Increased fasting serum glucose concentration is associated with adverse knee structural changes in adults with no knee symptoms and diabetes

Objective

There is evidence to suggest that elevated glucose concentration and clinical diabetes are associated with osteoarthritis (OA). However, the association may be confounded by knee symptoms, concomitant treatment for OA or diabetes. We performed a longitudinal cohort study to examine the relationship between serum glucose concentration and knee structure in adults with no knee symptoms or diabetes.

Methods

179 participants who had fasting serum glucose measurements at 1990–4, with no knee symptoms or diabetes (physician-diagnosed or fasting serum glucose ≥7 mmol/L), underwent knee MRI in 2003–4 and 2 years later. Body mass index was measured at 1990–4 and 2003–4. Cartilage volume and bone marrow lesions were determined from MRI at 2003–4 and 2006–7.

Results

Fasting serum glucose concentration was positively associated with the rate of tibial cartilage volume loss over 2 years in women (B = 44.2 mm³, 95% CI 4.6, 83.8) but not in men (B = 6.0 mm³, 95% CI −68.5, 80.6). Fasting serum glucose concentration was positively associated with incident bone marrow lesions in women (OR = 5.76, 95% CI 1.06, 31.21) but not in men (OR = 0.11, 95% CI 0.01, 1.79) with significant gender difference (p = 0.001 for interaction).

Conclusion

Increased fasting serum glucose concentration in a non-diabetic population was associated with adverse structural changes at the knee in women but not in men, suggesting that there may be susceptibility to knee structural change even below the arbitrary “diabetic range” of serum glucose levels. The sex differences warrant further investigation as this may be one mechanism underlying the sex difference in knee OA.     

酪氨酸激酶抑制化合物干预胶原诱导关节炎模型炎性细胞浸润及软骨破坏

背景：脾酪氨酸激酶是目前研究治疗类风湿关节炎的新靶点。 目的：研究小分子酪氨酸激酶抑制化合物HL131078对胶原诱导型关节炎小鼠膝关节炎性细胞浸润、软骨破坏的影响。 方法：将40只DBA/1系小鼠随机等分为空白组、模型组、阳性组和实验组。后3组小鼠尾部注射CⅡ型胶原溶液与弗氏完全佐剂(含结核杆菌)建立胶原诱导型关节炎小鼠模型。第1次免疫注射2周后,阳性组小鼠灌胃10 mg/kg R406,1次/d,连续28 d;实验组灌胃10 mg/kg小分子化合物HL131078,1次/d,连续28 d。 结果与结论：与模型组相比,实验组和阳性组小鼠平均关节炎指数分别于第29和26天时开始下降,且实验组小鼠膝关节的软骨破坏情况明显减轻,仍维持较好的完整性,膝关节腔内炎性细胞的浸润明显减轻,与阳性药物R406效果接近。说明小分子酪氨酸激酶抑制化合物HL131078可以有效缓解胶原诱导型关节炎小鼠膝关节腔内炎性细胞的浸润,减轻软骨破坏情况。 中国组织工程研究杂志出版内容重点：干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程     

Predicting knee cartilage loss using adaptive partitioning of cartilage thickness maps

This study investigates whether measures of knee cartilage thickness can predict future loss of knee cartilage. A slow and a rapid progressor group was determined using longitudinal data, and anatomically aligned cartilage thickness maps were extracted from MRI at baseline. A novel machine learning framework was then trained using these maps. Compared to measures of mean cartilage plate thickness, group separation was increased by focusing on local cartilage differences. This result is central for clinical trials where inclusion of rapid progressors may help reduce the period needed to study effects of new disease-modifying drugs for osteoarthritis.     

