2型糖尿病与骨质疏松症相关性研究进展

流行病学调查发现,2型糖尿病(type 2 diabetes mellitus,T2DM)患者与健康人群相比其骨折事件的发生率明显增高,因此骨质疏松及其骨折需引起患者足够的重视。虽然不同研究显示T2DM患者骨密度(bone mineral density,BMD)变化有所不同,但其骨折风险始终增加。在分子机制研究层面,T2DM相关性骨质疏松的发生可能与胰岛素生长因子-1、硬骨素、葡萄糖毒性、降钙素、骨钙素、氧化应激等多种代谢因素改变有关,并且在动物和临床研究均发现治疗糖尿病和骨质疏松的药物使用可造成骨代谢改变。在T2DM骨质疏松的预防和治疗过程中,监测、诊断和预防骨质疏松的危险因素,控制血糖稳定,保证足够的钙和维生素D的摄入,预防跌倒以及加强锻练对降低骨折风险和改善生活质量有重要意义。     

2型糖尿病合并骨质疏松症思者类胰岛素生长因子-1与骨转换关系研究

目的了解2型糖尿病合并骨质疏松患者其类胰岛素生长因子-1(IGF-1)的变化与骨转换之关系.方法分别测定2型糖尿病合并骨质疏松组(A组)、2型糖尿病未合并骨质疏松组(B组)、绝经后骨质疏松组(C组)和对照组(D组)的血清IGF-1、总碱性磷酸酶(总AKP)、骨特异碱性磷酸酶(骨AKP)、骨钙素(BGP)、尿吡啶啉(PYD)、尿脱氧吡啶啉(DPD),全段甲状旁腺素(IPTH),并进行组间比较和聚类相关分析.结果 A、C组病例其尿PYD和DPD值明显高于B、D组;而IGF-1水平则A、C组明显低于B和D组.聚类相关性分析表明在2型糖尿病合并骨质疏松组骨密度值与IGF-1关系最为密切,而在绝经后骨质疏松组则主要为绝经时间和骨吸收指标(PYD和DPD).结论骨形成减少是2型糖尿病合并骨质疏松的原因之一,而IGF-1的减少可能与2型糖尿病的骨形成减少有关.     

2型糖尿病患者骨质疏松发生率及骨代谢生化指标测定分析

目的 探讨2型糖尿病患者合并骨质疏松的发生率及骨代谢生化指标变化.方法 ①对142例2型糖尿病患者进行桡骨定量骨超声测定及骨钙素、尿1型胶原C端肽及血钙、磷、碱性磷酸酶等骨代谢生化指标检测,分别计算男、女2型糖尿病患者骨质疏松发生率并与非糖尿病对照人群进行比较;②分析糖尿病患者骨超声测定值(骨超声波波速,SOS,m/s)与其年龄、病程、代谢控制程度及体重指数等之间的关系;③根据骨超声测定结果将2型糖尿病患者分为合并骨质疏松组、骨量减少组与未合并骨质疏松组,比较组三间的骨代谢生化指标变化,并与健康对照组做比较.结果 ①糖尿病患者骨质疏松发生率明显高于非糖尿病人群,②糖尿病患者骨超声值与其年龄、病程、尿CTX及体重指数呈负相关,与骨钙素、糖化血红蛋白及空腹血糖未发现相关性;③糖尿病患者中合并骨质疏松组尿CTX测定明显高于骨量减少组及骨量正常组(P<0.05),血PTH在骨质疏松组明显高于骨量正常组,血钙、磷、碱性磷酸酶及血清骨钙素测定组间相比无显著性差异(P>0.05);总体糖尿病患者与非糖尿病对照人群相比血清骨钙素测定明显降低(P<0.05),尿CTX明显升高(P<0.05).结论 2型糖尿病患者较易患骨质疏松,其骨代谢改变特点是:骨形成下降、骨吸收增加,糖尿病骨代谢异常的发生与众多因素有关,在治疗糖尿病的同时,应注意骨质疏松的预防和治疗.     

