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。     

骨质疏松药物治疗率和依从性

骨质疏松症(osteoporosis,OP)是一种以骨量低下、骨微结构损坏,导致骨脆性增加,易发生骨折为特征的全身性骨代谢性疾病。骨质疏松性骨折是骨质疏松常见的并发症,多见于老年人,但在其他年龄段也有可能发病。脆性骨折好发部位多集中在髋关节、脊柱及腕关节。目前有多种现成的及有效的药物治疗骨质疏松症,如双膦酸盐、降钙素等。但由于医师及患者对骨质疏松知识不够熟悉、患者过度担心药物不良反应、抗骨质疏松药价格过高等因素的影响,骨质疏松症的患者接受药物治疗率与依从性仍较低,这导致了骨密度增加减慢,骨折发生率增加,很大程度的加重了临床和经济负担。因此,提高骨质疏松患者的药物治疗率及依从性变得至关重要,早期的抗骨质疏松治疗和长期坚持服药可以缓解骨量流失甚至提升骨量,显著降低患者骨折风险。本文主要回顾综述了骨质疏松药物治疗率及依从性现状,影响药物治疗率和依从性的原因,以及提出改善骨质疏松药物治疗率和依从性的措施。     

抗骨质疏松药物对骨质疏松症患者糖代谢、脂代谢的影响

骨质疏松症与心血管疾病已成为影响中老年人健康与生活质量的重要原因。研究发现糖代谢、脂代谢可以与骨代谢相互影响,而糖脂代谢异常可致心血管风险增高。目前现有研究发现抗骨质疏松药物可以影响心血管事件的发生,但关于其风险因素的研究却较少。因此,本文拟通过综述抗骨质疏松药物对患者糖代谢、脂代谢的影响,探讨抗骨质疏松药物非骨骼方面的益处和危害,使患者在控制骨折风险的同时,对心血管疾病进行管理,从而改善患者的整体状况。     

骨质疏松性骨折治疗方法研究进展

骨质疏松性骨折是骨质疏松症患者常见的并发症，常发生于股骨颈、胸腰椎和股骨转子间等部位。骨质疏松 性骨折的发病率除了与骨密度和骨强度的降低相关，还与年龄、性别、种族等危险因素密切相关。骨质疏松性骨折多发生在60岁以上的老年人群体，严重影响老年 人的生活质量。骨质疏松症的治疗药物分为抑制骨吸收以及促进骨形成两大类，抑制骨吸收类药物可防止骨吸收，而促进骨形成药物可以促进新骨形成。促进骨形成 类药物在患有严重骨质疏松症、替代性骨质疏松症药物失效、不耐受的个体、伴有其他骨质疏松症的禁忌症，以及糖皮质激素引起的骨质疏松症中可以起到主要作 用。而目前针对骨质疏松骨折的微创手术治疗主要包括经皮穿刺椎体后凸成形术及球囊扩张椎体后凸成形术。本综述的主要目的是讨论药物和手术治疗骨质疏松性骨 折治疗机制的研究进展。     

甲状旁腺素促进骨合成代谢的研究进展

随着年龄的增加，骨质疏松症患病率也随之增加，骨质疏松的严重后果是导致骨折，而骨质疏松性骨折愈合差及其众多的并发症给患者造成了极大的痛苦。目前治疗骨质疏松的药物主要是抗骨质吸收药物，不能恢复已经丢失的骨量。因此，临床上迫切需要一种既能够增加骨质疏松骨的强度又能加速其骨折愈合的治疗方法。     

骨转换标志物在骨质疏松症诊断与治疗中的应用进展

骨转换标志物为骨重塑期间骨组织的自身代谢产物,可分为骨吸收标志物和骨形成标志物。与骨密度相比,骨转换标志物能更敏感地反映体内骨代谢情况,其早期检测有助于及时发现骨质流失患者。在评估骨质疏松性骨折风险和抗骨质疏松症治疗效果监测上,骨转换标志物也有重要临床价值。近年来,骨转换标志物与骨质疏松症的相关研究逐渐增多,学者们对其认识进一步加强。该文从骨转换标志物及其临床应用两方面进行综述,以期为骨质疏松症的诊断和治疗提供参考。     

