双重抗骨质疏松药雷尼酸锶

不同于其他抗骨质疏松药,雷尼酸锶是新型具有双重药理作用的抗骨质疏松药物,即抑制骨吸收和促进骨形成.雷尼酸锶可改变骨微结构,增加骨密度和骨强度,从而降低骨折风险,改善患者生活质量.临床研究显示,它能降低绝经后骨质疏松患者椎体和非椎体骨折的风险,并具有作用长久、安全性好、耐受性好的特点.     

雷尼酸锶促进大鼠股骨骨质疏松性骨折愈合的研究

目的 探讨雷尼酸锶(strontium ranelate,SR)对大鼠股骨骨质疏松性骨折愈合的影响。方法 6个月龄Wistar雌性处鼠66只,切除双侧卵巢制作骨质疏松动物模型,模型建立成功后,在大鼠股骨中段横行截骨,制作大鼠股骨骨质疏松性骨折动物模型,术后死亡6只,然后将剩余60只大鼠随机分为实验组(SR干预治疗组）和空白对照组,每组30只。骨折术后第一天起,实验组给予SR 400 mg/(kg d)灌胃,对照组给予同等体积的生理盐水灌胃。通过影像学、组织学和免疫组织化学（骨形态发生蛋白-2,BMP-2)观察,骨组织形态计量学、骨密度（bone mineral density,BMD)和生物力学测量,观察骨折愈合情况。结果 实验组腰4、5椎体BMD、BMP-2阳性表达细胞数、骨小梁面积比、骨小梁平均宽度、最大负荷和最大桡度高于同时期对照组,差异有统计学意义(P <0. 01);骨小梁平均间隔小于同期对照组,差异有统计学意义(P <0. 01)。结论 SR具有抑制骨吸收和促进骨形成的双重作用,能增加BMD,加快骨痴形成,促进骨质疏松性骨折愈合,改善骨的显微结构,提高骨折愈合后骨的生物力学特性。     

雷尼酸锶对局部肌麻痹大鼠的骨量丢失及微结构退变的影响

目的 研究雷尼酸锶对局部肌肉麻痹大鼠的骨量丢失及微结构退变的影响。方法 21只3.5月龄的雌性SD大鼠随机分三组,每组各7只：肉毒素组(BTX组),右侧股四头肌肌注肉毒素建立局部肌肉麻痹废用模型;肉毒素+雷尼酸锶组(BTX+SR组),肌注肉毒素并予以雷尼酸锶灌胃处理;对照组。所有大鼠干预9周后处死,取双侧股骨,行显微CT扫描分析。结果 BTX组与对照组相比较,废用侧的股骨皮质骨矿物盐含量、皮质骨骨密度、皮质骨面积和截面总面积以及松质骨的骨体积分数、骨小梁厚度、骨小梁数量和骨小梁联接密度均明显下降;骨小梁面积分数、骨小梁间隔和结构模型指数显著增加(P＜0.05)。BTX+SR组与BTX组相比较,皮质骨骨密度、皮质骨面积和截面总面积以及松质骨的组织骨密度、骨体积分数、骨小梁厚度、骨小梁数量和骨小梁联接密度明显增加,骨小梁面积分数、骨小梁间隔和结构模型指数显著下降(P＜0.05)。BTX+SR组与BTX组和对照组比较,健侧松质骨的表观骨密度、组织骨密度、骨体积分数和骨小梁厚度均明显增加(P＜0.05)。结论 雷尼酸锶可阻止因局部肌肉麻痹导致的大鼠骨量丢失和微结构的退变。     

雷尼酸锶治疗骨质疏松症的研究进展

雷尼酸锶（Strontium Ranelate，SR）由一个有机酸（雷尼酸）和两个非放射性锶原子组成。SR具有双向调节作用，能诱导骨重建的解偶联，增加骨形成，减少骨吸收，但不抑制骨转换，是非常有潜力的新药，目前被认为是有效治疗骨质疏松症的药物之一。但国内相关研究还很少。     

