雷尼酸锶治疗骨质疏松症的研究进展

目的 对雷尼酸锶在骨质疏松症中的临床应用、作用机制进行综述和评价.方法 从人群试验、动物试验、细胞培养和不良反应等方面进行综述.结果 雷尼酸锶具有抗骨吸收和增进骨形成双重作用,其作用可能通过CaSR和增加血清IGF-1、降低高半胱氨酸.结论 雷尼酸锶作为一种新型抗骨质疏松药物,对骨质疏松症具有良好的疗效,代表了骨质疏松症治疗的一个重要发展方向,但应注意其不良反应.     

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.     

骨质疏松性骨折药物治疗的研究进展

骨质疏松症(osteoporosis,OP)是一种以低骨量和骨组织微结构破坏为特征,导致骨质脆性增加和易于骨折的全身性骨代谢性疾病。骨质疏松症患者最终结局常常是脆性骨折。骨质疏松症不利于骨折愈合,主要是由于骨质疏松症导致患者的骨吸收作用增强、新骨形成能力下降造成的。为了缩短骨质疏松症个体的骨折愈合时间、提高愈合质量,抑制骨吸收或促进骨形成的药物成为研究热点。而抗骨质疏松的治疗药物主要是通过抑制骨吸收或促进骨形成促进骨质疏松性骨折的愈合。所以现在已有大量的实验探讨了抗骨质疏松治疗药物对骨质疏松性骨折愈合的影响。同时还有关于抗骨质疏松药对骨修复影响的研究。这些研究的结果总结来说,指出了抗骨质疏松药可能对骨质疏松性骨折治疗有一定的作用。同时现在还没有明确的证据证明抗骨质疏松治疗不利于骨修复,故抗骨质疏松药在骨质疏松性骨折上有很大的应用前景。本文回顾综述了当下骨质疏松性骨折治疗的研究进展,总结了双膦酸盐、地诺单抗、雌激素、雷洛昔芬、特立帕肽、雷尼酸锶、他汀类药物以及一些正在研究中的抗骨质疏松药物对骨折愈合的影响及其作用机制。     

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。     

经皮球囊扩张椎体后凸成形术术后再发椎体骨折的危险因素和防治策略

目的探讨骨质疏松性椎体骨折PKP术后再发椎体骨折的危险因素,并提出对应的防治策略。方法对2007-01-2013-01本院行经皮球囊扩张椎体后凸成形术(percutaneous kyphoplasty,PKP)治疗的425例骨质疏松性椎体骨折患者进行回顾性分析。患者分为再发椎体骨折组和未再发椎体骨折的对照组。对两组患者基本情况、影像学资料、手术相关因素以及抗骨质疏松治疗进行分析。研究各因素与再发椎体骨折的关系。结果再发椎体骨折组(18例)比对照组(407例)骨密度低,平均骨折椎体数多,局部后凸角度大,椎体平均注入骨水泥量多,抗骨质疏松治疗依从性差,上述差异均有统计学意义。而两组在年龄、性别方面差异无统计学意义。结论骨密度低、多椎体骨折、术后病椎后凸角度大、椎体注入骨水泥量多、抗骨质疏松治疗依从性差,都是再发椎体骨折的危险因素。针对上述危险因素进行干预,可以降低再发椎体骨折的风险。     

