绝经后妇女血清基质金属蛋白酶与骨转换生化指标及骨密度的关系

目的探讨绝经后妇女血清基质金属蛋白酶(MMP)-1和MMP-2与骨密度及骨转换生化指标之间的关系。方法采用酶联免疫吸附法测定297名48~80岁女性志愿者的血清MMP-1、MMP-2和血清骨碱性磷酸酶(BAP)、血清骨钙素(OC)及血清Ⅰ型胶原氨基末端肽(NTX),用双能X线吸收法测定腰椎正位1~4总体、股骨颈、华氏区、髋部总体的骨密度。结果MMP-1与骨密度及骨转换生化指标无明显相关性;MMP-2与骨密度呈较弱的负相关,校正年龄与体重指数后,MMP-2与股骨颈、髋部骨密度的相关性消失;MMP-2与BAP、OC、NTX正相关(P<0.01);绝经后骨质疏松症患者血清MMP-2水平高于年龄匹配的正常对照组和骨量减少组(P<0.01)。结论绝经后妇女血清MMP-2与骨转换生化指标相关联,血清MMP-2水平升高可能为高骨代谢转换过程(如绝经后骨质疏松症)中的一种伴随表现。     

血清基质金属蛋白酶13及其抑制因子在绝经后妇女骨代谢中的浓度变化

目的 测定绝经后妇女血清基质金属蛋白酶-13 (MMP-13)和组织金属蛋白酶抑制因子1(TIMP-1)浓度,并探讨其与骨密度数值和骨代谢指标的关系.方法 选取武汉地区120名48 ～ 65岁绝经后女性,用酶联免疫吸附试验(ELISA)测定血清MMP-13、TIMP-1以及雌二醇(E2)、骨保护蛋白(OPG)、骨保护蛋白配体(OPGL),Ⅰ型原胶原N端前肽(PINP)和Ⅰ型胶原交联C末端肽(CTX)的浓度,计算MMP-13/TIMP-1比值,用双能X线吸收法(DEXA)测定腰椎正位、股骨颈、华氏区和大粗隆的骨密度(BMD).同时,按照WHO标准将入选女性分为骨密度正常组(n=28)、低骨量组(n=36)和骨质疏松组(n=56).结果 骨密度正常组、低骨量组和骨质疏松组MMP-13浓度比较差异有统计学意义[(27.08±1.41) μg/L、(45.64±1.62)μg/L及(44.25±1.21) μg/L;F=110.314,P=0.000],且低骨量组、骨质疏松组血清MMP-13均高于正常组(P均＜0.05),低骨量组MMP-13略高于骨质疏松组,但差异无统计学意义(P＞0.05);而TIMP-1在3组间差异无统计学意义(F=10.721,P=0.801).MMP-13/IIMP-1比值分别为0.185±0.062,0.311±0.053,0.332±0.063,3组差异有统计学意义(F=137.771,P =0.000),且低骨量组与骨质疏松组均高于骨密度正常组(P均＜0.05),但两组间差异无统计学意义(P＞0.05).骨质疏松组中血清MMP-13与骨密度(腰椎正位、股骨颈、华氏区)、血清E2、OPGL数值存在明显负相关性(r值分别为-0.296、-0.198、-0.301、-0.298、-0.233,P均＜0.05),和OPG、PINP和CTX存在明显正相关性(r值分别为0.228、0.315、0.312,P均＜0.05).低骨量组MMP-13与骨密度(腰椎正位、华氏区)和E2、CTX存在明显相关性(r值分别为-0.188、-0.196、-0.235、0.289,P均＜0.05).结论 血清MMP-13和MMP-13/TIMP-1比值与绝经后骨质疏松症妇女和绝经后低骨量组妇女骨代谢指标具有关联性.血清MMP-13浓度升高和MMP-13/TIMP-1比值升高可能为绝经后骨质疏松症和绝经后妇女早期骨代谢转换过程增快的表现.     

