简述骨关节炎特异性药物治疗的前景

目的探索骨关节炎（OA）特异性药物治疗的优势。方法近几年来临床开辟了用氨基葡萄糖、硫酸软骨素片口服治疗骨关节炎的新途径。结果特异性药物治疗（包括氨基葡萄糖、硫酸软骨素、双醋瑞因等）通过各种措施减轻疼痛和改善关节功能,延缓或阻断骨关节炎的关节结构改变,可成为治疗OA的病情改善药。结论众多基础及临床试验均表明,氨基葡萄糖、硫酸软骨素可缓解OA的关节症状,还可具备软骨保护和修复作用,且这两种药物的疗效维持时间也较长。     

壳聚糖衍生物治疗骨关节炎的研究进展

骨性关节炎(OA)是一种临床上常见的关节炎,致残率高,传统治疗较难延缓病情进展。壳聚糖的衍生物可以有效改善骨关节炎的症状,抑制疾病的进程。本文从临床和实验研究等方面概述了壳聚糖衍生物在治疗骨关节炎中的应用及其研究进展。     

改善病情抗风湿药和生物制剂治疗类风湿关节炎的研究进展

类风湿关节炎（RA）是一种以手、足的小关节受累为主,并可累及全身其他系统的慢性炎性疾病.目前治疗RA的药物主要包括：（1）非甾体抗炎药（NSAIDs）：主要作用是改善临床症状,但对阻止关节破坏的进展无明显影响;（2）糖皮质激素：能迅速减轻关节疼痛、肿胀,甚至可延缓关节的骨质破坏,但长期应用可引起许多不良反应;（3）改善病情抗风湿药（DMARDs）及生物制剂：可一定程度上缓解病情或阻止疾病的进展,是目前治疗RA的主要药物[1].虽然DMARDs及生物制剂能有效控制病情进展,但其在临床应用中的不良反应及相关风险值得关注,现将其临床治疗RA的研究进展作一综述.     

双醋瑞因治疗骨关节炎的临床研究进展

骨关节炎（OA）是导致老年人行动障碍的最常见原因之一,临床尚缺乏相关特异性药物治疗方案。OA治疗新药双醋瑞因可改善软骨代谢,有望延缓或逆转OA疾病进程,提高临床OA治疗水平。本文综述相关临床研究进展。     

中药防治骨性关节炎的作用机理研究进展

在祖国医学中，骨性关节炎属“痹谚”、“骨痹”等范畴，它是一种多发于中年后、累及手的小关节和负重关节为主的慢性、进行性、退行性变关节疾病。根据流行病学调查，55～64岁的人群中发病率高达40％。我国正在进入老龄化社会．因而老年OA的发病率也呈逐年上升的趋势，是老年人关节疼痛和致残的主要原因。目前西医在药物治疗重点集中于对症治疗，目的在于缓解疼痛、减轻炎症、延缓软骨退化。在OA治疗中结合中医药治疗，可调动机体的内在免疫能力，减轻炎症，延缓骨退化，改善功能，从而提高疗效，改善生存质量。中医辩证施治，整体观念较强，[第一段]     

醋氯芬酸联合骨疏康颗粒治疗老年性骨关节炎疗效观察

骨性关节炎(OA)是临床上最常见的老年性骨关节疾病[1],其病理基础是以软骨退行性改变和继发骨质增生为主要变化的慢性关节疾病.随着人口的老龄化,OA会更普遍.膝关节因负重较大,发生率较高.目前治疗的方法大多只能短期缓解症状,不能阻止或延缓疾病进展.采用醋氯芬酸片联合骨疏康颗粒治疗老年性OA,取得了较好的疗效,报告如下.     

透明质酸钠治疗骨性关节炎的疗效分析与思考

骨性关节炎（osteoarthritis,简称OA）是以局灶性关节软骨退行性变、软骨下骨质硬化及关节边缘骨赘形成为特征的一种慢性关节疾病;好发于老年人,尤其是中老年女性,其中膝关节骨性关节炎最常见。其病理特点为关节软骨变性、破坏、软骨下骨硬化,关节边缘和软骨下骨反应性增生、骨赘形成。OA治疗的目标是缓解症状、改善关节功能、改善病情和矫正畸形,因此OA治疗的首要任务是使患者达到症状的缓解。本科自2006～2008年以来,采用透明质酸钠注射治疗膝关节骨I生关节炎112例130个膝关节,取得了满意效果。现总结如下。     

