Effects of D-003, a mixture of high molecular weight aliphatic acids from sugar cane wax, on bones from ovariectomized rats

Bisphosphonates inhibit bone resorption through mechanisms involving the metabolic pathway from mevalonate to cholesterol. Mevalonate is a precursor of the lipoids required for osteoclast activity and thus inhibition of its synthesis affects bone metabolism. Inhibitors of hydroxymethylglutaryl CoA (HMGCoA) reductase might increase experimentally new bone formation through a mevalonate-dependent effect. D-003 is a mixture of high molecular weight fatty acids isolated from sugar cane wax, which inhibits cholesterol biosynthesis through indirect regulation of HMGCoA reductase activity. This study was undertaken to determine whether D-003 could prevent bone loss in ovariectomized rats. Sprague Dawley female rats were ovariectomized or sham operated and were randomly distributed into five groups: a control ovariectomized and a sham (false-operated) group receiving Tween/H2O vehicle, a group treated with alendronate (3 mg/kg/day) and two groups treated with D-003 (50 and 200 mg/kg/day). Treatments were administered for 3 months. At sacrifice, bones were removed and histological variables of bone resorption and formation were studied by histomorphometry. Ovariectomy diminished trabecular number and thickness and increased trabecular gap, osteoclast number and surface. Alendronate and D-003 prevented a decrease in trabecular number and thickness as well as increases in trabecular separation, osteoclast number and surface compared with ovariectomized controls, thus preventing the bone loss and decreased bone resorption induced by ovariectomy, but failed to increase osteoblast surface compared with control ovariectomized rats. In conclusion, D-003 (50 and 200 mg/kg/day) prevented bone loss and decreased bone resorption in ovariectomized rats, which suggests that this substance could be promising in preventing or treating osteoporosis.     

Comparison of the effects of D-003, a mixture of high-molecular-weight aliphatic acids from sugarcane wax, and pravastatin on bones and osteoclast apoptosis of ovariectomized rats

The mevalonate pathway is relevant in bone cells. Statins inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the key enzyme of this route, stimulating osteoblast differentiation and activity. Pravastatin increases bone formation markers in postmenopausal women and bone density in diabetics. D-003 is a mixture of high-molecular-weight acids purified from sugarcane wax which inhibits cholesterol biosynthesis through HMG-CoA reductase regulation, preventing bone loss in osteoporosis induced with ovariectomy and prednisolone in rats. We investigated the effects of D-003 (50 mg/kg) and pravastatin (20 mg/kg) orally administered for 12 weeks to ovariectomized rats. Female rats were randomized in four groups (10 rats/group): two control groups treated with the vehicle, one false-operated (sham) and another ovariectomized (positive control), while two other groups received D-003 or pravastatin. Bone resorption and formation was studied through histomorphometry and apoptosis through immunohistochemistry. D-003 and pravastatin significantly (p < 0.001) prevented the changes of trabecular bone versus ovariectomized rats and (p < 0.001) the increase of the surface and number of osteoclasts versus ovariectomized controls. D-003 and pravastatin, however, did not modify osteoblast surfaces, a bone formation marker D-003 and pravastatin increased osteoclast apoptosis and reduced (p < 0.05) osteoblast and osteocyte apoptosis versus ovariectomized controls; D-003 was more effective (p < 0.05) than pravastatin. In conclusion, D-003 (50 mg/kg) orally administered for 12 weeks prevented bone loss and bone resorption in ovariectomized rats, increasing osteoclast apoptosis. The preventive effects of D-003 on bone loss and resorption in ovariectomized rats are comparable to those of pravastatin. Both drugs inhibited osteoblast apoptosis but failed to change osteoblast surface. The effects of D-003 on bone cell apoptosis were greater than those of pravastatin. Therefore, D-003 could be used to prevent or treat bone loss in postmenopausal women, but further animal studies and clinical trials are required to confirm the clinical relevance of this potential effect.     