绝经后女性骨转换生化标志物水平与骨密度的相关性分析

目的探讨绝经后女性骨转换生化标志物水平与骨密度的相关性。方法选择2018年5月至2019年5月该院接诊的104例绝经后女性,其中53例骨质疏松症女性设为观察组,51例无骨质疏松症女性作为对照组,分析血清组织蛋白酶K(CatheK)、Ⅱ型前胶原氨基端前肽(PINP)、β胶原降解产物(β-crosslaps)、骨钙素及抗酒石酸酸性磷酸酶(TRAP)与股骨颈、腰椎骨密度之间的相关性。结果观察组患者血清CatheK、PINP、β-crosslaps、骨钙素及TRAP水平明显高于对照组,差异有统计学意义(P<0.05);观察组患者股骨颈、腰椎骨密度以及腰椎和髋部的总T值(简称T值)明显小于对照组,差异有统计学意义(P<0.05)。相关性分析结果提示,股骨颈骨密度、腰椎骨密度、T值与CatheK、PINP、β-crosslaps、骨钙素及TRAP均呈负相关(P<0.05)。结论绝经后女性血清骨转换生化标志物的表达和骨密度之间存在着密切关系。     

男性吸烟与骨密度及骨生化指标关系

目的:探讨男性吸烟与骨密度及骨生化指标关系.方法:用DXA仪测定腰椎及髋部BMD,用ELISA测定389例20～80岁健康男性血清骨特异性碱性磷酸酶(sBAP)和Ⅰ型胶原氨基末端肽(sNTX).结果:(1)腰椎正位总体、腰椎侧位、髋部总体、股骨颈及Ward's区BMD均与年龄呈显著负相关(均P＜0.05).各部位BMD均在20～29岁年龄组最高,29岁之后随增龄而缓慢下降;40～60岁各年龄组之间的BMD无显著差异.(2)除腰椎侧位BMD外,吸烟组其他各部位BMD显著低于非吸烟组;吸烟组的BAP显著高于非吸烟组,两组之间的sNTX无显著差异.(3)校正年龄与BMI后,烟龄与腰椎正位,髋部总体,股骨颈及Ward's区BMD均呈显著负相关(P＜0.05).每日吸烟量与腰椎正位及Ward's区BMD呈显著负相关(P＜0.05).结论:男性随年龄增长骨量丢失.男性吸烟者骨生化指标与骨转换水平增高,骨量丢失加速.吸烟等生活方式增高骨转换水平,影响骨转换的增龄性变化并加速骨量的丢失.吸烟是骨质疏松的一个危险因素.预防骨质疏松症(OP)应提倡戒烟.     

绝经后骨质疏松妇女外周血瘦素、雌激素及骨转换指标表达分析

目的 分析绝经后骨质疏松(OP)妇女外周血瘦素、雌激素及骨转换指标表达.方法 连续选择近期就诊的35例绝经后OP患者(绝经后OP组)和30例同龄、同性别及正常骨密度的健康体检者(对照组),均接受血清瘦素(LEP)、雌二醇(E2)、卵泡刺激素(FSH)、骨钙素(BGP)和碱性磷酸酶(AKP)等指标测定.结果 绝经后OP组的外周血LEP、E2浓度明显低于对照组,而血清BGP和AKP浓度则明显高于后者(P均＜0.01～0.05),两组间血清FSH浓度无明显区别(P＞0.05).结论 绝经后OP妇女存在着明确外周血瘦素及雌激素低水平表达,骨转换指标活跃.     

慢性阻塞性肺疾病患者血清MMP-9、TNF-α与骨转换生化指标及骨密度的关系

目的探讨慢性阻塞性肺疾病(COPD)并发骨质疏松患者血清基质金属蛋白酶(MMP-9)、肿瘤坏死因子-α(TNF-α)与骨转换标志物、骨密度的相关性。方法选取该院接诊稳定期COPD患者84例,根据患者骨密度(BMD)测试结果将其分为骨质疏松组(28例)、低骨量组(26例)与正常骨量组(30例),采用ELISA法检测各组MMP-9、TNF-α水平,以及骨转化生化标志物血清骨特异性碱性磷酸酶(sBAP)、血清骨钙素(sOC)、血清I型胶原羧基末端肽(sCTX)。结果骨质疏松组、低骨量组血清MMP-9、TNF-α水平高于正常骨量组,骨质疏松组血清MMP-9、TNF-α水平高于低骨量组,差异均有统计学意义(P0.05)。骨质疏松组sBAP、sOC低于正常骨量组,sCTX高于正常骨量组,低骨量组sBAP、sOC低于正常骨量组,骨质疏松组sBAP低于低骨量组,sCTX高于低骨量组,差异均有统计学意义(P0.05)。骨质疏松组、低骨量组腰椎骨密度、腰椎骨密度T值、股骨颈股密度与股骨骨密度T值均低于正常骨量组(P0.05),骨质疏松组腰椎骨密度、腰椎骨密度T值、股骨颈股密度与股骨骨密度T值低于低骨量组(P0.05)。血清MMP-9与骨转换生化指标、骨密度水平均呈负相关(P0.05);TNF-α与骨转换生化指标呈负相关(P0.05)。结论 COPD并发骨质疏松患者MMP-9、TNF-α呈现为高表达,与骨转换生化指标存在负相关性,同时与骨密度也存在一定关系。     

