Assessment of bone turnover and bone quality in type 2 diabetic bone disease： current concepts and future directions

Substantial evidence exists that in addition to the well-known complications of diabetes, increased fracture risk is an important morbidity. This risk is probably due to altered bone properties in diabetes. Circulating biochemical markers of bone turnover have been found to be decreased in type 2 diabetes （T2D） and may be predictive of fractures independently of bone mineral density （BMD）. Serum sclerostin levels have been found to be increased in T2D and appear to be predictive of fracture risk independent of BMD. Bone imaging technologies, including trabecular bone score （TBS） and quantitative CT testing have revealed differences in diabetic bone as compared to non-diabetic individuals. Specifically, high resolution peripheral quantitative CT （HRpQCT） imaging has demonstrated increased cortical porosity in diabetic postmenopausal women. Other factors such as bone marrow fat saturation and advanced glycation endproduct （AGE） accumulation might also relate to bone cell function and fracture risk in diabetes. These data have increased our understanding of how T2D adversely impacts both bone metabolism and fracture risk.

Influence of bone morphogenetic protein type IA receptor conditional knockout in lens on expression of bone morphogenetic protein 4 in lens

AIM: To investigate the influence of bone morphogenetic protein type IA receptor [BMPR-IA(ALK3)] conditional knockout in lens on expression of bone morphogenetic protein 4(BMP4) in lens during the development of the vertebrate eye.METHODS: Cre-positive mice were mated with Crenegative mice to generate 50% Cre-positive(conditional knockout, CKO) 4 embryos, 8 eyes and 50% Cre-negative offspring(wild type, WT) 4 embryos, 8 eyes. The embryos were fixed in 4% paraformaldehyde, embedded in paraffin, and sectioned to a thickness of 4 μm.Removal of paraffin wax and dehydrating for sections,and then the procedure of in situ hybridization was processed, BMP4 MK1784-m(BOSTER) was used, and observed the expression of BMP4 in the lens in experimental group and control group. We selected SPSS11.0 software for statistical analysis, P【0.05 showed that the difference was statistically significant.· RESULTS: Four embryos of each genotype were examined, totally we had 8 embryos, 16 eyes. We got the uniform outcomes in all the embryos. We found ALK3 was required during lens growing, but was not essential for the formation of lens. We observed that the expression of BMP4 in the lens was significantly reduced in all 8 ALK3 CKO lens, BMP4 expression was normal in all the 8 WT lens, P 【0.01. This phenomenon became increasingly visible in accordance with embryo development. The most apparent alteration was present at stage E15.5.CONCLUSION: ALK3 is essential for lens growth. The influence of ALK3 on the expression of BMP4 is present during the development of mice lens.

The biological function of type I receptors of bone morphogenetic protein in bone

Bone morphogenetic proteins （BMPs） have multiple roles in skeletal development, homeostasis and regeneration. BMPs signal via type I and type II serine/threonine kinase receptors （BMPRI and BMPRII）. In recent decades, genetic studies in humans and mice have demonstrated that perturbations in BMP signaling via BMPRI resulted in various diseases in bone, cartilage, and muscles. In this review, we focus on all three types of BMPRI, which consist of activin-like kinase 2 （ALK2, also called type IA activin receptor）, activin- llke kinase 3 （ALK3, also called BMPRIA）, and activin-like kinase 6 （ALK6, also called BMPRIB）. The research areas covered include the current progress regarding the roles of these receptors during myogenesis, chondrogenesis, and osteogenesis. Understanding the physiological and pathological functions of these receptors at the cellular and molecular levels will advance drug development and tissue regeneration for treating musculoskeletal diseases and bone defects in the future.