雷奈酸锶对骨质疏松性骨痛及骨密度疗效评价

目的研究雷奈酸锶联合钙剂在骨质疏松症治疗中对骨痛、骨密度及骨质疏松性骨折风险的作用,评价其疗效和安全性。方法 124例老年骨质疏松症患者被随机分为雷奈酸锶+钙剂组(SR+Ca组,62例)和钙剂组(Ca组,62例),进行开放、对比研究。雷奈酸锶+钙剂组:雷奈酸锶2g/d,口服,同时口服钙剂600mg/d;Ca组:钙剂600mg/d,口服。治疗前后分别测定两组患者腰背部自发性疼痛的VAS评分、L1-L4椎体、股骨颈、Wards三角、桡骨远端的BMD值及T值,并观察两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+钙剂组VAS评分明显改善,低于钙剂组,但骨痛缓解过程较为缓慢;雷奈酸锶+钙剂组L1-L4椎体、股骨颈、Wards三角、桡骨远端的BMD值及T值在治疗后6月及12月较治疗前上升显著,明显优于钙剂组(P<0.01)。骨质疏松脆性骨折的发生率钙剂组明显高于雷奈酸锶+钙剂组。雷奈酸锶的主要不良反应为恶心及腹泻,钙剂组主要为便秘。结论雷奈酸锶对骨痛的缓解作用较为缓慢,但经过足够的疗程依然能达到令人满意的效果。它能有效提高骨质量,降低骨质疏松脆性骨折的发生率,副反应少,是治疗骨质疏松症的良好选择。     

变频振动对尾吊大鼠失重性骨质疏松防治作用的研究

目的探讨变频振动对尾吊大鼠失重性骨质疏松模型的防治作用。方法采用目前世界上广泛应用且技术已经成熟的鼠尾悬吊动物模型模拟失重环境,应用电磁振动台将振动强度为0.5 g(g为加速度)在不同频率45 Hz、90 Hz、变频(5~90Hz)振动应力作用于3月龄SD雄性大鼠40只,随机分成5组,每组8只:对照组(非鼠尾悬吊组);45 Hz组、90 Hz组、变频(5~90 Hz)组,鼠尾悬吊非振动组,每次振动10 min,每天1次,每周5次,休息间隔为2天,共4周。所有对照组不进行振动治疗,但置于与振动治疗组相同噪音环境下。实验后用Micro-CT测量股骨远端骨量、自动化分析仪测定血生化指标以及Elisa试剂盒测定骨钙素。结果振动刺激对失重性骨质疏松骨微结构的恢复及骨密度有明显的改善作用,变频振动对骨微结构的恢复及增加骨密度一定程度上要好于固定频率振动。结论对尾吊大鼠28天的不同频率振动刺激使松质骨骨矿物质以及空间上的结构进行了重构,导致尾吊大鼠骨质疏松模型中骨量的增加,骨密度的提高,对失重性骨质疏松有一定的防治作用,为临床上防治微重力环境下骨丢失提供了实验依据。     

金乌骨胶囊联合雷尼酸锶治疗绝经后妇女 骨质疏松症的临床观察

目的 评价金乌骨胶囊联合雷尼酸锶治疗绝经后骨质疏松症有效性和安全性.方法 选70例绝经后妇女骨质疏松患者随机分治疗组与对照组各35例;对照组给金乌骨胶囊,口服,3次/d,3粒/次;治疗组在对照组基础上加用雷尼酸锶2mg/d,疗程14周;治疗前后检测采用超声骨密度仪测左侧跟骨低骨量.结果 两组绝经后妇女治疗后症状均有所减轻,骨密度较治疗前明显增加,骨折风险减少(P＜0.05);临床疗效优于单用金乌骨胶囊组(P＜0.05),临床症状好转达97.14％.结论 金乌骨胶囊联合雷尼酸锶治疗骨质疏松疗效比单一用药治疗效果及安全性更确切.     