Vitamin D status is associated with inflammatory biomarkers and clinical symptoms in patients with knee osteoarthritis

Background and aimThe association between vitamin D status and osteoarthritis (OA) and bone remodeling has been shown previously. The present study was conducted to determine the association between vitamin D status and inflammatory biomarkers and clinical symptoms in patients with knee OA.MethodsThis case–control study was performed on 124 subjects with mild to moderate knee OA and 65 healthy controls. Demographic data was collected from all participants at baseline. We used Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC Index) for evaluating the severity of clinical symptoms in these patients. Serum levels of vitamin D as well as markers of inflammation including interleukin 1-β (IL-1β), interleukin 6 (IL-6), interleukin 10 (IL-10), tumor necrosis factor-alpha (TNF-α), high-sensitivity C-reactive protein (hs-CRP), and nuclear factor k-B (NF-κB) p65 were evaluated for each participant.ResultsThe results of the present study showed that patients with knee OA had lower levels of vitamin D and higher levels of IL-1β, TNF-α, hs-CRP, and NF-кB p65 compared with healthy controls (P < 0.0001). The levels of IL-1β, TNF-α, and NF-кB p65 in knee OA patients with vitamin D insufficiency were significantly higher compared with the knee OA patients with sufficient vitamin D (P < 0.05). Based on the linear regression analysis, serum vitamin D levels were inversely correlated with IL-1β, TNF-α, hs-CRP, and NF-кB p65 levels (P < 0.0001). Patients with sufficient vitamin D levels had lower total and physical function WOMAC scores compared with patients with vitamin D insufficiency (P = 0.011 and P = 0.010, respectively).ConclusionThe results suggest a strong link between vitamin D deficiency and increased inflammatory biomarkers as well as increased severity of clinical symptoms in knee OA patients.     

富血小板血浆与透明质酸钠修复兔膝骨关节炎

 背景：研究表明,透明质酸钠可抑制膝骨关节炎对软骨的破坏,加速软骨细胞的再生,达到稳定和修复关节软骨的目的。目的：观察富血小板血浆与透明质酸钠治疗兔膝骨关节炎的疗效。方法：将40只新西兰大白兔随机均分为5组,联合组、玻璃酸钠组、富血小板血浆组与模型组制作右侧膝骨关节炎模型,造模后分别向膝关节腔内注射透明质酸钠联合自体富血小板血浆、玻璃酸钠、自体富血小板血浆与生理盐水进行治疗,1次/周,连续5周;对照组不做任何处理,为正常对照。治疗完成1周后,ELISA法检测血液中白细胞介素1、白细胞介素6、肿瘤坏死因子α水平,光镜下观察关节软骨的变化。结果与结论：与对照组比较,其余4组白细胞介素1、白细胞介素6、肿瘤坏死因子α水平均升高(P < 0.01);联合组、透明质酸钠组、富血小板血浆组白细胞介素1、白细胞介素6、肿瘤坏死因子α水平均低于模型组(P < 0.01或P < 0.05),且以联合组下降最显著。模型组关节软骨破坏明显,联合组、透明质酸钠组、富血小板血浆组关节软骨破坏程度轻于模型组,且以联合组破坏程度最轻。表明透明质酸钠配合自体富血小板血浆关节内注射可降低膝骨关节炎的炎症反应,保护关节软骨,效果优于单一药物注射。中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程     

超声评价膝关节软骨退行性变与手术的对照研究

目的 探讨膝关节软骨不同时期退行性变(退变)的超声表现,并进一步分析超声的诊断价值.方法　对行关节镜手术的9个膝关节用超声术中经皮实时观察,对关节置换术的2个膝关节标本(置生理盐水中)进行离体观察.总结正常软骨及Ⅰ～Ⅳ期软骨退变的超声表现.以此为超声诊断标准,术前检查40例患者的41个膝关节,将超声诊断与关节镜结果及手术切除标本对照.结果 正常软骨表现为高-低-高"夹心饼断面"样回声带,Ⅰ期退变常无异常,Ⅱ期退变软骨表面毛糙,轻度变薄或局部隆起,Ⅲ期退变软骨局部变薄,Ⅳ期退变软骨层完全丧失.超声诊断膝关节软骨退变的敏感性、特异性、准确性分别为64.9%、92.0%、76.5%.结论 除Ⅰ期外,其余各期关节软骨退变在超声上均有一定特点.超声可作为诊断膝关节软骨退变的重要辅助手段.     