Autologous bone marrow derived stem cell therapy in patients with type 2 diabetes mellitus-defining adequate administration methods

AIM To carry out randomized trial for evaluating effects of autologous bone marrow derived stem cell therapy(ABMSCT) through different routes.METHODS Bone marrow aspirate was taken from the iliac crest of patients. Bone marrow mononuclear cells were separatedand purified using centrifugation. These cells were then infused in a total of 21 patients comprising three groups of 7 patients each. Cells were infused into the superior pancreaticoduodenal artery(Group Ⅰ), splenic artery(Group Ⅱ) and through the peripheral intravenous route(Group Ⅲ). Another group of 7 patients acted as controls and a sham procedure was carried out on them(Group Ⅳ). The cells were labelled with the PET tracer F18-FDG to see their homing and in vivo distribution. Data for clinical outcome was expressed as mean ± SE. All other data was expressed as mean ± SD. Baseline and post treatment data was compared at the end of six months, using paired t-test. Cases and controls data were analyzed using independent t-test. A probability(P) value of < 0.05 was regarded as statistically significant. Measures of clinical outcome were taken as the change or improvement in the following parameters:(1) C-peptide assay;(2) HOMA-IR and HOMA-B;(3) reduction in Insulin dose; subjects who showed reduction of insulin requirement of more than 50% from baseline requirement were regarded as responders; and(4) reduction in HbA 1c. RESULTS All the patients, after being advised for healthy lifestyle changes, were evaluated at periodical intervals and at the end of 6 mo. The changes in body weight, body mass index, waist circumference and percentage of body fat in all groups were not significantly different at the end of this period. The results of intra-group comparison before and after ABMSCT at the end of six months duration was as follows:(1) the area under C-peptide response curve was increased at the end of 6 mo however the difference remained statistically non-significant(P values for fasting C-peptide were 0.973, 0.103, 0.263 and 0.287 respectively and the P values for stimulated C-peptide were 0.989, 0.395, 0.325 and 0.408 respectively for groups Ⅰ?to Ⅳ);(2) the Insulin sensitivity indices of HOMA IR and HOMA B also did not show any significant differences(P values for HOMA IR were 0.368, 0.223, 0.918 and 0.895 respectively and P values for HOMA B were 0.183, 0.664, 0.206 and 0.618 respectively for groups Ⅰto Ⅳ);(3) Group Ⅰshowed a significant reduction in Insulin dose requirement(P < 0.01). Group Ⅱ patients also achieved a significant reduction in Insulin dosages(P = 0.01). The Group Ⅰand Group Ⅱ patients together constituted the targeted group wherein the feeding arteries to pancreas were used for infusing stem cells. Group Ⅲ, which was the intravenous group, showed a non-significant reduction in Insulin dose requirement(P = 0.137). Group Ⅳ patients which comprised the control arm also showed a significant reduction in Insulin dosages at the end of six months(P < 0.05); and(4) there was a non-significant change in the Hb A1 c levels at the end of 6 mo across all groups(P = 0.355, P = 0.351, P = 0.999 and P = 0.408 respectively for groups Ⅰto Ⅳ). CONCLUSION Targeted route showed a significant reduction in Insulin requirement at the end of six months of study period whereas the intravenous group failed to show reduction.

Preventive effects of autologous bone marrow mononuclear cell implantation on intrahepatic ischemic-type biliary lesion in rabbits

BACKGROUND: The ischemic-type biliary lesion (ITBL) is one of the most serious biliary complications of liver transplantation. This study aimed to investigate the effects of autologous bone marrow mononuclear cell (BM-MNC) implantation on neovascularization and the prevention of intrahepatic ITBL in a rabbit model. METHODS: The rabbits were divided into control, experimental model, and cell implantation groups, with 10 in each group. The model of intrahepatic ITBL was established by clamping the hepatic artery and common bile duct. Autologous BM-MNCs were isolated from the tibial plateau by density gradient centrifugation and were implanted through the common hepatic artery. Changes in such biochemical markers as aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma-glutamyltranspeptidase, total bilirubin and direct bilirubin were measured. Four weeks after operation, cholangiography, histopathological manifestations, differentiation of BM-MNCs, microvessel density and the expression of vascular endothelial growth factor were assessed. RESULTS: Compared with the experimental model group, the BM-MNC implantation group showed superiority in the time to recover normal biochemistry. The microvessel density and vascular endothelial growth factor expression of the implantation group were significantly higher than those of the control and experimental model groups. The ITBL in the experimental model group was more severe than that in the implantation group and fewer new capillary blood vessels occurred around it. CONCLUSIONS: Implanted autologous BM-MNCs can differentiate into vascular endothelial cells, promote neovascularization and improve the blood supply to the ischemic bile duct, and this provides a new way to diminish or prevent intrahepatic ITBL after liver transplantation. (Hepatobiliary Pancreat Dis Int 2010; 9:593-599)

