雷奈酸锶对抗地塞米松诱导大鼠骨质疏松的作用

目的 研究雷奈酸锶对地塞米松诱导骨质疏松大鼠的作用。方法 30只雌性SD大鼠采用随机数字表法分为5组:空白组,骨质疏松模型组,雷奈酸锶高、中、低剂量组。5周后进行骨形态学及血清指标检测,同时考察不同浓度雷奈酸锶对成骨细胞的体外增殖影响。结果 较模型组(38.00±2.36)μm,雷奈酸锶中、高剂量组的平均骨小梁厚度(48.50±4.05)μm、(52.00±4.44)μm明显升高(P＜0.05),较模型组(189.90±19.27)μm,雷奈酸锶中、高剂量组的骨小梁间距(154.26±13.86)μm、(150.02±20.86)μm明显降低(P＜0.05),表明雷奈酸锶的干预能明显改善骨显微结构指标。雷奈酸锶组高剂量较模型组大鼠血清白介素-6(IL-6)、骨性特异性磷酸酶(BALP)、抗酒石酸酸性磷酸酶(TRACP-5b)、Ⅰ型胶原C端肽(CTX-I)明显降低(P＜0.05),骨钙素(OCN)、25羟基维生素D(25-HVD)明显升高(P＜0.05)。体外实验表明雷奈酸锶可促进成骨细胞增殖。结论 雷奈酸锶可促进成骨细胞增殖,改善骨形态及多项血清指标,对激素性骨质疏松有一定治疗作用。     

去睾丸大鼠骨质疏松模型的实验研究

目的：建立去睾大鼠骨质疏松模型，研究大鼠去睾后股骨颈骨密度及骨微结构的变化。方法：选用19只12－16周龄的Wistar雄性大鼠，随机分成去睾组和假去睾组，同条件下饲养18周。处死前用Hologic QDR-2000 DEXA测量大鼠腰椎、股骨颈、股骨粗隆部、股骨近端的骨密度。处死前第14、13天和第3、2天行骨荧光标记，大鼠处死后取左侧股骨近端行塑料包埋的骨组织切片及组织形态计量学分析。结果：去睾大鼠18周后腰椎、股骨颈、股骨粗隆部、股骨近端的骨密度均下降，与假去睾组有显的统计学差异（P＜0．01）。骨组织形态计量学静态参数表现为去睾组的骨小梁面积百分率（％Tb.Ar)减少46。4％（P＜0．01），骨小梁数目（Tb.N)减少43．8％（P＜0．01），骨小梁分离度（Tb.Sp)增加144．6％（P＜0．01）。动态参数表现为去睾组的骨荧光标记周长百分率（％L.Pm)增加124％（P＜0．01），骨形成率BFR／BS，BFR／BV和BFR／TV分别增加437．6％（P＜0．01），239．9％（P＜0．01），240．3％（P＜0．01）。代表骨吸收的参数骨小梁面积破骨细胞数（Oc.No)和骨小梁周长破骨细胞数（Oc.No/Pm)分别增加131．9％（P＜0．01），115．5％（P＜0．01）。结论：大鼠去睾18周后腰椎、股骨近端均出现骨丢失，表现为高转换型骨代谢，骨吸收大于骨形成而形成了骨质疏松模型。大鼠股骨颈是研究骨质疏松症动物模型的组织形态计量学的理想部位。     