雷奈酸锶对糖皮质激素诱导骨质疏松大鼠骨形态计量学的研究

目的观察雷奈酸锶对糖皮质激素诱导骨质疏松大鼠骨形态计量学的影响。方法 24只3.5月龄SPF级雄性SD大鼠适应性喂养1w后,随机等分为3组:Nrm组:正常对照组;Met组:皮下注射甲强龙(Met)5 mg/(kg.d),每周5次;SrR组:在Met组基础上给予雷奈酸锶900 mg/(kg.d)灌胃。实验期9w。第5腰椎(L5)和右侧股骨用于骨密度测定,右侧胫骨行骨形态计量学分析。结果 Met组L5和股骨BMD显著低于Nrm组;SrR组L5和股骨BMD显著高于Met组。Met组BV/TV,Tb.Th,Tb.N,%Ct.Ar显著低于Nrm组,Tb.Sp,%Ma.Ar,ES/BS显著高于Nrm组;SrR组BV/TV,Tb.Th,Tb.N,%Ct.Ar显著高于Met组;Tb.Sp,ES/BS显著低于Met组。结论给予大鼠SrR 900 mg/(kg.d)灌胃,在提高激素诱导骨质疏松大鼠的骨密度,促进骨形成,降低骨吸收,延缓骨量丢失方面有积极作用;对继发性骨质疏松的预防和治疗有一定前景。     

雷奈酸锶对大鼠骨质疏松性骨折愈合的骨密度及骨微结构影响

目的 观察雷奈酸锶对大鼠胫骨骨质疏松性骨折愈合过程中的骨密度、骨微结构及愈合后生物力学特性的影响.方法 72只雌性SD大鼠卵巢去势制造骨质疏松模型,造模成功后制造开放性骨折并予克氏针内固定.术后分为对照组和治疗组,分别给予生理盐水和雷奈酸锶625mg/( kg·d)灌胃给药.结果 在治疗后6、8w时两组骨性愈合率并无明显差异,但Micro CT检验数据结果显示治疗组骨密度(BMD);骨小梁体积(BV)、组织体积(TV)、骨体积分数(BV/TV)、平均骨小梁厚度(Tb.Th)、平均骨小梁数目(Tb.N)均明显高于对照组(P＜0.05),且治疗组最大压缩荷载在治疗后4w(48.1±:5.6(治疗组)vs 21.8±4.8(对照组))、8w时亦明显高于对照组(96.5±9.7(治疗组)vs68.2±7.4(对照组)).结论 雷奈酸锶能够抑制骨折后的骨量丢失,增加骨密度,促进骨折愈伤组织的生长,改善骨小梁三维结构及骨组织的力学性能,可用来促进骨质疏松性骨折的愈合并改善骨质量,预防再骨折.     

机械振动防治失重性骨质疏松的研究进展

随着载人空间站发展,在军事和民用都有着巨大应用价值,载人航天器围绕地球旋转时,由于离心力与重力相平衡,理论上其内部为零重力,这称之为失重。对于失重下的减少骨量丢失,药物预防或者治疗尚未达到理想的效果,并不能阻止失重状态下骨量的丢失,目前的研究证明了采用机械振动的方法可能是一种有效防治失重性骨质疏松的措施。因此本文对机械振动在动物、细胞、临床方面的研究现状以及防治失重性骨质疏松方面的临床应用前景进行综述。     

雷奈酸锶治疗老年男性骨质疏松性骨痛的疗效和安全性评价

【摘要】〓目的〓观察雷奈酸锶在男性骨质疏松症治疗中对骨痛的疗效,并评价其安全性。方法〓共纳入58例男性骨质疏松症患者,其中26例雷奈酸锶组,32例为钙剂组,分别测定两组患者治疗前后腰背部视觉疼痛模拟评分(VAS评分)、L1~L4椎体和Wards三角的骨密度值,并观察两组骨质疏松性骨折的发生率及服药后的不良反应。结果〓雷奈酸锶组患者治疗后6月及12月的VAS评分明显改善,低于钙剂组(P<0.001);雷奈酸锶组L1~L4椎体和Wards三角的骨密度值及T值在治疗后较治疗前上升显著,明显优于钙剂组(P<0.001)。雷奈酸锶组患者的主要不良反应为恶心及腹泻,钙剂组主要为便秘。结论〓雷奈酸锶能有效地提高骨质量和缓解骨痛,副反应少,是治疗男性骨质疏松性骨痛的良好选择。     