Thermal,infrared spectroscopy and molecular modeling characterization of bone:An insight in the apatite-collagen type I interaction

An insight into the interaction of collagen type I with apatite in bone tissue was performed by using differential scanning calorimetry, Fourier transform infrared spectroscopy, and molecular modeling. Scanning electron microscopy shows that bone organic content incinerate gradually through the different temperatures studied. We suggest that the amide regions of the type I collagen molecule (mainly C=O groups of the peptide bonds) will be important in the control of the interactions with the apatite from bone. The amide I infrared bands of the collagen type I change when interacting to apatite, what might confirm our assumption. Bone tissue results in a loss of thermal stability compared to the collagen studied apart, as a consequence of the degradation and further combustion of the collagen in contact with the apatite microcrystals in bone. The thermal behavior of bone is very distinctive. Its main typical combustion temperature is at 360°C with a shoulder at 550°C compared to the thermal behavior of collagen, with the mean combustion peak at ca. 500°C. Our studies with molecular mechanics (MM+ force field) showed different interaction energies of the collagen-like molecule and different models of the apatite crystal planes. We used models of the apatite (100) and (001) planes;additional two planes (001) were explored with phosphate-rich and calcium-rich faces;an energetic preference was found in the latter case. We preliminary conclude that the peptide bond of collagen type I is modified when the molecule interacts with the apatite, producing a decrease in the main peak from ca. 500°C in collagen, up to 350°C in bone. The combustion might be related to collagen type I, as the ΔH energies present only small variations between mineralized and non-mineralized samples. The data obtained here give a molecular perspective into the structural properties of bone and the change in collagen properties caused by the interaction with the apatite. Our study can be useful to understand the biological synthesis of minerals as well as the organic-inorganic interaction and the synthesis of apatite implant materials.

Profile of Bone Mass and Its Determining Factors in Type 2 Diabetes: Case-Control Study

Background: Type 2 diabetes mellitus, beyond its well-known cardiovascular and neurological complications, is now increasingly recognized as having deleterious effects on bone tissue. It’s thus presented as an independent risk factor for bone fragility with a considerable fracture risk relating to many more or less intricate parameters. The general objective of our study is to assess bone mass during type 2 diabetes in Senegalese women. Methodology: We had carried out a cross-sectional and descriptive study. Socio-demographic characteristics were collected on the basis of a questionnaire. Then each of the subjects had undergone a complete clinical examination followed by a blood sample for a biological assessment of certain cardiovascular risk factors. Bone mass was measured using a bio-impedancemeter. Results: We recruited 88 women with type 2 diabetes and 83 healthy control women. The mean age of diabetic subjects was 52.7 years ± 6.8 (with extremes of 39 and 74 years). In control, the mean age was 51.0 ± 8.5 years (with extremes of 35 and 72 years). Among the diabetic subjects, 22 subjects or 25% practiced a regular walk against 27 (32.5%) in the control. Forty-three among the diabetic subjects (48.8%) were known hypertensive and followed. According to the body mass index, 71 patients (80.7%) were overweight compared to 59 (71.1%) controls. According to the waist size, 80 (90.9%) diabetic subjects had an elevated waist size compared to 69 control women (83.1%). Among diabetic subjects, 41 patients (46.5%) were hyperglycemic imbalance according to fasting blood glucose and 59 patients (67%) according to glycated hemoglobin level. Thirty-seven diabetics (42%), had both high fasting blood glucose and elevated glycated hemoglobin. The mean duration of diabetes was 8.68 ± 7.18 years. We found significantly higher bone mass in type 2 diabetic subjects (p = 0.03). Among diabetics, 27.3% had low bone mass compared to 36.1% of control. It’s noted that the subjects of the “low bone mass” group among the control subjects also have a significant drop in other anthropometric parameters (weight, body mass index, waist size, muscle mass). It should also be noted that the fat mass is significantly higher in diabetic subjects with normal or even high bone mass. In control subjects, bone mass was positively correlated with weight (r = 0.36;p = 0.001), muscle mass (r = 0.93;p < 0.0001) and fasting blood glucose (r = 0.26;p = 0.02);and negatively correlate with age (r = 0.22;p = 0.04). On the other hand, in type 2 diabetic subjects, bone mass is positively correlated with age (r = 0.22;p = 0.04), muscle mass (r = 0.89;p < 0.0001) and the diabetes duration (r = 0.44;p = 0.001). Conclusion: Bone mass is higher in type 2 diabetics compared to healthy controls. Chronic hyperglycemia and the diabetes duration are believed to be responsible for the increase in bone mass. In addition, an increase in muscle mass would lead to an increase in bone mass.

