糖尿病性骨质疏松发病机制的研究进展

糖尿病性骨质疏松(Diabetic Osteoporosis,DO)是在糖尿病基础上并发的以单位体积骨量减少、骨脆性增加、骨折风险增高为特点的代谢性骨病,是糖尿病在骨骼系统的慢性并发症。其发病机制复杂,糖尿病性骨质疏松(DO)是糖尿病在骨骼系统的重要并发症,致残、致死率高,DO的治疗是目前临床上研究的热点之一,其发病机制复杂多样,更加深入了解其发病机制,明确糖尿病与骨质疏松之间的关系,对该疾病的预防和治疗有重要意义。本文主要就高血糖、胰岛素相对或绝对缺乏、糖尿病微血管病变、激素水平异常等因素进行简单综述。     

糖尿病性骨质疏松发病机制研究

糖尿病性骨质疏松（DO）是糖尿病在骨骼系统的重要并发症之一。探讨糖尿病并发骨质疏松的发生机制,对指导临床诊疗具有非常重要的意义。DO的病因和发病机制比较复杂,现有研究报道认为主要与高血糖、胰岛素不足和敏感性下降、慢性并发症、性激素、瘦素、骨保护素、遗传等因素相关;也有报道认为与口服降糖药有关。     

2型糖尿病性骨质疏松症发病机制研究进展

2型糖尿病属于临床常见病,可引发骨骼、血管、神经等多系统并发症,骨质疏松症是其常见并发症之一。2型糖尿病性骨质疏松症患者主要表现为骨代谢异常、骨脆性增加,易发生骨折。当前关于2型糖尿病性骨质疏松症发病机制的研究众多,其中涉及高血糖状态、氧化应激、糖尿病慢性并发症、细胞因子及激素水平变化等多个方面。笔者就国内外关于2型糖尿病性骨质疏松症发病机制的最新研究进行综述,旨在为下一步研究及临床工作提供参考。     

PPARs激动剂与骨质疏松症

过氧化物酶增殖激活受体(Peroxisome proliferator activated receptors,PPARs)是核激素受体家族中的配体激活受体,包括3种亚型：PPARα、PPARβ/δ和PPARγ,具有增强机体对胰岛素敏感性,调节体内糖平衡以及脂肪的分化、生成等多种生物学功能。PPARγ激动剂作为胰岛素增敏剂治疗2型糖尿病的重要药物,可引起糖尿病性骨质疏松症(Diabetic Osteoporosis,DO),DO发病机制复杂,致残、致死率高。本文主要对PPARs激动剂在治疗糖尿病中对骨的影响进行综述。     

2 型糖尿病性骨质疏松的鼠类模型的研究进展

2型糖尿病性骨质疏松(Type 2 Diabetic Osteoporosis,T2DOP)的病因复杂,对治疗带来困难,因此,建立符合人类2型糖尿病发病特点、骨代谢和骨结构的动物模型在T2DOP发病机制及其防治研究中的意义重大。由于鼠类的骨结构特点与人类相似,而且容易繁殖,目前国内外T2DOP动物模型研究也大多数在鼠类的研究。国内采用诱发性鼠类模型观察到其骨代谢和骨结构异常报道居多,国内外观察自发性2型糖尿病鼠类模型和转基因/基因敲除2型糖尿病鼠类模型的骨代谢和骨结构也存在异常,但是尚无一种既能在其骨骼成熟后发展为2型糖尿病,又能协同多基因和环境因素的2型糖尿病鼠类模型。故本文对研究的T2DOP鼠类模型的构建、骨代谢特征及其骨结构做一综述,为建立更为完善的2型糖尿病模型,进一步推动2型糖尿病性骨质疏松的机制研究和药物研发。     

氧化应激与糖尿病骨质疏松症相关性研究进展

糖尿病性骨质疏松是糖尿病并发单位体积内骨量减少、骨组织微结构改变、骨强度降低、脆性增加等易发生骨折的一种全身性、代谢性骨病,严重影响患者的健康和生活质量。近年,有关糖尿病骨矿代谢紊乱、骨量丢失、并发骨折等一系列问题的研究虽取得一定进展,但其发病机制仍未完全阐明。现有研究显示,糖尿病性骨质疏松除了与性别、年龄、糖尿病病程、营养状况、种族及遗传等因素有关之外,与氧化应激亦密切相关。本文就氧化应激与糖尿病性骨质疏松症的关系及其机制加以综述,为其预防和治疗提供理论依据。     