2型糖尿病患者骨质疏松发生率及骨代谢生化指标测定分析

目的 探讨2型糖尿病患者合并骨质疏松的发生率及骨代谢生化指标变化.方法 ①对142例2型糖尿病患者进行桡骨定量骨超声测定及骨钙素、尿1型胶原C端肽及血钙、磷、碱性磷酸酶等骨代谢生化指标检测,分别计算男、女2型糖尿病患者骨质疏松发生率并与非糖尿病对照人群进行比较;②分析糖尿病患者骨超声测定值(骨超声波波速,SOS,m/s)与其年龄、病程、代谢控制程度及体重指数等之间的关系;③根据骨超声测定结果将2型糖尿病患者分为合并骨质疏松组、骨量减少组与未合并骨质疏松组,比较组三间的骨代谢生化指标变化,并与健康对照组做比较.结果 ①糖尿病患者骨质疏松发生率明显高于非糖尿病人群,②糖尿病患者骨超声值与其年龄、病程、尿CTX及体重指数呈负相关,与骨钙素、糖化血红蛋白及空腹血糖未发现相关性;③糖尿病患者中合并骨质疏松组尿CTX测定明显高于骨量减少组及骨量正常组(P<0.05),血PTH在骨质疏松组明显高于骨量正常组,血钙、磷、碱性磷酸酶及血清骨钙素测定组间相比无显著性差异(P>0.05);总体糖尿病患者与非糖尿病对照人群相比血清骨钙素测定明显降低(P<0.05),尿CTX明显升高(P<0.05).结论 2型糖尿病患者较易患骨质疏松,其骨代谢改变特点是:骨形成下降、骨吸收增加,糖尿病骨代谢异常的发生与众多因素有关,在治疗糖尿病的同时,应注意骨质疏松的预防和治疗.     

2型糖尿病合并骨质疏松症患者类胰岛素生长因子-1与骨转换关系研究

目的 了解2型糖尿病合并骨质疏松患者其类胰岛素生长因子－1（IGF－1）的变化与骨转换之关系。方法 分别测定2型糖尿病合并骨质疏松组（A组）、2型糖尿病未合并骨质疏松组（B组）、绝经后骨质疏松组（C组）和对照组（D组）的血清IGF－1、总碱性磷酯酶（总AKP）、骨特异碱性磷酸酶（骨AKP）、骨钙素（BGP）、尿吡啶啉（PYD）、尿脱氧吡啶啉（DPD），全段甲状旁腺素（IPTH），并进行组间比较和聚类相关分析。结果 A、C组病例其尿PYD和DPD值明显高于B、D组；而IGF－1水平则A、C组明显低于B和D组。聚类相关性分析表明在2型糖尿病合并骨质疏松组骨密度值与IGF－1关系最为密切，而在绝经后骨质疏松组则主要为绝经时间和骨吸收指标（PYD和DPD）。结论 骨形成减少是2型糖尿病合并骨质疏松的原因之一，而IGF-1的减少可能与2型糖尿病的骨形成减少有关。     

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。     

胰岛素抵抗致骨强度下降的机制研究

胰岛素抵抗是2型糖尿病重要的发病机制之一，随着胰岛素抵抗程度的增加，骨成长和骨重塑过程变化导致骨折风险增加。在胰岛素抵抗的患者中，并不完全表现为骨密度减少的骨质疏松症，也可能表现为正常或者高骨密度，导致2型糖尿病患者骨密度未见明显异常而骨折风险增加，这可能是由于成骨细胞和破骨细胞对胰岛素敏感度降低或者胰岛素抵抗导致的低度炎症、维生素D降低、骨细胞间隙矿化等因素影响骨形成和骨吸收的平衡。胰岛素抵抗导致骨强度下降的机制有待充分阐明以期其指导胰岛素抵抗患者的抗骨质疏松治疗。     