The Impact of Severity of Periodontal Bone Loss and the Levels of Glycated Hemoglobin (HbA1c) on the Periodontal Clinical Parameters of the 2017 World Workshop among Type 2 Diabetic Patients in Saudi Arabia

Background: Type-2 diabetic patients (uncontrolled levels of glucose blood) usually have periodontal diseases and alveolar bone loss. Objectives: The present study was designed to clarify the impact of severity of periodontal bone loss and the levels of glycated hemoglobin (HbA1c) on the periodontal clinical parameters of the 2017 World Workshop among type 2 diabetic patients in Saudi Arabia (Saudi and non-Saudi). Material and Methods: This study was done on 298 type 2 diabetic patients, selected from the internship clinics, College of Dentistry, King Khalid University, Abha, Saudi Arabia. The selection of patients was dependent on the levels of glycated hemoglobin (HbA1c), and they were categorized into controlled (<7% HbA1c) and uncontrolled type 2 diabetics (>7% HbA1c). All patients were divided according to the severity of periodontal bone loss into three groups, group I: mild periodontal bone loss, group II: moderate periodontal bone loss, and group III: severe periodontal bone loss. Clinical evaluation of periodontal diseases was carried out by clinical parameters according to the 2017 World Workshop. All data were collected and analyzed. A p-value of <0.05 was considered significant, and of <0.001 was considered highly significant. Results: The severity of periodontal bone loss were determined in controlled type 2 diabetics (<7% HbA1c) and compared to uncontrolled type 2 diabetics (>7% HbA1c). An increased percentage of patients with severe periodontal bone loss was observed in uncontrolled type 2 diabetics (>7% HbA1c) (42.9%), as compared to controlled type 2 diabetics (<7% HbA1c) (30.5%) without statistically significant (p = 0.251). An increased mean of age, clinical attachment loss (CAL), and percentage of radiographic bone loss (% RBL) were detected in controlled type 2 diabetics (<7% HbA1c), as compared to uncontrolled type 2 diabetics (>7% HbA1c). In contrast, we found an increased mean of plaque control record (PCR), gingival bleeding index (GBI), and periodontal pocket depth (PPD) in uncontrolled type 2 diabetics (>7% HbA1c) more than in controlled type 2 diabetics (<7% HbA1c) without statistically significant (p > 0.05). Moreover, the mean of age, PCR, CAL, % RBL, and PPD were more in the patients with severe periodontal bone loss, as compared to the patients with mild and moderate periodontal bone. Highly statistically significant differences were recorded (p < 0.001). Conclusion: This study demonstrates the role of uncontrolled diabetes as a risk factor for the increase in the severity of periodontal bone loss. Thus, we suggest including the glycated hemoglobin (HbA1c) levels with periodontal parameters in the evaluation of periodontal bone loss among type 2 diabetics.

Usage of buttress plate internal fixation associated with autografting of fibula and iliac bone for the treatment of distal femoral C_3 type fracture

To assess the effect of using buttress plate associated with antografting of fibula and iliac bone for the treatment of distal femoral C3 type fracture.Methods Seventeen cases of distal femoral C3 type fracture using buttress plate associated with antografting of fibula and iliac bone were analyzed retrospectively.Results All cases were followed up for an average of 24 months（8～55 months）.The average time of octets bridge forming were 4 months（3～5 months） while the average time for bone union were 8 months （6～14 months）.According to Shelbourne rating system,result of all 18 cases were excellent and no malunion,infection were found.Conclusion Buttress plate associated with antografting of fibula and iliac bone is an effective alternative for the treatment of distal femoral C3 type fracture.It can provide more stable fixation to the bone and earlier functional exercises can be achieved.5 refs,3 figs,1 tab.

