The effect of a simultaneous dietary administration of xylitol and ethanol on bone resorption

Our previous studies have shown that dietary xylitol supplementation diminishes bone resorption in rats, as well as protects against ovariectomy-induced increase of bone resorption during experimental osteoporosis. Interestingly, ethanol, when given simultaneously with xylitol, is known to increase blood concentration of xylitol. On the other hand, ethanol, when given alone, has been shown to increase bone resorption. The aim of the present study was to evaluate the effects of a simultaneous dietary administration of 10% xylitol and 10% ethanol on bone resorption. Bone resorption was determined using measurement of urinary excretion of hydrogen 3 (3H) radioactivity in 3H-tetracycline prelabeled rats. Already 4 days after the beginning of dietary supplementations, excretion of 3H was about 15% lower in the xylitol group (diet supplemented with 10% xylitol) and about 25% lower in the xylitol-ethanol group (diet supplemented with 10% xylitol and 10% ethanol) as compared to the controls. The excretion of 3H in these groups remained smaller than that of the controls throughout the entire study period of 40 days. The excretion of 3 H in the xylitol-ethanol group remained also smaller than that of the xylitol group. Bone mineral density and bone mineral content were determined with a peripheral quantitative computed tomography (pQCT) system from the rat tibiae at the end of the experiment. Trabecular bone mineral density and trabecular bone mineral content were significantly greater in the xylitol group and in the xylitol-ethanol group compared to the controls. They were also greater in the xylitol-ethanol group as compared to the xylitol group. Cortical bone mineral density and cortical bone mineral content did not differ significantly between the groups. In conclusion, a simultaneous dietary supplementation with 10% xylitol and 10% ethanol seems to diminish bone resorption and to increase trabecular bone mineral density and trabecular bone mineral content in rats. These effects seem to be stronger than the effects induced by 10% xylitol supplementation alone.     

Effects of isometric strength training followed by no exercise and Humulus lupulus L-enriched diet on bone metabolism in old female rats

We investigated in female rats the effects on bone metabolism of a prolonged no-training period, subsequent to an isometric exercise program, performed during young adulthood and those of a long-term consumption of Humulus lupulus L-enriched diet (genistein 1.92 and daidzein 1.24 mg/kg diet) combined or not with isometric training. Forty-eight rats (4 weeks old) were randomly divided into 4 groups: trained (C-Tr) or nontrained rats (C-NTr) fed with control diet and trained (H-Tr) or nontrained rats (H-NTr) fed with Humulus lupulus L-enriched diet. The diets lasted 100 weeks. Training was followed over a 25-week period. Bone parameters were measured at week 100. Our results showed that no significant difference was observed among the 4 groups in uterine relative weight, calcium (Ca) intake, fecal Ca, urinary Ca excretion, net Ca absorption, plasma Ca, and bone Ca content. Calcium balance was significantly enhanced in H-NTr rats in comparison with C-NTr and C-Tr rats. Isometric strength training led to a significant increase in total bone mineral density (BMD), diaphyseal BMD, and osteocalcin-deoxypyridinoline ratio in C-Tr rats compared with the other groups. The main findings of the present study indicate that in female rats, a 25-week isometric strength training performed during young adulthood followed by a prolonged no-training period increases BMD values and osteocalcin-deoxypyridinoline ratio, whereas long-term consumption of Humulus lupulus L-enriched diet does not improve bone parameters. It suggests that bone gains induced by exercise do not decrease immediately after cessation of training and also confirms the importance of the practice of physical activity during puberty and young adulthood to maximize the achieved peak bone density.     

Effects of chronic prednisolone treatment on bone resorption and bone composition in intact and ovariectomized rats and in ovariectomized rats receiving beta-estradiol