2型糖尿病性骨质疏松降糖药物的选择

近年来,随着对糖尿病性骨质疏松研究的深入,2型糖尿病性骨质疏松降糖药物的选择也越来越引起人们的重视。肠促胰素、二甲双胍、胰岛素促泌剂等在抑制骨吸收、促进骨合成及诱导骨髓间充质细胞分化等多个层面上对2型糖尿病性骨质疏松可能有正面影响。胰岛素对骨质疏松的影响虽然有争议,但早期持续胰岛素治疗对糖尿病性骨质疏松的发生和发展可能具有控制和延缓作用,噻唑烷二酮类药物可显著增加2型糖尿病女性患者骨折发生率。     

T1DM增加骨质疏松性骨折风险的相关机制研究进展

正糖尿病在全世界范围内发病率逐渐增加[1-2],其与患者的肥胖、胰岛素抵抗、胰腺的β细胞功能缺陷有关[3-4],胰岛素代谢功能紊乱影响葡萄糖、蛋白质、脂质的代谢调节,从而引发各种并发症。李健等[5]研究显示糖尿病大鼠模型的骨吸收加快而骨形成不足,导致其骨量下降和骨形态计量学特性改变。研究发现1型糖尿病(type 1 diabetes mellitus,T1DM)患者发生骨折的风险增高,随着人口老龄化的加剧,     

肝源性骨质疏松的发病机制研究

在我国,骨质疏松的患病率越来越高。临床实践中发现,肝病患者更容易发生骨质疏松,甚至进一步发展为骨质疏松性骨折,患者的生活质量大大地降低。研究显示,约30%慢性肝病患者可发生骨折。肝源性骨质疏松的发病机制与很多因素有关,包括了糖代谢紊乱、纤维连接蛋白、胰岛素样生长因子1、各种细胞因子、维生素D的减少以及性激素的失衡等等。本文就肝病患者中发生骨量丢失的机制进行综述。     

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。     

Bone fragility in type 2 diabetes mellitus

The number of patients with osteoporosis or type 2 diabetes mellitus (T2DM) is increasing in aging and westernized societies. Both disorders predispose elderly people to disabling conditions by causing fractures and vascular complications, respectively. Recent animal studies have shown that administration of osteocalcin, which is specifically secreted from osteoblasts, can increase insulin secretion and ameliorate hyperglycemia, obesity, and high triglyceride levels in mice fed a high-fat diet. Moreover, several studies have shown that antagonism of Wnt signaling by oxidative stress contributes to the development of osteoporosis, as well as insulin resistance and hyperlipidemia. Thus, bone metabolism and glucose/fat metabolism seem to be etiologically related to each other. Meta-analyses of multiple clinical studies in humans have shown that hip fracture risk of T2DM patients is increased by 1.4-1.7-fold, although bone mineral density (BMD) is not diminished. Vertebral fracture risk of T2DM patients is also increased, and BMD is not sensitive enough to assess the risk. These findings suggest that bone fragility in T2DM, which is not reflected by BMD, depends on bone quality deterioration rather than bone mass reduction. Thus, surrogate markers are needed to replace the insensitivity of BMD in assessing fracture risks of T2DM patients. Pentosidine, the endogenous secretory receptor for advanced glycation endproducts, and insulin-like growth factor-I seem to be such candidates, although further studies are required to clarify whether or not these markers could predict the occurrence of new fractures of T2DM patients in a prospective fashion.     

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.     

老年男性2型糖尿病患者各种钙调激素与骨密度改变的关系

目的测定老年男性2型糖尿病患者各种钙调激素及骨密度,探讨老年男性2型糖尿病患者骨质疏松的发病机理,为其防治提供理论依据。方法用双能X线吸收法测定70例老年男性2型糖尿病患者及60例年龄、体重指数相匹配的对照者的腰椎及髋部骨密度,并采用放免法测定血清骨钙索(BGP)、抗酒石酸酸性磷酸酶(TRAP)、甲状旁腺素(PTH)、降钙素(CT)、1,25(OH)2D3、25(OH)D3、尿羟脯氨酸(HOP)等,两组进行比较。结果 老年男性2型糖尿病患者较对照组骨密度显著降低。血BGP、CT、1,25(OH)2D3浓度低于对照组(P<0.05).TRAP、PTH、尿HOP显著高于对照组(P<0.05)。结论老年男性2型糖尿病患者PTH、CT、1,25(OH)2D3等钙调激素分泌及代谢失常,影响骨代谢,出现糖尿病性骨质疏松,表现为骨吸收增加,骨形成减少与缓慢,骨吸收过程大于骨形成。     