不同髋关节置换术式治疗老年髋关节骨折内固定失败患者的临床效果及对髋关节功能的影响

目的比较不同髋关节置换术式治疗老年髋关节骨折内固定失败患者的临床效果。方法回顾性分析2012年1月至2022年1月收治的老年髋关节骨折内固定失败患者80例的临床资料,根据手术方案分为对照组39例和观察组41例。对照组采用半髋关节置换术,观察组采用全髋关节置换术。比较2组临床指标、Harris髋关节评分、临床疗效、骨代谢生化指标[骨碱性磷酸酶(BALP)、骨钙素、Ⅰ型前胶原氨基端原肽(PⅠNP)以及抗酒石酸性磷酸酶(TRACP-5b)],统计2组术后并发症发生情况。结果80例患者均成功完成手术及随访,随访时间(6.16±0.38)个月。观察组手术时间、下床活动时间长于对照组,术中失血量多于对照组(P<0.05)。随着术后时间延长,2组Harris髋关节评分呈上升趋势,且术后1、3、6个月,观察组高于对照组(P<0.05)。术后6个月,观察组总优良率[95.12%(39/41)]高于对照组[79.49%(31/39)],差异有统计学意义(P<0.05)。术后6个月,2组BALP、骨钙素、PⅠNP水平升高,TRACP-5b水平降低,且观察组BALP、骨钙素、PⅠNP水平高于对照组,TRACP-5b水平低于对照组(P<0.05,P<0.01)。2组并发症发生率比较差异无统计学意义(P>0.05)。结论全髋关节置换术治疗老年髋关节骨折内固定失败患者较半髋关节置换术临床疗效显著、骨代谢能力更佳,且不增加并发症发生风险。

温肾通络止痛方对小鼠H型骨微血管内皮细胞/骨髓间充质干细胞共培养体系的影响

背景:骨骼依赖血管与骨细胞之间的密切连接来维持完整性,骨骼处在生理低氧环境中,因此在低氧环境下研究血管生成与骨生成具有重要意义。目的:探究在低氧环境下温肾通络止痛方对H型骨微血管内皮细胞/骨髓间充质干细胞共培养体系的影响及相关机制。方法:运用酶消化法及流式分选技术,分选小鼠H型血管特异型骨微血管内皮细胞;应用骨髓贴壁法分离获取小鼠骨髓间充质干细胞;采用Transwell小室以及缺氧培养工作站建立两种细胞低氧共培养体系,使用50,100μg/m L质量浓度温肾通络止痛方冻干粉进行干预;通过划痕迁移实验与管形成实验评估共培养体系内H型骨微血管内皮细胞的成血管功能;通过碱性磷酸酶染色与茜素红染色评估共培养体系内骨髓间充质干细胞的成骨分化能力;使用Western Blotting与q-PCR检测共培养体系内H型骨微血管内皮细胞中PDGF/PI3K/AKT信号轴相关分子的蛋白表达及mRNA表达。结果与结论:(1)与常氧组相比,低氧组H型骨微血管内皮细胞划痕迁移率及新生血管长度均显著升高(P<0.05),骨髓间充质干细胞成骨分化能力增强(P<0.05);PDGF/PI3K/AKT信号轴相关分子的蛋白、mRNA表达升高(P<0.05);(2)与低氧组相比,经不同质量浓度温肾通络止痛方干预后H型骨微血管内皮细胞划痕迁移率及新生血管长度进一步提高(P<0.05),骨髓间充质干细胞成骨分化能力更强(P<0.05),PDGF/PI3K/AKT信号轴相关分子的蛋白、mRNA表达也进一步升高(P<0.05)。结果表明:低氧条件下H型血管生成及骨生成可能与PDGF/PI3K/AKT信号轴有关,而温肾通络止痛方可能通过激活PDGF/PI3K/AKT信号轴促进“H型血管生成-骨生成”作用从而防治骨质疏松症。