甲状旁腺激素1-34促进尾悬吊再负重大鼠骨质量恢复

以往研究中已经证实甲状旁腺激素1-34（PTH1-34）抗骨质疏松效果,然而PTH1-34对于拟失重再负重大鼠骨量的恢复是否有促进作用尚未见报道。目的：观察尾悬吊大鼠再负重骨量的变化及PTH1-34干预对该过程的影响及机制。方法：5月龄大鼠24只分为4组,每组6只：对照组（Control组）、尾悬吊（Unloading）4周组（Unloading）, UL组）、尾悬吊2周再负重（Reloading）2周组（UL+RL组）、尾悬吊2周再负重加PTH1-34干预2周组（20ug/kg/d, 5 days/week, UL+RL+PTH组）;4周后处死大鼠,分离左侧胫骨制备硬组织切片,行骨组织形态计量学分析;检测左侧股骨骨密度;取右侧胫骨制备组织匀浆,提取蛋白和RNA,分别采用Western blot和Realtime PCR检测骨钙素（OCN）的表达;三点弯曲试验分析右侧股骨最大载荷和弹性模量。结果：1、骨密度：CL组显著高于其余三组（P < 0.05）,UL+RL组和UL+RL+PTH组均显著高于UL组（P < 0.05）;UL+RL+PTH组显著高于UL+RL组（P <0.05）; 2、骨组织形态计量学：BV/TV：CL组显著高于UL、UL+RL、UL+RL+PTH组（P < 0.05）,UL组显著低于UL+RL组和UL+RL+PTH组（P < 0.05）;UL+RL+PTH组显著高于UL+RL组（P <0.05）;Tb.N：CL组显著高于其余三组（P < 0.05）,UL+RL+PTH组显著高于UL组（P < 0.05）;Tb.Th：任意两组间比较,差异无统计学意义（P >0.05）;Tb.Sp：CL组显著低于UL、UL+RL、UL+RL+PTH（P < 0.05）,UL组显著低于UL+RL组和UL+RL+PTH组（P < 0.05）; 3、生物力学分析结果：最大载荷：UL组显著低于其余三组,UL+RL组显著低于CL组（P < 0.05）;弹性模量：CL组显著高于其余三组（P < 0.05）,UL+RL+PTH组显著高于UL组、UL+RL组（P < 0.05）;4、Western blot： OCN蛋白表达在CL组和UL+RL+PTH组显著高于UL组（P < 0.05）;5、Realtime PCR检测结果：各组间的mRNA表达水平无显著差别。结论：尾悬吊2周可诱发大鼠下肢骨量丢失、力学性能下降、OCN含量减少,再负重2周后上述改变可得到部分恢复,PTH1-34干预能促进这一过程。     

不同咀嚼压力对大鼠正畸移动牙压力侧牙槽骨改建的影响

目的 研究不同咀嚼压力对大鼠正畸移动牙压力侧牙槽骨改建的影响。方法 选取8周龄雄性SD大鼠45只,按随机数字表法分为基线组5只、软食组20只和硬食组20只。基线组大鼠在实验初始处死、取材。软食组和硬食组建立上颌右侧第一磨牙近中移动模型,左侧不加力作为对照。各组喂以相应饮食,分别于加力后第3、5、7、14天各处死5只大鼠,取双侧上颌骨。Micro CT测量加力磨牙近中移动距离及压力侧牙槽骨骨体积/组织体积（BV/TV）、骨小梁分离度（Tb.Sp）和骨小梁厚度（Tb.Th）。抗酒石酸酸性磷酸酶（TRAP）染色计数破骨细胞数量;原位杂交染色观察细胞核因子-κB受体活化因子配体（RANKL）和骨保护素（OPG）mRNA表达随时间变化情况。结果 第14天时软食加力组牙齿移动距离小于硬食加力组（P<0.05）。软食加力组与硬食加力组压力侧牙槽骨BV/TV、Tb.Sp、Tb.Th差异无统计学意义。细胞计数和原位杂交结果显示,在第5、7天,软食加力组的破骨细胞数量和RANKL/OPG比值均低于硬食加力组（P<0.05）。结论 较小的咀嚼压力会减低大鼠正畸牙压力侧牙槽骨中的破骨活动,减小牙齿...     