老年2型糖尿病双能X线及定量CT测量骨密度的临床分析

目的 探讨老年2型糖尿病临床与不同骨密度(BMD)测定方法之间的关系和特点。方法 测定45例老年2型糖尿病患者的空腹(FBG)及餐后血糖(PBG)、糖化血红蛋白(HbAlc)、胆固醇(TC)、甘油三脂(TG)、骨钙素(BGP)、血清Ⅰ型胶原C端肽(CICP)、血清骨特异性碱性磷酸酶(B-ALP)、尿吡啶啉(Pyd)、脱氧吡啶啉(D-Pyd)、尿羟脯胺酸(Hyp),对同一病人同时行双能X线测定(DEXA)及定量CT测定(QCT),并进行分组比较。结果 本组45例病人中同时用DEXA及QCT测定骨密度均有骨质疏松者18例,占45％(18/40),其中男性4例,女性14例,女性占骨质疏松组的77.78％(14/18)。单用DEXA测量出骨质疏松者23例,单用QCT测量出骨质疏松者21例,其中5例有2例示QCT正常,而用DEXA测定有骨质疏松;3例用QCT测定已有腰椎骨质疏松,而DEXA示腰椎正常,但股骨颈部有骨质疏松。结论 老年2型糖尿病的骨质疏松与糖尿病病程、餐后血糖、胆固醇密切相关。骨形成指标(BGP、CICP)在骨质疏松组中非但不降,反比非骨质疏松组有明显升高。本研究显示老年2型糖尿病同时用DEXA及QCT测定骨密度有很好的相关性,r=0.770,P<0.01,故仅做腰椎QCT也可作为老年2型糖尿病骨质疏松的诊断依据。     

Plasminogen Activator Inhibitor-1 Is Involved in Streptozotocin-Induced Bone Loss in Female Mice

In diabetic patients, the risk of fracture is high because of impaired bone formation. However, the details of the mechanisms in the development of diabetic osteoporosis remain unclear. In the current study, we investigated the role of plasminogen activator inhibitor (PAI)-1 in the pathogenesis of type 1 diabetic osteoporosis by using PAI-1–deficient mice. Quantitative computed tomography analysis showed that PAI-1 deficiency protected against streptozotocin-induced bone loss in female mice but not in male mice. PAI-1 deficiency blunted the changes in the levels of Runx2, osterix, and alkaline phosphatase in tibia as well as serum osteocalcin levels suppressed by the diabetic state in female mice only. Furthermore, the osteoclast levels in tibia, suppressed in diabetes, were also blunted by PAI-1 deficiency in female mice. Streptozotocin markedly elevated the levels of PAI-1 mRNA in liver in female mice only. In vitro study demonstrated that treatment with active PAI-1 suppressed the levels of osteogenic genes and mineralization in primary osteoblasts from female mouse calvaria. In conclusion, the current study indicates that PAI-1 is involved in the pathogenesis of type 1 diabetic osteoporosis in females. The expression of PAI-1 in the liver and the sensitivity of bone cells to PAI-1 may be an underlying mechanism.Type 1 diabetes is a disease in which patients have little or no insulin secretion and hyperglycemia. A decrease in bone mineral density (BMD) and a marked increase in fracture risk have been described in patients with type 1 diabetes (1,2). The detrimental skeletal effects of glucose toxicity, insulin deficiency, and diabetes complications might partly explain the association between type 1 diabetes and osteoporosis (3–5). Previous findings suggest that a decrease in osteoblastic bone formation is a major contributor to diabetic osteoporosis (4,6). However, the pathogenesis of this skeletal fragility and markers for the evaluation of bone metabolism in type 1 diabetic patients remain to be fully clarified.Plasminogen activator inhibitor (PAI)-1 functions as the principal inhibitor of plasminogen activators and, hence, fibrinolysis. PAI-1 has been of particular focus in cardiovascular disease because of strong positive correlations between serum PAI-1 levels and cardiovascular risk (7). Several reports have shown that circulating PAI-1 levels are elevated in type 1 and type 2 diabetic patients and in animal models (8,9). Furthermore, Ma et al. (10) reported that PAI-1 contributes to the development of diabetes. PAI-1 has various functions, including regulating the degradation of the extracellular matrix, cell migration, and apoptosis (11), which may be related to osteoblast differentiation and function. Daci et al. (12) previously reported that PAI-1 deficiency partially protected against bone loss in estrogen-deficient mice. These findings suggest that PAI-1 may contribute to impairment of bone remodeling and the development of osteoporosis. However, the role of PAI-1 in the pathogenesis of diabetic osteoporosis has not yet been elucidated. In the current study, we examined the effects of PAI-1 deficiency on streptozotocin-induced diabetic bone loss by using wild-type and PAI-1–deficient mice.     