TGF-β_1、BMP-2和TypeⅡ Collagen在黄韧带中的表达及意义

目的研究TGF-1β、BM P-2和typeⅡco llagen在退行性腰椎滑脱(degenerative lum bar spondy lo listhes is,DLS)和腰椎间盘突出症(lum bar d isc hern iation,LDH)黄韧带中的表达及其意义。方法37例手术切除的腰椎椎板间部黄韧带标本分为3组,第1组为退行性腰椎滑脱组(DLS)10例;第2组为腰椎间盘突出症组(LDH)17例,第3组为正常对照组10例,其中7例取自腰椎骨折手术病人,3例取自意外死亡者。应用EnV is ion二步免疫组化的方法检测其TGF-1β、BM P-2和typeⅡco llagen的表达情况,普通光镜观察,计算出各标本的表达阳性率和表达强度,数据以x-±s标准差及表达强度表示,结果分别用Spss统计软件和R id it进行分析。结果TGF-1β、BM P-2和typeⅡco llagen的阳性表达产物见于成纤维细胞、成软骨细胞和软骨细胞中,而Ⅱ型胶原染色还可同时见于基质。TGF-1β、BM P-2和typeⅡco llagen在DLS组中的表达明显高于LDH组和正常组(P<0.01或P<0.05),Ⅱ型胶原基质染色明显深于LDH组和对照组。LDH组的TGF-1β和typeⅡco llagen的表达阳性率和表达强度与正常组之间差异无显著性(P>0.05),而BM P-2的表达阳性率和表达强度在LDH组与正常组之间具有统计学意义(P<0.01)。结论黄韧带所受到的异常机械牵张力可以增加TGF-1β在黄韧带细胞中的合成,而TGF-1β则促进退行性腰椎滑脱黄韧带中的Ⅱ型胶原合成,导致黄韧带的退变和肥厚。BM P-2在退变黄韧带中的表达异常增高,可能与黄韧带的软骨化倾向有关。

2型糖尿病男性患者系统性炎症指标与骨密度的关系

目的评估2型糖尿病(T2DM)男性患者系统性炎症指标与骨密度(BMD)的关系。方法261例男性T2DM患者依据诊断标准分为骨量正常组(96例)、骨量减少组(111例)以及骨质疏松组(54例),比较3组系统性炎症指标和骨代谢指标的差异。多因素有序Logistic回归分析男性T2DM患者骨量正常向骨质疏松进展的影响因素。受试者工作特征(ROC)曲线评价炎症指标对T2DM男性患者骨质疏松的预测价值。分析炎症指标与患者不同部位BMD及骨转换指标(BTM)的相关性。结果骨质疏松组中血小板计数(PLT)、血小板与淋巴细胞计数比值(PLR)、全身免疫炎症指数(SII)、中性粒细胞与淋巴细胞计数比值(NLR)明显高于骨量正常组(P<0.05)。多因素有序Logistic回归分析发现PLR与SII升高为T2DM男性患者从骨量正常进展为骨质疏松过程中的危险因素。ROC曲线显示PLR预测骨量减少的曲线下面积(AUC)为0.590,截断值为96.67;SII的AUC为0.613,截断值为307.9;二者联合AUC为0.612;但两指标对预测骨质疏松方面无明显价值。在骨质疏松和骨量减少患者中,SII、PLR、PLT与腰椎L1-4 BMD及左髋关节BMD值均呈负相关(P<0.05);SII与左股骨颈BMD值也呈负相关(P<0.05)。结论炎症指标PLR、SII对男性T2DM患者从骨量正常进展为骨量减少和骨质疏松具有一定的预测价值。

