5'AMP via phosphodiesterase (PDE) enzymes. Rolipram is a selective PDE4 inhibitor reported to have anti-inflammatory effects and used in the treatment of asthma and chronic obstructive pulmonary disease (COPD). The current study was designed to determine whether Rolipram could prevent and restore bone loss in ovariectomized (OVX) rats. Six-month-old Sprague Dawley rats underwent either sham-operated or bilateral ovariectomy, and were left untreated for 60 days to develop osteopenia. Then they were treated with vehicle, 6 mg/kg PGE(2), 3 microg/kg Alendronate or 0.1-1.0 mg/kg Rolipram for 60 days. At sacrifice, the right tibiae were processed for quantitative bone histomorphometric measurements. The right femurs were measured by dual energy A-ray absorptiometry and the 5th lumbar vertebrae were subjected to micro-computed tomography to access bone mass and architecture changes. Our results indicated that OVX induced negative bone balance in all five bone sites we tested, with bone resorption exceeding bone formation. Rolipram at 0.1-0.6 mg/kg dose levels prevented while at 1 mg/kg restored ovariectomy-induced cancellous and cortical bone loss in the tibia, femur and lumbar vertebra. Dynamic bone histomorphometry suggested that these beneficial effects were achieved by partially maintaining the elevated bone formation at the trabecular bone surface and increasing bone formation at the periosteal bone surface of the cortex. Furthermore, it reduced bone turnover at the trabecular and the endocortical bone surfaces. The prevention of further bone loss effects were comparable to those of an anti-resorption agent (Alendronate) but were not as great as those of an anabolic agent (PGE(2)). In addition, Rolipram treatment increased body and muscle weights compared to the vehicle-treated OVX rats. In conclusion, our study in an osteopenic rat model suggested that a selective PDE4 inhibitor may be used for the treatment of established osteoporosis.     

The effects of royal jelly protein on bone mineral density and strength in ovariectomized female rats

[Purpose]Sex hormones deficiency leads to dramatically bone loss in particular postmenopausal women. Royal jelly has anti-osteoporosis effect due to maintain bone volume in that condition. We hypothesized that royal jelly protein (RJP, a latent residue after extracting royal jelly) also prevents bone deficient in ovariectomized (OVX) female rats, the animal model of postmenopausal women. [Methods]Female Sprague-Dawley rats (n = 30, 6 weeks age old) were sham operated (Sham; sham operated group, n = 7), OVX control group (OC, n = 7), OVX with low RJP intake group (ORL, n = 8), and OVX with high RJP intake group (ORH, n = 8) during 8 weeks experimental periods. In the end point of this experiment, the bone samples (lumbar spine, tibia, and femur) were surgically removed under anesthesia. These bone samples were evaluated bone mineral density (BMD) and bone strength.[Results]BMD of lumbar spine in RJP intake groups (ORL, ORH) were higher than that in OC group (p < 0.05 and p < 0.01) in RJP intake volume dependent manner. BMD of tibial proximal metaphysis and diaphysis in RJP intake groups were also higher than these in OC group (p < 0.01 and p < 0.01 / p < 0.05 and p < 0.001). In addition, breaking force of femur in RJP intake groups were significantly increase compared with that in OC group (p < 0.001 respectively). [Conclusion]These findings indicate that RJP contribute to prevent sex hormone related bone abnormality     

Effect of pre- and post-surgery treatment with risedronate on trabecular bone loss in ovariectomized rats.