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。     

骨质疏松症的药物治疗进展

骨质疏松症是一种以骨量降低、骨微结构破坏、骨脆性增加、骨强度下降、骨折风险性增大为特征的全身性、代谢性骨骼系统疾病。由于骨质疏松症是一种全身性的疾病,骨质疏松症的原始治疗、骨质疏松性骨折术后及术后再骨折过程中抗骨质疏松药物的治疗非常重要,临床应用的抗骨质疏松药物主要包括两大类：骨吸收抑制类及促进骨形成类。随着骨代谢途径认识的不断加深,不断升级目前已有药物、已有药物的合理配伍使用、研发新型的改变细胞功能和基因表达的药物、继承和发展祖国传统中医药等都是值得探索的方向。随着这些新进展、新方案逐步通过临床试验的检验,将会给骨质疏松症的治疗带来新的希望。     

防治骨质疏松症的药物研究进展

骨质疏松症主要表现在骨BMD减少,骨质量(骨微结构,骨的转换,骨矿化,骨微损伤累积)降低,诱导骨强度下降,微骨折增加.在临床上,系统性骨质疏松症的典型表现是骨质疏松性疼痛和骨折,而最常见的骨质疏松性骨折部位是:髋部,腰椎和腕部.骨质疏松症可预防,如果早期诊断,可得到治疗.目前有两大类药物可治疗和预防骨质疏松症.① 抗骨代谢类药物; ②促骨合成药.近年来,大量的基础、临床研究表明vitamin D及其类似物不仅通过抑制骨吸收,而且有促进骨合成作用来防治骨质疏松症,笔者就骨质疏松症的药物研究进展作一综述,为更好的预防和治疗骨质疏松症具有很好的指导意义.     

阿伦膦酸盐降低骨质疏松性椎体骨折风险的作用

骨质疏松症已成为全球严重的公共卫生问题,防治骨质疏松症和骨质疏松性骨折已成为目前关注的课题。骨质疏松性骨折最常见于椎体。阿伦膦酸盐是临床上治疗骨质疏松症的常用药物。众多文献表明,阿伦膦酸盐能明显增加患者骨密度（BMD）,使其发生椎体骨折和再骨折的危险性降低。与其他抗重吸收药物比较,阿伦膦酸盐增加BMD的作用较强。但目前尚未有文献对阿伦膦酸盐预防椎体强化术后椎体再骨折的疗效进行明确报道。     

Are Antiresorptive Drugs Effective Against Fractures in Patients with Diabetes?

We studied whether the reduction in bone turnover by use of antiresorptive drugs is detrimental in patients with diabetes who already have low bone turnover due to hyperglycemia in a nationwide cohort study from Denmark. All users of antiresorptive drugs against osteoporosis between 1996 and 2006 (n = 103,562) were the exposed group, with three age- and gender-matched controls from the general population (n = 310,683). Patients on bisphosphonates and raloxifene had a higher risk of hip, spine, and forearm fractures. However, no difference was observed in the antifracture efficacy between patients with diabetes and nondiabetic controls or between patients with type 1 and type 2 diabetes. Too few were users of strontium to allow analysis for this compound. The excess risk of fractures among patients treated with bisphosphonates or raloxifene compared to nonexposed controls was due to the higher a priori risk of fractures among patients treated for osteoporosis. Diabetes does not seem to affect the fracture-preventive potential of bisphosphonates or raloxifene. The low-turnover state of diabetes thus does not seem to be a hindrance to the effect of these drugs against osteoporosis. Therefore, patients with diabetes should receive treatment for osteoporosis in the same way as nondiabetic patients.     

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.     

间充质干细胞源性外泌体在糖尿病性骨质疏松中的研究进展

糖尿病性骨质疏松是糖尿病常见的并发症之一,是在糖尿病基础上继发的以骨量减少、骨脆性增加、骨折风险增加为主要特征的代谢性骨病.常规的抗骨质疏松药物对糖尿病性骨质疏松的疗效有限,存在增加非典型骨折的风险,因此亟待寻找新的积极高效的治疗手段.外泌体是一类包含蛋白质、脂质、核酸等物质的胞外囊泡,介导细胞间通讯发挥对靶细胞的生物...     