雷奈酸锶对绝经后妇女骨质疏松症性骨痛及骨密度和骨代谢的影响

目的:研究雷奈酸锶在绝经后妇女骨质疏松症治疗中对骨痛、骨密度、骨代谢及骨质疏松性骨折风险的作用,评价其疗效和安全性。方法:40例老年绝经后骨质疏松症妇女被随机分为雷奈酸锶组(20例)和对照组(20例),进行开放、对比研究。雷奈酸锶组:雷奈酸锶2 g.d-1,口服,同时口服钙剂600 mg.d-1;对照组:钙剂600 mg.d-1,口服。治疗前后分别测定2组患者腰背痛的VAS评分、L1-L4椎体、股骨颈、全髋的骨密度值及T值、骨代谢指标,并观察2组骨质疏松性骨折的发生率及服药后的不良反应。结果:治疗后雷奈酸锶组VAS评分明显改善,低于对照组,但骨痛缓解过程较为缓慢;雷奈酸锶组L1-L4椎体、股骨颈、全髋的骨密度值及T值在治疗6月后较治疗前上升显著,明显优于对照组(P<0.01);骨代谢指标在治疗6月后骨钙素(N-MID)明显上升,β-CTX明显下降,与对照组有显著性差异(P<0.01);骨质疏松脆性骨折的发生率对照组明显高于雷奈酸锶组;雷奈酸锶的主要不良反应为恶心、腹泻及皮疹,对照组主要为便秘。结论:雷奈酸锶能有效缓解骨质疏松症骨痛,但作用较为缓慢。它能有效提高骨质量,改善骨代谢标志物,降低骨质疏松脆性骨折的发生率,不良反应少。     

乳腺癌术后发生肝脏转移的相关危险因素分析

目的 研究损毁下丘脑弓状核对大鼠骨组织形态计量学的影响.方法 选用新生期SD雌性大鼠12只,随机分成2组:皮下注射10%谷氨酸单钠组(MSG实验组),同法注射等体积生理盐水组(NS对照组),各组大鼠皆存活至120d处死,取左侧胫骨上段制成不脱钙骨切片,行骨组织形态计量学研究.结果 与NS对照组相比,MSG实验组的骨小梁面积百分数(%Tb.Ar)降低23.21%(P<0.05),骨小梁宽度(Tb.Th)降低9.74%(P<0.05),骨小梁数量(Tb.N)减少14.65%(P<0.05),骨小梁分离度(Tb.Sp)升高24.04%(P<0.05).骨小梁荧光周长百分数(%L.Pm)降低32.89%(P<0.05),骨矿化沉积率(MAR)增加11.83%(P<0.05),骨形成率(BFR/TV、BFR/BV、BFR/BS)分别降低34.96%、16.91%、24.60%(P<0.05).骨小梁周长破骨细胞数量增加100%.结论 MSG损伤弓状核引起大鼠骨转换降低,骨形成减少,骨吸收增加,导致骨质疏松.     

激素治疗对阿霉素肾病大鼠上颌骨骨密度的影响

摘要： 目的 研究甲泼尼龙激素治疗对阿霉素肾病大鼠上颌骨骨密度 （BMD） 的影响。方法 将 40 只大鼠随机分为 4 组, 空白对照组、 激素组、 阿霉素肾病组、 阿霉素+激素组。阿霉素肾病组及阿霉素＋激素组采用间隔 1 周 2 次尾静脉注射盐酸阿霉素 4 mg/kg 建立大鼠阿霉素肾病模型, 空白对照组和激素组尾静脉注射生理盐水 4 mg/kg。建模后激素组及阿霉素＋激素组给予甲泼尼龙 30 mg/ （kg·d） 灌胃, 空白对照组及阿霉素肾病组给予等体积生理盐水灌胃。每日 1 次, 连续 10 周。采用酶联免疫吸附试验 （ELISA） 测定骨钙素 （BGP）、 Ⅰ型原胶原 N-端前肽 （PINP）、 β- Ⅰ型胶原交联 C 末端肽 （CTX） 水平; 并行上颌骨 micro-CT 三维扫描检测骨小梁厚度 （Tb.Th）、 骨小梁间隙 （Tb.Sp）、骨小梁数目 （Tb.N）、 骨体积分数 （BVF）、 BMD。结果 与其余 3 组相比, 阿霉素＋激素组 BGP、 PINP 降低, CTX 升高（P＜0.05）。经 micro-CT 三维扫描分析, 阿霉素＋激素组上颌骨发生明显骨质疏松现象, 包括骨显微结构的改变, BMD 降低、 BVF 降低、 Tb.Th 减少以及 Tb.Sp 增宽 （P＜0.05）。但各组 Tb.N 差异无统计学意义。结论 阿霉素肾病大鼠本身存在骨代谢异常, 大剂量激素治疗可加速骨质疏松的发生, 使其骨代谢水平下降, 影响骨小梁结构。     