糖尿病合并骨质疏松与糖尿病微血管并发症的相关性研究

糖尿病(diabetes mellitus,DM)合并骨质疏松(osteoporosis,OP)和糖尿病微血管病变均是糖尿病的慢性并发症,由于发病的隐匿性,常常不被重视。随着人口老龄化程度的增加及医疗诊断水平的提高,糖尿病合并骨质疏松和DM微血管并发症的发病率及检出率呈现逐年上升趋势,近年来相关的研究也开始被广泛开展。糖尿病微血管病变及骨血流量减少可能导致骨量丢失和骨脆性增加,且微血管并发症的出现是DM患者骨量减少的临界因素。因此积极探讨DM合并骨质疏松与DM其他慢性微血管并发症之间的相关性,有助于早期对DM患者的不良结局进行综合性防范,改善患者预后。本文就糖尿病肾病(diabetic nephropathy,DN)、糖尿病视网膜病变(diabetic retinopathy,DR)、糖尿病周围神经病变(diabetic peripheral neuropathy,DPN)以及糖尿病足(diabetic foot,DF)与糖尿病合并骨质疏松症(diabetic osteoporosis,DOP)的相关性研究作一综述。     

糖尿病性膀胱病的发病机制及治疗进展

糖尿病性膀胱病(DCP)是临床常见的糖尿病慢性并发症之一,其起病隐匿,可以导致膀胱感觉受损、容量增加等相关的病理生理变化等,导致糖尿病患者的生活质量明显下降,这引起了越来越多的研究人员及临床工作者的重视。本文对糖尿病性膀胱病近5年相关的研究成果作分析总结,拟深入阐明糖尿病性膀胱病的发病机制及其治疗进展,并对其未来的研究前景进行展望。     

转化生长因子-β超家族对新骨生成的调节作用

目的　对近年来国内外有关转化生长因子 - β(TGF- β)超家族对新骨形成作用的研究进行综述。方法　广泛查阅相关文献 ,对 TGF- β、骨形成蛋白 (BMPs)及激活素 (ACT)在新骨形成 ,尤其是牵张性新骨形成(DO)作用进行分析综合。结果　 TGF- β、BMPs及 ACT对新骨形成均有促进作用 ,其作用机制各有特点。BMPs启动间充质细胞向骨细胞系分化 ,TGF- β刺激骨形成前体细胞生长分化 ,ACT增强 BMPs成骨 ,本身也促进成骨细胞增殖和胶原合成。结论　 TGF- β超家族对新骨形成的调控 ,有助于缩短 DO的周期     

氧化应激与糖尿病性勃起功能障碍

勃起功能障碍(ED)是糖尿病进程中常见的并发症,其发病机制十分复杂,涉及到神经及神经递质、血管及血管活性物质、内分泌、代谢等多方面因素。糖尿病状态下,自由基增多引发氧化应激损伤,影响到糖尿病性ED发生发展中的各个环节。本文针对氧化应激在糖尿病性勃起功能障碍进程中的作用作一综述。     

肠促胰素与糖尿病性骨质疏松症的研究进展

糖尿病（Diabetes,DM）、骨质疏松症（Osteoporosis,OP）是两种常见的慢性病,在DM患者中存在的代谢紊乱可致OP发生的风险机率大大增加,严重影响患者的生活质量,而由此导致的OP称为糖尿病性骨质疏松症(Diabetic osteoporosis,DOP),主要指糖尿病所致骨量减少,骨组织微结构破坏,骨脆性增加,易于骨折的一种全身性代谢性疾病 。对DOP的治疗首先要控制血糖,血糖是基础,而肠促胰素（Incretin）作为一种降糖药物已应用于临床,在减重及降糖方面效果突出,但最近研究显示肠促胰素在降糖的同时对OP有一定的改善,本文将简单阐述肠促胰素对DOP的影响。     

Rosiglitazone Inhibits Bone Regeneration and Causes Significant Accumulation of Fat at Sites of New Bone Formation

