香叶木素通过抑制破骨细胞分化治疗早期骨关节炎的可行性研究

目的验证香叶木素治疗早期骨关节炎(OA)的可行性。方法收集人体骨关节炎软骨下骨标本,通过ACLT法手术建立小鼠骨关节炎模型,通过组织染色检测破骨细胞数量,通过显微CT检测小鼠软骨下骨结构变化。通过CCK-8法检测香叶木素对BMMs细胞的细胞毒性;通过细胞因子诱导骨髓来源巨噬细胞(BMMs)分化成破骨细胞,建立破骨细胞分化模型,并将其分为单纯诱导组及不同浓度的香叶木素诱导组;通过TRAP染色检测香叶木素对破骨细胞分化的影响;PCR法检测破骨细胞分化标记基因(TRAP,CTSK)的表达情况。结果在人体标本中,患侧软骨下骨标本中的破骨细胞数量明显少于健侧(P<0.05)。在小鼠骨关节炎模型中,术后小鼠的胫骨平台软骨下骨TRAP染色阳性的破骨细胞数量明显多于假手术组(P<0.05),小鼠膝关节软骨下骨显微CT扫描结果显示,术后的软骨下骨呈现明显的骨质疏松表现;通过CCK-8法对BMMs的活性检测,在香叶木素浓度为20μmol/L以上的处理组细胞数量较空白对照组明显减少(P<0.05),其余浓度的处理组培养至5 d仍未见明显细胞毒性;TRAP染色结果显示,成破骨细胞分化诱导7～9 d后,香叶木素(5μmol/L)诱导组TRAP染色阳性的多核细胞数量较空白对照组明显减少(P<0.05);PCR检测显示,破骨细胞分化相关基因在香叶木素(2.5μmol/L)诱导组表达水平已经明显降低(P<0.05)。结论①小鼠模型中,早期OA的软骨下骨成骨质疏松样改变,人体晚期骨关节炎软骨下骨中的破骨细胞数量明显降低;②香叶木素可以抑制破骨细胞分化。因此,推测香叶木素有望通过抑制破骨细胞分化,降低早期骨关节炎软骨下骨丢失,进而对早期骨关节炎具有一定的治疗作用。     

不均匀沉降与透明质酸钠联合有限关节镜清理治疗膝骨关节炎的临床疗效分析

目的本课题主要研究膝关节骨性关节炎行膝关节镜有限清理术后行不均匀沉降术或患膝关节腔注射玻璃酸钠对比的临床疗效效果。方法随机数字表法将40例患者随机分为两组(对照组与实验组)。实验组为20例,行膝关节镜有限清理术后患膝行腓骨近端截骨,对照组20例,膝关节镜清理术后立即由股四头肌腱外侧向内下刺入关节囊注射透明质酸钠,2毫升/次,1次/周,共注射5次为1个疗程。结果术后1个月,实验组Lysholm评分及AKS评分,与对照组相比,差异无统计学意义,胫股间隙对比无统计学意义;术后6个月,实验组Lysholm评分及AKS评分优良率差异有统计学意义,胫股间隙两组有统计学意义;术后1年,实验组Lysholm评分及AKS评分优良率均显著优于对照组,差异有统计学意义,胫股间隙对比差异有统计学意义。结论膝关节骨性关节炎行膝关节镜有限清理术后行不均匀沉降术比术后联合注射玻璃酸钠远期效果更佳。     

辛伐他汀与Bio-Oss骨粉混合物对种植体周围缺损骨重建中破骨细胞的作用

目的探讨辛伐他汀与Bio-Oss骨粉复合物对兔胫骨种植体周围骨缺损内骨重建中破骨细胞的作用。方法选择24只健康日本大耳白兔,分别在双侧胫骨体部上1/3处各植入1枚种植体,并在种植体一侧建立骨缺损区。分为S0.5(0.5mg辛伐他汀+Bio-Oss骨粉),S1.0(1.0mg辛伐他汀+Bio-Oss骨粉),CB(单纯Bio-Oss骨粉),C0(空白对照)组,每组6只。分别于术后4、8周各处死动物3只,行组织学观察和破骨细胞特殊染色计数分析。结果组织学观察:各组8周均比4周新生骨面积大。4、8周时S1.0、S0.5较CB、C0新生骨面积大。抗酒石酸酸性磷酸酶(TRAP)特殊染色:各组4周破骨细胞计数差异具有统计学意义,S1.0组破骨细胞计数最多;C0组最少。结论辛伐他汀与Bio-Oss骨粉复合物可促进骨重建,且促进骨缺损中破骨细胞的生成。     