右归饮联合盐酸雷洛昔芬给药治疗小鼠骨质疏松症

目的 观察右归饮和盐酸雷洛昔芬联合给药对骨质疏松模型小鼠的治疗作用,并研究其作用机制。方法 将C57BL/6雌性小鼠切除卵巢制备骨质疏松模型,手术12周后将小鼠随机分为4组：模型组、右归饮（0.1 g/只）组、盐酸雷洛昔芬（10mg/kg）组和联合给药（右归饮0.1 g/只与盐酸雷洛昔芬10 mg/kg联合给药）组,另设假手术组,连续7周每天ig给药1次。给药结束后,将动物处死,Micro-CT测定骨密度和骨组织微形态,并测定骨形态计量指标——骨体积分数（BV/TV）、骨表面积/骨体积（BS/BV）、骨小梁的平均厚度（Tb.Th）、骨小梁数量（Tb.N）、骨小梁分离度（Tb.Sp）;试剂盒法测定血清中I型胶原氨基端（P1NP）、胶原羧基端（CTx）水平;分离并培养骨髓间充质干细胞,体外培养7 d,CCK-8法测定细胞增殖率,试剂盒法检测分化相关指标碱性磷酸酶（ALP）水平。结果 与模型组比较,右归饮组、盐酸雷洛昔芬组和联合给药组的骨密度、BV/TV、Tb.Th、Tb.N显著升高,BS/BV和Tb.Sp显著降低（P<0.05）;与盐酸雷洛昔芬组比较,联合给药组的BV/TV、Tb.Th、Tb.N显著升高,BS/BV和Tb.Sp显著降低（P<0.05）。联合给药组P1NP水平、细胞增殖率均显著高于其他各组（P<0.05、0.01）。ALP水平显著高于假手术组、模型组、盐酸雷洛昔芬组,显著低于右归饮组（P<0.01）。结论 在给药时间相同的前提下,右归饮和盐酸雷洛昔芬联合给药比单独给药更有效地抑制小鼠骨丢失,通过促进细胞的增殖和分化提高骨形成能力,达到增加骨密度、治疗骨质疏松的效果。     

炔雌醇对绝经后骨质疏松症模型小鼠骨质量的影响

目的 探究炔雌醇对绝经后骨质疏松症模型小鼠骨质量的影响。方法 将30只SPF级C57雌性小鼠随机分为3组,每组10只,分别为假手术组、模型组和炔雌醇组,炔雌醇组每天ig炔雌醇100μg/kg,假手术组和模型组均ig给予等体积蒸馏水,给药12周后取材,分别观察脏器系数、主要脏器和骨组织病理学切片,分析Micro CT、生物力学和血清生化指标。结果 与模型组相比,炔雌醇组小鼠体质量显著下降（P<0.05、0.01）。炔雌醇组的脏器系数除了子宫与模型组和假手术组有显著性差异,其余均没有显著性差异,主要脏器未发现明显的病变。骨组织脱钙切片显示,与模型组相比,炔雌醇组骨小梁结构致密,脂肪细胞较少。与模型组相比,炔雌醇组生物力学的最大载荷和弹性模量得到了明显的提高（P<0.05、0.01）。与模型组比较,炔雌醇组小鼠的骨小梁骨密度（Tb.BMD）、骨小梁数（Tb.N）、骨小梁厚度（Tb.Th）和骨体积分数（Tb.BV/TV）水平均显著增加,骨小梁分离度（Tb.Sp）数值显著减少（P<0.01）。与模型组比较,炔雌醇组血清骨钙素（OCN）和I型前胶原N端前肽（PINP）的平均水平显...     