胰岛素样生长因子1对2型糖尿病合并骨质疏松中骨钙素表达的影响

随着流行病学的调查研究发现,2型糖尿病患者与健康人群相比,其罹患骨折事件的发生率明显增高,所以骨质疏松及骨折等并发症需引起2型糖尿病患者的足够重视。在分子机制层面的研究显示,2型糖尿病合并骨质疏松的发生可能与胰岛素样生长因子1、葡萄糖毒性、硬骨素、骨钙素及氧化应激等多种代谢途径的改变有关。胰岛素样生长因子1是骨形成的调节因子,在调节成骨细胞和破骨细胞介导的骨骼重建过程中起着重要的作用。骨钙素是由成骨细胞产生的一种非胶原蛋白,能够反映成骨细胞的活性,常作为骨形成和骨转换的特异性指标。有研究显示,胰岛素样生长因子1以浓度依赖方式刺激骨钙素的合成增加,本文试就胰岛素样生长因子1对2型糖尿病合并骨质疏松中骨钙素表达的影响做一综述,探讨在2型糖尿病合并骨质疏松患者中胰岛素样生长因子1与骨钙素之间的相关性,以期对2型糖尿病合并骨质疏松患者能够进行早期诊断及治疗,预防骨折事件的发生,提高患者生活质量。     

Osteoporosis in patients with diabetes mellitus.

Demographic trends with longer life expectancy and a lifestyle characterized by low physical activity and high-energy food intake contribute to an increasing incidence of diabetes mellitus and osteoporosis. Diabetes mellitus is a risk factor for osteoporotic fractures. Patients with recent onset of type 1 diabetes mellitus may have impaired bone formation because of the absence of the anabolic effects of insulin and amylin, whereas in long-standing type 1 diabetes mellitus, vascular complications may account for low bone mass and increased fracture risk. Patients with type 2 diabetes mellitus display an increased fracture risk despite a higher BMD, which is mainly attributable to the increased risk of falling. Strategies to improve BMD and to prevent osteoporotic fractures in patients with type 1 diabetes mellitus may include optimal glycemic control and aggressive prevention and treatment of vascular complications. Patients with type 2 diabetes mellitus may additionally benefit from early visual assessment, regular exercise to improve muscle strength and balance, and specific measures for preventing falls.     

骨转换标志物在糖尿病中的研究进展

随着糖尿病和骨质疏松症在我国的广泛流行,糖尿病性骨质疏松症已成为糖尿病患者致死、致残的重要原因,严重影响患者的生活质量,并给个人、社会带来沉重负担。1型糖尿病患者骨密度降低,骨折风险增加;2型糖尿病患者骨密度常增高或正常,但骨折风险也是增加的,这不能仅靠双能X线骨密度来解释。骨转换标志物具有灵敏度高、特异性强、稳定性好等优点,近年来在糖尿病中得到广泛研究,如骨碱性磷酸酶、1型原胶原N-端前肽、1型胶原交联C-末端肽、骨钙素、骨保护素、脱氧吡啶啉等。骨转换标志物反映骨吸收和骨形成的具体变化情况,反映骨强度,较骨密度更早的反映骨量变化,大量临床研究发现,它为临床早期发现和诊断糖尿病性骨质疏松症,评估糖尿病患者骨折风险提供了新思路。联合检测骨转换标志物和骨密度,更全面、合理的评估骨转换,及时发现高危人群,更有利于糖尿病性骨质疏松症患者的早期诊断及治疗,预防骨折的发生。本文将对骨转换标志物在糖尿病中的研究进展作一综述。     