Monitoring strontium ranelate therapy in patients with osteoporosis

Purpose  The purpose of this study was to review the monitoring of strontium ranelate osteoporosis therapy. Methods  The method used in this study was comprehensive literature review with clinical perspectives. Results  Changes in bone turnover markers (BTM) or bone mineral density (BMD) have been documented in osteoporosis clinical trials. However, neither BMD nor BTM changes fully explain the observed fracture risk reduction in treated patients. If changes in BMD or BTM on therapy would be easily discernable in individual patients, and were strongly associated with fracture risk reduction, monitoring individuals would be more useful. BMD changes in patients on strontium ranelate are of a greater magnitude and hence can be easily determined in an individual patient. In addition, there exists a better correlation between fracture risk reduction and increases in BMD. Conclusions  The strong correlation between measured BMD increases and fracture risk reduction in patients on strontium ranelate therapy will be of clinical benefit to physicians wishing to evaluate both treatment persistence and fracture risk reduction.     

雷奈酸锶联合鲑鱼降钙素针剂对老年骨质疏松压缩性骨折疗效临床观察

目的探讨雷奈酸锶联合鲑鱼降钙素针剂治疗老年骨质疏松椎体压缩性骨折的疗效及对患者骨密度、骨代谢的影响。方法 80例老年椎体压缩性骨折患者随机分为对照组和治疗组。两组患者均进行保守治疗,治疗组在入院后第1天接受雷奈酸锶联合鲑鱼降钙素针剂治疗。分别在治疗前和治疗6个疗程后评定两组患者视觉模拟疼痛评分(VAS)及Oswestry功能障碍指数评分(ODI);检测患者骨密度及骨钙素(BGP)和β-胶原降解产物(β-Cross Laps);并观察治疗组药品不良反应发生情况。结果治疗6个疗程后两组患者VAS与ODI评分均较治疗前有明显改善(P0.05),且治疗组患者评分明显低于对照组(P0.05)。治疗6个疗程后,治疗组患者骨密度较术前显著改善(P0.05),血清BGP和β-Cross Laps较治疗前有显著改变(P0.05),且均明显优于对照组(P0.05);而对照组治疗前后上述指标无明显变(P0.05)。两组药品不良反应发生率比较,差异无统计学意义(P0.05)。结论雷奈酸锶联合鲑鱼降钙素针剂治疗老年骨质疏松椎体压缩性骨折疗效较好,能增加患者骨密度,降低血清BAP和CTX水平,值得推广。     

The Effects of Strontium Ranelate in Asian Women with Postmenopausal Osteoporosis

The aim of this study was to assess the efficacy and safety of strontium ranelate in the treatment of postmenopausal women with osteoporosis in Taiwan. In this 12-month multicenter, randomized, double-blind, placebo-controlled study, 125 women with osteoporosis were randomly given either strontium ranelate 2 g daily or placebo. Lumbar spine, femoral neck, and total-hip bone mineral density (BMD) and biochemical markers of bone turnover were measured; adverse events and tolerability were recorded and assessed. Subjects treated with strontium ranelate showed significant increases in BMD of 5.9% at the lumbar spine, 2.6% at the femoral neck, and 2.7% at the total hip, while the placebo group exhibited no significant change at 12 months. Serum level of a formation marker (bone-specific alkaline phosphatase) was also significantly increased at 6 and 12 months. Thus, although the sample size and the treatment duration of this study could not show its effect of reducing osteoprotic fractures, strontium ranelate showed bone protection effects by increasing BMD and concentrations of a bone formation marker. Safety assessment revealed adverse events were mild and not significantly different from placebo. An erratum to this article can be found at     