To examine the interactions between estrogen deficiency and glucocorticoid excess on bone metabolism the osteopenic effects of a standard dose of prednisolone (2 mg/kg BW.day) were studied in sham-ovariectomized (Sham-OVX), ovariectomized (OVX), and OVX rats given replacement beta-estradiol (OVX + E2). For 12 weeks six groups of female albino rats aged 4 months which had their skeletons labeled with 45Ca were fed matched amounts of low-calcium (0.1% Ca) hydroxyproline-free diet. The six treatment groups were: group 1, Sham-OVX; group 2, Sham-OVX + prednisolone; group 3, OVX; group 4, OVX + prednisolone; group 5, OVX + E2; group 6, OVX + E2 + prednisolone. Bone resorption was estimated by studying the urinary excretion of hydroxyproline and 45Ca. Parathyroid function was assessed indirectly from urinary cAMP excretion. Treatments did not influence parathyroid activity or serum levels of calcium or 1,25-dihydroxyvitamin D. However, ovariectomy increased bone resorption and induced osteopenia whereas prednisolone decreased bone resorption and formation and caused osteopenia. Ovariectomy increased the rate of bone resorption in prednisolone-treated rats; prednisolone lowered the rates of bone resorption and formation in OVX rats. The osteopenic effects of prednisolone and ovariectomy were additive and independent. E2 protected bone from the osteopenic effects of ovariectomy but did not affect bone loss induced by prednisolone. These results suggest prophylactic estrogen should help to avoid bone loss from estrogen deficiency in patients requiring chronic high dose glucocorticoid treatment.     

跑台运动对去卵巢大鼠肱骨无机矿物质含量的影响

目的观察中等强度跑台运动对去卵巢大鼠肱骨无机矿物质含量的影响。方法将60只成年雌性SD大鼠按体重随机分为假手术组、去卵巢静止组和去卵巢运动组,每组20只。去卵巢运动组每周进行4次时间45 min、速度18 m/min、跑道倾角5°的跑台训练,持续训练14 w。末次训练24～36 h后或停训16 w时处死各组一半大鼠,比色法测定血清钙磷水平;1/万天平称量肱骨湿重、去脂肪干重以及煅烧后的灰重。结果去卵巢16 w和32 w时,去卵巢静止组肱骨湿重/体重、肱骨去脂肪干重/体重和肱骨灰重/体重均显著低于假手术组(P<0.05);血钙水平的差异只在去卵巢16 w时显著(P<0.05),而血磷水平无显著变化。训练刚结束时,去卵巢运动组肱骨湿重/体重、肱骨去脂肪干重/体重和肱骨灰重/体重显著高于去卵巢静止组(P<0.05,P<0.01),但所有差异在停训16 w时消失;血钙、血磷水平均无显著变化。结论中等强度跑台运动能减缓去卵巢大鼠肱骨无机矿物质含量的丢失。     

Prevention of involutional bone loss by exercise

To ascertain whether exercise could prevent involutional bone loss, we studied 18 postmenopausal women, half of whom exercised for 1 h three times a week. Total and regional bone mass were measured before and after 1 year of exercise by the techniques of total-body neutron activation analysis (total body calcium) and photon absorptiometry (bone mineral content) of the distal radius. Total body potassium was measured by whole body counting. Bone mineral content and total body potassium did not change significantly in either group. Total body calcium increased in the exercise group from 781 +/- 95 g of 801 +/- 118 g (SD). In contrast, total body calcium decreased in each subject in the sedentary group. The daily calcium balance derived from the difference in total body calcium measurements was significantly different in the two groups of women (P less than 0.001). These data support the hypothesis that exercise can modify involutional bone loss.     

Effects of dietary sodium chloride loading on parathyroid function, 1,25-dihydroxyvitamin D, calcium balance, and bone metabolism in female rats during chronic prednisolone administration

The effects of dietary sodium chloride supplements (8 g/100 g diet) on parathyroid function, serum 1,25-dihydroxyvitamin D [1,25-(OH)2D], calcium balance, bone metabolism, and bone composition were studied in rats treated with prednisolone (2 mg/kg w X day) for 12 weeks. Animals on a low calcium diet (0.1% Ca) received the following treatments: group 1, control; group 2, NaCl; group 3, prednisolone; group 4, NaCl plus prednisolone. Parathyroid function was assessed indirectly from urinary cAMP excretion: bone resorption was estimated by studying urinary hydroxyproline excretion and mobilization of 45Ca from bone. Dietary salt loading increased the urinary excretion of calcium, 45Ca, cAMP, and hydroxyproline and raised serum 1,25-(OH)2D and net calcium absorption, but lowered calcium retention, femoral calcium, and total body calcium. Prednisolone slowed body growth and lowered net calcium absorption, calcium retention, femoral calcium, and total body calcium. Urinary calcium excretion was higher in rats receiving salt and prednisolone in combination than in animals taking salt without prednisolone, but other responses to salt and prednisolone were independent. Thus, salt and prednisolone each elicit osteopenia, and salt causes bone loss in rats receiving prednisolone. The osteopenic effect of salt is attributed to primary augmentation of urinary calcium excretion and secondary increases in PTH-medicated bone resorption. Although salt-treated rats have higher blood levels of 1,25-(OH)2D, bone loss occurs because alimentary calcium absorption is not elevated sufficiently to offset urinary calcium losses. Prednisolone lowers bone formation and net calcium absorption without lowering serum 1,25-(OH)2D values. The parathyroid-vitamin D axis remains intact in prednisolone-treated rats, as they show increases in PTH and 1,25-(OH)2D after salt treatment.     