蛇床子素对青年大鼠骨代谢的影响研究

目的 探讨蛇床子素对青年大鼠骨代谢的影响.方法 30只雌性wistar大鼠按体重随机分为A、B、C组,A组为正常对照组给予等体积蒸馏水灌胃,B组给予雌二醇灌胃,C组给予蛇床子素灌胃.3组分别在灌胃后4、8、12周分别测定全身骨密度,并在12周后检测左侧股骨和腰椎骨密度及右侧股骨和第4腰椎生物力学性能;检测血清抗酒石酸酸性磷酸酶-5b(TRAP-5b)和骨钙素(0C)含量,分析右侧胫骨骨形态计量学.结果 B、C组灌胃12周后全身骨密度及离体骨密度均高于A组,但C组低于B组(P＜0.01).B、C组生物力学性能指标均高于A组,C组股骨弹性模量和腰椎最大载荷低于B组(P＜0.05).B、C组TRAP-5b水平均低于A组,OC水平高于A组(P＜0.01);C组TRAP-5b水平高于B组,OC水平低于B组(P＜0.01).B、C组胫骨骨组织中骨小梁数量密集,骨小梁分离度低于A组,B组骨小梁数量高于C组,骨小梁分离度低于C组.结论 蛇床子素能够提高青年大鼠骨密度、生物力学性能及骨组织微结构,增加青年大鼠骨质量,但其作用效果略低于雌激素.     

雷奈酸锶临床研究进展

目的 对抗骨质疏松药物雷奈酸锶的整个研究过程进行分析,评价其各阶段研究的有效性.方法 简要总结雷奈酸锶各个阶段研究试验情况,系统概括近10年来雷奈酸锶的研究结论.结果 雷奈酸锶具有双重抗骨质疏松作用,能够有效地预防骨质疏松患者骨密度下降,显著降低骨质疏松骨折发生危险.结论 口服雷奈酸锶是治疗骨质疏松症的一种有效办法,应当成为抗骨质疏松治疗的一种新选择.     

Inhibitory effect of vitamin K2 (menatetrenone) on bone resorption in ovariectomized rats: a histomorphometric and dual energy X-ray absorptiometric study.

To clarify how vitamin K2 prevents bone loss in vivo, it was given to ovariectomized 20-week-old rats for 2 weeks. Bone mineral density (BMD) in the whole femur and in 7 specific portions (F1 to F7 from the proximal to the distal end) was determined by dual-energy X-ray absorptiometry, and histomorphometry was also performed in proximal tibial metaphysis. Ovariectomy (OVX) resulted in significant decreases in the BMD in the whole femur and the F1, F2, F6 and F7 portions. Histomorphometrical analysis of the tibia showed that the bone volume/tissue volume (BV/TV), trabecular thickness (Tb.Th) and trabecular number (Tb.N) were decreased, while trabecular separation (Tb.Sp) and osteoclast number/bone surface (Oc.N/BS) were increased by OVX. The parameters for bone formation were not changed by OVX. These data indicate that the bone loss within 2 weeks is due to the enhancement of bone resorption. Vitamin K2 at 50 mg/kg inhibited the decrease in the BMD of the whole femur together with the F6 and F7 portions. Vitamin K2 also inhibited the decrease in Tb.N and the increases in Tb.Sp, Oc.N/BS and osteoclast surface/bone surface (Oc.S/BS) caused by OVX. These results suggest that vitamin K2 prevents bone loss through the inhibition of bone resorption and osteoclast formation in vivo.     

Strontium ranelate: a new paradigm in the treatment of osteoporosis

In vitro, strontium ranelate increases collagen and non-collagenic protein synthesis by mature osteoblast-enriched cells. The effects of strontium ranelate on bone formation were confirmed as the drug enhanced preosteoblastic cell replication. In the isolated osteoclast, a preincubation of bone slices with strontium ranelate induced a dose-dependent inhibition of the bone resorbing activity of treated rat osteoclast. Strontium ranelate dose-dependently inhibited preosteoclast differentiation. The drug was administered in 160 early postmenopausal women, in a 24-month, double-blind, placebo-controlled, prospective randomised study. At the conclusion of the study, the percentage variation of lumbar bone mineral density (BMD) from baseline was significantly different in the group receiving strontium ranelate 1000 mg/day as compared with placebo (+5.53 versus -0.75%, respectively). Increase in total hip and neck BMD averages were 3.2 and 2.5%, respectively. The effect of strontium ranelate in postmenopausal women with established osteoporosis was assessed during a multinational, prospective, double-blind, randomised, placebo-controlled trial. Strontium ranelate (500, 1000, 2000 mg/day) or placebo were given to 353 Caucasian women with prevalent vertebral osteoporosis. At the conclusion of this 2-year study, the annual increase in lumbar BMD of the group receiving strontium ranelate 2000 mg was 7.3% (p < 0.001). A significant increase in bone alkaline phophatase (p = 0.002) over a 6-month period and a significant decrease in N-telopeptide crosslinks (p = 0.004) throughout the 2-year period were seen in the group receiving 2000 mg of strontium ranelate. During the second year of treatment, the dose of 2000 mg was associated with a 44% reduction in the number of patients experiencing a new vertebral deformity. Bone histomorphometry showed no mineralisation defects. The primary analysis of the SOTI study, evaluating the effect of strontium ranelate 2000 mg on vertebral fracture rates, revealed a 41% reduction in the relative risk of patients experiencing a first new vertebral fracture with strontium ranelate throughout the 3-year study. The TROPOS study showed a significant reduction in the risk of experiencing a first non-vertebral fracture in the group treated with strontium ranelate throughout the 3-year study. A reduction in the risk of experiencing a hip fracture was also demonstrated in the patients treated for ≥ 18 months.     