Effect of strontium ranelate on fracture healing in the osteoporotic rats

The aim of this study was to evaluate the effect of strontium ranelate (SrR) on fracture healing in the osteoporotic rat model. Forty female Sprague–Dawley rats aged 3 months were enrolled in the study. Osteoporosis was induced by bilateral ovariectomy and subsequent daily heparin injection started 1 week after surgery and lasted for 4 weeks. Osteoporosis was confirmed by a reduction of bone mineral density (BMD). Twenty of the osteoporotic rats were assigned to the SrR group and the remaining 20 to the control group. An open right tibial midshaft transverse fracture was created and then an intramedullary fixation was performed. SrR group was treated by 450 mg/kg/day SrR per oral. Six weeks after surgical induction of fracture, all animals were sacrificed. One animal from each group died after ovariectomy. Two tibiae from the control group failed to unite. SrR‐treated group showed higher mechanical strength and fracture stiffness when compared to the control group (p = 0.006, p = 0.001, respectively). SrR‐treated group had mature woven bone or predominantly woven bone compared with osteoporotic control group (p = 0.038). SrR‐treated group's callus maturity was significantly higher than control group (p = 0.001). SrR is associated with better fracture healing in the osteoporotic rat model. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29:138–142, 2011     

骨形成蛋白联合雷奈酸锶对成骨细胞增殖和分化的影响

目的探索骨形成蛋白(bone morphogenetic protein,BMP)联合雷奈酸锶(strontium ranelate,SR)对成骨细胞增殖和分化的影响,为临床上两者联合使用可行性提供细胞学基础。方法获取SD大鼠成骨细胞,随机分为对照组、SR组、BMP组和BMP-SR组等4组,培养基中分别添加安慰剂、SR、BMP-2和SR联合BMP-2干预,培养12 d后,通过MTT法检测细胞的增殖情况,碱性磷酸酶(alkaline phosphatase,ALP)及茜素红染色观察细胞的功能状态,蛋白电泳观察骨钙素(osteocalcin,OCN)及Runx2蛋白的表达情况。结果 SR及BMP-2单独作用于成骨细胞时,都可以明显促进成骨细胞的增殖,增加ALP活性及矿化能力,同时明显促进OCN及Runx2蛋白的表达;联合使用效果明显优于单独使用,比较差异有统计学意义(P0.05)。结论 BMP-2及SR都可以明显促进成骨细胞增殖和分化,且联合使用效果更佳。     

Strontium ranelate improves bone strength in ovariectomized rat by positively influencing bone resistance determinants

Summary  Treatment of adult ovariectomized (OVX) rats with strontium ranelate prevented vertebral biomechanics degradation as a result of the prevention of bone loss and micro-architecture deterioration associated to an effect on intrinsic bone material quality. Strontium ranelate influenced the determinants of bone strength by prevention of ovariectomy-induced changes which contribute to explain strontium ranelate antifracture efficacy. Introduction  Strontium ranelate effects on the determinants of bone strength in OVX rats were evaluated. Methods  Adult female Sprague–Dawley rats were OVX, then treated daily for 52 weeks with 125, 250, or 625 mg strontium ranelate/kg. Bone strength, mass, micro-architecture, turnover, and intrinsic quality were assessed. Results  Strontium ranelate prevented ovariectomy-induced deterioration in mechanical properties with energy necessary for fracture completely maintained vs. SHAM at 625 mg/kg/day, which corresponds to the clinical dose. This was related to a dose-dependent effect on bone volume, higher trabeculae number, and lower trabecular separation in strontium ranelate vs. OVX. Load and energy required to induce lamella deformation were higher with strontium ranelate than in OVX and in SHAM, indicating that the bone formed with strontium ranelate is able to withstand greater damage before fracture. Bone formation was maintained high or even increased in strontium ranelate as shown by mineralizing surfaces and alkaline phosphatase while strontium ranelate led to reductions in deoxypyridinoline. Conclusion  Strontium ranelate administered at 625 mg/kg/day for 52 weeks prevented OVX-induced biomechanical properties deterioration by influencing the determinants of bone strength: it prevented bone loss and micro-architecture degradation in association with an effect on intrinsic bone quality. These beneficial effects on bone contribute to explain strontium ranelate antifracture efficacy.     