Thiazolidinediones (TZDs), peroxisome proliferator-activated receptor gamma activators, and insulin sensitizers represent drugs used to treat hyperglycemia in diabetic patients. Type 2 diabetes mellitus (T2DM) is associated with a twofold increase in fracture risk, and TZDs use increases this risk by an additional twofold. In this study, we analyzed the effect of systemic administration of the TZD rosiglitazone on new bone formation in two in vivo models of bone repair, a model of drilled bone defect regeneration (BDR) and distraction osteogenesis (DO) and a model of extended bone formation. Rosiglitazone significantly inhibited new endosteal bone formation in both models. This effect was correlated with a significant accumulation of fat cells, specifically at sites of bone regeneration. The diminished bone regeneration in the DO model in rosiglitazone-treated animals was associated with a significant decrease in cell proliferation measured by the number of cells expressing proliferating cell nuclear antigen and neovascularization measured by both the number of vascular sinusoids and the number of cells producing proangiogenic vascular endothelial growth factor at the DO site. In summary, rosiglitazone decreased new bone formation in both BDR and DO models of bone repair by mechanisms which include both intrinsic changes in mesenchymal stem cell proliferation and differentiation and changes in the local environment supporting angiogenesis and new bone formation. These studies suggest that bone regeneration may be significantly compromised in T2DM patients on TZD therapy.     

Holistic perspective of the role of gut microbes in diabetes mellitus and its management

The gut microbiota (GM) plays a role in the development and progression of type 1 and type 2 diabetes mellitus (DM) and its complications. Gut dysbiosis contributes to the pathogenesis of DM. The GM has been shown to influence the efficacy of different antidiabetic medications. Intake of gut biotics, like prebiotics, probiotics and synbiotics, can improve the glucose control as well as the metabolic profile associated with DM. There is some preliminary evidence that it might even help with the cardiovascular, ophthalmic, nervous, and renal complications of DM and even contribute to the prevention of DM. More large-scale research studies are needed before wide spread use of gut biotics in clinical practice as an adjuvant therapy to the current management of DM.     

Metformin revisited: Does this regulator of AMP-activated protein kinase secondarily affect bone metabolism and prevent diabetic osteopathy?

Patients with long-term type 1 and type 2 diabetes mellitus(DM) can develop skeletal complications or “diabetic osteopathy”. These include osteopenia, osteoporosis and an increased incidence of low-stress fractures. In this context, it is important to evaluate whether current anti-diabetic treatments can secondarily affect bone metabolism. Adenosine monophosphateactivated protein kinase(AMPK) modulates multiple metabolic pathways and acts as a sensor of the cellular energy status; recent evidence suggests a critical role for AMPK in bone homeostasis. In addition, AMPK activation is believed to mediate most clinical effects of the insulin-sensitizer metformin. Over the past decade, several research groups have investigated the effects of metformin on bone, providing a considerable body of pre-clinical(in vitro, ex vivo and in vivo) as well as clinical evidence for an anabolic action of metformin on bone. However, two caveats should be kept in mind when considering metformin treatment for a patient with type 2 DM at risk for diabetic osteopathy. In the first place, metformin should probably not be considered an antiosteoporotic drug; it is an insulin sensitizer with proven macrovascular benefits that can secondarily improve bone metabolism in the context of DM. Secondly, we are still awaiting the results of randomized placebo-controlled studies in humans that evaluate the effects of metformin on bone metabolism as a primary endpoint.     

Diabetes mellitus and cellular replacement therapy: Expected clinical potential and perspectives

Diabetes mellitus(DM) is the most prevailing disease with progressive incidence worldwide. Despite contemporary treatment type one DM and type two DM are frequently associated with long-term major microvascular and macrovascular complications. Currently restoration of failing β-cell function, regulation of metabolic processes with stem cell transplantation is discussed as complements to contemporary DM therapy regimens. The present review is considered paradigm of the regenerative care and the possibly effects of cell therapy in DM. Reprogramming stem cells, bone marrowderived mononuclear cells; lineage-specified progenitor cells are considered for regenerative strategy in DM. Finally, perspective component of stem cell replacement in DM is discussed.     