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。     

雷奈酸锶对磷酸钙骨水泥强化大鼠椎体骨质量和生物力学性能的影响

[目的]探讨雷奈酸锶对磷酸钙骨水泥强化的大鼠骨质疏松椎体骨质量和生物力学性能的影响。[方法]20只12周龄雌性SD大鼠,行双侧卵巢切除制备骨质疏松模型。4周后再行L_4椎体磷酸钙骨水泥(CPC)强化术,随机分为两组:雷奈酸锶组给予雷奈酸锶混悬溶液灌胃,剂量为900 mg 1 (kg·d);生理盐水组给予等重量生理盐水灌胃,再饲养8周后处死两组大鼠,分离取L_4椎骨测量L_4椎体骨密度,显微CT分析L_4椎体骨微结构相关指标,包括骨小梁体积分数(BV/TV,%)、平均骨小梁厚度(Tb.Th,mm)、平均骨小梁数目(Tb.N,1/mm)、骨小梁分离度(Tb.Sp,mm)、骨小梁结构异性程度(DA)并进行椎体压缩实验。[结果]雷奈酸锶组处理8周后,雷奈酸锶组大鼠L4椎体骨密度较生理盐水组显著升高[(0.202±0.003) g/mm~2vs (0.173±0.002) g/mm~2,P0.05];骨微观结构方面,雷奈酸锶组大鼠L_4椎体BV/TV、 Tb.N明显升高,而Tb.Sp明显降低,两组间差异有统计学意义(P0.05);椎体压缩实验中,雷奈酸锶L_4椎体最大压缩负荷(Max.L)和刚度(S)均显著大于生理盐水组,差异均有统计学意义(P0.05)。[结论]雷奈酸锶能增加磷酸钙骨水泥强化的大鼠骨质疏松椎体骨量,改善骨微观结构,提高椎体的抗压缩强度。     

抗骨质疏松药物对骨折愈合影响的研究进展北大核心CSCD

骨质疏松症是以骨量减少、骨微细结构受损及骨强度降低,导致骨脆性增加、易发生骨折的全身性骨病,好发于绝经后的妇女及老年人.骨折是骨质疏松症最常见和最严重的并发症.随着我国社会人口老龄化,骨质疏松相关骨折发病率将逐年增加.2002年至2006年北京地区50岁以上人群中女性髋部骨折发生率增加约58%,男性髋部骨折发生率增加约49%[1].骨质疏松症患者骨折愈合缓慢,治疗此类骨折还需抗骨质疏松治疗.抗骨质疏松药物通过抑制骨吸收或促进骨形成干扰骨组织的代谢.骨折愈合是骨折后骨组织的自我修复过程,也是骨代谢的一种表现形式.使用干扰骨代谢的抗骨质疏松药物对骨折愈合有何影响,目前文献报道不多,本文就此作一综述.     

微量元素锶与骨质疏松症

随着世界范围内老龄人口的不断增加,骨质疏松症已经成为严重危害中老年人健康的常见病、多发病。骨质疏松症患者不仅易于发生骨折,他们在接受牙种植、人工关节置换等治疗时,还经常存在生物植入材料骨整合不佳、甚至松动脱落的问题,严重限制了中老年患者生活质量的提高。因此,探索各种科学、合理的方法改善骨质疏松症患者的骨代谢状况,预防骨质疏松性骨折的发生,促进骨质疏松性骨折的愈合,改善骨质疏松状态下植入体的骨整合已经成为骨科、矫形外科、口腔颌面外科以及老年医学等多学科领域内亟待解决的难题。近期的研究发现,微量元素锶是一种具有促进成骨和抑制骨吸收双重作用的抗骨质疏松药物,本文就微量元素锶治疗骨质疏松症的研究进展作一综述。     

骨水泥强化骨质疏松性椎体椎弓根螺钉的研究进展

目前椎弓根螺钉固定技术作为脊柱后路稳定的"金标准",已被广泛应用于临床.如果病人合并骨质疏松症,其内固定失败的风险将大大增加.骨水泥强化技术不仅能够显著提高骨质疏松性椎体术后骨质疏松椎体的稳定性,还能明显改善固定节段的周期性抗屈能力,为骨质疏松性椎体提供坚强、持久的内固定,从而有效重建脊柱的稳定性.但骨水泥强化技术也存在并发症,如骨水泥渗漏、加快邻近节段退变、增加骨折风险等.本文通过对骨水泥强化椎弓根螺钉固定的力学特性、骨水泥的选择、强化方式及近远期并发症等方面对骨水泥强化椎弓根螺钉固定技术进行综述.     