雷奈酸锶治疗人工关节磨损颗粒诱导骨溶解的实验研究

目的研究雷奈酸锶治疗人工关节磨损微粒诱导骨溶解的作用,探讨防治人工关节置换术后假体松动的可能性。方法采用小鼠建立Co—Cr-Mo微粒诱导骨溶解的颅骨模型,分为4组：A组为空白组,B组为颗粒对照组,C组为低剂量治疗组,D组为高剂量治疗组。28d后取出颅骨进行HE染色观察颅骨骨溶解面积,通过EUSA方法检测TNF—α和RANKL的表达,qRT-PCR方法检测RANKL和OPG的表达并分析RANKL／OPG比率变化。结果雷奈酸锶可以明显抑制微粒诱导的骨溶解,对下调TNF-α和RANKL蛋白有确切的疗效,而且这种改变与雷奈酸锶的剂量有关。虽然其对OPG基因转录的抑制作用不太明显,但是对RANKL基因转录和RANKL／OPG基因转录比率的调节与HE染色切片上骨溶解程度相一致。结论雷奈酸锶能够抑制小鼠颅骨骨溶解模型中TNF-α和RANKL的表达,并下调RANKL/OPG基因转录比率,从而抑制了由微粒诱导的骨溶解,为临床预防人工关节置换术后假体松动提供了理论依据。     

维生素K2对绝经后骨质疏松症的防治作用及血清组织蛋白酶K影响

目的研究维生素K_2对绝经后女性骨质疏松患者骨密度、骨代谢及血清组织蛋白酶K(cathe K)的影响。方法选取自2014年5月至2016年1月我院骨质疏松患者,共有120例符合纳入标准。患者随机分为维生素K_2组、雷奈酸锶组和空白对照组(各N=40)。雷奈酸锶组每天口服2 g雷奈酸锶。维生素K_2组给予固力康胶囊:每次15 mg,每天3次。药物治疗前、术后6个月检测其骨密度,同时测量血清中血清骨钙素(BGP)、β-胶原降解产物(β-crosslaps)、Ⅰ型前胶原氨基端前肽(PINP)、血清组织蛋白酶K(cathe K)及抗酒石酸酸性磷酸酶(TRAP)水平。结果药物治疗前后,各组的骨密度,骨代谢指标和cathepsin K均有不同的变化;相对空白对照组,维生素K_2组、雷奈酸锶组髋部及腰椎密度都有不同程度的升高,其中雷奈酸锶组骨密度变化更明显,和其他组比较有明显的统计学意义(P0.05);雷奈酸锶组破骨活性(β-crosslaps、TRAP)最低,成骨活性(BGP、PINP)较高,而维生素E组破骨活性降低(β-crosslaps、TRAP),成骨活性(BGP、PINP)也增高,各组比较有明显的统计学意义(P0.05);相对于其他组,雷奈酸锶组cathepsin K下降的最明显,各组比较有明显的统计学意义(P0.05)。结论适量维生素K_2可以通过促进成骨活性,降低破骨活性及cathepsin K表达来改善绝经后女性骨质疏松患者髋部及腰部的骨密度。     

Strontium ranelate does not stimulate bone formation in ovariectomized rats

INTRODUCTION: Strontium ranelate (SrR) is suggested to function as a dual-acting agent in the treatment of postmenopausal osteoporosis with anti-resorptive and anabolic skeletal benefits. We evaluated the effects of SrR on the skeleton in ovariectomized (OVX) rats and evaluated the influence of dietary calcium. METHODS: Three-month old virgin female rats underwent ovariectomy (OVX, n = 50) or SHAM surgery (SHAM, n = 10). Four weeks post-surgery, rats were treated daily by oral gavage with distilled water (10 ml/kg/day) or SrR (25 or 150 mg/kg/day) for 90 days. Separate groups of animals for each dose of SrR were fed a low (0.1%) or normal (1.19%) calcium (Ca) diet. Static and dynamic histomorphometry, DXA, mu-CT, mechanical testing, and serum and skeletal concentrations of strontium were assessed. RESULTS: SrR at doses of 25 and 150 mg/kg/day did not increase bone formation on trabecular or periosteal bone surfaces, and failed to inhibit bone resorption of trabecular bone regardless of Ca intake. There were no improvements in bone mass, volume or strength with either dose of SrR given normal Ca. CONCLUSION: These findings demonstrate that SrR at dosages of 25 and 150 mg/kg/day did not stimulate an anabolic bone response, and failed to improve the bone biomechanical properties of OVX rats.