Strontium ranelate: a new paradigm in the treatment of osteoporosis

In vitro, strontium ranelate increases collagen and non-collagenic protein synthesis by mature osteoblast-enriched cells. The effects of strontium ranelate on bone formation were confirmed as the drug enhanced preosteoblastic cell replication. In the isolated osteoclast, a preincubation of bone slices with strontium ranelate induced a dose-dependent inhibition of the bone resorbing activity of treated rat osteoclast. Strontium ranelate dose-dependently inhibited preosteoclast differentiation. The drug was administered in 160 early postmenopausal women, in a 24-month, double-blind, placebo-controlled, prospective randomised study. At the conclusion of the study, the percentage variation of lumbar bone mineral density (BMD) from baseline was significantly different in the group receiving strontium ranelate 1000 mg/day as compared with placebo (+5.53 versus -0.75%, respectively). Increase in total hip and neck BMD averages were 3.2 and 2.5%, respectively. The effect of strontium ranelate in postmenopausal women with established osteoporosis was assessed during a multinational, prospective, double-blind, randomised, placebo-controlled trial. Strontium ranelate (500, 1000, 2000 mg/day) or placebo were given to 353 Caucasian women with prevalent vertebral osteoporosis. At the conclusion of this 2-year study, the annual increase in lumbar BMD of the group receiving strontium ranelate 2000 mg was 7.3% (p < 0.001). A significant increase in bone alkaline phophatase (p = 0.002) over a 6-month period and a significant decrease in N-telopeptide crosslinks (p = 0.004) throughout the 2-year period were seen in the group receiving 2000 mg of strontium ranelate. During the second year of treatment, the dose of 2000 mg was associated with a 44% reduction in the number of patients experiencing a new vertebral deformity. Bone histomorphometry showed no mineralisation defects. The primary analysis of the SOTI study, evaluating the effect of strontium ranelate 2000 mg on vertebral fracture rates, revealed a 41% reduction in the relative risk of patients experiencing a first new vertebral fracture with strontium ranelate throughout the 3-year study. The TROPOS study showed a significant reduction in the risk of experiencing a first non-vertebral fracture in the group treated with strontium ranelate throughout the 3-year study. A reduction in the risk of experiencing a hip fracture was also demonstrated in the patients treated for > or = 18 months.     

三七总苷对高脂血症性骨质疏松大鼠骨代谢的影响

目的：研究三七总苷（PNS）对大鼠高脂血症性骨质疏松的作用。方法：取SPF级3月龄未交配SD大鼠30只随机分为3组,每组10只。正常对照组：普通饲料喂养,蒸馏水5mL·kg^-1·d^-1灌胃;模型组：脂肪乳剂5mL·kg^-1·d^-1灌胃;PNS组：上午予脂肪乳剂5mL·kg^-1·d^-1灌胃,下午予PNS200mg·kg^-1·d^-1灌胃,连续20周。实验结束后用骨组织形态计量学方法,测定大鼠右侧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。结果：与模型组比较,PNS组游离脂肪酸（FFA）、TC、低密度脂蛋白胆固醇（LDL—C）均明显降低（P〈0．05）,高密度脂蛋白胆固醇（HDL—C）明显升高（P〈0．05）;松质骨形态计量学静态参数骨小梁面积百分数（％Tb．Ar）、骨小梁数量（Tb．N）、骨小梁厚度（Tb．Th）均增加（P〈0．01）,骨小梁分离度（Tb．Sp）明显减小（P〈0．01）;动态参数荧光周长百分率（％L．Pm）、骨形成率（BFR／BS、BFR／By）均明显增加（P〈0．05）。结论：脂肪乳剂长期灌胃可导致大鼠脂质代谢紊乱,并伴有高脂血症性骨质疏松症。PNS可显著降低血脂并促进骨的形成,对大鼠高脂血症所致骨质疏松有一定防治作用。     