瘦素通过细胞因子在RANKL/RANK/OPG系统中的作用对破骨细胞形成的调节

RANKL/RANK/OPG系统是近年来发现的破骨细胞分化过程中的一个重要信号传导通路,是成骨细胞作用于破骨细胞的重要途径。细胞因子与RANKL/RANK/OPG系统关系密切,瘦素通过免疫系统影响细胞因子的分泌进而影响RANKL/RANK/OPG系统的平衡,抑制破骨细胞分化,起到抑制破骨细胞的生成、抑制骨吸收的作用。     

Investigational drugs for the treatment of osteoarthritis

Introduction: Osteoarthritis (OA) is a common joint disease with multiple pathophysiological processes, affecting the whole joint. Current therapeutic options such as NSAIDs can provide a palliative effect on symptoms but have limited effect on disease progression. New drugs targeting OA structures may retard disease progression at an earlier stage and delay the need for joint replacement.

Areas covered: Some drugs have entered into clinical trials and a few, such as strontium ranelate, do have improvements in both pain and structure changes. However, most of them have failed in clinical trials largely due to increased side effects or the failure to identify the right OA phenotype for the right drug in clinical design. This review describes various investigational drugs developed for the treatment of OA covering those at stages from preclinical experiments to early phase clinical trials. They include drugs for slowing cartilage degradation, regulating cartilage metabolism, targeting subchondral bone, controlling inflammation and relieving pain.

Expert opinion: Treatment options for OA remain limited. However, with the emergence of sensitive tools to detect early disease progression and identification of different OA phenotypes, disease-modifying anti-OA drugs with increased benefit and reduced risks will become available for OA treatment in the near future.     

Investigational drugs for the treatment of osteoarthritis,an update on recent developments

ABSTRACT

Introduction: Osteoarthritis (OA) is the leading cause of pain, loss of function, and disability among elderly, with the knee the most affected joint. It is a heterogeneous condition characterized by complex and multifactorial etiologies which contribute to the broad variation in symptoms presentation and treatment responses that OA patients present. This poses a challenge for the development of effective treatment on OA.

Areas covered: This review will discuss recent development of agents for the treatment of OA, updating our previous narrative review published in 2015. They include drugs for controlling local and systemic inflammation, regulating articular cartilage, targeting subchondral bone, and relieving pain.

Expert opinion: Although new OA drugs such as monoclonal antibodies have shown marked effects and favorable tolerance, current treatment options for OA remain limited. The authors believe there is no miracle drug that can be used for all OA patients’; treatment and disease stage is crucial for the effectiveness of drugs. Therefore, early diagnosis, phenotyping OA patients and precise therapy would expedite the development of investigational drugs targeting at symptoms and disease progression of OA.     

Effect of cadmium on osteoclast differentiation during bone injury in female mice

Cadmium (Cd) is a toxic heavy metal that represents an occupational hazard and environmental pollutant toxic heavy metal, which can cause osteoporosis following accumulation in the body. The purpose of this study was to investigate the effect of Cd on bone tissue osteoclast differentiation in vivo. Female BALB/c mice were randomly divided into three groups and given drinking water with various concentrations of Cd (0, 5, and 25 mg/L) for 16 weeks, after which the mice were sacrificed after collecting urine and blood. The level of Cd, calcium (Ca), phosphorus (P), trace elements, and some biochemical indicators were measured, and the bone was fixed in a 4% formaldehyde solution for histological observation. Bone marrow cells were isolated to determine the expression of osteoclast‐associated mRNA and proteins. Cd was increased in the blood, urine, and bone in response to Cd in drinking water in a dose‐dependent manner. The content of iron (Fe), manganese (Mn), and zinc (Zn) was significantly increased, whereas Ca and P were decreased in bone compared to the control group. Cd affected the histological structure of the bone, and induced the upregulation and downregulation of tartrate‐resistant acid phosphatase 5b (TRACP‐5b) and estradiol in the serum, respectively. Cd had no significant effect on the alkaline phosphatase activity in the serum. The expression of osteoclast marker proteins, including TRACP, cathepsin K, matrix metalloprotein 9, and carbonic anhydrases were all increased in the Cd‐treated bone marrow cells. Cd significantly increased the expression of receptor activator of nuclear factor kappa B ligand (RANKL), but had lower effect on the expression of osteoprotegerin (OPG) in both bone marrow cells and bone tissue. Thus, Cd exposure destroyed the bone microstructure, promoted the formation of osteoclasts in the bone tissue, and accelerated bone resorption, in which the OPG/RANKL pathway may play an important role.     