2型糖尿病合并骨质疏松骨量及血清瘦素、骨代谢指标对照分析

目的 分析2型糖尿病(2DM)合并骨质疏松(OP)患者骨量及血清瘦素、骨代谢指标.方法 连续选择近期就诊的37例2DM合并OP患者、41例单纯OP患者和28例同龄、同性别及正常骨密度(BMD)的健康体检者(对照组),三组对象接受了腰椎L1～L4 BMD、左侧股骨颈BMD、血清瘦素(LEP)、骨钙素(BGP)和碱性磷酸酶(AKP)等指标测定.结果 2DM合并OP组的腰椎L1～L4及股骨颈BMD、外周血LEP浓度明显低于单纯OP患者和对照组,而血清BGP和AKP浓度则明显高于后两者(P均＜0.01～0.05).结论 2DM合并OP患者存在着较明确骨量减少及血清LEP低水平表达,但骨转换指标活跃.     

绝经年限、体质量和人体质量指数与绝经后妇女的骨密度变化

背景绝经后妇女易于发生骨质疏松,不同年龄和体质量的人群,其骨量丢失的规律不同.目的分析年龄、绝经年限、绝经年龄、身高、体质量及人体质量指数对绝经后妇女骨密度的影响.设计以绝经妇女为研究对象,随机抽样检测.单位一所省级中医药研究院药品临床研究基地,一所大学医院骨科及一所大学骨伤系. 对象2000-09/2003-08福州地区自然绝经后妇女603例.方法采用随机抽样方法,记录患者年龄、绝经年限、绝经年龄、身高、体质量及人体质量指数,采用双能X射线骨密度仪检测腰椎和股骨颈、大转子及Ward's区骨密度,用SPSS软件相关回归分析.主要观察指标年龄、绝经年限、绝经年龄、身高、体质量和人体质量指数与骨密度的相关性及回归方程.结果绝经后妇女的年龄、绝经年限、体质量和人体质量指数与腰椎、股骨颈、大转子及Ward's区骨密度的相关性十分显著;低体质量组骨密度明显低于超体质量组(P＜0.01);影响腰椎、大转子骨密度的主要因素为年龄和体质量,影响股骨颈骨密度的重要因素为绝经年限和体质量.影响腰椎骨密度的因素依次为年龄、体质量和绝经年龄,回归方程y=0.927-0.009 3X1+0.003 7X2+0.004X3,影响股骨颈骨密度的因素依次有绝经年限、体质量和绝经年龄,回归方程y=0.687-0.008 1X1+0.004 8X2-0.003 4X3,影响大转子骨密度的因素依次有年龄、体质量和绝经年限,回归方程y=0.591-0.003 8X1+0.004 2X2-0.002 4X3,影响Ward's区骨密度的因素依次有年龄、人体质量指数和绝经年限,回归方程y=0.686-0.007 2X 1+0.013 6X2-0.004 6X3.结论绝经后女性随着年龄的增大,其腰椎和髋部的骨密度呈下降趋势,对于体瘦者,患骨质疏松的危险性要大于正常体质量组及肥胖组.     

