Effects of Promethazine on Bone Mass and on Bone Remodeling in Ovariectomized Rats: A Morphometric, Densitometric, and Histomorphometric Experimental Study

The effect of promethazine on bone is debated. We studied the effect of promethazine on bone and the mechanism of action involved by densitometric and histomorphometric measurements in female Wistar rats (100 days old, mean weight 25 ± 20 g). A control group of 15 rats was not manipulated. An experimental group of 15 rats were ovariectomized (OVX) at 100 days of life and fed a diet supplemented with 4.8 mg/kg promethazine hydrochloride (OVX + Prom). The group that underwent OVX and a group of 15 rats that underwent sham ovariectomy (Sham-OVX) were not treated with promethazine. After 30 days, all the rats were killed. Their femur and 5th lumbar vertebra were dissected and cleaned of soft tissue. Femoral length and vertebral height were measured with a caliper and bones were weighed on a precision balance. The bone mineral content (BMC) and bone mineral density (BMD) of the whole right femurs and 5th lumbar vertebras were measured by dual-energy X-ray absorptiometry (DXA). Trabecular bone volume (Cn-BV-TV%), trabecular number (Tb-N mm⁻¹), trabecular thickness (Tb-Th μm), and trabecular separation (Tb-Sp μm) were measured in the femurs by histomorphometric study of nondecalcified bone. Our results showed that promethazine significantly inhibited postovariectomy loss of bone mass (P < 0.0001) by significantly reducing bone resorption, as shown by the smaller trabecular spaces observed in the treated OVX rats (P < 0.0001). Received: 1 June 1998 / Accepted: 17 February 1999     

中等强度跑台运动对去卵巢大鼠后肢骨骨矿物含量和骨密度的双重调节作用

目的 观察中等强度跑台运动对去卵巢大鼠后肢骨骨矿物含量(BMC)和骨密度(BMD)的影响.方法 将60只3月龄未经产雌性SD大鼠按体重随机分为假手术、去卵巢静止、去卵巢运动Ⅰ、去卵巢运动Ⅱ、去卵巢运动Ⅲ和去卵巢运动Ⅳ 6个组.各运动组经1周的跑台适应训练后,按实验设计分别进行为期14周的正式跑台训练.实验结束时,腹主动脉取血处死大鼠,双能χ-射线骨密度仪检测右侧游离股骨和胫骨的BMC和BMD.结果 ①与假手术组相比,去卵巢静止组股骨近端和远端以及胫骨近端BMC和BMD显著下降,但股骨中段以及胫骨中段和远端BMC和BMD无显著变化.②与去卵巢静止组相比,去卵巢运动Ⅰ组股骨近端和远端BMC显著增加,股骨中段以及胫骨3个部位BMC均无显著变化;去卵巢运动Ⅱ组和Ⅲ组股骨和胫骨3个部位BMC 均无显著变化;去卵巢运动Ⅳ组股骨3个部位BMC均无显著变化,而胫骨3个部位BMC均显著下降.③与去卵巢静止组相比,去卵巢运动Ⅰ组股骨近端和远端以及胫骨近端BMD 显著增加, 而股骨中段和胫骨中段和远端BMD无显著变化;去卵巢运动Ⅱ组和Ⅲ组股骨和胫骨任何部位BMD均没有显著变化;去卵巢运动Ⅳ组股骨3个部位BMD无显著变化,而胫骨3个部位BMD却显著下降.结论 较低中等强度跑台运动能减缓去卵巢大鼠股骨近端和远端骨矿物含量和骨密度的下降;而较高中等强度跑台运动却能加速去卵巢大鼠胫骨近端骨矿物含量和骨密度的下降.     