Genex可注射型人工骨在胫骨平台粉碎性骨折治疗中的应用

目的 探讨吉莱骨粉(Genex)可注射型人工骨在胫骨平台粉碎性骨折治疗中的临床效果.方法 将本院收治的胫骨平台粉碎性骨折60例,需要手术治疗且有明显的骨缺损需植骨修复重建的患者按照数字表法随机分为两组,对照组30例采用传统的自体骨植骨治疗;观察组30例给予自体骨/Genex可注射型人工骨填充修复(可注射型硫酸钙-磷酸钙制剂复合填充)治疗,并比较两组的临床效果.结果 观察组的总优良率为93.33％明显高于对照组的76.67％ (P＜0.05),对照组的骨折愈合时间为(18.72±4.58)周;观察组的骨折愈合时间为(14.63±5.98)周,两组比较差异具统计学意义(t=6.5864,P=0.0382).结论 Genex可注射型人工骨在胫骨平台粉碎性骨折能够缩短患者的治疗时间,使伤肢的功能得到更好的恢复.     

胫骨高位截骨术治疗膝内翻骨关节炎的研究进展

胫骨高位截骨术作为治疗内翻膝关节单间室骨关节炎的一种选择,目的是缓解疼痛、改善功能、延缓膝关节置换,并保留患者高水平的活动。截骨术获得成功的关键首先是严格地选择患者、全面的病史和体格检查、精确的术前计划,同时需要有熟练的手术技术作为保障,使用适当的固定技术和康复治疗方案有助于获得长期的良好结果。本文对胫骨高位截骨术的适应证、患者选择、术前计划、手术技术、固定方法、并发症和临床疗效等方面进行综述。     

同种异体骨在治疗胫骨平台骨折中的应用

目的：探讨同种异体骨在治疗胫骨平台骨折中植骨的临床效果。方法：对2003年1月～2007年12月随访资料完整的行同种异体骨植骨治疗胫骨平台骨折者98例进行回顾分析,全部病例术前均作X线拍片和CT扫描,术中采用解剖型钢板或锁定钢板（LCP）固定。结果：随访时间8个月～3年,平均28．5个月。按照Merchant评分标准优良率为92.3％。结论：应用同种异体骨植入治疗胫骨平台骨折疗效满意。     

内侧开放性胫骨高位截骨治疗内翻膝关节炎的临床疗效

目的探讨内侧开放性胫骨高位截骨(HTO)治疗内翻膝关节炎的临床疗效。方法34例内翻膝关节炎患者,均采用内侧开放性胫骨高位截骨治疗,并对其进行随访,观察分析患者的手术效果及术后并发症发生情况,同时比较患者术前及术后末次随访时的膝关节功能美国特种外科医院(HSS)评分。结果34例患者均获得随访,随访时间6~12个月,平均随访8.9个月。术后末次随访时,患者中优20例,良13例,可1例,差0例。患者术后末次随访时的膝关节功能HSS评分(89.6±3.9)分高于术前的(63.2±6.4)分,差异具有统计学意义(P<0.05)。术后所有患者的膝关节内侧疼痛症状均得到有效改善,未出现血管神经损伤、内固定断裂及感染等并发症;其中2例外侧铰链皮质骨折患者延迟下地,定期复查后均愈合良好;2例患者因合并皮肤疾病及糖尿病出现伤口愈合不良,经多次换药及伤口护理,于术后1个月左右伤口愈合并给予拆线,术后复查X线提示患者矫形效果满意、下肢力线良好。结论内翻膝关节炎患者采用内侧开放性胫骨高位截骨治疗效果显著,可有效改善患者膝关节疼痛症状,且术后并发症少。