Osteoporosis in diabetes mellitus: Possible cellular and molecular mechanisms

Osteoporosis,a global age-related health problem in both male and female elderly,insidiously deteriorates the microstructure of bone,particularly at trabecular sites,such as vertebrae,ribs and hips,culminating in fragility fractures,pain and disability.Although osteoporosis is normally associated with senescence and estrogen deficiency,diabetes mellitus(DM),especially type 1 DM,also contributes to and/or aggravates bone loss in osteoporotic patients.This topic highlight article focuses on DM-induced osteoporosis and DM/ osteoporosis comorbidity,covering alterations in bone metabolism as well as factors regulating bone growth under diabetic conditions including,insulin,insulin-like growth factor-1 and angiogenesis.Cellular and molecular mechanisms of DM-related bone loss are also discussed.This information provides a foundation for the better understanding of diabetic complications and for development of early screening and prevention of osteoporosis in diabetic patients.     

The biology of fracture healing in osteoporosis and in the presence of anti-osteoporotic drugs

Compromised bone strength in osteoporosis predisposes patients to an increased fracture risk. The management of these fractures is complicated due to the poor bone quality, which may lead to inadequate fixation strength and stability. While a number of studies using osteoporotic animal models have shown a detrimental impact on fracture healing, clinical evidence regarding whether fracture healing is impaired in the presence of osteoporosis is complicated by numerous associated conditions including advancing age.The mechanism of some anti-osteoporotic medications creates concern about a potential detrimental impact on fracture healing, while others appear to enhance fracture healing. The current evidence indicates that the beneficial effects of anti-osteoporosis treatment exceeds any concerns about possible adverse consequences on fracture healing in most circumstances.     

降糖药物对骨代谢及骨折风险的影响

2型糖尿病(Type 2 diabetes mellitus,T2DM)是一种发病率很高的慢性病,过去20年进行的一些研究调查了糖尿病(diabetes mellitus,DM)与骨质疏松症及骨代谢之间的关系,脆性骨折(无外伤或较微外伤情况下引起的骨折)增加的风险已经在T2DM患者中表现出来~([1])。在大多数T2DM患者中,抗DM药物对于血糖控制是不可或缺的,然而,它们在骨代谢及对骨折风险有着不同的影响,二甲双胍,磺酰脲类不增加骨折风险,噻唑烷二酮类药物的使用会导致骨质流失加速和骨折风险增加,基于肠降血糖素的治疗方案对骨骼安全性的数据有限,仍需进一步基础及临床研究以明确,钠葡萄糖协同转运蛋白2抑制剂可能通过引发甲状旁腺机能亢进而增加骨折风险,同时,使用胰岛素治疗的患者可能需更多关注DM并发症及低血糖所致的骨折风险增加。本文拟对降糖药物T2DM患者骨代谢及骨折风险的影响作一综述,为T2DM患者药物降糖治疗提供指导。     

Energy Excess,Glucose Utilization,and Skeletal Remodeling: New Insights

Skeletal complications have recently been recognized as another of the several comorbidities associated with diabetes. Clinical studies suggest that disordered glucose and lipid metabolism have a profound effect on bone. Diabetes‐related changes in skeletal homeostasis result in a significant increased risk of fractures, although the pathophysiology may differ from postmenopausal osteoporosis. Efforts to understand the underlying mechanisms of diabetic bone disease have focused on the direct interaction of adipose tissue with skeletal remodeling and the potential influence of glucose utilization and energy uptake on these processes. One aspect that has emerged recently is the major role of the central nervous system in whole‐body metabolism, bone turnover, adipose tissue remodeling, and beta cell secretion of insulin. Importantly, the skeleton contributes to the metabolic balance inherent in physiologic states. New animal models have provided the insights necessary to begin to dissect the effects of obesity and insulin resistance on the acquisition and maintenance of bone mass. In this Perspective, we focus on potential mechanisms that underlie the complex interactions between adipose tissue and skeletal turnover by focusing on the clinical evidence and on preclinical studies indicating that glucose intolerance may have a significant impact on the skeleton. In addition, we raise fundamental questions that need to be addressed in future studies to resolve the conundrum associated with glucose intolerance, obesity, and osteoporosis. © 2015 American Society for Bone and Mineral Research.