The purposes of the present study were to differentiate the effects of pre-surgery treatment with risedronate and post-surgery treatment with a reduced dosing frequency of risedronate on trabecular bone loss in ovariectomized rats and to determine whether post-surgery treatment with a reduced dosing frequency of risedronate would have a beneficial effect on trabecular bone loss after pre-surgery treatment with risedronate by means of bone histomorphometric analysis. The short-term experiment (6 weeks) was performed on fifty, 4-month-old, female Sprague-Dawley rats randomized into five groups (n=10 in each group). Forty rats were treated with vehicle or risedronate for 4 weeks before ovariectomy (OVX), and then treated with either vehicle or risedronate for 2 weeks following OVX (the Vehicle-OVX-Vehicle [OVX control], Vehicle-OVX-Risedronate [post-OVX treatment with risedronate], Risedronate-OVX-Vehicle [pre-OVX treatment with risedronate], and Risedronate-OVX-Risedronate [continuous treatment with risedronate] groups). The remaining 10 rats were treated with vehicle for 6 weeks, with a sham operation performed 4 weeks after the start of the experiment (the Vehicle-Sham-Vehicle [Sham control] group). During the 4 weeks prior to surgery, risedronate was administered five times a week subcutaneously at a dose of 2.5 mug /kg body weight, and during the 2 weeks after surgery, the dosing frequency was reduced to twice a week. The long-term experiment (10 weeks) had the same design as the short-term one, except that the post-OVX treatment was 6 weeks. In the short-term experiment, both pre- and post-OVX treatments with risedronate prevented trabecular bone loss of the proximal tibial metaphysis 2 weeks after OVX. In long-term experiment, however, pre- and post-OVX treatments with risedronate attenuated trabecular bone loss until 6 weeks after OVX, with pre-OVX treatment having a less pronounced effect than post-OVX treatment. In the short- and long-term experiments, pre-and post-OVX treatments had an additive effect on trabecular bone mass. The present study has shown the efficacy of pre-OVX treatment with risedronate or post-OVX treatment with a low dosing frequency of risedronate for preventing trabecular bone loss early after OVX. Post-OVX treatment with a low dosing frequency of risedronate was beneficial for attenuating trabecular bone loss late after OVX. Treatment with risedronate before OVX had an additive effect on trabecular bone mass with the treatment after OVX, suggesting that treatment with a low dosing frequency of risedronate might be acceptable for reducing OVX-induced trabecular bone loss after treatment with risedronate prior to OVX.     

MSTN is an important myokine for weight-bearing training to attenuate bone loss in ovariectomized rats

Journal of Physiology and Biochemistry - Weight-bearing training, as one of resistance exercises, is beneficial to bone health. Myostatin (MSTN) is a negative regulator of skeletal muscle growth...     

Postnatal intracerebroventricular exposure to neuropeptide Y causes weight loss in female adult rats

We investigated the effect of repetitive postnatal (2-7 days) intracerebroventricular administration of neuropeptide Y (NPY) on food intake and body weight gain in the 3- to 120-day-old Sprague-Dawley rats. NPY caused a 32% transient increase in body weight gain with elevated circulating insulin concentrations within 24 h. This early intervention led to the persistence of hyperinsulinemia and relative hyperleptinemia with euglycemia in the 120-day-old female alone. This perturbation was associated with 50% suppression in adult female hypothalamic NPY concentrations and a 50-85% decline in NPY immunoreactivity in the paraventricular and arcuate nuclei. This change was paralleled by a approximately 20% decline in food intake and body weight gain at 60 and 120 days. However, when exogenous NPY was stereotaxically reinjected into the paraventricular nucleus of the approximately 120-day-old adult females who were pretreated with NPY postnatally, an increase in food intake and body weight gain was noted, attesting to no disruption in the NPY end-organ responsivity. We conclude that postnatal intracerebroventricular NPY has long-lasting effects that predetermine the resultant adult phenotype in a sex-specific manner.     

Supraphysiological testosterone enanthate administration prevents bone loss and augments bone strength in gonadectomized male and female rats

High-dose testosterone enanthate (TE) may prevent hypogonadism-induced osteopenia. For this study, 3-mo-old male and female Fisher SAS rats underwent sham surgery, gonadectomy (GX), or GX plus 28 days TE administration (7.0 mg/wk). GX reduced serum sex hormones (i.e., testosterone, dihydrotestosterone, and estradiol) (P < 0.05) in both sexes and bone concentrations of testosterone (males only), and estradiol (females only). GX also elevated urine deoxypyridinoline/creatinine in both sexes and serum osteocalcin (females only), findings that are consistent with high-turnover osteopenia. GX reduced cancellous bone volume (CBV) and increased osteoid surfaces in tibia of both sexes. GX males also experienced reduced trabecular number and width and increased trabecular separation, whereas GX females experienced increased osteoblast and osteoid surfaces. Bone biomechanical characteristics remained unaffected by GX, except that femoral stiffness was reduced in females. In contrast, TE administration to GX rats elevated serum and bone androgens to supraphysiological concentrations in both sexes but altered neither serum nor bone estradiol in males. Additionally, TE did not prevent GX-induced reductions in serum or bone estradiol in females. TE also reduced markers of high-turnover osteopenia in both sexes. In males, TE prevented GX-induced changes in trabecular number and separation, CBV, and osteoid surfaces while diminishing osteoblast and osteoclast surfaces; however, these changes were not fully prevented in females. In both sexes, TE increased femoral length and femoral maximal strength to above that of Sham and GX animals while preventing the loss of femoral stiffness in females. In conclusion, TE administration appears protective of cancellous bone in male rats and augments cortical bone strength in both sexes.