Exposure to tobacco smoke increases bone loss in spontaneously hypertensive rats

Abstract

Purpose: To define if exposure to tobacco smoke (TS) could induce reduction of bone mass and impairment of bone architecture, features observed in osteoporosis in normotensive rats and the influence of TS exposure on the osteoporotic features exhibited in the spontaneously hypertensive (SH) rats.

Methods: Normotensive Wistar Kyoto (WKY) and SH rats were exposed to filtered air or TS for 8?weeks, then their proximal femurs were extracted for micro-computed tomography (micro-CT) assessment, histological and immune-histological examinations to quantify the adverse influence of TS exposure on the bone mass and density, as well as bone architecture.

Results: We found that TS exposure not only induced significant decreases in bone mineral density (BMD), bone volume (BV), cortical and trabecular thickness (Ct.Th and Tb.Th), trabecular surface area (Tb.Ar), expression of hypoxia-inducible factor-1α (HIF-1α) in the trabecular marrow, delayed ossification of cartilage, as well as statistical increases in trabecular separation (Tb.SP) and the number of trabecular marrow adipocytes in both WKY and SH rats, but also exacerbated multiple features of osteoporosis exhibited in SH rats, including decreased BMD, Ct.Th, Tb.Ar, HIF-1α expression, delayed cartilage ossification, and increased Tb.SP.

Conclusions: Our results show that TS exposure can reduce bone mass and impair bone architecture and exacerbate multiple features of osteoporosis exhibited in SH rats.     

白藜芦醇对去卵巢大鼠股骨骨保护素及核因子κB受体活化子配体表达的影响

目的：观察白藜芦醇对去卵巢大鼠股骨骨保护素（OPG）及核因子κB受体活化子配体（RANKL）表达的影响。方法：健康3月龄雌性SD大鼠48只，按体重随机分为6组：假手术组（SHAM）、单纯卵巢切除组（OVX）、17β-雌二醇组（ERT，0．1mg·kg^-1·d^-1）。低、中、高剂量白藜芦醇组（RL、RM、RH，每天分别给予10、20、40mg／kg白藜芦醇）。除假手术组外其余各组均切除双侧卵巢。术后1周开始给药，给药8周后处死所有大鼠，测定股骨骨密度（BMD）及骨生物力学性能：弹性模量（ELASTIC）、刚度（STIFFNESS）、最大应力（M-STRESS）最大承载力（M-LORD）。用免疫组织化学染色方法观察股骨OPG、RANKL的表达。结果：与OVX组比较，20、40mg·kg^-1·d^-1白藜芦醇均能上调股骨OPG表达（P〈0．05）。与OVX组比较，20、40mg·kg^-1·d^-1白藜芦醇均下调RANKL的表达，改善股骨骨密度及生物力学性能（P〈0．05）。结论：白藜芦醇在体内可上调骨组织中OPG的表达，下调RANKL的表达，这可能是其改善股骨骨密度及生物力学性能的作用机制。     