D-003 does not possess oestrogenic potential in-vivo: findings of the uterotrophic assay

D-003 is a mixture of long-chain fatty acids purified from sugarcane wax that inhibits both cholesterol synthesis prior to mevalonate formation, and lipid peroxidation. D-003 has been shown to prevent bone loss and bone resorption in ovariectomized rats, and significantly improves bone resorption markers in postmenopausal women with reduced bone mineral density. As hormone-replacement therapy, D-003 displays cholesterol-lowering and anti-resorptive effects. We have studied its potential oestrogenic activity in-vivo using the uterotrophic assay. Rats were randomly distributed into five groups: a sham-operated group and four groups of ovariectomized rats, one treated with vehicle, one with D-003 (50 mg kg(-1)), one with oestradiol benzoate (30 microg kg(-1)) and one with D-003 (50 mg kg(-1)) plus oestradiol benzoate (30 microg kg(-1)). Treatments were administered for 14 days. Ovariectomy decreased the values of relative uterus weight, epithelium cell height and endometrial thickness compared with sham-operated rats, and these effects were all significantly reduced with oestradiol benzoate, but not with D-003. Concurrent administration of D-003 and oestradiol benzoate had statistically similar effects on all variables as oestradiol benzoate alone. In conclusions, D-003 orally given at 50 mg kg(-1), a dose that prevents bone loss and bone resorption in ovariectomized rats, did not display oestrogenic/anti-oestrogenic activity in-vivo, as assessed in the uterotrophic assay.     

Long-term effects of D-003, a mixture of high molecular weight acids from sugarcane wax, on bones of ovariectomized rats: a one year study

This study was done to determine the long-term effect of D-003 on bones of ovariectomized (ovx) rats distrib-uted in 4 groups: a false-operated and three groups of ovx rats: one treated with the vehicle and two with D-003 (5 and 250 mg/kg). D-003 significantly prevented, in a dose-dependent fashion, the trabecular bone volume (TBV), trabecular number (TbN) and trabecular thickness (TbTh) reduction induced in ovx rats and the increase of trabecular separation (TbSp) osteoclast number (OcN) and osteoclast surface (OcS/BS) increased in the positive controls versus the sham group. It is concluded that D-003 administered for 12 months prevented bone loss and decreased bone resorption in ovx rats, without evidences of impaired bone quality.     

Effect of D-003, a mixture of very high molecular weight aliphatic acids, on prednisolone-induced osteoporosis in Sprague-Dawley rats

BACKGROUND: Drugs inhibiting cholesterol biosynthesis may affect bone metabolism through inhibition of the mevalonate pathway resulting in the inhibition of protein prenylation required for osteoclast activity. D-003 is a mixture of high molecular weight aliphatic primary acids purified from sugar-cane (Saccharum officinarum) wax, with cholesterol-lowering effects demonstrated in experimental and clinical studies. D-003 inhibits cholesterol biosynthesis through indirect regulation of HMG-CoA reductase activity. A previous study demonstrated that D-003 prevented bone loss and bone resorption on ovariectomy-induced osteoporosis in rats. Corticosteroid-induced osteoporosis is the result of changes affecting calcium homeostasis, but the hallmark of corticosteroid-induced bone loss is the direct effects on bone cells, such as inhibition of osteoblastogenesis, promotion of apoptosis of osteoblasts and osteocytes, and decrease in bone formation. OBJECTIVE: To determine whether D-003 could prevent the bone loss induced with prednisolone in Sprague-Dawley rats. METHODS: Rats were randomly distributed in five groups (ten rats per group): a sham-operated control and four groups orally treated with prednisolone 6 mg/kg for 80 days; a positive control orally treated with vehicle; and three groups orally treated with D-003 at 5, 25 and 200 mg/kg, respectively. Rats were killed, bones removed and histological variables of bone resorption and formation studied for histomorphometry. RESULTS: Compared with the sham group, prednisolone significantly (p < 0.01) reduced trabecular bone volume (TBV), while D-003 significantly (p < 0.001) and dose-dependently prevented the prednisolone-induced reduction of TBV. Treatment with prednisolone lowered (p < 0.001) trabecular thickness (TbTh) and number (TbN), while increasing (p < 0.001) the gap between trabeculae. D-003 (5, 25 and 200 mg/kg/day) significantly (p < 0.001) and dose-dependently prevented the reduction of TbTh and TbN and the increase of trabecular gap induced with prednisolone. Treatment with prednisolone increased both the surface and number of osteoclasts compared with sham (p < 0.001). D-003 (5-200 mg/day), however, prevented this effect (p < 0.001 for all comparisons). D-003 also prevented (p < 0.001) the reduction of osteoblast surface (ObS/BS) induced by prednisolone. Osteonecrotic areas were observed in all positive controls, but in none of the sham animals. Positive controls showed hypertrophy of bone marrow adipocytes and lipid-laden pluripotential stromal cells in bones. A significant and dose-dependent reduction of the frequency of animals showing prednisolone-induced osteo-necrosis was observed across the doses of D-003 (5, 25 and 200 mg/kg) investigated here. CONCLUSIONS: D-003 (5, 25 and 200 mg/kg) prevented trabecular bone loss and femoral neck osteonecrosis induced with prednisolone in Sprague Dawley rats, also increasing osteoblast surface and reducing bone resorption parameters. These results suggest that D-003 could be useful for managing corticosteroid-induced osteoporosis.     

