Micro-CT检测中等强度跑台运动对去卵巢大鼠腰椎微结构的影响

目的用micro-CT方法,评估中等强度跑台运动对去卵巢大鼠腰椎微结构的影响。方法将30只3月龄雌性SD大鼠按体重分层后随机分为假手术、去卵巢静止和去卵巢运动三个组。运动组每周进行4次45min、速度18 m/min、坡度5°的跑台训练。正式运动处理14周时,取第2腰椎检测骨密度,取第4腰椎行micro-CT分析及三维结构重建;取第3腰椎椎体进行椎体压缩实验。结果去卵巢运动组第2腰椎骨密度、第3腰椎最大载荷、最大应力和弹性模量以及第4腰椎骨小梁体积和骨小梁数目显著高于去卵巢静止组,骨小梁分离度显著低于去卵巢静止组,而骨小梁厚度无显著变化。结论中等强度跑台运动能改善去卵巢大鼠腰椎的微结构。     

阿司匹林对去势大鼠腰椎骨密度及微观结构的影响

目的:研究阿司匹林对去势(卵巢切除)大鼠腰椎骨密度及微观结构的影响。方法:取48只3月龄SD雌性大鼠随机分为6组:去势组(OVX组)、对照组(Sham组)及4个阿司匹林治疗组(Aspirin组),每组8只。OVX组及Aspirin组采用卵巢切除法建立骨质疏松模型。去势后1周,阿司匹林治疗组剂量分别为2.25、4.46、8.92及26.75 mg/kg(A1、A2、A3及A4组),每天灌胃一次,OVX组及Sham组予同等量生理盐水灌胃。灌胃3个月后处死,剖取腰椎椎体,以双能X线吸收骨密度测量仪(DXA)和Micro-CT进行测量分析。结果:DXA分析结果显示:阿司匹林各剂量组BMD值较OVX组有统计学差异(P<0.01)。Micro-CT分析表明:与OVX组比较,阿司匹林各剂量组BV/TV、Tb.Th、Tb.N、BMD均显著性提高(P<0.01),BS/BV、Tb.Sp显著性降低(P<0.01),阿司匹林各剂量组BV/TV、BS/BV、Tb.Th、Tb.N、Tb.Sp、BMD与Sham组相比有统计学差异(P<0.01)。结论:阿司匹林可以改善去势大鼠骨小梁结构,增加骨质密度,对去势大鼠骨质疏松具有防治作用,其作用途径可能包括抑制骨吸收和刺激骨形成两方面。     

Silicon Supplementation Improves the Bone Mineral Density of Calcium-Deficient Ovariectomized Rats by Reducing Bone Resorption

The purpose of this study was to investigate the effect of silicon (Si) supplementation on bone mineral density (BMD) and bone metabolism parameters relative to calcium (Ca) intake levels in ovariectomized rats. A total of 72 female Wistar rats (6 weeks) were ovariectomized (OVX) and divided into six groups, and Si (500 mg of Si per kilogram of feed) was or was not administered with diets containing various levels of Ca (0.1%, 0.5%, and 1.5%) for 10 weeks. The groups were as follows: (1) Ca-deficient group (0.1% Ca), (2) Ca-deficient with Si supplementation group, (3) adequate Ca group (0.5% Ca), (4) adequate Ca with Si supplementation group, (5) high Ca group (1.5% Ca), and (6) high Ca with Si supplementation group. Si supplementation significantly increased the BMD of the femur and tibia in Ca-deficient OVX rats, while no change was observed with Si supplementation in the BMD of the spine, femur, and tibia in the adequate and high Ca groups. Serum alkaline phosphatase and osteocalcin levels were not affected by Si supplementation or Ca intake levels. C-telopeptide type I collagen levels were significantly decreased as a result of Si supplementation in Ca-deficient OVX rats. In summary, Si supplementation produced positive effects on bone mineral density in Ca-deficient OVX rats by reducing bone resorption. Therefore, Si supplementation may also prove to be helpful in preventing osteoporosis in postmenopausal women whose calcium intake is insufficient.     