Pamidronate in children and adolescents with osteogenesis imperfecta: effect of treatment discontinuation

CONTEXT: Cyclical iv pamidronate is a widely used symptomatic therapy of osteogenesis imperfecta (OI). What happens after treatment discontinuation is unknown. OBJECTIVE: The objective of this study was to assess the effect of pamidronate discontinuation in pediatric patients with moderate to severe OI types I, III, and IV. DESIGN: This was an open-label controlled and observational study in patients who had received pamidronate for more than 3 yr. SETTING: This study was performed at a pediatric metabolic bone research unit. PATIENTS: In the controlled study, 12 pairs of patients were matched for age, OI severity, and duration of pamidronate treatment. Pamidronate was stopped in one patient of each pair; the other continued to receive treatment. In the observational study, 38 OI patients were examined (mean age, 13.8 yr). Intervention: The intervention was discontinuation of pamidronate treatment for 2 yr. MAIN OUTCOME MEASURES: The main outcome measures were lumbar spine bone mineral content and areal bone mineral density (aBMD), biochemical markers of bone metabolism, fracture incidence, and clinical evaluation. RESULTS: In the controlled study, bone resorption activity was higher after treatment discontinuation. Bone mineral content continued to increase in both groups. aBMD z-scores decreased in the untreated group, but increased in the continuation cohort. Fracture rates and functional status were similar between groups. In the observational study, bone resorption activity increased after treatment discontinuation, but remained significantly lower than in untreated OI patients. Bone mineral content and aBMD continued to increase, whereas aBMD z-scores decreased. Changes were faster in patients who continued growing. CONCLUSIONS: Bone metabolism is still suppressed 2 yr after pamidronate discontinuation. Bone mass gains continue after treatment is stopped, but lumbar spine aBMD increases less than in healthy subjects. The size of these effects is growth dependent.     

Running has a negative effect on bone metabolism and proinflammatory status in male aged rats

Animal models for male osteoporosis are scarce. This study aimed at identifying the impact of different living conditions on bone structure and metabolism as well as the inflammatory status in a rat model of age-related male osteoporosis. Bone mineral density, bone histomorphometric data, ex vivo osteoclast generation, and bone metabolism serum marker as well as intracellular cytokine expressions were evaluated in 23-month-old male Sprague-Dawley rats subjected to different housing conditions from the age of 5 months. Running rats were housed individually and were exercised voluntarily in running wheels attached to their cages. Dieting rats were housed individually, too, but were fed to pair weight with the running rats. Walking rats were exercised mildly by use of a treadmill (800m/day, 5 days a week) and social rats were kept as four in a cage and fed ad libitum. Whereas no marked differences could be found for bone mineral density, trabecular bone volume as well as trabecular bone surface were diminished in walking rats. The ex vivo osteoclast generation assay revealed no significant differences between groups. Osteoblasts of running rats were not only decreased in number, but displayed also a lower activity as indicated by decreased serum osteocalcin levels. Osteoclast activity was increased in the same group as indicated by elevated CTX (c-terminal telopeptide of type I collagen) levels. Additionally, production of tumor necrosis factor (TNF)-alpha and interferone (IFN)-gamma by CD8(+) T cells was elevated in running rats. In conclusion, running has a negative effect on bone metabolism and proinflammatory status in male aged rats.     

Effect of endogenous subclinical hyperthyroidism on bone metabolism and bone mineral density in premenopausal women.