Bone loss preventing effect of sophorae fructus on ovariectomized rats

The preventive effects of Sophorae Fructus extracts (I: hot water extract and II: combination product using I) on bone loss in ovariectomized (OVX) rats were investigated. Sophorae Fructus extracts were orally administrated to OVX rats for 9 weeks. Ovariectomy caused the increase of body weight and deoxypyridinoline (Dpd: bone resorption marker) and decrease of calcium (Ca: bone formation marker) level in serum. Dpd level were significantly decreased and Ca levels were elevated at 9 weeks in Sophorae Fructus extracts administered groups after ovariectomy at a dose of 0.556 g/kg/day compared with control group. In administered groups, trabecular bone area (TBA) in the tibia and lumbar were also increased compared with control group in histomorphological analysis. The preventive or treatment effects of Sophorae Fructus extracts on bone loss in OVX rats appears to be due to suppression of bone turnover.     

In vivo antiosteoporotic activity of a fraction of Dioscorea spongiosa and its constituent, 22-O-methylprotodioscin

The antiosteoporotic activity of the 90 % EtOH fraction of the water extract of rhizomes of Dioscorea spongiosa and methylprotodioscin, its major constituent, were examined in the model of postmenopausal bone loss using ovariectomized (OVX) rats or mice. After 6 weeks treatment, the proximal tibia of rats or mice and the distal femora of mice were scanned by peripheral quantitative computed tomography (pQCT). Both the 90 % EtOH fraction (100 mg/kg/d) and methylprotodioscin (50 mg/kg/d) significantly inhibited bone loss in bone mineral content (BMC) and bone mineral density (BMD) in total, cancellous and cortical bones, and the decrease in bone strength indexes induced by OVX, without side effect on the uterus.     

不同疗程阿仑膦酸钠对去卵巢大鼠骨骼的影响

目的　探讨阿仑膦酸钠 (固邦 )不同疗程对去卵巢大鼠所致骨质疏松的骨计量学参数的影响。方法　用 3mon龄♀SD大鼠 ,阿仑膦酸盐 1mg·kg- 1 ·d- 1 ,分别灌胃给药 30d和 90d ,体内双荧光标记。实验终止时处死大鼠 ,取左侧胫骨近心端行骨组织形态计量学分析。结果　去卵巢大鼠骨小梁面积百分率分别减少 2 5 % (30d)和 62 % (90d) ,出现骨吸收大于骨形成的高转换型骨质疏松 ;阿仑膦酸钠 30d和 90d均完全对抗去卵巢大鼠的骨高转换。与OVX组比较 ,阿仑膦酸钠作用 30d骨量增加 45 % ,90d骨量增加2 1 9% ,有效防止去卵巢后骨质疏松。结论　阿仑膦酸钠 30d和 90d均通过抑制骨吸收和骨高转换对去卵巢大鼠有预防骨质疏松的作用 ,而阿仑膦酸钠 90d的作用比 30d的强。     

Alleviation of ovariectomy-induced osteoporosis in rats by <Emphasis Type="Italic">Panax notoginseng</Emphasis> saponins