Maintenance of bone mineral density of femoral cortex in ovariectomized rats after withdrawal of concurrent administration of human parathyroid hormone (1–34) and incardronate disodium (YM175)

The aim of this study was to evaluate the potential use of a combination of human parathyroid hormone (1–34) [hPTH(1–34)] and bisphosphonate (incadronate disodium cycloheptylaminomethylenedisphosphonate monohydrate, YM175) as a therapy for osteoporosis. We examined the effects of concurrent administration of PTH and YM175 or single administration and the persistence of their therapeutic effect after withdrawal on bone mineral density (BMD) of the femur in ovariectomized rats with established osteopenia. One hundred and two 11-week-old Sprague-Dawley rats were divided into sham operation and ovariectomy (OVX) groups. OVX rats were untreated for the first 4 weeks post ovariectomy to allow for the development of moderate ovariectomy to allow for the development of moderate osteopenia. These animals were then subjected to various treatment regimens with either PTH, YM175, or both for 4 weeks. The animals were then killed at 4 or 12 weeks, after withdrawal of the treatment and the bone mineral density (BMD) of distal, middle, proximal part, and total area of the femur were determined by dual-energy X-ray absorptiometry (DXA). In the distal femur (cancellous bone-rich region), treatment with YM failed to restore BMD in OVX rats, while treatment with PTH alone (P<.01) or PTH + YM175 (P<.01) reversed BMD in OVX rats after 4 weeks of treatments. The restored distal BMD by PTH or PTH + YM175 treatments could be maintained thereafter until 12 weeks withdrawal. In midshaft of the femur (cortical bone-rich region), treatment with PTH (P<.05), YM175 (P<.05), and PTH + YM175 (P<.01) all could increase BMD after 4 weeks of treatments in the OVX rats, but only concurrent treatment with PTH + YM175 maintained the BMD of femoral midshaft for 12 weeks after withdrawal of the treatment. These results suggest that (1) concurrent treatment with PTH and YM175 could result in a bone gain not only in cancellous bone but also in cortical bone of the femur, and (2) the restored BMD could be maintained for 12 weeks after cessation of the treatment in cortical bone only by concurrent use of PTH + YM175 in immature ovariectomized rats     

切除卵巢大鼠胫,股骨不同部位骨量的双能X线吸收法测量

目的：测定切除卵巢大鼠后肢骨不同部位骨量丢失的情况。方法：应用双能Ｘ线吸收法动态观察切除卵巢大鼠及对照组大鼠后肢骨不同部位骨密度。结果：实验组术后４周即可在股骨远端检测到明显的骨量丢失，与对照组比较差异显著。结论：股骨远端骨量变化最明显     

The effects of nandrolone decanoate on bone mass and metabolism in ovariectomized rats with osteopenia

The effects of nandrolone decanoate (ND) treatment on bone mass and metabolism were studied in ovariectomized (OVX) rats with osteopenia. The 6-month-old rats were divided into Sham (n = 12) and OVX (n = 24). The OVX rats were allowed to lose bone for 6 weeks. At 6 weeks post ovariectomy, the OVX rats were divided into two groups: (1) OVX + Vehicle and (2) OVX + ND. The effects of ND on bone mineral density (BMD), bone mineral content (BMC), and bone metabolism were studied by dual-energy X-ray absorptiometry (DXA) and biochemical markers including urinary pyridinoline (Pyr), deoxypyridinoline (Dpyr), and serum osteocalcin. After 24 weeks of treatment, histomorphometry of the right tibiae and the wet weight of the gastrocnemius and soleus skeletal muscles were also examined. Ovariectomy resulted in a significant increase in biochemical markers and a significant decrease in spine BMD (0.221 ± 0.016 g/cm² in OVX group vs 0.239 ± 0.008 g/cm² in Sham group) and BMC (0.550 ± 0.055 g in OVX group vs 0.605 ± 0.042 g in Sham group) at 6 weeks post ovariectomy. Spine BMD (0.227 ± 0.017 g/cm²), femoral BMD (0.263 ± 0.012 g/cm²), and bone density of femur (1.035 ± 0.036 g/cm³) in the OVX + ND group were significantly greater than those in the OVX + Vehicle group (0.204 ± 0.013 g/cm² for spine BMD, 0.243 ± 0.009 g/cm² for femoral BMD, 0.938 ± 0.06 g/cm³ for bone density of femur) after 24 weeks of treatment. ND treatment decreased urinary Pyr and Dpyr significantly in OVX rats. Histomorphometric findings indicated that ND-treated rats had greater cancellous bone volume, greater trabecular number, greater trabecular thickness, and less trabecular separation than vehicle-treated OVX rats. OVX rats had greater wet weight of the gastrocnemius and soleus muscles than rats treated with ND. The data suggest that the effect of ND on bone mass is not influenced by the condition of the muscles in OVX rats. Our findings indicate that ND blocks further bone loss by inhibition of bone resorption in OVX rats with osteopenia. Received: August 25, 1999 / Accepted: January 28, 2000     