牛津单髁置换术应用于单间室部分软骨损伤的疗效研究

目的 评估膝关节单髁置换术治疗部分软骨磨损单间室骨性关节炎的疗效。方法 回顾性分析2008年4月至2019年4月在同济大学附属杨浦医院采用膝关节单髁置换术治疗的102例（115膝）内侧间室软骨部分磨损（PTCL）膝骨性关节炎的患者资料,经匹配年龄、性别、体重指数和随访时间的102例（115膝）软骨全层磨损（FTCL）的患者为对照组。采用OKS评分、AKS评分和疼痛视觉模拟评分（VAS评分）对术前、术后膝关节功能进行评估,X线进行影像学评估。结果 所有患者均获得了完整的随访,术后平均随访（60.0±19.6）个月（24～152个月）。FTCL组和PTCL组患者术后末次随访OKS评分、AKS-Knee评分、AKS-Function评分、VAS评分均较术前明显改善（P<0.05）。术后1年、2年和末次随访,PTCL与FTCL组间OKS评分、AKS-Knee评分、AKS-Function评分、VAS评分比较,差异无统计学意义（P>0.05）。共有6膝翻修,FTCL组3膝（2.6%）,PTCL组3膝（2.6%）。结论 不能简单地将PTCL视为膝关节单髁手术禁忌证,应该根据软骨损伤的程...     

The pathology of the end-stage osteoarthritic lesion of the knee: potential role in cartilage repair

The purpose was to explore whether there were any pathological characteristics of the end-stage osteoarthritic sclerotic lesion that have potential to participate in cartilage repair.Specimens harvested following total knee surgery were examined for gross pathology including staining with Safranin O. Multiple small sections of the lesion were placed in tissue culture for 6 weeks. Gross examination and photographic documentation was made at 3 and 6 weeks. At 6 weeks the specimens from culture were subject to histological examination. The pathology of the end-stage osteoarthritic lesion showed sclerotic bone, dead osteons, hypervascularity and scattered cartilaginous aggregates. Additional observations showed multiple pitting on the sclerotic surface, which histologically was related to three events; fragmentation of dead bone, ruptured blood vessels, and eroded aggregates. There were no pathological or biological changes in the specimens following the time in tissue culture.The in-depth pathological evaluation showed the end-stage osteoarthritic lesion to have certain features with potential to facilitate cartilage repair. The cartilaginous aggregates may be a participant in cartilage repair following surgery. The cartilaginous aggregates remained unchanged in the tissue culture absent the normal synovial joint chemical and physical environment and therefore further testing with a different experimental model would be necessary to establish these aggregates as a source of cartilage regeneration. The multiple small depressions in this lesion may have potential to be a “home” for therapeutics.     

膝关节软骨损伤的研究进展

本文通过系统回顾分析中老年患者膝关节软骨损伤的流行病学特点、病因及可能的发病机制,进而探讨软骨损伤后的危害性,归纳外科治疗膝关节软骨损伤术式的选择及存在的优缺点,以及软骨损伤最新研究进展情况。     

富血小板血浆修复膝关节骨关节炎

BACKGROUND: Platelet-rich plasma (PRP) containing high levels of platelet-derived growth factor for knee osteoarthritis has achieved good clinical results; however, the effects of RPR on the repair of damaged articular cartilage are still controversial. OBJECTIVE: To study the effects of RPR on the repair of damaged articular cartilage in a rabbit model of knee osteoarthritis. METHODS:The model of osteoarthritis in the rabbit right knee was established by Hulth’s method. Autologous PRP (0.5 mL) (PRP group), sodium hyaluronate (0.5 mL) (sodium hyaluronate group), and normal saline (model group) were injected into the right knee joint cavity, respectively. The morphology of articular surface and nitric oxide contents in knee joint fluid were observed and determined at 8 weeks after surgery. RESULTS AND CONCLUSION: The morphology of articular cartilage in the PRP group was better than that in the other three groups. Mankin scores of articular cartilage and nitric oxide contents of knee joint fluid in the PRP group were significantly decreased compared with the model and sodium hyaluronate groups that in (P < 0.05), while increased compared with the sham-operation group (P < 0.05). Our results suggest that repair effects of PRP on the damaged articular cartilage are superior to sodium hyaluronate treatment. 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程     