To examine the effects of Panax notoginseng saponins (PNS), the main active components of Panax notoginseng, on ovariectomy-induced osteoporosis in rats. A total of 72 six-month-old female rats were randomly assigned to sham-operated group and five ovariectomized (OVX) groups: OVX with distilled water (5 ml/kg/day, p.o.), OVX with graded doses of PNS (75, 150, 300 mg/kg/day, p.o.), and OVX with nilestriol (1 mg/kg/week, p.o.). Animals were sacrificed after a 13-week treatment course. Compared with the OVX group, PNS administration prevented OVX-induced decrease in bone mineral density (BMD) of lumbar vertebrae and total femur, and significantly increased bone structural biomechanical properties. Improvements of BMD and biomechanical properties were accompanied by the beneficial changes of PNS on trabecular microarchitecture in the tibial metaphysis. PNS at the highest dose significantly prevent decrease in trabecular bone volume over bone total volume, trabecular number, trabecular thickness, connectivity density, and increase in trabecular separation and structure model index in OVX rats. The bone-modulating effects of PNS may be due to the increased bone formation and decreased bone resorption, as was evidenced by the elevated level of serum alkaline phosphatase and decreased level of urinary deoxypyridinoline. PNS treatment is able to enhance BMD, bone strength, and prevent the deterioration of trabecular microarchitecture without hyperplastic effect on uterus. Therefore, PNS might be a potential alternative medicine for the prevention and treatment of postmenopausal osteoporosis.     

Effect of concurrent administration of alendronate sodium and retinol on development of changes in histomorphometric parameters of bones induced by ovariectomy in rats

Retinol is a commonly used vitamin, especially by elderly people. Alendronate sodium, an aminobisphosphonate, is a potent antiresorptive drug used in the treatment of osteoporosis in postmenopausal women. Frequently, alendronate sodium and retinol are used concurrently. There are no reports on the interaction between alendronate sodium and retinol. The aim of the present study was to investigate the effect of concurrent administration of alendronate sodium and retinol on bone remodeling in ovariectomized rats. The histomorphometric parameters of long bones were studied. The experiments were carried out on 3-month-old Wistar rats, divided into 7 groups: I (C) - sham operated control rats, II (OVX) - ovariectomized control rats, III (OVX + ALN) - ovariectomized rats + alendronate sodium (3 mg/kg po), IV (OVX + R-1) - ovariectomized rats + retinol (700 IU/kg po), V (OVX + R-2) - ovariectomized rats + retinol (3500 IU/kg po), VI (OVX + ALN + R-1) - ovariectomized rats + alendronate sodium (3 mg/kg po) + retinol (700 IU/kg po), VII (OVX + ALN + R-2) - ovariectomized rats + alendronate sodium (3 mg/kg po) + retinol (3500 IU/kg po). The drugs were administered to the rats daily by oral gavage (alendronate sodium in the morning, retinol in the afternoon) for 28 days. Body mass gain, bone mass, mineral content in the tibia, femur and L-4 vertebra, histomorphometric parameters of the right tibia (width of osteoid, periosteal and endosteal transverse growth, area of the transverse cross section of the bone marrow cavity and the cortical bone) and the right femur (width of epiphyseal and metaphyseal trabeculae, width of epiphyseal cartilage) were studied. Bilateral ovariectomy induced osteopenic skeletal changes in mature female rats. Alendronate sodium administered at a dose of 3 mg/kg po daily inhibited the development of changes induced by ovariectomy in the skeletal system of rats. Retinol, especially administered at the dose of 3500 IU/kg daily, intensified the changes in the osseous system caused by estrogen deficiency in rats. Retinol administered concurrently with alendronate sodium attenuated the antiresorptive effect of alendronate sodium on the skeletal system in ovariectomized rats.     