骨诱导膜中H型血管动态表达及耦合骨生成修复大段骨缺损

背景:骨诱导膜技术治疗大段骨缺损存在骨修复缓慢、成骨质量不佳等问题。H型血管具有诱导成骨作用,可增强局部成血管-成骨偶联作用,促进骨修复,但H型血管在骨诱导膜中的作用鲜有报道。目的:构建SD大鼠胫骨大段骨缺损模型,观察骨诱导膜中H型血管表达特征,进而明确骨诱导膜中H型血管表达高峰点与植骨最佳时期。方法:采用随机数字表法将60只SD大鼠随机分为对照组(n=30)与模型组(n=30),两组又各自分为骨水泥植入后4,6,8周3个亚组,每组10只大鼠。对照组与模型组大鼠均构建右侧胫骨4 mm骨缺损模型,模型组植入聚甲基丙烯酸甲酯骨水泥诱导骨生物膜形成,对照组不植入骨水泥。骨水泥植入后4,6,8周,每个时间点随机取6只大鼠,模型组切取骨诱导膜组织,对照组切取对应部位的非骨性软组织,通过免疫荧光鉴定H型血管动态表达,苏木精-伊红染色观察诱导膜组织形态改变,血管造影观察血管形成情况,免疫组化染色检测成骨细胞特异性转录因子表达;每个时间点剩余4只大鼠,模型组切开诱导膜后取出骨水泥,植入自体尾骨,对照组骨缺损区植入自体尾骨,植骨后8周进行胫骨缺损部位Micro-CT评估。结果与结论:①免疫荧光染色显示,模型组H型血管表达在骨水泥植入后6周最明显,模型组骨水泥植入后各时间点的H型血管表达高于对照组(P<0.05);②苏木精-伊红染色与血管造影检测显示,模型组骨水泥植入后各时间点的新生血管数、血管体积均大于对照组(P<0.05),模型组组内新生血管数、血管体积大小顺序为:骨水泥植入后8周>骨水泥植入后6周>骨水泥植入后4周;③免疫组化染色显示,模型组骨水泥植入后各时间点的成骨细胞特异性转录因子阳性表达高于对照组(P<0.05),模型组成骨细胞特异性转录因子阳性表达在骨水泥植入后6周最明显;④Micro-CT检测显示,模型组3个亚组的骨修复效果明显优于对照组对应的亚组,模型组骨水泥植入后6周亚组的骨修复效果优于骨水泥植入后4,8周亚组。结果表明:骨诱导膜中H型血管呈动态表达并在骨水泥植入后6周达高峰,在骨水泥植入后6周进行骨诱导膜植骨可获得良好的骨修复效果。

2型糖尿病的内脏型肥胖患者中骨量变化的机制研究及相关治疗

内脏型肥胖及2型糖尿病(type 2 diabetes mellitus,T2DM)的患病率随着我国生活和经济的发展、老龄化趋势的严峻在不断上升,对人们的健康及生活质量产生了严重的影响。两者均可对骨骼健康造成严重破坏,从而引发骨质疏松症(osteoporosis,OP)。除了人们熟知的遗传因素、生活方式、饮食习惯、性激素、年龄等可以影响骨骼健康以外,本文将从脂肪因子、肌因子、骨因子、肝因子和炎症细胞因子等几方面来阐述内脏型肥胖对T2DM患者骨量变化的影响,并对内脏型肥胖的诊断及T2DM肥胖患者的相关治疗进行综述。

大麻素Ⅱ型受体在股骨头坏死中的研究进展

大麻素Ⅱ型受体(CB2R)是内源性大麻素系统的重要组成部分,因其具有镇痛、抗炎、抗癫痫、抗纤维化及调节骨代谢等作用,已被广泛应用于临床及研究。近年来利用CB2R治疗多种疑难疾病已成为研究热点,尤其是对于骨科疾病的治疗。目前针对早中期股骨头坏死(ONFH)患者尚无疗效确切的方法,由于CB2具有抗炎、缓解疼痛、促进BMSCs成骨分化以及维持骨重塑稳态等作用,因此对其展开研究,希望CB2R能成为治疗ONFH的有效靶点。

Bone health in diabetes and prediabetes

Bone fragility has been recognized as a complication of diabetes,both type 1 diabetes (T1D) and type 2 diabetes (T2D),whereas the relationship between prediabetes and fracture risk is less clear.Fractures can deeply impact a diabetic patient’s quality of life.However,the mechanisms underlying bone fragility in diabetes are complex and have not been fully elucidated.Patients with T1D generally exhibit low bone mineral density (BMD),although the relatively small reduction in BMD does not entirely explain the increase in fracture risk.On the contrary,patients with T2D or prediabetes have normal or even higher BMD as compared with healthy subjects.These observations suggest that factors other than bone mass may influence fracture risk.Some of these factors have been identified,including disease duration,poor glycemic control,presence of diabetes complications,and certain antidiabetic drugs.Nevertheless,currently available tools for the prediction of risk inadequately capture diabetic patients at increased risk of fracture.Aim of this review is to provide a comprehensive overview of bone health and the mechanisms responsible for increased susceptibility to fracture across the spectrum of glycemic status,spanning from insulin resistance to overt forms of diabetes.The management of bone fragility in diabetic patient is also discussed.