Effect of Intermittent and Daily Regimens of Minodronic Acid on Bone Metabolism in an Ovariectomized Rat Model of Osteoporosis

The goal of the study was to compare the effects of minodronic acid on bone mineral density (BMD) and bone turnover in a rat ovariectomized (OVX) osteoporosis model, using two intermittent treatment regimens (weekly and 4 continuous days every 4 weeks) and a daily regimen. Female F344 rats (age 14 weeks) underwent ovariectomy or a sham operation. Minodronic acid was orally administered at 0.042, 0.21, and 1.05 mg/kg in the intermittent regimens, and at 0.03 and 0.15 mg/kg in the daily regimen for 12 weeks from the day after surgery. Minodronic acid dose-dependently ameliorated the decreases in areal BMD of the lumbar vertebrae and femur, and volumetric BMD of total and trabecular bone in the distal femur. Minodronic acid also suppressed the increase in urinary deoxypyridinoline levels and reduced serum osteocalcin levels. In bone histomorphometry, all three minodronic acid regimens suppressed OVX-induced increases in bone turnover at the tissue level and ameliorated all structural indices, except that an effect on trabecular thickness only occurred with daily treatment. In conclusion, minodronic acid administered weekly or for 4 continuous days every 4 weeks suppressed increased bone resorption and BMD to a similar extent to that of a similar total dose given daily in a rat OVX model.     

Specific evaluation of localized bone mass and bone loss in the rat using dual-energy X-ray absorptiometry subregional analysis

Dual-energy X-ray absorptiometry (DXA), together with the use of ultra-high resolution software, recently appeared as an accurate method for determining bone mineral density (BMD) in the rat. In order to assess the ability of this technique to detect changes in bone mass in the rat rapidly and precisely, we measured BMD at various sites of the femur using DXA subregional analysis. In particular, we studied the BMD of the metaphyseal part of the femur (M-BMD) rich in trabecular bone, and compared the values obtained with the cancellous bone volume measured by histomorphometry. In short-term ovariectomized animals (experiment 1), M-BMD was the only parameter to differentiate statistically between 10 ovariectomized (OVX) and 10 SHAM-operated (SHAM) rats (–11.2%,p<0.01) 9 days after surgery. M-BMD still expressed the greatest variation between OVX and SHAM rats 42 days following ovariectomy (experiment 2) (–16.1%,p<0.001 v –6.2%,p<0.01 for the total femur BMD) and confirmed previous data demonstrating a greater loss of cancellous than cortical bone after cessation of ovarian activity. M-BMD was highly correlated with cancellous bone volume (BV) in normal (r=0.82,p<0.001,n=30), OVX (r=0.77,p<0.001,n=22) and SHAM (r=0.88,p<0.001,n=21) rats. Furthermore, subcutaneous treatment with rat parathyroid hormone fragment (1–34) (r-PTH(1-34)) partially and significantly protected animals from trabecular osteopenia induced by OVX; there was a similar degree of protection of BV and M-BMD (50% and 61% respectively), while BMD of the entire femur achieved complete protection. This M-BMD measurement, specifically reflecting cancellous bone mass as confirmed by the correlation study and the response to PTH treatment, is a sensitve and simple method which can be used to assess any precocious modifications of bone density under physiopathological or therapeutic conditions in experimental rat models of bone loss.     