The effects of long-term exposure to extremely low-frequency magnetic fields on bone formation in ovariectomized rats

The effects of long‐term extremely low‐frequency magnetic field (ELF‐MF) exposure on bone formation and biochemical markers were investigated in ovariectomized rats. Sixty mature female Sprague–Dawley rats were randomly divided into four different groups (n = 15): (i) unexposed control (CTL); (ii) ovariectomized only (OVX); (iii) non‐ovariectomized, exposed (SHAM + ELF‐MF); and (iv) ovariectomized, exposed (OVX + ELF‐MF). The third and fourth groups were exposed to 1.5 mT ELF‐MF for 4 h a day for 6 months. Bone mineral density (BMD) was determined using dual energy X‐ray absorption (DEXA) measurements. The formation and resorption of bone were evaluated using bone‐specific alkaline phosphatase (BAP), osteocalcin, osteoprotogerin, and N‐telopeptide. After 6 months of ELF‐MF therapy, BMD values were significantly lower in the OVX group and higher in the OVX + ELF‐MF and SHAM + ELF‐MF groups than they were before therapy (P < 0.001). Although there was no significant difference in BMD values among the groups before therapy, the BMD values increased significantly after 6 months in the OVX + ELF‐MF and SHAM + ELF‐MF groups and were reduced in the OVX group compared to the CTL group (P < 0.001). The concentrations of BAP, osteocalcin, osteoprotogerin, and N‐telopeptide in the three experimental groups also changed in a significant way compared to the CTL group. The results of the present study suggest that osteoporosis can be inhibited by ELF‐MF stimulation treatments. It was also concluded that ELF‐MF may be useful in the prevention of osteoporosis in ovariectomized rats. Bioelectromagnetics 33:543–549, 2012. © 2012 Wiley Periodicals, Inc.     

去卵巢大鼠腰椎骨微结构变化的动态观察

目的:动态观察去卵巢大鼠腰椎骨微结构的变化。方法:将90只3月龄雌性SD大鼠按体重进行分层随机抽样分组,分为基础组(10只)、假手术组(40只)和去卵巢组(40只)。手术前(0周)处死基础组大鼠,手术后3、6、12、24周时,分批处死假手术和去卵巢组大鼠各8-10只。从每组随机取6只大鼠的第5腰椎行micro-CT扫描及三维结构重建,选取椎体1 mm处,2.0 mm×3.5mm,厚0.9 mm的骨组织为感兴趣区域(interesting area),进行骨形态计量学分析。结果:与同一时间点假手术组大鼠比较,去卵巢3周时,第5腰椎体积骨密度(v BMD)、骨体积分数(BV/TV)、骨小梁数目(Tb.N)、骨小梁厚度(Tb.Th)、骨小梁间隙(Tb.Sp)和结构模型指数(SMI)均无显著变化;去卵巢6周时,Tb.Th显著下降(P0.05),而其他指标均无显著变化;从去卵巢12周到24周时,不仅Tb.Th显著下降(P0.05),而且v BMD、BV/TV和Tb.N也显著下降(P0.05),同时Tb.Sp和SMI显著增加(P0.05)。结论:3月龄大鼠在去卵巢后的6周时骨小梁厚度变薄,12周以后,体积骨密度和骨体积分数下降,骨小梁数目减少。     

Combined Effects of Phytoestrogen Genistein and Silicon on Ovariectomy-Induced Bone Loss in Rat