不同阶段2型糖尿病诱发骨质疏松症的致病机制研究进展

大量临床研究表明,2型糖尿病(type 2 diabetes mellitus,T2DM)患者的骨折风险明显增加。因此,T2DM诱发的骨质疏松症(osteoporosis,OP)被认为是最严重的糖尿病并发症之一。骨脆性增加是糖尿病性骨质疏松症(diabetic osteoporosis,DOP)的典型特征,其发病机制是多因素引起的,包括肥胖、高胰岛素血症、高血糖(hyperglycemia,HG)、晚期糖基化终产物(advanced glycation end products,AGEs)积聚和氧化产物积累以及微血管病变的存在等。这些因素在T2DM不同时期是相互平衡或相互促进的,而肿瘤坏死因子-α(tumor necrosis factor,TNF-α)、白细胞介素-1(interleukin 1,IL-1)、白细胞介素-6(interleukin 6,IL-6)等炎症因子的异常活化打破了骨形成和骨吸收的代谢平衡,导致骨脆性增加。骨强度和骨折风险的变化取决于疾病进展的阶段。因此,糖尿病骨病的病理生理变化可以通过分别考虑糖尿病早期和晚期骨骼相关因素来广泛讨论,其中早期阶段以胰岛素抵抗和高胰岛素血症为特征,这些因素会导致糖尿病发病和初始阶段的骨密度(bone mineral density,BMD)增加。而晚期阶段的特征是β细胞衰竭,AGEs和氧化产物的堆积,加速衰老和血管并发症的发展。为此,本文希望对T2DM的不同阶段与骨代谢的关系进行综述,以便更好的认识T2DM的进展加速骨脆性风险的病理过程和致病机制,为治疗T2DM和T2DM诱发的OP、降低T2DM患者骨折发生的风险发挥积极的作用。     

Changes of serum levels of osteocalcin,alkaline phosphatase,IGF-I and IGF-binding protein-3 during fracture healing

The purpose of this study was to determine the changes in serum markers relating to bone formation during fracture healing. Ten consecutive patients with fractures treated with or without surgery were included. Sera were collected periodically from patients for 80-280 (average 180) days after the fracture. The concentrations of intact osteocalcin, bone-specific alkali phosphatase (ALP), insulin-like growth factor (IGF)-I and IGF-binding protein (IGFBP)-3 in the serum were measured by ELISA. All these serum markers increased or decreased after fracture and fluctuated during fracture healing, however, this pattern differed among the cases. In conclusion, serum markers such as osteocalcin, ALP, IGF-I and IGFBP-3 reflected in part the osteoblastic activity during bone formation.