In this cross-sectional study, we evaluated 15 premenopausal women to elucidate whether bone turnover is increased and bone mineral density is reduced due to endogenous subclinical hyperthyroidism. Each patient had normal free thyroxine (FT4) and free triiodothyronine (FT3) levels associated with a stable suppression (<0.1 mU/L) of serum thyrotropin (TSH) levels during a period ranging between 6 and 11 months. Metabolic parameters of bone turnover (serum osteocalcin, bone specific alkaline phosphatase, procollagen I C-terminal peptide reflecting bone formation; urinary deoxypyridinoline and calcium excretion reflecting bone resorption) were assessed. Bone mineral density was measured at lumbar 1-4 vertebrae, femoral neck, and the forearm (midshaft radius and distal radius) by dual energy x-ray absorptiometry. All measurements were compared with 15 healthy age-, height-, and weight-matched premenopausal women who served as control group. Our findings suggest that endogenous subclinical hyperthyroidism is not associated with increased bone turnover, and bone mineral density is not reduced in premenopausal women, at least in the short term.     

Small bowel resection in the rat: the effect upon bone and mineral metabolism

BACKGROUND AND AIMS: We analyzed bone and mineral metabolism after long-segment small bowel resection in the rat to detect functional and morphological alterations and to determine the development of osteopathy. METHODS: Twelve-week-old male Lewis rats were randomized into short (8-week) or long (16-week) follow-up groups. Sham operation, resection of the proximal third of the small bowel, resection of the distal third of the bowel and resection of the entire jejunum and ileum were carried out. Nineteen days before the end of the experiment the animals were transferred into a metabolic cage to analyze weight gain/loss, food intake, and fecal excretion/24 h. At the end of the experiment the animals were killed; blood samples and bowel and bone specimens were collected, length, weight, volume, density, mineral content, and fracturing energy were determined, and bone histology was examined. The calcium/phosphorus ratio, nonmineralized tissue content and the ratio fracturing energy/mean bone density were calculated. RESULTS: After 8 weeks there were significant differences to the control group in body weight, weight gain, food efficiency, femur length, weight, volume, mineral content, mineral density, fracturing energy per bone volume, and bone density but not in bone calcium or magnesium. After 16 weeks there were differences in body weight, weight gain, food efficiency, femur length, weight, volume, bone mineral content and density, bone minerals, and nonmineralized tissue but not in fracturing energy; the average values of all these parameters were lower in the resected groups, and lowest in the group after resection of the entire jejunum and ileum. Bone histology showed a reduction in trabecular bone mass after long-segment small bowel resection. CONCLUSIONS: Long-segment small bowel resection causes a significant loss of body weight despite of a comparable mean chow ingestion resulting in a significant decreased food efficiency. We conclude that there is no inverse relationship of bone calcium content and the fracture risk, and that there is no severe mineralization defect after long-segment small bowel resection.     

Low estrogen and high parathyroid hormone-related peptide levels contribute to accelerated bone resorption and bone loss in lactating mice

Providing enough calcium for milk production stresses calcium homeostasis in lactating mammals. A universal response to these demands for calcium appears to be the mobilization of maternal skeletal reserves, and bone loss during lactation has been well documented. However, the regulation of calcium and skeletal metabolism during lactation remains enigmatic. Our study was designed to examine mineral and bone metabolism in lactating mice. We found that mice lose bone rapidly at all sites during lactation. Bone mineral density as determined by dual-energy x-ray absorptiometry was 20 to 30% lower at the spine, femur, and total body in lactating compared with either age-matched virgin or pregnant mice. The decrease in bone mineral density was accompanied by dramatic reductions in bone volume and changes in trabecular architecture. Bone loss was also accompanied by increases in bone turnover as determined by biochemical markers and histomorphometry. PTHrP levels were elevated during lactation and correlated positively with markers of bone resorption and negatively with bone mass at all sites. Estrogen levels were low during lactation and correlated negatively with bone resorption markers. Finally, estrogen and pamidronate treatment lowered rates of bone resorption to baseline virgin levels and mitigated, but did not prevent, bone loss. These data suggest that the combination of estrogen deficiency and elevations in circulating PTHrP during lactation act to stimulate bone resorption and promote bone loss.     