绝经后女性骨密度测定的临床价值与护理探讨

目的探讨绝经后妇女骨密度测定对防治骨质疏松性骨折的临床价值与护理对策。方法对 12 8例绝经后妇女按不同的绝经年龄分成 3组 ,采用法国Challenger双能X线骨密度仪检测受试者的腰椎 :腰 2 (L2 )、腰 3(L3)、腰 4 (L4 )正位 ,左髋部 :股骨颈、Ward三角、大转子 ,左前臂 :超远端、远端的骨密度 (BMD) ,分析不同绝经年龄与骨质疏松 (OP)患病率的关系 ,并提出相应的预防和护理措施。结果本组平均绝经年龄 4 9 4 6± 3 4岁 ,OP的患病率为 6 4 84 % ,低骨量为 2 9 16 % ,正常骨量为 6 0 0 % ,三组不同绝经年龄的OP发病率有显著性差异 (P <0 0 5 )。8个区域的OP发生部位依次为腰椎、前臂、左髋部 (股骨颈、Ward三角、大转子 )。结论绝经年龄越早OP的发生率就越高 ,对绝经后妇女进行BMD测定 ,能早期发现OP并进行干预性治疗 ,减少OP性骨折 ,提高生活质量。护理人员应做好OP的健康教育工作     

骨钙素基因Hind Ⅲ多态性与福州地区汉族绝经后妇女骨密度的相关性

背景:骨质疏松症是一种多基因遗传病,骨钙素受体基因多态性与骨密度关系存在地域和人群的差异.目的:观察绝经后妇女骨钙素基因型频率分布及其与骨密度的关系,探讨福州地区汉族绝经后妇女骨质疏松症的遗传易感基因.方法:用聚合酶链式反应限制性片段长度多态性分析201例汉族绝经后妇女骨钙素基因型,用双能X射线吸收法测定腰椎、股骨颈,大转子和Ward's三角4个部位骨密度值.结果与结论:福州地区汉族绝经后妇女骨钙素基因型频率分布符合Hardy-Weinberg定律(χ2=2.29,P > 0.05),基因多态性分布依次为HH 5%、hh 46%、Hh 49%,与福州、北京、广州、台湾地区骨钙素基因Hind Ⅲ位点多态性分布频率差异无显著性意义(P > 0.05).但是与日本人、白种人差异明显(P < 0.05).且HH基因型在大转子骨密度明显高于hh型(P < 0.05),但不同基因型在第2~4腰椎、股骨颈、Ward's三角区的骨密度差异无显著性意义.提示绝经后妇女骨钙素基因型与大转子骨密度可能存在一定关联.     

骨搬移、骨延长术治疗长骨慢性骨髓炎和感染性骨不连体会

目的探索分析IIizarov骨搬移、骨延长术治疗长骨感染和肢体短缩,以及感染所致骨折不愈合的临床疗效。方法回顾性分析2011年6月-2013年10月,用骨感染病灶清除、IIizarov外固定支架固定及骨干骺端截骨骨搬移和骨延长术治疗13例长骨感染、缺损的股骨、胫骨和腓骨慢性骨髓炎和感染性骨不连患者,其中股骨和胫骨慢性骨髓炎8例（伴股骨病理性骨折1例）,感染性骨不连4例;腓骨慢性骨髓炎1例。结果13例患者感染均得到一期治愈,窦道愈合,骨搬移结合处正常愈合。其中2例出院后自行搬移过程中出现钉道感染（1例经再次清创后治愈,1例经清创后感染复发截肢）,1例在骨愈合后发生再骨折,经髓内钉固定后骨折愈合。13例患者骨搬移长度5～13cm,平均7．5cm;13例患者中有11例骨搬移后双下肢等长,2例患侧下肢较健侧下肢短缩。所有患者未出现神经损伤。结论IIizarov骨搬移和骨延长技术是治疗长骨感染及感染性骨不连的一种有效办法,手术可祛除感染,治愈窦道,恢复肢体长度,从而解决患者痛苦,提高其生活质量。     