Effect of whole body vibration exercise on muscle strength and proprioception in females with knee osteoarthritis

The purpose of this study was to assess the effect of whole body vibration (WBV) exercise on muscle strength and proprioception in female patients with osteoarthritis in the knee (knee-OA). A single blinded, randomised, controlled trial was performed in an outpatient clinic on 52 female patients diagnosed with knee-OA (mean age 60.4 years ± 9.6). They were randomly assigned to one of 3 groups: 1. WBV-exercise on a stable platform (VibM; n = 17 (mean age, 61.5 ± 9.2)), WBV-exercise on a balance board (VibF; n = 18 (mean age, 58.7 ± 11.0)), or control group (Con; n = 18 (mean age, 61.1 ± 8.5)).The WBV groups trained twice a week for 8 weeks, with a progressively increasing intensity. The WBV groups performed unloaded static WBV exercise.The following were measured: knee muscle strength (extension/flexion) and proprioception (threshold for detection of passive movement (TDPM)). Self-reported disease status was measured using WOMAC.It was found that muscle strength increased significantly (p < 0.001) in VibM compared to Con. Isometric knee-extension significantly increased (p = 0.021) in VibM compared to Con. TDPM was significantly improved (p = 0.033) in VibF compared to Con, while there was a tendency (p = 0.051) for VibM to perform better compared to Con. There were no effects in the self-reported disease status measures.This study showed that the WBV-exercise regime on a stable platform (VibM) yielded increased muscle strength, while the WBV-exercise on a balance board (VibF) showed improved TDPM. The WBV-exercise is a time-saving and safe method for rehabilitation of women with knee-OA.     

关节制动对大鼠膝关节软骨缺损修复的影响

BACKGROUND: Joint immobilization is one of the methods used to treat joint pain and joint injury in the department of orthopedics. Compared with other treatment methods, immobilization can reduce the pain of the damaged synovial joints and avoid the contact stress and friction between the joints. However, immobilization can cause some serious complications such as joint contracture, osteoporosis and cartilage degeneration. OBJECTIVE:To observe the effects of joint immobilization on the repair of cartilage injury of knee joint in rats. METHODS: Osteochondral full-thickness defects (2.5 mm in diameter; 2 mm in depth) were created in the left femoral condyle fossa with a corneal trephine. 36 animals were randomly assigned into immobilization group and control group (n=18 per group). In the control group, animal models were established, without any treatment. In the immobilization group, after model establishment, rats were immobilized by a designed and modified simplified miniature Ilizarov fixator.  RESULTS AND CONCLUSION: (1) Repair rate of cartilage defect: No significant difference in repair rate was detected between immobilization group and control group. (2) Histological staining: Regeneration tissue was mainly fiber cells in both groups. At 8 weeks after surgery, Wakitani score and Mankin score were higher in the immobilization group than in the control group (P < 0.05). (3) Cartilage metabolic marker detection: Compared with the control group, at 8 weeks, C-telopeptide of type II collagen levels in the urine were significantly higher in the immobilization group than in the control group (P < 0.05). (4) Results indicated that persistent immobilization could result in cartilage degeneration, and it was detrimental for cartilage repair. 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程     

Comparison of stress on knee cartilage during kneeling and standing using finite element models

Kneeling is a common activity required for both occupational and cultural reasons and has been shown to be associated with an increased risk of knee disorders. While excessive contact pressure is considered to be a possible aggressor, it is not clear whether and to what extent stress on the cartilage during kneeling is different from that while standing. In this study, finite element models of the knee joint for both kneeling and standing positions were constructed. The results indicated differences in high-stress regions between kneeling and standing. And both the peak von-Mises stress and contact pressure on the cartilage were larger in kneeling. During kneeling, the contact pressure reached 4.25 MPa under a 300 N compressive load. It then increased to 4.66 MPa at 600 N and 5.15 MPa at 1000 N. Changing the Poisson's ratio of the cartilage, which represents changes in compressibility caused by different loading rates, was found to have an influence on the magnitude of stress.     