Effect of thyrotoxicosis and its treatment on mineral and bone metabolism

Mineral metabolism and bone histomorphometric status were evaluated in 31 hyperthyroid patients (HT) without clinical or radiological bone disease, both before and after treatment of hyperthyroidism. Blood and urine biochemical data were compared with those obtained in sex and age-matched controls. Iliac bone biopsies were available from 12 untreated HT and from 6 of them after treatment for analysis of trabecular bone. Mean plasma calcium was increased in HT but true hypercalcemia was seen in only one case and mean plasma immunoreactive parathormone (iPTH) was normal. Urine calcium excretion was markedly increased, especially in the fasting state. Biochemical parameters decreased after treatment, except for serum alkaline phosphatase and iPTH that, respectively, remained high and increased. Untreated state was characterized by an hyperremodelling state with enhanced activities of bone formation and bone resorption. Bone mineralization was normal. The mineral and bone changes were related to serum thyroid hormone levels. After treatment, the extent of formation surfaces still increased. The fact that, even though calcium metabolism abnormalities were corrected, active resorption surfaces did not change, suggests that trabecular osteoclastic resorption is not an important cause of mobilization of bone calcium to extracellular fluids in HT.     

Benefits of 2 years of intense exercise on bone density, physical fitness, and blood lipids in early postmenopausal osteopenic women: results of the Erlangen Fitness Osteoporosis Prevention Study (EFOPS)

BACKGROUND: Growing evidence indicates that physical exercise can prevent at least some of the negative effects on health associated with early menopause. Here we determine the effects of intense exercise on physical fitness, bone mineral density (BMD), back pain, and blood lipids in early postmenopausal women. METHODS: The study population comprised 50 fully compliant women, with no medication or illness affecting bone metabolism, who exercised over 26 months (exercise group [EG]), and 33 women who served as a nontraining control group (CG). Two group training sessions per week and 2 home training sessions per week were performed in the EG. Both groups were individually supplemented with calcium and cholecalciferol. Physical fitness was determined by maximum strength and cardiovascular performance. Bone mineral density was measured at the lumbar spine (dual-energy x-ray absorptiometry [DXA] and quantitative computed tomography [QCT]), the proximal femur (DXA), and the forearm (DXA). In serum samples taken from a subset of the study participants, we determined bone formation (serum osteocalcin) and resorption (serum cross-links) markers as well as blood lipid levels. Vasomotor symptoms related to menopause and pain were also assessed. RESULTS: After 26 months, significant exercise effects determined as percentage changes compared with baseline were observed for physical fitness (isometric strength: trunk extensors [EG +36.5% vs CG +1.7%], trunk flexors [EG +39.3% vs CG -0.4%], and maximum oxygen consumption [EG +12.4% vs CG -2.3%]); BMD (lumbar spine [DXA L1-L4, EG +0.7% vs CG -2.3%], QCT L1-L3 trabecular region of interest [EG +0.4% vs CG -6.6%], QCT L1-L3 cortical region of interest [EG +3.1% vs CG -1.7%], and total hip [DXA, EG -0.3% vs CG -1.7%]); serum levels (total cholesterol [EG -5.0% vs CG +4.1%] and triglycerides [EG -14.2% vs CG +23.2%]); and pain indexes at the spine. CONCLUSION: General purpose exercise programs with special emphasis on bone density can significantly improve strength and endurance and reduce bone loss, back pain, and lipid levels in osteopenic women in their critical early postmenopausal years.     

Changes in (markers of) bone metabolism during high dose corticosteroid pulse treatment in patients with rheumatoid arthritis.

OBJECTIVE: To examine the effect of high dose corticosteroid pulse treatment (three times 200 mg dexamethasone intravenously in eight days) on calcium and bone metabolism in 17 consecutive patients with active rheumatoid arthritis (RA). METHODS: Bone formation was quantified by measurement of serum alkaline phosphatase, osteocalcin, and carboxyterminal propeptide of type I procollagen (pro-I-CPP) concentrations. Bone resorption was measured by urinary excretion of calcium, hydroxyproline, (free and total) deoxypyridinoline (Dpyr), (free and total) pyridinoline (Pyr), and serum concentrations of the carboxyterminal cross linked telopeptide of type I collagen (I-CTP). Disease activity of RA was measured by erythrocyte sedimentation rate, C reactive protein, and Ritchie and Thompson joint scores. RESULTS: Disease activity was initially high, and decreased during corticosteroid pulse treatment and the following five weeks. Osteocalcin, alkaline phosphatase, and pro-I-CPP concentrations were initially within normal limits, while I-CTP, Dpyr, and Pyr were increased. Osteocalcin and pro-I-CPP concentrations decreased (p < 0.01) during corticosteroid pulse treatment, but rapidly returned to baseline after the treatment. No changes were observed in alkaline phosphatase and urinary excretion of calcium and hydroxyproline. Bone resorption measured by serum I-CTP and urinary excretion of Pyr and Dpyr was unchanged or decreased (p < 0.05-0.01), depending on the time of measurement and the parameter measured. CONCLUSIONS: In these patients with active RA, bone resorption was increased, while bone formation was within normal limits. During high dose corticosteroid pulse treatment, bone formation was only transiently decreased, while markers of bone resorption were unchanged or decreased. Because corticosteroid pulse treatment has only a short term negative effect on bone formation, and because it probably reduces bone resorption, at least partly as a result of the decreased disease activity, the effect of corticosteroid pulse treatment on bone may be assumed to be relatively mild.     