Effect of obstructive sleep apnea on type 2 diabetes mellitus: A comprehensive literature review

Obstructive sleep apnea (OSA) is frequently associated with obesity and metabolic syndrome. Also frequently associated with metabolic syndrome is type 2 diabetes mellitus (T2DM). Therefore, it is common to find OSA and T2DM together in individuals with metabolic syndrome. Additionally, both OSA and T2DM have a common pathophysiological link with development of insulin resistance. Individuals with severe insulin resistance are likely to have inadequate glycemic control. Long standing poorly controlled T2DM is associated with debilitating microvascular complications such as retinopathy, nephropathy, neuropathy and macrovascular complications such as coronary artery and cerebrovascular disease. There is extensively published literature exploring the cause-effect relationship between OSA and T2DM. In this article we provide an in-depth review of the complex pathophysiological mechanisms linking OSA to T2DM. Specifically, this review focusses on the effect of OSA on the microvascular complications of T2DM such as retinopathy, nephropathy and neuropathy. Additionally, we review the current literature on the effect of continuous positive airway pressure use in individuals with T2DM and OSA.     

Lifelong reversal of the metabolic abnormalities of advanced diabetes in rats by whole-pancreas transplantation

Evidence suggests that metabolic abnormalities are responsible for the widespread microvascular complications of insulin-dependent diabetes mellitus (IDDM). Interest in endocrine pancreas replacement therapy, including pancreas transplantation, is based on the hope that such treatment will reverse the complications of IDDM by providing more precise metabolic control than conventional therapy. To determine if whole pancreas transplantation is capable of reversing well-established metabolic abnormalities of diabetes mellitus (DM) and maintaining strict metabolic control for life, we performed monthly metabolic studies for 2 years in 141 nondiabetic control rats, 273 diabetic control rats with alloxan-induced DM, and 267 diabetic rats that received syngeneic whole pancreaticoduodenal transplants 6, 9, 12, 15, 18, and 21 months after induction of DM with alloxan. Whole-pancreas transplantation in rats with long-standing DM permanently reversed the metabolic disorders. Elevated plasma glucose concentrations were permanently reduced to normal, depressed plasma insulin levels were permanently increased to normal, elevations of BUN and serum creatinine were permanently normalized, and there was a striking gain in body weight. Hyperglycemia during glucose tolerance tests was of lesser magnitude and shorter duration than normal, as a result of greater-than-normal plasma insulin levels. The only abnormality that persisted was hyperglucagonemia, but it did not interfere with control of hyperglycemia and is of unknown significance. These results indicate that whole-pancreas transplantation produces the most complete and sustained correction of the metabolic abnormalities of experimental DM of any available therapeutic modality.     

Alveolar distraction osteogenesis versus inlay bone grafting in posterior mandibular atrophy: a prospective study

OBJECTIVE: The objective of this study was to compare bone gain, implant survival, implant success, bone resorption, and complication rate in groups of patients who underwent distraction osteogenesis (DO) and inlay bone grafting (Inlay) for preprosthetic issues in the atrophic posterior mandible. STUDY DESIGN: Twelve surgical sites were randomly assigned to 2 treatment groups: group A: DO and group B: Inlay. After 3 to 4 months, 16 fixtures in the DO group and 21 in the Inlay group were placed for fixed prosthetic rehabilitation. The median follow-up was 26 months. RESULTS: The median bone gain was 10 versus 5.8 mm (DO versus Inlay, P = .003); the median bone resorption was 1.4 mm versus 0.9 mm (DO versus Inlay, P = .088). The implant survival rate was 100% for each group, while the implant success rate was 93.7% (DO) versus 95.2% (Inlay) (P > .05). The complication rate was 60% for DO and 14.3% for Inlay (P < .05). CONCLUSION: DO obtained more vertical bone gain than Inlay, but was more prone to complications in the pre-implantology phase. The implant results in each group were comparable to those in native alveolar bone.     

Photobiomodulation treatments drive osteogenic versus adipocytic fate of bone marrow mesenchymal stem cells reversing the effects of hyperglycemia in diabetes

Lasers in Medical Science - Diabetes mellitus (DM) is a chronic metabolic disease that affects bone metabolism, which can be related to a reduced osteogenic potential of bone marrow mesenchymal...