Strontium ranelate in osteoporosis

Strontium ranelate is composed of an organic moiety (ranelic acid) and of two atoms of stable non-radioactive strontium. In vitro, strontium ranelate increases collagen and non-collagenic proteins synthesis by mature osteoblast enriched cells. The effects of strontium ranelate on bone formation were confirmed as strontium ranelate enhanced pre-osteoblastic cells replication. The stimulation by strontium ranelate of the replication of osteoprogenitor cells and collagen as well as non-collagenic protein synthesis in osteoblasts provides substantial evidence to categorise SR ranelate as a bone forming agent. In the mouse calvaria culture system, SR ranelate induces a dose-dependent inhibition of labelled calcium release. The inhibitory effects of SR ranelate on bone resorption were close to those of salmon calcitonin. In the isolated rat osteoclast assay, a pre-incubation of bone slices with SR ranelate induced a dose-dependent inhibition of the bone resorbing activity of a treated rat osteoclast. SR ranelate also dose-dependently inhibited, in a chicken bone marrow culture, the expression of both CA II and the alpha-subunit of the vitronectin receptor. These effects showing that SR ranelate significantly affects bone resorption due to direct and/or matrix-mediated inhibition of osteoclast activity and also inhibits osteoclasts differentiation are compatible with the profile of an anti-resorptive drug. In normal rats, administration of SR ranelate induces an improvement in the mechanical properties of the humerus and/or the lumbar vertebra associated with a commensurate increase in bone dimension, shaft and volume. This was not related to any change in the stiffness, suggesting the absence of a mineralisation defect. After oral administration of SR ranelate in humans, the absolute bio-availability of SR ranelate is 27 % after a dose of 2g is given as sachets. The simultaneous intake of SR ranelate and calcium remarkably reduces the bio-availability of SR. SR ranelate was administered in 160 early postmenopausal women, in a 24-month, double-blind, placebo-controlled, prospective randomized study. Daily oral dose of 125 mg, 500 mg, 1 g of SR ranelate were compared to a placebo. At the conclusion of the study, the percent variation of lumbar adjusted BMD from baseline was significantly different in the group receiving 1 g/day of SR as compared to placebo (+ 1.41 % versus 0.98 % respectively). Increase in total hip and neck BMD averages respectively 3.2 % and 2.5 %. SR ranelate does not induce any significant adverse reaction compared to those observed in women receiving a placebo for the same duration. In a phase II study, the effect of SR ranelate in postmenopausal women with vertebral osteoporotic fractures were assessed during a double-blind, placebo-controlled trial. SR ranelate (500 mg, 1 g, 2 g per day) or placebo were given to 353 Caucasian women with prevalent osteoporosis. At the conclusion of this two-year study, the annual increase in lumbar adjusted BMD of the group receiving 2 g of SR ranelate was + 2.97 %. This result was significantly different as compared to placebo. A significant decrease in pyridinium crosslinks (NTX) and an increase in bone specific alkaline phosphatase were evident after 3 and 6 months of treatment. During the second year of treatment, the dose of 2 g was associated with a 4 % reduction in the number of patient experiencing a new vertebral deformity. Bone histomorphometry showed no mineralisation defects. The same percentage of withdrawal following an adverse effect was observed for patients receiving placebo and for those receiving 2 g of strontium ranelate. Currently, strontium ranelate is further investigated in a large Phase III program that includes two extensive trials for the treatment of severe osteoporosis, one assessing SR ranelate effects on the risk of vertebral fractures (SOTI) and one evaluating the effects of SR ranelate on peripheral (non spinal) fractures (TROPOS). The primary analysis of the SOTI study, evaluating the effect of 2 g of strontium ranelate on vertebral fracture rates are expected to be released during the summer 2002.     

Menatetrenone prevents osteoblast dysfunction in unilateral sciatic neurectomized rats

Menatetrenone (MK-4) inhibits bone resorption and enhances osteoblast-induced mineralization. In this study, we examined whether MK-4 administration had beneficial effects on osteoblast dysfunction and trabecular microstructure as well as on bone volume loss in a rat model of osteopenia. Male Sprague-Dawley rats were neurectomized and administered MK-4 as a daily supplement. On Day 21 after neurectomy, significant bone loss was observed in the positive control rats. MK-4 prevented the decrease in bone mineral density of the distal metaphysis of the femur. The osteoclast surface per bone surface (Oc.S/BS) and the number of osteoclasts per bone perimeter (N.Oc/B.Pm) were reduced and the mineral apposition rate (MAR) decreased in the immobilized rats on Day 42, suggesting suppression of bone turnover. In contrast, administration with a low dose of menatetrenone led to an increase of MAR and bone formation rate (BFR), while Oc.S/BS and N.Oc/B.Pm remained at normal levels. These data suggested that MK-4 reduced the loss of trabecular bone, prevented osteoblast dysfunction to a certain extent, and contributed to preservation of the trabecular microstructure in this rat model of osteopenia induced by sciatic neurectomy.