Restoration of ovariectomy-induced osteopenia by nitroglycerin

Nitric oxide (NO) is known to inhibit osteoclastic bone resorption. Previously, we demonstrated that the NO donor nitroglycerin (NG) prevented ovariectomy (OVX)-induced bone loss. The current study shows that NG restores ovariectomy-induced osteopenia. Twenty-four female Sprague-Dawley rats, 36 weeks of age, underwent OVX, and a further six rats were sham-operated. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometric (DXA) scanning prior to OVX, at 6 weeks postsurgery, and at 6 weeks posttreatment. OVX rats were then assigned to four groups and treated with either (1) vehicle, (2) 17-β-estradiol, (3) NG (0.2 mg/kg/day), or (4) a combination of estrogen and NG (n = 6/group). During the first 6-week post-OVX period, there was a significant decrease in the BMD in all ovariectomized (OVXed) rats (−11.0%, P < 0.001). There were no significant changes in BMD during the entire 12-week period in sham-operated rats. During the second 6-week period (after developing bone loss), there was no further significant loss of BMD in OVXed controls. BMD loss and loss of femur weight produced by OVXed were restored by treatment with estrogen, NG, or the two agents together during the second 6-week period (P < 0.01). The effects of estrogen and NG together, however, were not additive. The BMD of rats treated with NG alone, at 12 weeks, was similar to that of animals treated with estrogen alone or with estrogen and NG, and was comparable to that of sham-operated rats. The increased urinary excretion of deoxypyridinolines caused by OVX was negated by estrogen, NG, and estrogen together with NG (P < 0.01). In contrast to estrogen, NG did not decrease the post-OVX-induced increase of serum osteocalcin levels, suggesting that NG may also have a positive effect on bone formation. In summary, the results suggest that the NO donor, NG, reverses the OVX-induced bone loss in rats, and these effects are likely due to decreased bone resorption and, perhaps, increased bone formation. Received: 24 December 1998 / Accepted: 1 July 1999     

Isoflavones with supplemental calcium provide greater protection against the loss of bone mass and strength after ovariectomy compared to isoflavones alone

Although hormone replacement therapy (HRT) and calcium (Ca) supplementation preserve bone mass more when combined, there is a growing concern over the safety of HRT that necessitates thorough investigation of effective, alternative treatments for bone loss. While plant-derived estrogen-like compounds such as isoflavones preserve bone, it is not known whether isoflavones and Ca supplementation attenuate losses in bone mass and strength to a greater extent when combined. This study compared the effects of an isoflavone extract + high Ca to isoflavone extract or high Ca alone on preservation of bone mineral density (BMD) and biomechanical strength in ovariectomized (ovx) rats. Rats were sham-operated (n = 10) or ovx (n = 40). Shams were fed a 0.2% Ca diet. Ovx rats were randomized to a 0.2% Ca diet alone (OVX) or with isoflavone extract (IE; 1.6 g/kg diet) or to a high Ca diet (Ca; 2.5%) alone or a high Ca diet with the isoflavone extract (IE + Ca) for 8 weeks. BMD of femur and lumbar spine were measured by dual-energy X-ray absorptiometry. The biomechanical strength of femurs and individual vertebra was measured by three-point bending and compression testing, respectively. The average food intake was lowest (P < 0.05) among sham and IE groups and greatest (P < 0.05) among the OVX group. Final body weight was lowest (P < 0.05) among shams and highest (P < 0.05) among the OVX group while IE + Ca were lighter (P < 0.05) than all ovx groups. Femur and vertebra BMD was greater (P < 0.05) among IE + Ca and sham rats compared to IE, Ca, or OVX rats. Although there were differences in femur BMD among groups, biomechanical properties at the femur midpoint did not differ among groups, possibly due to the lack of cortical bone loss at this site. Conversely, vertebra biomechanical strength was greater (P < 0.05) among IE + Ca and Ca alone groups compared to IE alone. Uterine weight was higher (P < 0.05) among shams than OVX and IE with no difference among shams, Ca, or IE + Ca rats, suggesting that the isoflavones did not have an uterotrophic effect. In conclusion, isoflavones combined with high Ca are more protective against the loss of femur and vertebra BMD than isoflavones or high Ca diet alone.     