Evidence for dramatically increased bone turnover in spontaneously hypertensive rats

Using the 3H-tetracycline model, whole-body skeletal bone resorption was compared among male and female spontaneously hypertensive (SHR) rats and normotensive Wistar Kyoto (WKy) and Sprague-Dawley (SD) rats. Immature animals undergoing rapid skeletal growth and bone sculpting showed a tendency for decreased indices of skeletal resorption in females compared with males. By 24 weeks of age, the indices of the rate of resorption and extent of metabolically reactive bone in male rats were decreased a mean of 68% and 74%, respectively, compared with values obtained at 8 weeks. By comparison, values for 24-week-old females decreased only 26% and 56%, respectively, evidence for a significantly elevated level of resorptive activity in mature females compared with males in each of the 3 rat strains. Within-sex comparisons of 24-week-old animals indicated that bone resorptive activity was similar between normotensive male and normotensive female groups. By comparison, the resorptive activity was significantly increased in both male and female hypertensive rats compared with normotensive controls. This condition was exaggerated in female hypertensive rats, which showed an approximate 81% and 44% increase in the indices of rate of resorption and extent of metabolically reactive bone compared with normotensive WKy controls. The results indicate a marked sexual dichotomy in the decline of skeletal bone resorptive activity following maturation and slowing of skeletal growth. They further indicate a significant elevation of whole skeleton bone turnover in male SHR rats and dramatically increased bone turnover in female SHR rats.     

The effect of a gonadotropin-releasing hormone agonist analog (nafarelin) on bone metabolism

The effect on bone metabolism of an agonist analog of GnRH, nafarelin, was studied in 16 premenopausal women, who received 200 micrograms nafarelin/day for 6 months, and 9 premenopausal women, who received 400 micrograms nafarelin/day for 6 months, followed by a 6-month follow-up period. Bone mineral content in the forearm (measured by single photon absorptiometry) and in the spine (measured by dual photon absorptiometry) significantly decreased after 6 months of treatment with 400 micrograms nafarelin, but 6 months after termination of treatment all bone mineral measurements had returned to pretreatment levels. The bone mineral measurements in the 200 micrograms group did not change throughout the study. In both treatment groups the biochemical estimates of bone turnover increased significantly to postmenopausal levels. Withdrawal of treatment resulted in an abrupt decrease in the bone resorption parameters (fasting urinary hydroxyproline to creatinine and calcium to creatinine excretion ratios and serum phosphate), whereas there was a protracted fall in the bone formation parameters (plasma bone Gla protein and serum alkaline phosphatase) 6 months after termination of treatment. Our findings demonstrate that nafarelin in both doses increased biochemical indices of bone turnover, that 400 micrograms/day nafarelin resulted in a significant decrease in bone mineral content, and that these effects were reversible.     