WJD 5~h Anniversary Special Issues(1):Insulin Insulin and bone:Recent developments

While insulin-like growth factorⅠis a well-known anabolic agent in bone evidence is beginning to accumulate that its homologue,insulin,also has some anabolic properties for bone.There is specific evidence that insulin may work to stimulate osteoblast differentiation,which in turn would enhance production of osteocalcin,the osteoblast-produced peptide that can stimulate pancreaticβcell proliferation and skeletal muscle insulin sensitivity.It is uncertain whether insulin stimulates bone directly or indirectly by increasing muscle work and therefore skeletal loading.We raise the question of the sequence of events that occurs with insulin resistance,such as type 2 diabetes.Evidence to date suggests that these patients have lower serum concentrations of osteocalcin,perhaps reduced skeletal loading,and reduced bone strength as evidenced by microindentation studies.

Decreased bone mineral density in young male veterans on Pioglitazone

Background and objective: Epidemiological and observational studies indicate that thiazolidinedione (TZD) therapy with rosiglitazone and pioglitazone is associated with an increased risk of fractures. The effect of TZDs on bone mineral density (BMD) in men with type 2 diabetes is still in debate. The objective of the study was to investigate changes in BMD and bone turnover markers (BTM) associated with Pioglitazone use in men. Design and Methods: This prospective cross sectional comparative study evaluated the changes in BMD and BTM in male veterans aged less than 55 years, with diabetes with or without use of pioglitazone. In a 6 month follow up study, main outcome measures included BMD at AP spine, femur and wrist;and BTM (osteocalcin and CTx) at a referral center, with no interventions. Results: Pioglitazone use was associated with significant decrease in BMD (annualized %change of >3%) at femoral neck, total hip and 1/3rd radius;increase in CTx by 29% and decrease in osteocalin by 20% at 6months. Conclusions: Even in young men pioglitazone use was associated with bone loss. The changes in BTM suggest effect of pioglitazone on both osteoblast and osteoclast activity.

In Vivo Testing of Canine Prosthetic Femoral Components with HA-Ti Ladder-type Coating on Vacuum Plasma-sprayed Ti Substrate

Summary： The purpose of the present study was to observe the structure and functional change of the bone-coating-prosthesis interface in vivo and to evaluate the histocompatibility of self-made prosthetic femoral components in the body and the degree of their bonding with the surrounding bone tissues as well as their stability. Six mature beagle dogs underwent bilateral hip replacement with prosthetic femur components. Three groups were established in terms of different coating of prothesis （four joints in each group）： atmosphere （A） plasma-sprayed pure titanium （Ti） prosthetic joint with hydroxyapatite （HA） coating （HA＋Ti＋A group）; vacuum （V） plasma-sprayed pure Ti prosthetic joint with HA coating （HA＋Ti＋V group）; vacuum plasma-sprayed pure Ti prosthetic joint with Ti-HA stepped coating （Ti＋HAG＋Ti＋V group）. The hip joints were functionally evaluated, and subjected to X-ray examination, biomechanics inspection, and histological examination. As a result, X-ray imaging revealed all prosthetic joints were in a good location and no dislocation of joint was found. Shear strength of interface was significantly higher in Ti＋HAG＋Ti＋V group than in HA＋Ti＋V group （P〈0.05） and HA＋Ti＋A group （P〈0.05） at 28th week. Histological examination showed the amount of newborn bone in Ti＋HAG＋Ti＋V group was more than in HA＋Ti＋V group and HA＋Ti＋A group after 28 weeks. It was suggested that vacuum plasma-sprayed pure Ti prosthetic joint with TI-HA stepped coating could improve the bonding capacity of bone-prosthesis, enhance the stability of prosthesis, and increase the fixion of prosthetic femoral components because of better bone growth. This new type of biological material in prosthetic femoral components holds promises for application in clinical practice.