Effect of body weight on osteopenia in ovariectomized rats

Summary Bilateral ovariectomies or sham surgeries were performed in female Sprague Dawley rats that were 78 days of age and weighed an average of 210 g. Food was available ad libitum to the control rats and to a group of ovariectomized rats (obese OVX). The food consumption of a second group of ovariectomized rats (weight-matched OVX) was restricted to match their body weights to those of the control rats. All rats were sacrificed at 14 weeks postovariectomy. Radioimmunoassay of terminal serum estradiol confirmed the success of ovariectomy. The estradiol concentration in control rats was 24.9±20.2 pg/ml, whereas the hormone was undetectable (<10 pg/ml) in both groups of OVX rats. The final body weights of control and weight-matched OVX rats were nearly identical (∼260 g). In contrast, obese OVX rats weighed significantly more than both of the above groups (∼320 g,P<0.001). The proximal tibia and lumbar vertebra were processed undecalcified for quantitative bone histomorphometry. Tibial trabecular bone volume (TBV) was determined to be 17.6±4.5%, 7.9±5.3%, and 3.6±3.1% for the control, obese OVX, and weight-matched OVX groups, respectively. Tibial TBV for both OVX groups was significantly less than the control value (P<0.001). The difference in tibial TBV between obese OVX and weight-matched OVX rats was also statistically significant (P<0.02). Histologic indices of bone resorption and formation were indicative of increased bone turnover in the proximal tibia of both OVX groups. In comparison to control rats, both groups of OVX rats exhibited a strong trend for a reduction in vertebral TBV, but no significant differences were observed among the three groups. Our results suggest that increased body weight provides partial protection against osteopenia in the long bones of OVX rats. However, it is important to note that this protective effect is only partial and that marked osteopenia develops in the long bones of OVX rats regardless of body weight.     

强骨颗粒剂对去卵巢大鼠骨生化药理作用的探讨

目的 观察中药制剂强骨颗粒剂防治去卵巢所致骨质疏松大鼠的疗效,探讨其生化药理作用。方法 30只雌性Wistar大鼠,分为模型组（去卵巢）,假手术组（行假手术）、强骨颗粒（QGKL）组3组。观察了强骨颗粒对大鼠骨密度,血清骨钙素（S－BGP）,骨中水含量,骨灰重,子宫指数（子宫重量／体重）和肾脏指数（肾脏重量／体重）,红细胞和肾线粒体膜Ca^2 -ATPase活性、膜流动性的影响。结果 与去卵巢组比较,强骨颗粒可升高大鼠骨密度,抑制血清BGP升高,增加骨中水含量,增加肾脏指数、Ca^2 -ATPase活性和膜流动性。结论 强骨颗粒剂对去卵巢大鼠的骨质疏松有明显的防治作用,作用途径可能通过全身多方面的整体调节。     

Partial Prevention of Long-Term Femoral Bone Loss in Aged Ovariectomized Rats Supplemented with Choline-Stabilized Orthosilicic Acid

Silicon (Si) deficiency in animals results in bone defects. Choline-stabilized orthosilicic acid (ch-OSA) was found to have a high bioavailability compared to other Si supplements. The effect of ch-OSA supplementation was investigated on bone loss in aged ovariectomized (OVX) rats. Female Wistar rats (n = 58, age 9 months) were randomized in three groups. One group was sham-operated (sham, n = 21), and bilateral OVX was performed in the other two groups. OVX rats were supplemented orally with ch-OSA over 30 weeks (OVX1, n = 20; 1 mg Si/kg body weight daily) or used as controls (OVX0, n = 17). The serum Si concentration and the 24-hour urinary Si excretion of supplemented OVX rats was significantly higher compared to sham and OVX controls. Supplementation with ch-OSA significantly but partially reversed the decrease in Ca excretion, which was observed after OVX. The increase in bone turnover in OVX rats tended to be reduced by ch-OSA supplementation. ch-OSA supplementation increased significantly the femoral bone mineral content (BMC) in the distal region and total femoral BMC in OVX rats, whereas lumbar BMC was marginally increased. Femoral BMD was significantly increased at two sites in the distal region in OVX rats supplemented with ch-OSA compared to OVX controls. Total lumbar bone mineral density was marginally increased by ch-OSA supplementation. In conclusion, ch-OSA supplementation partially prevents femoral bone loss in the aged OVX rat model.     