Effects of chronic administration of zonisamide,an antiepileptic drug,on bone mineral density and their prevention with alfacalcidol in growing rats

We investigated the effects of chronic administration of zonisamide, an antiepileptic agent, on bone metabolism in growing rats. Administration of zonisamide at a dose of 80 mg/kg per day, s.c. for 5 weeks significantly decreased bone mineral density (BMD) at the tibial metaphysis and the diaphysis. The percent rate of decrease in BMD at the tibial metaphysis and the tibial diaphysis was 9.2% and 5.0%, respectively. There was no significant difference between these groups in the growth of the rats. Treatment with zonisamide at a dose of 80 mg/kg increased serum pyridinoline level, a marker of bone resorption, while it does not affect the serum intact osteocalcin level, a marker of bone formation. Combined administration of alfacalcidol, an active vitamin D(3) metabolite, at a dose of 0.1 microg/kg per day with zonisamide prevented a decrease in BMD and showed an increase of serum pyridinoline levels. These results suggest that zonisamide may cause bone loss by accelerating bone resorption rather than inhibiting bone formation. Moreover, the bone loss induced by zonisamide could be prevented by combining zonisamide with alfacalcidol.     

Effects of tibolone on the development of osteopenia induced by ovariectomy in rats

Experimental osteopenia caused by ovariectomy in rats may reflect postmenopausal bone changes, which are the effect of osteogen deficiency. The aim of the present study was to investigate the effects of tibolone (0.25 mg/kg/day and 2.5 mg/kg po) administered for 4 weeks on the development of osteopenia caused by bilateral ovariectomy in 3-month-old female Wistar rats. The experiments were carried out on six groups of animals: I (C) - control sham operated rats, II (OVX) - ovariectomized rats, III (OVX + T-0.25) - ovariectomized rats which were administered tibolone at a dose of 0.25 mg/kg, IV (OVX + T-2.5) - ovariectomized rats which were administered tibolone at a dose of 2.5 mg/kg, V (T-0.25) - sham operated rats which were administered tibolone at a dose of 0.25 mg/kg, VI (T-2.5) - sham operated rats which were administered tibolone at a dose of 2.5 mg/kg. The following parameters were examined in all the groups: body weight gain, bone mass, length and diameter, mineral and calcium contents in the tibia and femur, endosteal and periosteal transverse growth, endosteal and periosteal osteoid width, transverse cross-section area of the cortical diaphysis and that of the marrow cavity in the tibia, epiphyseal cartilage width, trabeculae width in the epiphysis and metaphysis of the femur. Mechanical properties of the femur were also studied. Bilateral ovariectomy induced osteopenic skeletal changes in mature female rats. Tibolone (0.25 mg/kg/day and 2.5 mg/kg/day po) administered to ovariectomized rats for 28 days decreased the development of osteopenic skeletal changes induced by bilateral ovariectomy.     

Morphometric evidence that YM175, a bisphosphonate, reduces trabecular bone resorption in ovariectomized dogs with dietary calcium restriction

We examined mechanisms by which incadronate disodium (YM175) prevented bone resorption in ovariectomized dogs with dietary calcium restriction using the morphometrical method. YM175 (0.01-1.0 mg/kg) was given to ovariectomized dogs for 18 months. Because lumbar bone mineral density remained constant at month 17, we assumed that the trabecular bone resorption rate was equal to the bone formation rate and that wall thickness equaled resorption cavity depth. YM175 decreased both the bone resorption rate per number of osteoclasts and resorption cavity depth of cancellous pockets which were increased in ovariectomized dogs. These results suggest that YM175 reduces bone loss by decreasing the resorbing activity of osteoclasts.     

Effects of simvastatin on the development of osteopenia caused by ovariectomy in rats

Simvastatin is a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the rate-determining enzyme for cholesterol synthesis which is used in the treatment of hypercholesterolemias, particularly in type IIa and IIb hyperlipoproteinemias, frequently in postmenopausal women. Inhibition of cholesterol synthesis by simvastatin may cause disorders of bone remodelling. The aim of the present study was to investigate the effects of simvastatin (3 mg and 6 mg/kg/day per os) administered for 4 weeks on the development of ovariectomy-induced osteopenia in 3-month-old female Wistar rats. The experiments were carried out on six groups of animals: I (C)--sham operated rats, II (S-3)--sham operated rats + simvastatin 3 mg/kg/day p.o., III (S-6)--sham operated rats + simvastatin 6 mg/kg/day p.o., IV (OVX)--ovariectomized rats, V (OVX + S-3)--ovariectomized rats + simvastatin 3 mg/kg/day p.o., VI (OVX + S-6)--ovariectomized rats + simvastatin 6 mg/kg/day p.o. In all the groups, we examined body weight gain, and macrometrical, histomorphometrical and mechanical parameters. Bilateral ovariectomy induced osteopenic skeletal changes in mature female rats. In cortical bone, ovariectomy intensified resorption processes at the marrow cavity, as indicated by a decrease in endosteal transverse growth and an increase in transverse cross-section surface area of the marrow cavity in the tibia. Intensification of resorption processes was observed in cancellous bone (a statistically significant decrease in the width of trabeculae in the epiphysis and metaphysis of the femur). Structural changes in the long bones resulting from bilateral ovariectomy were manifested by deterioration of mechanical properties of the shaft and neck of the femur. The force needed to fracture the neck and shaft of the femur was significantly smaller than that in sham operated rats. Simvastatin (3 and 6 mg/kg/day p.o.) slightly influenced bone remodelling in sham operated rats. Simvastatin (3 and 6 mg/kg p.o. daily) administered to ovariectomized rats intensified bone formation processes and decreased bone resorption processes induced by bilateral ovariectomy, showing stronger activity at 6 mg/kg.     