抗骨质疏松症药物对糖尿病患者糖代谢及骨代谢的影响

糖尿病是骨质疏松性骨折的危险因素之一,无论是 1 型还是 2 型糖尿病患者,其发生骨质疏松症和糖尿病性骨折的风险均显著升高。研究表明,糖尿病患者骨转换指标明显低于正常人群,尤其是骨形成动力不足。目前针对糖尿病合并骨质疏松症患者的抗骨质疏松治疗尚无明确的指南。抗骨质疏松症药物尤其是抗骨吸收药物,可进一步降低骨转换,同时,其可能影响骨钙素（osteocalcin,OC）等细胞因子的分泌从而对糖代谢产生不利影响。而目前许多动物实验及临床研究发现,常用抗骨质疏松症药物用于糖尿病患者不仅有抗骨质疏松作用,甚至可能对糖代谢产生积极影响。本文通过综述抗骨质疏松症药物对糖尿病患者糖代谢及骨代谢的影响,旨在为糖尿病患者抗骨质疏松治疗及避免糖尿病性骨折的发生提供有效的参考。     

Use of Strontium as a Treatment Method for Osteoporosis

Given its increasing incidence and serious complications, osteoporosis requires safe and effective long-term treatment. Strontium ranelate (SR), a new anti-osteoporotic treatment with a unique mode of action, has been investigated in the SOTI (Spinal Osteoporosis Therapeutic Intervention) and the TROPOS (Treatment of Peripheral Osteoporosis) trials, two major 3-year multinational placebo-controlled phase 3 randomized clinical trials. Unlike antiresorptive agents, SR produced steady and significant bone mineral density increases that correlated directly with decreases in vertebral and hip fracture risk. The safety profile of SR was almost similar to placebo in both trials. A slight but significant increased risk of thromboembolism events was noted from the pooled phase 3 studies data. However, this increased was not found in a large retrospective observational study. Thus, SR demonstrates broad spectrum safety and efficacy in reducing the risks of both vertebral and nonvertebral (including hip) fractures in a wide variety of patients, and should be considered as a first-line option to treat women at risk of osteoporotic fractures, whatever their age, the severity of the disease, and their risk factors.     

维生素k2 —新型骨质疏松防治药物

骨质疏松症是以骨量减少及骨组织的微观结构退化为特征的系统性骨骼疾病,主要表现为骨密度减少,骨质量降低,骨强度下降及骨折增加。维生素K2在骨形成及维持骨健康方面扮演重要角色且具有良好的药用安全性。临床上,可利用维生素K2防治妇女绝经导致的骨质疏松及其他类型的骨质疏松症,大量的人体试验研究证实,定期摄入维生素K2不仅可显著增加骨密度,而且可改善骨质量,从而提高骨强度,有效降低骨折风险及减少骨流失。     

椎体成形术后应用唑来膦酸联合维生素K2治疗老年性椎体压缩骨折

目的观察椎体成形术后应用唑来膦酸联合维生素K2治疗老年性椎体压缩性骨折的3年临床疗效。 方法2013年1月至2015年1月共收治老年性椎体压缩性骨折患者525例,其中女412例,男113例;年龄64～91岁,平均( 79 ± 11)岁。所有患者均予CT引导下椎体成形术手术治疗,术后2～4 d给予唑来膦酸静脉输注,同时补充维生素K2以及钙剂、维生素D。获得术前、术后1周和术后3年腰背痛视觉模拟评分(VAS)评分、Oswestry功能障碍指数(ODI),术前及术后3年骨密度、骨代谢指标的数据。采用配对样本t检验的方法对术后与术前,术后不同时间获得的各组数据进行统计分析。 结果坚持1年随访为189(36%)人,2年随访为131(25%)人,坚持3年随访的患者为56(10.7%)人,56例中17例为发生再次椎体骨折。经3年随访,患者腰背痛VAS评分(t＝3.01)、ODI评分(t＝0.98)、骨密度同术前比较均有明显改善,且差异有统计学意义(P<0.05) 。骨代谢指标中,骨钙素较术前明显提高(t＝5.75),β-CTX较术前显著下降(t＝3.06),差异有统计学意义(P<0. 05),其他指标变化无统计学差异。 结论老年性椎体压缩性骨折患者长期随访治疗的依从性不高。经过椎体成形术后联合多种抗骨质疏松药物3年的干预治疗,可以明显缓解患者临床症状、改善生活质量、促进骨形成、抑制骨吸收、提高骨密度。     