This study was performed to evaluate the effect of concomitant supplementation of genistein and silicon on bone mineral density and bone metabolism-related markers in ovariectomized rat. Three-month-old Sprague Dawley female rats were subjected to bilateral ovariectomy (OVX) or sham surgery, and then the OVX rats were randomly divided into four groups: OVX-GEN, OVX-Si, OVX-GEN-Si, and OVX. Genistein and silicon supplementation was started immediately after OVX and continued for 10 weeks. In the OVX-GEN group, 5 mg genistein per gram body weight was injected subcutaneously. The OVX-Si group was given soluble silicon daily in demineralized water (Si 20 mg/kg body weight/day). The OVX-GEN-Si group was given subcutaneous injections of 5 mg genistein per gram body weight, at the same time, given soluble silicon daily (Si 20 mg/kg body weight/day). The results showed that the genistein supplementation in the OVX rats significantly prevented the loss of uterus weight; however, the silicon supplementation showed no effect on the uterus weight loss. The lumbar spine and femur bone mineral density was significantly decreased after OVX surgery; however, this decrease was inhibited by the genistein and/or silicon, and the BMD of the lumbar spine and femur was the highest in the OVX-GEN-Si-treated group. Histomorphometric analyses showed that the supplementation of genistein and/or silicon restored bone volume and trabecular thickness of femoral trabecular bone in the OVX group. Besides, the treatment with genistein and silicon for 10 weeks increased the serum levels of calcium and phosphorus in the OVX rats; serum calcium and serum phosphorus in the OVX-GEN-Si group were higher than those in the OVX-GEN and OVX-Si group (P < 0.05). At the same time, the treatment with genistein and/or silicon decreased serum alkaline phosphatase (ALP) and osteocalcin, which were increased by ovariectomy; serum ALP and osteocalcin in the OVX-GEN-Si group were lower than those in the OVX-GEN and OVX-Si groups (P < 0.05). The results above indicate that genistein and silicon have synergistic effects on bone formation in ovariectomized rats.     

Anti-resorptive effect of pilose antler blood (Cervus nippon Temminck) in ovariectomized rats

Anti-bone resorption activity of pilose antler blood (Cervus nippon Temminck) were evaluated in ovariectomized Wistar rats. The rats were randomly divided into sham operated group (SHAM), ovariectomized group (OVX) and pilose antler blood treated group. The ovariectomized rats were treated with pilose antler blood orally in 4000 microl/kg daily doses for 10 weeks. Compared with SHAM group, serum 17 beta-estradiol level decreased significantly and osteocalcin level increased significantly in OVX group, indicating successful model of osteoporosis. The experiments showed that the bone mineral density of the lumbar spine and left femur in OVX group decreased remarkably compared to SHAM group but normalized by treatment with pilose antler blood. Additionally, serum levels of insulin-like growth factor-land testosterone were lower obviously in OVX group than those in SHAM group but preserved by pilose antler blood treatment. However, no obvious changes in serum levels of calcium, phosphorus, total alkaline phosphatase and osteoprotegerin were observed among three groups. These results suggested that administration of pilose antler blood was effective in alleviating osteoporosis in ovariectomized rats.     

Analysis of Bacteria,Parasites, and Heavy Metals in Lettuce (<Emphasis Type="Italic">Lactuca sativa</Emphasis>) and Rocket Salad (<Emphasis Type="Italic">Eruca sativa</Emphasis> L.) Irrigated with Treated Effluent from a Biological Wastewater Treatment Plant

The purpose of this study was to verify the effect of organic gallium on ovariectomized osteopenic rats. Thirty Wistar female rats used were divided into three groups: (1) sham-operation rats (control), (2) ovariectomized (OVX) rats with osteopenia, and (3) OVX rats with osteopenia treated with organic gallium. Treatments were performed over an 8-week period. At sacrifice, the fifth lumbar vertebral body, one tibia, one femur, and the fourth lumbar vertebrae were removed, subjected to micro-CT for determination of trabecular bone structure, and then processed for histomorphometry to assess bone turnover. The femoral neck was used for mechanical compression testing. Treatment with organic gallium increased bone volume in OVX animals. Organic gallium-treated animals had significant increases in trabecular and cortical thickness and bone strength. The plasma total calcium and inorganic phosphate concentrations in OVX rats decreased and bone mineral content in the lumbar vertebrae and femur increased after treatment with organic gallium. These data provide an important proof of concept that organic gallium may represent a powerful approach to treating or reversing severe osteoporosis in humans.     