Raloxifene similarly affects the skeletal system of male and ovariectomized female rats

Raloxifene, a selective estrogen receptor modulator, is used for prevention and treatment of osteoporosis in postmenopausal women. Raloxifene use in male subjects is increasingly considered and a few clinical studies of its effect on bone turnover have already been performed. The aim of the present study was to investigate the effects of raloxifene on the skeletal system of healthy mature male rats. The experiments were performed on mature male Wistar rats, treated daily with raloxifene hydrochloride at a dose of 5 mg/kg po for 4 weeks. Bone mass, mineral content, macrometric and histomorphometric parameters, as well as mechanical properties were examined. For comparison, we also studied the effects of raloxifene on the skeletal system of mature ovariectomized female rats. Raloxifene administration to male rats caused statistically significant increases in the bone mass/body mass ratio, bone mineral content/body mass ratio and bone mineral content/bone mass ratio in comparison with those of the control rats. Bone mechanical properties and most of histomorphometric parameters remained unchanged. Also in ovariectomized female rats, raloxifene administration caused statistically significant increases in the bone mass/body mass ratio, bone mineral content/body mass ratio and bone mineral content/bone mass ratio in comparison with the results obtained in the ovariectomized control rats, to the level of sham-operated control rats. Moreover, raloxifene counteracted the development of changes in histomorphometric parameters caused by ovariectomy in female rats, but did not significantly affect bone mechanical properties. In conclusion, the changes induced by raloxifene in the skeletal system of male rats were similar to those induced by the drug in ovariectomized female rats.     

Effect of tamoxifen on bone mineral density and blood lipids in ovariectomized rats

Tamoxifen is widely used in breast cancer therapy and in the treatment of all stages of breast cancer including chemoprevention in women at high risk of the disease. The most important aspect of tamoxifen therapy concerns its influence on bone tissue and lipid metabolism. The aim of the study was to evaluate the effect of tamoxifen on bone metabolism and blood cholesterol levels in ovariectomized rats. The study was performed on Wistar rats treated with tamoxifen at 2 and 4 mg/kg/24 h. Total serum cholesterol and low density cholesterol were significantly increased in ovariectomized rats (3.24 mmol/l and 2.06 mmol/l) in comparison with sham operated control (2.68 mmol/l and 1.44 mmol/l) (p < 0.05). Total serum cholesterol and low density cholesterol in tamoxifen-treated rats were significantly decreased in comparision with the values in both sham-operated and ovariectomized control. Bone mineral content (BMC) and bone mineral density (BMD) of femurs of ovariectomized rats (0.32 g and 0.081 g/cm2) decreased significantly compared to sham-operated controls (0.42 g and 0.098 g/cm2) (p < 0.05). Tamoxifen prevented the bone mass reduction induced by ovariectomy. The treatment with tamoxifen at doses of 2 mg/kg/24 h and 4 mg/kg/24 h significantly increased BMC and BMD in comparison with ovariectomized control. The results suggest a beneficial influence of tamoxifen on bone tissue and lipid metabolism.     