Correlation among geometric,densitometric, and mechanical properties in mandible and femur of osteoporotic rats

We have previously demonstrated bone loss of the mandible and femur in experimental osteoporotic rats and its prevention by medication, using peripheral quantitative computed tomography (pQCT). In the present study, the mechanical properties of the mandible and femur and the correlation to their geometric and densitometric properties were studied in ovariectomized rats with or without etidronate treatment. Fifty-four Wistar strain SPF female rats, 26 weeks old, were randomly assigned to four groups: (1) Basal group (12 rats, 1.0% Ca diet); (2) Sham group (Sham-operated, 12 rats, 0.1% Ca diet); (3) OVX group (ovariectomized, 15 rats, 0.1% Ca diet); (4) Treated group (OVX + etidronate, 15 rats, 0.1% Ca diet). Total bone mineral density (BMD), cortical BMD, cross-sectional cortical bone area, cross-sectional cortical bone thickness, crosssectional moment of inertia (CSMI), and polar strength index (SSI) of the mandible and femur were measured by pQCT. The failure load of mandible and femur was evaluated by three-point bending. The failure load of both bones was significantly lower in the Sham group compared with the Basal group. The OVX group further had a 8% and 7% decrease in the failure load for mandible and femur, respectively, compared to the Sham group. Treatment with etidronate led to an increase in the failure load compared with the OVX group. The failure load was related to the pQCT-assessed variables, especially with cortical bone area and total BMD. Moreover, the geometric and densitometric properties and failure load in the mandible showed a correlation to those in the femur.     

Effects of progesterone on postovariectomy bone loss in aged rats

The effects of progesterone on oophorectomy-induced bone loss in aged rats were evaluated. Female rats aged 12 months were divided into three groups: (1) sham-operated controls (SHAM); (2) oophorectomized (OVX); (3) OVX rats treated with progesterone (OVX + PROG). After 20 weeks the dry weight, bone ash, and calcium content of femur, tibia, and fourth lumbar vertebra were significantly lower in OVX than in sham rats. These reductions did not occur in OVX rats treated with PROG. There was no difference in the bone composition between the control and progesterone-treated rats. Vertebral bone histomorphometry showed increased bone resorption as well as increased bone formation parameters in OVX rats. Progesterone treatment inhibited the increased resorption indices, but the bone formation remained elevated. The results indicate that progesterone therapy prevents the postovariectomy bone loss in aged rats. The protective effect of progesterone is mediated by inhibition of bone resorption while maintaining the increased bone formation. These findings suggest that progesterone alone may be a valuable agent for management of postmenopausal osteoporosis.     

Temporal relationship between bone loss and increased bone turnover in ovariectomized rats

Summary To characterize osteopenic changes in ovariectomized (OVX) rats as a function of time, female Sprague Dawley rats (240 g body weight, 90 days old) were subjected to bilateral ovariectomy or sham surgery and killed at various times from 14–180 days postovariectomy. The proximal tibial metaphysis was processed undecalcified for quantitative bone histomorphometry. Osteopenia and increased indices of bone resorption and formation were detected in OVX rats as early as 14 days. Longitudinal bone growth was also significantly increased by ovariectomy at 14 days, but returned to control levels at all later times. In OVX rats, osteopenia became progressively more pronounced with time up to 100 days postovariectomy, after which trabecular bone volume appeared to stabilize at the markedly reduced level of 5%. Changes in osteoclast surface, osteoblast surface, and fluoro-chrome-based indices of bone formation in OVX rats followed a similar time course. The maximal increase in these parameters occurred during the first several months postovariectomy followed by a gradual decline toward control levels. Our results indicate that the initial rapid phase of bone loss in OVX rats is coincident with the maximal increase in bone turnover. At later times postovariectomy, bone loss and bone turnover both subside. These findings emphasize the close temporal association between the development of osteopenia and increased bone turnover in OVX rats.     