Anabolic effects of recombinant human parathyroid hormone (1 - 84) and synthetic human parathyroid hormone (1 - 34) on the mandibles of osteopenic ovariectomized rats with maxillary molar extraction.

In rodent osteoporosis models such as ovariectomized (OVX) rats, intermittently administered human parathyroid hormone (hPTH) has an anabolic effect in vertebrae and long bones. In the present experiments, subcutaneously injected hPTH(1 - 34) or hPTH(1 - 84) dose- and time-dependently increased bone mineral density (BMD) as measured by dual energy X-ray absorptiometry in mandibles, L2 to L4 vertebrae and femurs of such rats. The highest dose (15.9 nmol/kg, s. c.) of either peptide given four times weekly for 10 weeks completely reversed the effects of overiectomy on BMD. Significant elevation in lumbar BMD after 10 weeks was observed with hPTH(1 - 34) or hPTH(1 - 84) at 1.1 nmol/kg, whereas hPTH(1 - 34) at 1.1 and 4.2 nmol/kg significantly increased BMD of the whole bone and the metaphysis of the femur and the diaphysis of the bone, respectively. In contrast, significant effects of hPTH(1 - 84) administration on BMD increase in the femur were observed at 4.2 and 15.9 nmol/kg in the whole bone and the metaphysis, and in the diaphysis, respectively. Maxillary molar extraction left mandibular BMD in rats with intact ovaries unchanged, but significantly decreased mandibular BMD in OVX rats. Administration of hPTH(1 - 84) for 10 weeks in OVX rats without or with extraction significantly increased BMD in the mandibular molar region at doses of 15.9 and 4.2 nmol/kg, respectively, indicating that efficacy was increased by extraction. A significant BMD increase in the molar region in OVX rats with extraction occurred at only 1.1 nmol/kg of hPTH(1 - 34) and 4.2 nmol/kg of hPTH(1 - 84). Also, BMD of the ramus region was increased by administration of both peptides to a lesser extent than that of the molar region in these rats. Thus, intermittent administration of hPTH, especially hPTH(1 - 34), has an anabolic effect on bone, particularly alveolar bone. Such treatment may increase alveolar bone mass in postmenopausal women with osteoporosis.     

Comparison of the Therapeutic Effects of Yeast-incorporated Gallium with those of Inorganic Gallium on Ovariectomized Osteopenic Rats

The purpose of this study was to verify the effect of organic gallium on ovariectomized osteopenic rats. Thirty Wistar female rats used were divided into three groups: (1) sham-operation rats (control), (2) ovariectomized (OVX) rats with osteopenia, and (3) OVX rats with osteopenia treated with organic gallium. Treatments were performed over an 8-week period. At sacrifice, the fifth lumbar vertebral body, one tibia, one femur, and the fourth lumbar vertebrae were removed, subjected to micro-CT for determination of trabecular bone structure, and then processed for histomorphometry to assess bone turnover. The femoral neck was used for mechanical compression testing. Treatment with organic gallium increased bone volume in OVX animals. Organic gallium-treated animals had significant increases in trabecular and cortical thickness and bone strength. The plasma total calcium and inorganic phosphate concentrations in OVX rats decreased and bone mineral content in the lumbar vertebrae and femur increased after treatment with organic gallium. These data provide an important proof of concept that organic gallium may represent a powerful approach to treating or reversing severe osteoporosis in humans.     