Clinical relevance of diagnosing vertebral fractures by vertebral fracture assessment

Low bone mineral density and the presence of vertebral fractures are independent predictors for future vertebral and non-vertebral fractures. Combining the conventional measurement of bone mineral density of spine and hips with the morphometry of the thoracal and lumbar vertebrae on lateral images using dual energy x-ray absorptiometry scanners, a technique called vertebral fracture assessment, facilitates detection of vertebral fractures in those patients at older age and with clinical risk factors for osteoporosis. Particularly, the finding of one or more vertebral deformities in patients with osteopenia is clinically important, because this might prompt the start of anti-osteoporotic treatment.     

Physical activity effects on bone metabolism

The incidence of osteoporotic fractures rises exponentially with age and is increasing faster than the demographic increase in the aging population. Physical activity has great potential to reduce the risk for osteoporotic fractures. Three independent but interactive factors contribute to the risk of fractures: bone strength, the risk of falling, and the effectiveness of neuromuscular response that protects the skeleton from injury. Exercise can reduce fracture risk not only by preventing bone loss, but by decreasing the risk of falling and the force of impact by improving strength, flexibility, balance, and reaction time. Extreme inactivity causes rapid bone loss of up to 40%, while athletic activity results in bone hypertrophy of up to 40%. Exercise intervention programs have reduced bone loss or increased bone mass in both men and women of various ages and initial bone status. These benefits have been shown for arm bone mineral content, total body calcium, spine, calcium bone index, tibia, and calcaneus. In both middle-aged and elderly women, physical activity intervention reduced bone loss or increased bone mass. The mechanisms for maintenance of skeletal integrity rely on a cellular response to hormonal and mechanical load stimuli. Studies in animal models show that training affects cellular activity. In osteoporotics, cellular erosion is increased and mineral apposition rate (MAR) decreased compared with normal age-matched controls. In contrast to this, sows trained on a treadmill 20 min per day for 20 weeks had greater active periosteal surface, periosteal MAR, and osteonal MAR than untrained sows.     

Osteopenia: A Diagnostic and Therapeutic Challenge

We discussed whether we are able to select a subgroup of patients with osteopenia having a high fracture risk, in which anti-osteoporotic drug treatment can be advocated. We concluded that in individuals in whom, based on clinical risk factors, a dual-energy x-ray absorptiometry (DXA) was performed in which osteopenia was diagnosed, anti-osteoporotic treatment should be prescribed in those patients with prevalent vertebral fractures, and in patients chronically using glucocorticoids, in a dosage of 7.5 mg per day or more. Although recent developments with regard to high-resolution imaging techniques (eg, peripheral quantitative computed tomography) seem to be promising, until now they do not provide substantial more reliable information than DXA in the prediction of fractures. We think that more data are urgently needed, since safe and effective drugs are available, but there is uncertainty to which patients with osteopenia these drugs should be prescribed.     

Bone Volume Fraction Explains the Variation in Strength and Stiffness of Cancellous Bone Affected by Metastatic Cancer and Osteoporosis