Hydrolyzed collagen improves bone status and prevents bone loss in ovariectomized C3H/HeN mice

Summary

This study evaluates the effect of hydrolyzed collagen (HC) on bone health of ovariectomized mice (OVX) at different ages. Twenty-six weeks after the OVX procedure, HC ingestion was still able to improve significantly bone mineral density (BMD) and some femur biomechanical parameters. Moreover, HC ingestion for 1?month before surgery prevented BMD decrease.

Introduction

HC can play an important role in preserving BMD before osteoporosis appears. The aim of this study was to evaluate the effect of HC on bone health of ovariectomized mice at different ages.

Methods

Female C3H mice were either OVX at 3 or 6?months and fed for 6?months (first experiment) or 3?months (second experiment) with diet including 0, 10, or 25?g/kg of HC. In the second experiment, one group received HC 1?month before surgery, and two groups received the supplementation immediately after surgery, one fed ad libitum and the other by gavage. Mice treated with raloxifene were used as a positive control. BMD, femur intrinsic and extrinsic biomechanical properties, and type I collagen C-terminal telopeptide were measured after 12 and 26?weeks. Food intake and spontaneous physical activity were also recorded.

Results

The OVX procedure increased body weight, while food intake decreased, thus suggesting that resting metabolism was decreased. Ingestion of 25?g/kg of HC for 3 or 6?months reduced bone loss significantly in, respectively, 3- and 6-month-old OVX mice. The lowest HC concentration was less efficient. HC ingestion for 3?months is as efficient as raloxifene to protect 3-month-old OVX mice from bone loss. Our results also demonstrated that HC ingestion before surgery prevented the BMD decreases.

Conclusion

This study confirms that dietary collagen reduces bone loss in OVX mice by increasing the diameter of the cortical areas of femurs and can have a preventive effect.     

前交叉韧带切断对卵巢切除大鼠股骨骨折愈合的影响

目的观察前交叉韧带切断(OA动物模型)对双侧卵巢切除大鼠(OVX绝经后骨质疏松模型)股骨骨折愈合的影响。方法12周龄SD大鼠共70只，分成基础对照组(Basal)、假手术组(Sham)、双侧卵巢切除术组(OVX)、卵巢切除 前交叉韧带切断术组(OVX OA)、假手术 骨折组(Sham F)、卵巢切除术 骨折组(OVX F)、卵巢切除 前交叉韧带切断 骨折组(OA OVX F)，每组10只大鼠。所有受试大鼠在处死前第10d天和第4d天分别皮下注射盐酸四环素和钙黄绿素行双荧光标记。基础对照组在实验开始时杀死，其余6组在术后6W杀死，取大鼠右侧股骨标本。然后，分别进行CR摄片、组织形态学染色，以及应用Norland-XR36双能X线骨密度仪(DXA)测量右股骨远段骨密度和中段骨密度，并将股骨远段及骨折段骨痂进行硬组织包埋、切片，作骨组织形态计量学测量。结果①OVX OA组与OVX组比较，股骨远段。BMD和BWTV显著增加；②OVX F组与Sham F组比较，骨痂(股骨中段)BMD和BV／TV显著降低：③OVX OA F组与OVX F组比较，骨痂(股骨中段)BMD利BV／TV无统计学差异。结论①骨质疏松不仅延缓骨折愈合过程，而且降低骨折愈合质量；②在此动物模型中，骨性关节炎延缓股骨骨质疏松的发生，但是，对骨质疏松性骨折的愈合没有确切的促进作用。     