跑台运动训练和停训对去卵巢大鼠体成分和骨密度的影响

目的:研究中等强度跑台运动训练和停训对去卵巢大鼠骨密度和体成分的影响。方法:将60只成年雌性SD大鼠按体重分层后随机分为假手术组、去卵巢静止组和去卵巢运动组,每组20只。去卵巢运动组大鼠每周进行4次时间45min、速度18m/min、跑道倾角5℃的跑台训练,持续训练14周时,将各组大鼠又随机分为两个亚组,即:假手术-16周(Sham-16)和假手术32周(Sham-32)组、去卵巢-16周(OVX-16)和去卵巢-32周(OVX-32)组以及去卵巢运动(EX)和停训组(DEX)。分别在末次训练结束36-48小时内或停训16周时,用双能X线骨密度仪检测各组大鼠体成分和骨密度的变化。结果:(1)训练结束时,OVX-16组大鼠体脂重量和含量显著高于Sham-16和EX组,而瘦体含量、全身骨密度和腰椎骨密度显著低于Sham-16和EX组,各组其他检测指标无显著变化。(2)停训16周时,OVX-32组大鼠体重、脂肪重量和体脂含量显著高于Sham-32组,而全身、腰椎和左右股骨骨密度以及瘦体含量显著低于Sham-32组;DEX组大鼠脂肪重量和体脂含量显著高于OVX-32组,而瘦体含量显著低于OVX-32组。结论:跑台运动对去卵巢大鼠体成分和骨密度的改善效应在停训16周时均未能被保持。     

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.     

Alfacalcidol restores cancellous bone in ovariectomized rats

Active vitamin D metabolites have been demonstrated to reduce vertebral and hip fractures in elderly patients. A number of in vitro and in vivo pre-clinical studies have suggested that vitamin D may effectively stimulate osteoblastic activity and exert an anabolic effect on bone. The current study was designed to further explore the ability of an active vitamin D analog to restore bone in a skeletal site with established osteopenia in ovariectomized (OVX) rats. Female Sprague Dawley rats at five months of age and 8 weeks after sham ovariectomy or ovariectomy were randomly divided into 7 groups with 10 per group. At the beginning of the treatments, one group of sham-operated rats and one group of OVX rats were sacrificed to serve as baseline controls. Another group of sham-operated rats and one group of OVX rats were treated with vehicle for 4 weeks. The OVX rats in the remaining groups were treated with alfacalcidol at 0.05, 0.1 or 0.2 microg/kg/d by daily oral gavage, 5 days/week for 4 weeks. As expected, estrogen depletion caused high bone turnover and cancellous bone loss in lumbar vertebra of OVX rats. Alfacalcidol treatment at 0.1 or 0.2 but not 0.05 microg/kg/d increased serum calcium and phosphorus in OVX rats as compared with vehicle treatment. In addition, serum parathyroid hormone was suppressed, whereas serum osteocalcin was increased by alfacalcidol at all dose levels. Furthermore, histomorphometric data of 2nd lumbar vertebral body revealed that cancellous bone volume in OVX rats treated with alfacalcidol at 0.1 or 0.2 microg/kg/d was increased to the level of sham-operated rats treated with vehicle. This increment in cancellous bone mass was accompanied by increases in trabecular number and thickness and a decrease in trabecular separation. Moreover, osteoclast surface and number were significantly decreased, whereas bone formation variables such as mineralizing surface and bone formation rate were significantly increased in alfacalcidol- treated OVX rats compared with those of vehicle-treated OVX rats. Finally, a linear regression analysis showed that alfacalcidol treatment dose-dependently altered most of the variables measured in the current study. In conclusion, alfacalcidol completely restores cancellous bone by stimulating bone formation and suppressing bone resorption in lumbar vertebra of OVX rats when the treatment is started at an early phase of osteopenia. The evidence of increased bone formation by alfacalcidol treatments further supports the notion that active vitamin D metabolites or their analogs may exert anabolic effects on bone.     