基于Hedgehog通路探讨补肾活血方对实验性膝骨性关节炎兔退变软骨的保护作用

目的:探究补肾活血方(BSHX)对实验性膝骨性关节炎兔退变软骨的保护作用及其可能的机制。方法:将新西兰兔分为对照(control)组、模型(model)组、BSHX(1. 86 g/kg)组、Hedgehog通路激活剂SAG(20 mg/kg)组和BSHX+SAG组,每组6只。测定兔膝关节宽度,处死兔后观察膝关节软骨大体情况,对软骨退变情况进行评定;HE染色和番红O染色观察膝关节软骨组织病理形态学变化;ELISA法检测软骨组织中肿瘤坏死因子α(TNF-α)和白细胞介素1β(IL-1β)水平;免疫组化法检测软骨组织中基质金属蛋白酶13(MMP-13)和II型胶原(Col-II)蛋白表达;Western blot法检测软骨组织中Shh、Ptch1、Smo和Gli1蛋白表达。结果:与control组相比,model组膝关节宽度增大,软骨退变评分、软骨分级和Mankin评分升高,软骨组织中TNF-α和IL-1β水平升高,MMP-13阳性表达率升高,Col-II阳性表达率降低,Shh、Ptch1、Smo和Gli1蛋白表达升高(P<0. 05)。与model组相比,BSHX组膝关节宽度减小,...     

选择性切断膝关节神经支对膝骨性关节炎模型兔关节软骨超微结构的影响

目的观察选择性切断膝关节神经支对兔膝骨性关节炎模型关节软骨超微结构的影响。方法采用Huhh法复制兔膝骨性关节炎模型,通过外科显微镜下选择性切断兔膝关节神经支,对关节软骨等结构进行形态学观察,运用TUNEL法检测软骨细胞的凋亡,并应用透射电镜观察关节软骨超微结构的变化。结果模型组兔膝关节软骨出现退变的表现,软骨细胞过度凋亡,其凋亡指数（31．25±6．83）明显高于正常组（3．16±0．65;P〈0．05）。模型组关节软骨超微结构明显受损,软骨细胞出现核固缩,线粒体肿胀,粗面内质网扩张、脱颗粒;软骨基质内胶原纤维断裂溶解,结构模糊。治疗组兔膝关节软骨退变有明显改善,细胞凋亡指数（15．43±3．72）明显低于模型组（P〈0．05）,关节软骨超微结构较模型组有明显改善。结论选择性切断膝关节神经支对膝骨性关节炎模型兔关节软骨细胞凋亡有抑制作用,并能改善关节软骨的超微结构。     

膝骨性关节炎中医手法与功能锻炼后的生物力学分析

背景：应用现代步态分析技术诊断、评估膝骨性关节炎患者足底压力分布的报道较少,尚未建立骨性关节炎患者特征性的足底压力数据库。目的：评估中医手法结合功能锻炼对膝关节骨性关节炎的治疗效果。方法：选取符合条件的左侧膝关节骨性关节炎患者40例,随机分为2组。对照组20例采用常规治疗法,治疗组20例运用中医手法结合功能锻炼治疗。分别对治疗前及治疗后3个月的症状体征进行日本矫形外科学会评分及步态测试,比较各组治疗前后疗效的差异。结果与结论：在减轻步行时疼痛方面,治疗组和对照组均有显著疗效,两组疗效差异无显著性意义。治疗组在上下楼梯、关节屈曲活动度方面的效果治疗前后差异显著,对照组则不明显;其中治疗后关节的屈曲活动治疗组显著优于对照组。在消肿方面两组无明显差异。治疗组日本矫形外科学会评分总评分显著高于治疗前(P < 0.05),对照组在疗前疗后无统计学差异。在步态指标上,两组足底各区受力时间百分比、单足支撑期参数和足底压力峰值都有改善,但治疗前后差异不明显。而治疗组步角的改善在治疗后效果显著,与对照组相比也具有显著意义。治疗组指标虽然具有诸多方面的改善,但并没有达到正常值。中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程     