补正续骨丸对去卵巢大鼠骨量及其相关骨折的作用机制研究

目的探索中药复方补正续骨丸对去卵巢大鼠骨量及相关骨折的影响。方法雌性大鼠卵巢切除法(OVX)造PMOP模型,分组给药6周后DXA行大鼠股骨BMD检测; HE染色测量股骨骨小梁密度; ELISA检测法检测大鼠血清中P1NP、β-CTX; Western blot法检测大鼠股骨中4EBP-1、p70S6K蛋白表达;同时比较不同处理组大鼠骨折愈合时间及相同时间骨痂密度,观察补正续骨丸对OVX大鼠骨折愈合时间及骨痂密度的影响。结果补正续骨丸可增加OVX大鼠股骨BMD、减少骨小梁断裂、降低去卵巢大鼠血清中β-CTX水平、抑制mTOR1信号通路中p70S6K、4EBP1的蛋白表达,补正续骨丸可促进OVX大鼠骨折处骨痂密度增加及减少骨折愈合时间。结论中药复方补正续骨丸通过抑制mTOR1信号通路中p70S6K、4EBP1蛋白的表达抑制骨吸收、促进OVX大鼠骨折的愈合。     

Regional analysis of bone mineral density in the distal femur and proximal tibia using peripheral quantitative computed tomography in the ratin vivo

The use of peripheral quantitative computed tomography (pQCT) was investigated for the measurement of volumetric bone mineral density (BMD) in mg·cm⁻³. Two studies were undertaken. In the first study, the precision of pQCTin vivo andex vivo was tested at 14 weeks postovariectomy (OVX). In the second study, the efficacy of a standard antiresorptive treatment, 17β-estradiol (E2), was tested 6 weeks post-OVX. The precision for total (compact plus trabecular) BMD was 1.3–1.9%, and that for trabecular BMD was 2.4–2.7%. There was excellent agreement between trabecular BMD measurementsin vivo andex vivo (r=0.91). Significant reductions in trabecular BMD were observedin vivo at 14 and 6 weeks following ovariectomy in the femur, in each study. The loss of trabecular BMD depended on slice location, and varied from 0 to 22% at 6 weeks, and from 0 to 26% at 14 weeks (P<0.001, at the affected locations). The antiresorptive effect of treatment was demonstrated in the 6-week study: there was no significant difference in BMD between sham-operated and E2-treated OVX rats.     

The Less Potent Estrogenic Effect of Tamoxifen on Bone in Ovariectomized Rats With Established Osteopenia

The longitudinal effects of tamoxifen (TAM) treatment on bone metabolism, spinal bone mineral density (BMD), and bone mineral content (BMC) were compared with those of estrogen in ovariectomized (OVX) rats with established osteopenia. The 6-month-old rats were divided into Sham (n = 8) and OVX (n = 24) groups. First, the OVX rats were allowed to lose bone for 6 weeks. Six weeks after ovariectomy they were divided into three groups: (1) OVX rats treated with solvent vehicle (OVX+Vehicle), (2) OVX rats injected with TAM subcutaneously six times a week at a dosage of 1.0 mg/kg body weight (OVX+TAM), (3) OVX rats injected with 17-β estradiol subcutaneously six times a week at a dosage of 0.1 mg/kg body weight (OVX+ET). The longitudinal effects of TAM and estrogen on bone were studied by dual energy X-ray absorptiometry (DXA) and biochemical markers including urinary pyridinoline (Pyr) and deoxypyridinoline (Dpyr). Ovariectomy resulted in a significant increase in urinary Pyr, Dpyr, and a significant decrease in spine BMD and BMC. TAM treatment completely inhibited the further bone loss in OVX rats with established osteopenia, however, estrogen increased spine BMD and BMC significantly compared with OVX+Vehicle, OVX+TAM, and baseline of treatment. Both TAM and estrogen treatment decreased urinary Pyr and Dpyr significantly in OVX rats. Our findings indicate that TAM acts as an estrogen agonist with respect to effects on spine BMD, BMC, and bone resorption in OVX rats with established osteopenia, but fails to restore spine BMD and BMC to the extent observed with estrogen in this study.