The selective estrogen receptor modulator SCH 57068 prevents bone loss, reduces serum cholesterol and blocks estrogen-induced uterine hypertrophy in ovariectomized rats

Our objective was to determine the effects of SCH 57068 alone and with 17 beta-estradiol (E(2)) on bone, lipids and uteri in ovariectomized (OVX) rats. In OVX animals lumbar vertebral and femoral bone mineral density (BMD) were significantly higher after 12 weeks of treatment with SCH 57068 than in untreated OVX controls. Similarly BMD was superior in OVX + E(2) + SCH 57068 treated animals than in OVX + E(2) controls. SCH 57068 also significantly reduced the increase in bone turnover markers, serum pyridinoline and serum osteocalcin levels, induced by OVX, and increased mechanical bone strength. SCH 57068 also significantly reduced the rise in serum cholesterol and low-density lipoprotein cholesterol induced by OVX. SCH 57068 had no stimulatory effect on uterine epithelium when given alone in OVX rats. SCH 57068 (1 and 2.5 mg/kg) reduced uterine weight and blocked endometrial stimulation induced by E(2). In summary, SCH 57068 adds to the positive effects of E(2) on bone and lipid metabolism but blocks the stimulatory effects of E(2) on the uterus. Potentially, E(2) + SCH 57068 could be combined for the treatment and prevention of breast cancer or as a novel hormone replacement therapy.     

跑台运动训练和停训对去卵巢大鼠体成分和骨密度的影响

目的：研究中等强度跑台运动训练和停训对去卵巢大鼠骨密度和体成分的影响。方法：将60只成年雌性SD大鼠按体重分层后随机分为假手术组、去卵巢静止组和去卵巢运动组,每组20只。去卵巢运动组大鼠每周进行4次时间45min、速度18m／rain、跑道倾角5℃的跑台训练,持续训练14周时,将各组大鼠又随机分为两个亚组,即：假手术-16周（Sham．16）和假手术32周（Sham-32）组、去卵巢-16周（OVX-16）和去卵巢-32周（OVX-32）组以及去卵巢运动（EX）和停训组（DEX）。分别在末次训练结束36—48小时内或停训16周时,用双能X线骨密度仪检测各组大鼠体成分和骨密度的变化。结果：（1）训练结束时,OVX-16组大鼠体脂重量和含量显著高于Sham-16和EX组,而瘦体含量、全身骨密度和腰椎骨密度显著低于Sham-16和EX组,各组其他检测指标无显著变化。（2）停训16周时,OVX-32组大鼠体重、脂肪重量和体脂含量显著高于Sham-32组,而全身、腰椎和左右股骨骨密度以及瘦体含量显著低于Sham．32组;DEX组大鼠脂肪重量和体脂含量显著高于OVX-32组,而瘦体含量显著低于OVX-32组。结论：跑台运动对去卵巢大鼠体成分和骨密度的改善效应在停训16周时均未能被保持。     

Short term effects on bone quality associated with consumption of soy protein isolate and other dietary protein sources in rapidly growing female rats

Beneficial effects of soy protein consumption on bone quality have been reported. The effects of other dietary protein sources such as whey protein hydrolysate (WPH) and rice protein isolate (RPI) on bone growth have been less well examined. The current study compared effects of feeding soy protein isolate (SPI), WPH and RPI for 14 d on tibial bone mineral density (BMD) and bone mineral content (BMC) in intact and ovariectomized (OVX) rapidly growing female rats relative to animals fed casein (CAS). The effects of estrogenic status on responses to SPI were also explored. Tibial peripheral quantitative computerized tomography (pQCT) showed all three protein sources had positive effects on either BMD or BMC relative to CAS (P < 0.05), but SPI had greater effects in both intact and OVX female rats. SPI and E2 had positive effects on BMD and BMC in OVX rats (P < 0.05). However, trabecular BMD was lower in a SPI + E2 group compared to a CAS + E2 group. In OVX rats, SPI increased serum bone formation markers, and serum from SPI-fed rats stimulated osteoblastogenesis in ex vivo. SPI also suppressed the bone resorption marker RatLaps (P < 0.05). Both SPI and E2 increased alkaline phosphatase gene expression in bone, but only SPI decreased receptor activator of nuclear factor-kappaB ligand (RANKL) and estrogen receptor gene expression (P < 0.05). These data suggest beneficial bone effects of a soy diet in rapidly growing animals and the potential for early soy consumption to increase peak bone mass.     