膝关节软骨损伤的治疗进展

[摘要]膝关节具有多样且复杂的运动形式,是人体承重最大的关节,最易导致关节软骨损伤。由于其再生修复的能力很弱,故其损伤后很难自身修复,进而导致骨关节炎的发生。膝关节软骨损伤后目前主要有以下的手术治疗方式：①自体骨软骨移植技术（马赛克移植技术）;②同种异体骨软骨移植技术;③自体软骨细胞移植; ④合成或生物支架植入（组织工程技术）;⑤微骨折技术;⑥粉碎软骨修复技术;⑦生物制剂辅助治疗。通过选择性运用上述治疗可以在短期内改善临床症状,延迟或者避免行关节置换手术,本文将对其一一进行综述。     

膝骨关节炎时关节滑液中炎症相关物质的表达

背景：膝骨关节炎的主要改变是关节软骨面的退行性病变和继发性的骨质增生,病变的机制还不明确,但现已有实验证实膝骨关节炎的发病与炎症相关物质有密切的关系。 目的：分析炎症相关物质在膝骨关节炎发病机制中的作用。 方法：按美国风湿病学分会制定的诊断标准选择膝骨关节炎患者60例,来自因外伤截肢或半月板损伤性手术治疗的患者(排除膝关节内损伤)60例作为对照组,抽取两组患者膝关节液,采用酶联免疫吸附试验方法检测白细胞介素1β、白细胞介素6、白细胞介素8、白细胞介素10、肿瘤坏死因子α、碱性成纤维细胞生长因子、骨桥蛋白水平,采用一氧化氮检测试剂盒检测一氧化氮水平,按TBA荧光法测定过氧化脂质浓度。 结果与结论：膝骨关节炎患者表达高水平白细胞介素1β、白细胞介素6、白细胞介素8、白细胞介素10、肿瘤坏死因子α、碱性成纤维细胞生长因子、骨桥蛋白、一氧化氮和过氧化脂质水平均明显高于对照组;这些细胞因子及一氧化氮、过氧化脂质与膝骨关节炎的病变呈正相关。结果提示这些炎症相关物质确实参与了人膝骨关节炎的发病进程。 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程全文链接：     

Ultrastructural change of the subchondral bone increases the severity of cartilage damage in osteoporotic osteoarthritis of the knee in rabbits

Osteoporotic osteoarthritis is a phenotype of osteoarthritis (OA) manifested as fragile and osteoporotic subchondral bone. However, the ultrastructural features of subchondral bone in osteoporosis OA have not been determined. The study was aimed to investigate the ultrastructural dynamic changes of subchondral bone in osteoporotic OA model and how the ultrastructural damage in the subchondral bone caused by osteoporosis deteriorated the cartilage damage in OA. Eighteen rabbits were equally randomized to three groups, including the control, the OA and the osteoporotic OA groups. The structural changes of cartilage were evaluated by HE and safranin-O fast green staining, the Mankin’s grading system was used to assess the stage of OA progression. And microstructural or ultrastructural changes in subchondral bone were assessed by micro-computed tomography or by scanning electron microscopy. According to the changes of cartilage histopathology, the OA group was in the early pathological stage of OA while the osteoporotic OA group was in the middle stage of OA based on Mankin’s grading system. In addition, the damage of cartilage surface, reduction in the number of chondrocytes and the matrix staining were more increased in the osteoporotic OA group compared to the OA group. Compared to the OA group, the subchondral bone in the microstructure and ultrastructure in the osteoporotic OA group showed more microfracture changes in trabecular bone with more destructions of the tree-like mesh. Moreover, the collagen fibers were random rough with a fewer amount of bone lacunae in subchondral cortical plate in the osteoporotic OA group compared to the OA group. These findings indicated that the subchondral bone ultrastructure in the osteoporotic OA model was characterized by the destruction of the network structure and collagen fibers. The subchondral bone ultrastructural damage caused by osteoporosis may change mechanical properties of the upper cartilage and aggravate OA cartilage. Therefore, early diagnosis and treatment of osteoporosis is of great significance to prevent early OA from further developing osteoporotic OA.