原发性或转移性骨肿瘤易误诊为原发性骨质疏松症

目的探讨原发性骨肿瘤及转移性骨肿瘤与原发性骨质疏松症的临床特点,以减少误诊误治。方法回顾分析我科2010年9~10月收治5例原发性骨肿瘤及转移性骨肿瘤误诊为原发性骨质疏松症的临床资料。结果本组5例均有不同程度的疼痛、乏力、食欲减退、体重减轻。1例伴腰椎压缩性骨折,1例在1年内先后左腕、右踝及左胫骨骨折。均在外院首诊为骨质疏松症,入我院后经完善医技检查最终确诊为肺腺癌骨转移3例,多发性骨髓瘤、前列腺癌骨转移各1例。结论恶性肿瘤和骨质疏松症均是中老年人常见疾病,两者鉴别困难。故在诊断原发性骨质疏松症前,应注重病史采集和体格检查,建立比较完整的排除诊断项目,以降低原发性骨肿瘤及转移性骨肿瘤的误诊率。     

Mesenchymal Stem Cells for Bone Repair and Metabolic Bone Diseases

Human mesenchymal stem cells offer a potential alternative to embryonic stem cells in clinical applications. The ability of these cells to self-renew and differentiate into multiple tissues, including bone, cartilage, fat, and other tissues of mesenchymal origin, makes them an attractive candidate for clinical applications. Patients who experience fracture nonunion and metabolic bone diseases, such as osteogenesis imperfecta and hypophosphatasia, have benefited from human mesenchymal stem cell therapy. Because of their ability to modulate immune responses, allogeneic transplant of these cells may be feasible without a substantial risk of immune rejection. The field of regenerative medicine is still facing considerable challenges; however, with the progress achieved thus far, the promise of stem cell therapy as a viable option for fracture nonunion and metabolic bone diseases is closer to reality. In this review, we update the biology and clinical applicability of human mesenchymal stem cells for bone repair and metabolic bone diseases.BMMNC = bone marrow mononuclear cell; BMP = bone morphogenic protein; BMT = bone marrow transplant; ESC = embryonic stem cell; FCS = fetal calf serum; iPSC = induced pluripotent stem cell; MSC = mesenchymal stem cell; OI = osteogenesis imperfecta; TNSALP = tissue nonspecific alkaline phosphataseRecent advances in stem cell research have prompted development of cell-based therapies for bone repair and treatment of metabolic bone diseases. Stem cells are defined by their ability to self-renew and their totipotency or potential to form cells derived from all 3 germ layers. In contrast, cells with self-renewal capacity but more restricted potential are called progenitor cells or tissue stem cells (eg, hematopoietic stem cells or mesenchymal stem cells [MSCs]). Finding an ideal stem cell for clinical applications with high self-renewal capacity and multipotent potential has been a challenge. In recent years, substantial advances have been made in examining the potential of stem cells, especially human embryonic stem cells (ESCs), in regenerative medicine. The ability of human ESCs to self-renew for prolonged periods without differentiation and, most importantly, their ability to differentiate into a large variety of tissues from all 3 germ layers were first characterized by Thomson et al.¹ These unique properties of ESCs, specifically self-renewal and pluripotency, made human ESCs ideal candidates for regenerative medicine.Initial enthusiasm for human ESCs has been tempered and limited by a number of issues, some of which were predicted on the basis of studies with murine ESCs, which were developed more than a decade earlier. Therapeutic use of human ESCs is complicated by immunologic incompatibility and possible development of malignant neoplasms or teratomas from administered cells.^2,3 This complication is further hampered by the legal and ethical issues that surround derivation of ESCs from human embryos and their use in research. Thus, despite the ability of human ESCs to self-renew and to differentiate into many cell types, these controversies have restricted their use for therapeutic purposes and prompted scientists to seek other options, such as examining the potential of adult stem cells for regenerative medicine.For editorial comment, see page 859Adult stem cells are present in substantial numbers in many tissues throughout life; however, their frequency decreases with age. Tissues that harbor MSCs or MSC-like cells include blood,⁴ adipose tissue,⁵ skin,⁶ trabecular bone,⁷ and fetal blood, liver, and lung.^8,9 The mesenchymal stem-like cells have also been identified in umbilical cord blood¹⁰ and placenta.¹¹ Despite sharing similar characteristics, these MSCs from different sources differ in their differentiation potential and gene expression profile.¹² Among the different types of adult stem cells, stem cells harbored in the bone marrow are considered to have the highest multilineage potential¹³ and have been studied for therapeutic purposes. Bone marrow is known to be a rich environment for many cell types. Among these cells are phenotypically and functionally diverse types of cells, collectively referred to as stromal cells. The MSCs comprise a small fraction (<0.01%) of stromal cells. We review the current literature on the biology and specific characteristics of human MSCs (Figure). We also describe recent advances in the use of systemic human MSC therapy in clinical studies related to fracture nonunion and metabolic bone diseases. We reviewed the PubMed literature using the keyword stem cells. The inclusion criteria were use of MSCs in animal models of bone repair and for clinical applications, especially in fracture nonunion, osteogenesis imperfecta (OI), and hypophosphatasia, as well as embryonic and induced pluripotent stem cells (iPSCs) and their use in clinical applications. Additional articles were obtained by assessment of references in the published reviews.Open in a separate windowFIGURE.Developmental hierarchy of stem cells (SCs) and therapeutic potential of human mesenchymal stem cells (MSCs). On fertilization of an egg, a blastocyst forms. The inner cell mass of the blastocyst consists of the most primitive SC or totipotent SC. This totipotent SC can give rise to cells of embryonic and extraembryonic origin. Pluripotent SCs are multipotent SCs that can self-renew and differentiate into hematopoietic SCs, endothelial SCs, and MSCs. Hematopoietic SCs differentiate into blood cells, whereas endothelial progenitors give rise to mature endothelial cells. However, MSCs are characterized by their multilineage differentiation potential, including for bone, cartilage, and adipose tissue. Human MSCs have been tested in several clinical applications to repair bone in different types of bone disease, including fracture nonunion, osteogenesis imperfecta, and hypophosphatasia.     