In vivo anti-osteoporotic activity of isotaxiresinol, a lignan from wood of Taxus yunnanensis

Isotaxiresinol, the main lignan isolated from the water extract of wood of Taxus yunnanensis, was investigated for its effect on bone loss, on serum biochemical markers for bone remodeling and on uterine tissue, using ovariectomized (OVX) rats as the model of postmenopausal osteoporosis. After oral administration of isotaxiresinol (50 and 100mg/kg/d) for 6 weeks, bone mineral content (BMC) and bone mineral density (BMD) in total and cortical bones were increased as compared to those of OVX control rats, and decreases of three bone strength indexes induced by OVX surgery were prevented. Serum biochemical markers for bone remodeling revealed that isotaxiresinol slightly increased bone formation and significantly inhibited bone resorption without side effect on uterine tissue. These results suggest that isotaxiresinol may be useful for treatment of postmenopausal osteoporosis, especially for prevention of bone fracture induced by estrogen deficiency.     

Effect of dietary calcium: Phosphorus ratio on bone mineralization and intestinal calcium absorption in ovariectomized rats

We investigated the effect of dietary calcium:phosphorus (Ca:P) ratio on bone mineralization and intestinal Ca absorption in ovariectomized (OVX) rat models of osteoporosis and sham-operated rats. Thirty 12-wk-old female Wistar rats were divided into three groups of OVX rats and three groups of sham rats. Thirty days after the adaptation period, OVX rats and sham rats were fed a diet formulated Ca:P, 1:0.5, 1:1 or 1:2 (each diet containing 0.5% Ca), respectively for 42 d. In both sham and OVX rats, serum osteocalcin, a marker of bone turnover, was increased by decreasing Ca:P ratio (1:2). In contrast, rats fed the Ca:P = 1:0.5 diet (dietary P restriction) suppressed the increased serum parathyroid hormone, osteocalcin and urinary deoxypyridinoline, and increased Ca absorption in both sham and OVX rats compared to the Ca:P = 1:1 and 1:2 diets. Especially, in OVX rats, the decreased bone mineral density of the fifth lumbar was also suppressed when rats were fed the Ca:P = 1:0.5 diet. These results indicated that the elevation of dietary Ca:P ratio may inhibit bone loss and increase intestinal Ca absorption in OVX rats.     

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.     

Hesperidin inhibits ovariectomized-induced osteopenia and shows differential effects on bone mass and strength in young and adult intact rats.

The main aim of this study was to investigate the bone-sparing effect of hesperidin, one of the main flavonoid present in oranges, in two age groups of ovariectomized female rats, compared with their intact controls. Young (3 mo) and adult (6 mo) female Wistar rats were sham operated (SH) or ovariectomized (OVX) and then pair-fed for 90 days a casein-based diet supplemented or not with 0.5% hesperidin (Hp; n = 10/group). In older rats, Hp intake led to a partial inhibition of OVX-induced bone loss, whereas a complete inhibition was obtained in younger animals. At both ages, while plasma osteocalcin concentrations were unchanged, urinary excretion of deoxypyridinoline was reduced by Hp intake, suggesting that Hp was able to slow down bone resorption. Unexpectedly, in intact young rats, Hp consumption resulted in a significant increase in bone mineral density (BMD). Indeed, 6-mo-old HpSH rats had a similar BMD to 9-mo-old nontreated SH adult rats, suggesting an accelerated bone mass gain in the young rats. In contrast, in intact adult rats, Hp did not further increase BMD but did improve their bone strength. The results of this study show a protective effect of Hp on bone loss in OVX rats of both ages without uterine stimulation and accompanied by a lipid-lowering effect. The unexpected and intriguing findings obtained in intact rats showing improved BMD in young rats and improved femoral load in adult rats merit further investigation. The bone and lipid benefits of hesperidin make it an attractive dietary agent for the management of the health of postmenopausal women.