柚皮苷联合运动对去势大鼠骨量和骨强度的影响

目的观察柚皮苷（NG）联合中强度跑台运动对去势大鼠骨质疏松模型的治疗效果。方法2月龄雌性SD大鼠80只,用随机数字法分为假手术组（SHAM）、去势组（OVX）、去势＋不同浓度（40、100、200 mg/kg）柚皮苷组（OVX＋NG）、去势＋跑台＋柚皮苷组（OVX＋EX＋NG）、去势＋跑台组（OVX＋EX）、雌激素组（OVX＋E2）,每组10只。大鼠切除卵巢2个月后开始给药,给药60 d后观察各组大鼠股骨骨密度（BMD）,Micro-CT参数,血清生化指标及及股骨力学性能与组织学改变。结果柚皮苷与跑台运动干预60 d后,OVX＋EX＋NG组大鼠股骨颈力学强度、股骨BMD、BV/TV、Tb.N、Tb.Th等均高于单纯去势组（P〈0.05）,OVX＋EX＋NG组治疗效果与柚皮苷浓度呈正相关,以200 mg/kg柚皮苷效果最佳;200 mg/kg柚皮苷联合中强度跑台运动可进一步提高治疗效果。OVX＋NG组大鼠血清骨钙素升高,Ⅰ型胶原C端肽（CTX-1）降低;OVX＋EX组大鼠骨钙素与CTX-1均降低;OVX＋EX＋NG组大鼠骨钙素水平与柚皮苷组（200 mg/kg）无差异,但高于OVX＋EX。OVX＋EX＋NG组CTX-1水平低于单纯柚皮苷组和单纯跑台组（P〈0.05）。结论柚皮苷联合中强度跑台运动可提高去势大鼠股骨BMD,增加骨小梁数目,改善骨代谢指标,提高股骨力学性能。     

High calcium diet reduces blood pressure in exercised and nonexercised hypertensive rats

The effects of long-term high calcium diet and physical exercise and their combined effects on the development of hypertension, plasma and tissue atrial natriuretic peptide, and arterial function were studied in spontaneously hypertensive rats with Wistar-Kyoto rats serving as normotensive controls. Hypertensive rats were made to exercise by running on a treadmill up to 900 m/day. Calcium supplementation was instituted by increasing the calcium content of the chow from 1.1% to 2.5%. During the 23-week study, calcium supplementation attenuated the rise in blood pressure in both trained and nontrained hypertensive animals, whereas exerise training had no significant effect on blood pressure. The high calcium diet alone was associated with reduced plasma and ventricular tissue contents of atrial natriuretic peptide, both of which were increased by exercise. Responses of mesenteric arterial rings in vitro were examined at the end of the study. Neither increased dietary calcium nor endurance training affected the contractile sensitivity of endothelium-intact preparations to potassium chloride or norepinephrine. However, a high calcium diet enhanced the arterial relaxation induced by the return of potassium to the organ bath upon precontraction with potassium-free solution, and also moderately augmented relaxations to acetylcholine, sodium nitrite, and isoproterenol. Exercise training did not affect the potassium relaxation rate, but enhanced responses to acetylcholine isoproterenol, and sodium nitrite. In conclusion, enhanced arterial potassium relaxation, a response reflecting the function of the vascular sodium pump, paralleled well the long-term blood pressure lowering action of increased dietary calcium intake in exercised and nonexercised hypertensive rats. However, augmented arterial relaxation to agonists could also be observed in the absence of reduced blood pressure following regular physical exercise.     

Estrogen regulates the rate of bone turnover but bone balance in ovariectomized rats is modulated by prevailing mechanical strain

Estrogen deficiency induced bone loss is associated with increased bone turnover in rats and humans. The respective roles of increased bone turnover and altered balance between bone formation and bone resorption in mediating estrogen deficiency-induced cancellous bone loss was investigated in ovariectomized rats. Ovariectomy resulted in increased bone turnover in the distal femur. However, cancellous bone was preferentially lost in the metaphysis, a site that normally experiences low strain energy. No bone loss was observed in the epiphysis, a site experiencing higher strain energy. The role of mechanical strain in maintaining bone balance was investigated by altering the strain history. Mechanical strain was increased and decreased in long bones of ovariectomized rats by treadmill exercise and functional unloading, respectively. Functional unloading was achieved during orbital spaceflight and following unilateral sciatic neurotomy. Increasing mechanical loading reduced bone loss in the metaphysis. In contrast, decreasing loading accentuated bone loss in the metaphysis and resulted in bone loss in the epiphysis. Finally, administration of estrogen to ovariectomized rats reduced bone loss in the unloaded and prevented loss in the loaded limb following unilateral sciatic neurotomy in part by reducing indices of bone turnover. These results suggest that estrogen regulates the rate of bone turnover, but the overall balance between bone formation and bone resorption is influenced by prevailing levels of mechanical strain.