Bone and joint infection

Older adults are at risk for the immune dysfunction associated with advanced age, which contribute to their increased risk of infection. Hematogenous osteomyelitis occurs not only in children, but also in older adults. Iatrogenic septic arthritis can be occured after the intraarticular injection for the osteoarthritis in aging society. Tuberculous spondylitis occurs in older adults and the differential diagnosis with pyogenic spondylitis and vertebral metastasis is important.     

Bone formation and inflammation

Role of BMP signaling is crucial in the osteoblast differentiation and bone formation. BMP induces expression of Runx2, a master gene for osteogenesis, and cooperates with Runx2 in mature osteoblast to express target genes. These functions are suppressed by TGF-beta-induced Smad7 together with Smurf1 by various mechanisms, including degradation of type I receptor, Smadl/5, and Runx2. Bone remodeling is achieved by "coupling" of osteoblasts and osteoclasts. Although excess maturation and activation of osteoclasts is well described during inflammation, effect of inflammation to the osteoblast function is still unclear. Further exploration in this area thus might lead to discovery of novel therapeutic targets of inflammatory bone diseases.     

Bone and mineral metabolism

Although bones are normally thought of as supporting structures that fracture when one falls, bone is actually a very active metabolic organ. It is vital in the regulation of calcium and phosphate metabolism, magnesium storage, and in buffering metabolic acido-sis. Bone and mineral metabolism and some of their disorders are presented in this article.     

2型糖尿病患者骨密度与骨钙素变化研究

目的 :研究 2型糖尿病患者骨密度的变化以及与骨钙素和胰岛功能的关系。方法 :使用定量超声骨量 (QUS)分析系统测定 71例 2型糖尿病踝中部骨超声指数 (OSI) ,根据其测定结果将 2型糖尿病患者分为骨量正常组、骨量减低组和骨质疏松组 ,并与同年龄的正常对照组相比较。同时测定 2型糖尿病患者的血清骨钙素 (BGP)、C肽、血糖、血钙、血磷及血浆硷性磷酸酶等进行组间比较。结果 :2型糖尿病患者OSI低于对照组 ,差异显著 (P <0 .0 1)。 2型糖尿病BGP和C肽值三组间相比较差异显著 (P <0 .0 1)。结论 :2型糖尿病患者骨质疏松的发生比例高于正常人。骨密度降低者BGP和C肽呈同步降低 ,说明2型糖尿病患者的骨质疏松可能与胰岛功能降低有关。血浆骨钙素测定可以作为骨质疏松的监测指标之一。早期诊断糖尿病并及时予以有效的治疗 ,必要时早期使用胰岛素将可能会防止糖尿病患者骨质疏松的发生