Preventing nontraumatic fractures in millions of patients with osteoporosis or metastatic cancer may significantly reduce the associated morbidity and reduce health-care expenditures incurred by these fractures. Predicting fracture occurrence requires an accurate understanding of the relationship between bone structure and the mechanical properties governing bone fracture that can be readily measured. The aim of this study was to test the hypothesis that a single analytic relationship with either bone tissue mineral density or bone volume fraction (BV/TV) as independent variables could predict the strength and stiffness of normal and pathologic cancellous bone affected by osteoporosis or metastatic cancer. After obtaining institutional review board approval and informed consent, 15 patients underwent excisional biopsy of metastatic prostate, breast, lung, ovarian, or colon cancer from the spine and/or femur to obtain 41 metastatic cancer specimens. In addition, 96 noncancer specimens were excised from 43 age- and site-matched cadavers. All specimens were imaged using micro-computed tomography (micro-CT) and backscatter emission imaging and tested mechanically by uniaxial compression and nanoindentation. The minimum BV/TV, measured using quantitative micro-CT, accounted for 84% of the variation in bone stiffness and strength for all cancellous bone specimens. While relationships relating bone density to strength and stiffness have been derived empirically for normal and osteoporotic bone, these relationships have not been applied to skeletal metastases. This simple analytic relationship will facilitate large-scale screening and prediction of fracture risk for normal and pathologic cancellous bone using clinical CT systems to determine the load capacity of bones altered by metastatic cancer, osteoporosis, or both.     

Predicting vertebral fracture incidence from prevalent fractures and bone density among non-black,osteoporotic women

We evaluated the ability of bone density and vertebral fractures at baseline to predict vertebral fracture incidence in a cohort of postmenopausal women with osteoporosis. The study population was 380 postmenopausal women (mean age 65 years) treated for osteoporosis in a randomized, placebo-controlled, clinical trial of the bisphosphonate etidronate at seven geographic centers in the United States. Baseline measurements of bone mineral density were obtained in 1986 by quantitative computed tomography at the spine and dual-photon absorptiometry at the lumbar spine and hip. Vertebral fractures were documented on serial spine radiographs. Proportional hazards models were used to evaluate the ability to predict the risk of subsequent fractures during an average of 2.9 years of follow-up. Presence of one or two fractures increased the rate of new vertebral fractures 7.4-fold (95% confidence interval = 1.0 to 55.9). Additional fractures at baseline further increased the fracture rate. A decrease of 2 standard deviations in spinal bone density by absorptiometry was associated with a 5.8-fold increase in fracture rate (95% confidence interval = 2.9 to 11.6). The lowest and highest quintiles of bone density had absolute fracture rates of 120 and 6 cases per 1000 patient-years, respectively. In general, the simultaneous use of two predictors (bone density and prevalent fractures or two bone density measurements) improved fracture prediction, compared with the use of a single predictor. We conclude that both bone density and prevalent vertebral fractures are strong, complementary predictors of vertebral fracture risk. The results suggest that physicians can use bone density and prevalent vertebral fractures, individually or in combination, as risk factors to identify patients at greatest risk of new fractures.     

Skeletal morbidity in men with prostate cancer: quality-of-life considerations throughout the continuum of care

OBJECTIVE: With current treatments, men usually survive many years after being diagnosed with prostate cancer. However, without supportive care, the systemic effects of prostate cancer and therapies such as androgen deprivation therapy (ADT) can undermine skeletal integrity, resulting in skeletal complications that may erode quality of life (QOL). Prostate cancer patients are at risk for fractures from cancer treatment-induced bone loss. In addition, they are also at risk for pathologic fractures, severe bone pain, and other sequelae from bone metastases, which almost invariably occur during the progression of prostate cancer. This review investigates the incidence and pathophysiology of bone loss and skeletal morbidity in prostate cancer patients and reviews available treatment options for maintaining skeletal health throughout the continuum of care for these patients. METHODS: Studies were identified through MEDLINE searches, review of bibliographies of relevant articles, and review of abstracts from national meetings. RESULTS: Several supportive care options are available to prevent generalized and localized bone loss, including calcium and vitamin D supplements and bisphosphonates. Oral calcium and vitamin D supplementation alone, however, appears to be insufficient to prevent bone loss during ADT. Zoledronic acid administered every 3 months during ADT or every 3 to 4 weeks for patients with bone metastases can reverse bone loss and reduce skeletal morbidity, respectively, in patients with prostate cancer. CONCLUSIONS: Skeletal complications contribute to the erosion of QOL in prostate cancer patients. Palliative care can provide important benefits to these patients. Some agents, such as zoledronic acid, may provide skeletal health benefits throughout the course of prostate cancer progression. Further investigations of the QOL impact of these benefits are warranted.