联合应用特乐定与固邦对去卵巢大鼠骨骼作用研究

目的　观察特乐定与固邦联合用药是否对大鼠骨骼产生增强疗效的作用。方法　 3mon龄♀SD大鼠 4 2只 ,体重 (2 6 6± 2 2 ) g ,随机分为 6组 ,除了第 1组实行Sham手术外 ,其余 5组均实行去卵巢 (Ovx)手术。Sham大鼠给予蒸馏水 ,各Ovx大鼠分别给予蒸馏水、1mg·kg-1·d-1固邦、2 70mg·kg-1·d-1的葡萄糖酸钙、5 6mg·kg-1·d-1的特乐定及结合 1mg·kg-1·d-1固邦与 5 6mg·kg-1·d-1的特乐定。实验期限为 3mon ,处死前注射荧光标记。实验结束后取左侧胫骨近心端 ,行骨组织形态计量学分析。结果　固邦增加大鼠骨量 ,抑制去卵巢大鼠的骨形成指标 (%L .Pm ,BFR/BS)和骨吸收指标 (N .Oc/Tb .Pm)。单独补充葡萄糖酸钙未能缓解Ovx大鼠的骨量丢失。特乐定亦未能有效恢复Ovx大鼠丢失的骨量。固邦与特乐定联合用药虽然增加去卵巢大鼠的骨量 ,但其骨量不比单用固邦的骨量高。结论　固邦与特乐定的联合应用 ,不能发生疗效增强的效果 ,不推荐两药同时使用     

Effect of administration of alendronate sodium and retinol on the mechanical properties of the femur in ovariectomized rats

Alendronate sodium, an aminobisphosphonate with potent antiresorptive activity, is used in the treatment of postmenopausal osteoporosis. Retinol, as a component of multivitamin preparations, is frequently used especially by elderly people. There are no reports on the interaction of alendronate sodium and retinol. The aim of the present study was to investigate the effect of administration of alendronate sodium and retinol on mechanical properties of the femoral bone in bilaterally ovariectomized rats. The experiments were carried out on 3-month-old Wistar rats, divided into 7 groups: I - sham-operated control rats, II - ovariectomized control rats, III - ovariectomy + alendronate sodium 3 mg/kg po, IV - ovariectomy + retinol 700 IU/kg po, V - ovariectomy + retinol 3500 IU/kg po, VI - ovariectomy + alendronate sodium 3 mg/kg po + retinol 700 IU/kg po, VII - ovariectomy + alendronate sodium 3 mg/kg po + retinol 3500 IU/kg po. The drugs were administered to the rats daily by oral gavage for 28 days. Body mass gain, bone mass, bone mineral content and calcium content in the femur and L-4 vertebra and mechanical properties of the whole femur (extrinsic stiffness, ultimate load, breaking load, deformation caused by the ultimate load) and the neck of the femur (load at fracture), were examined. Bilateral ovariectomy induced osteopenic changes in the rat skeletal system. Alendronate sodium (3 mg/kg po) counteracted the development of osteopenia induced by ovariectomy. Retinol at both used doses unfavorably affected the examined bone parameters of ovariectomized rats. Retinol administered with alendronate sodium lessened the preventive action of alendronate on the development of osteopenic changes in the skeletal system of ovariectomized rats.     

淫羊藿总黄酮与雌激素合用对去卵巢大鼠骨质疏松的影响

目的　研究淫羊藿总黄酮 (EF)与己烯雌酚 (DES)合用对去卵巢大鼠骨质疏松的影响。方法　大鼠双侧卵巢去除术后预防用药 90d ,用骨组织形态计量学等方法 ,测定大鼠胫骨近端松质骨静态参数和动态参数 ,并观察血清生化指标和子宫内膜厚度。结果　DES 2 2 5 μg·kg-1·d-1可对抗去卵巢大鼠体重增加、血清总胆固醇增加、骨转换增高和骨丢失 ,但是使子宫内膜厚度增加。单用EF 30 0mg·kg-1·d-1对骨丢失没有对抗作用 ,DES 2 2 5 μg·kg-1·d-1和EF30 0mg·kg-1·d-1联合用药效应超过DES单独应用 ,而且不刺激子宫内膜增加。结论　EF与DES联合用药对去卵巢大鼠骨丢失的骨量增加有协同作用 ,而且没有刺激子宫的副作用。