维骨力治疗骨性关节炎临床观察

骨性关节炎(OA)亦称退行性关节炎,是中老年人最常见的以软骨破坏为主的慢性关节炎。由于病变关节的疼痛,功能障碍,最终丧失劳动力。OA的发病率随年龄增长而增加。 　　对OA的处理,多用非甾体类的消炎止痛药对症治疗,但仅能控制其症状,不能阻止软骨破坏的病程发展,且又常因药物的副作用关系,不得不停止用药,待病变发展至软骨严重破坏,则需外科手术治疗,诸如作关节清理术、关节融合术及关节置换术等等。 　　维骨力有效成分为硫酸氨基葡萄糖(250mg/片),是意大利罗达药厂生产的专门治疗OA的特异性药物,既能消炎止痛,减轻OA患者的临床症状,又能中止关节软骨的破坏,早期被破坏的软骨亦得以修复,从而恢复患者的关节功能,延缓了OA的退变过程,使需要外科手术治疗的病人大大减少。维骨力在国外使用已非常普遍,国内1996年才进入市场。为了观察维骨力对广州地区OA病者的治疗效果及其安全性,特作本临床观察研究。     

骨关节炎患者滑膜和关节软骨中金属蛋白酶组织抑制物—1的研究

目的：了解骨关节炎（OA）滑膜和关节软骨中金属蛋白酶酶抑制－1（TIMP－1）的分布及变化,探讨OA滑膜和关节软骨中TIMP－1变化与OA发病和治疗的关系。方法：应用免疫组织化学方法对26例OA及3例正常人的滑膜和关节软骨中TIMP－1的分布和阳性程度进行观察,结果：17例OA滑膜标本TIMP－1染色阳性,分布于滑膜衬里细胞、血管内皮细胞和质皮巨噬细胞等部位。阳性颗粒位于细胞浆中,程度多为弱阳性。16例OA关节软骨标本TIMP－1染色阳性。讨论：OA患者滑膜和关节软骨中TIMP－1分布减少和含量较低可能与OA的发病有一定关系。设想利用TIMP－1或其类似物可抑制关节软骨破坏和改善OA的病情。     

微小RNA在骨性关节炎病情发展过程中的研究进展

骨性关节炎(OA)是以关节软骨的变性或破坏、继发性骨质增生为特征,且受环境和多种基因影响的慢性非炎症性关节疾病。微小RNA(miRNA)是一种内源性非编码RNA小分子,可以调节机体软骨细胞的增殖、凋亡及分化,在OA发病机制、病情进展相关的基因表达中发挥重要作用。本文通过对OA组织中miRNA的异常表达和介导信号通路的调控途径进行综述,并讨论miRNA在调节OA中的重要性,进一步阐明miRNA调节OA发生和进展新机制,及其在软骨组织损伤修复中的作用和应用前景,为临床诊断、病情干预和治疗提供新的思路。     

复方夏天无片联合盐酸氨基葡萄糖治疗早中期膝关节骨性关节炎的初步探讨

目的 研究复方夏天无片在早中期膝关节骨性关节炎中的临床疗效和安全性。方法 本研究将2010年8月至2011年2月间120例患者分为2组。实验组用复方夏天无片联合盐酸氨基葡萄糖,对照组单纯用盐酸氨基葡萄糖,治疗半年后采用Lequensne指数作为疗效评分标准,观察治疗前后膝关节症状,比较2组之间膝关节症状及不良反应。结果 随访3个月,实验组和对照组的疗效相比较,差异无统计学意义(P>0.05);但随访半年后,2组相比疗效差异有统计学意义(P<0.05)。2组的不良反应相比无统计学意义(P>0.05)。结论 本研究表明复方夏天无片联合盐酸氨基葡萄糖在治疗早中期膝关节骨性关节炎症状改善优于单纯使用盐酸氨基葡萄糖。复方夏天无片不良反应小、安全性高,对于膝关节骨关节炎具有较好的疗效。     

Green-lipped mussel extract (Perna canaliculus) and glucosamine sulphate in patients with knee osteoarthritis: therapeutic efficacy and effects on gastrointestinal microbiota profiles

Objective

To investigate how changes in the gastrointestinal tract (GIT) microbiota profile may influence nutraceutical efficacy in osteoarthritis (OA) and allow the formulation of a hypothesis that explains in part the inconsistent and contentious findings from OA clinical studies with green-lipped mussel (GLM) and glucosamine.

Methods

A non-blinded randomised clinical trial was conducted with 38 subjects diagnosed with knee OA. Each participant received either 3,000 mg/day of a whole GLM extract or 3,000 mg/day of glucosamine sulphate (GS), p.o. for 12 weeks. Faecal microbial analyses were carried out after collecting stools at T ₀ and T ₁₂ weeks. Additional pharmacometric measures were obtained from changes in arthritic scores in the Western Ontario McMaster Universities Arthritis Index (WOMAC) and the Lequesne algofunctional indices and the Gastrointestinal Symptom Rating Scale (GSRS). An intention-to-treat analysis was employed and participant data collected at T ₀, T ₆ and T ₁₂ weeks.

Results

There were no statistically significant changes in bacterial growth patterns determined by the Wilcoxon test. In both groups there was a trend towards a decrease in Clostridium and Staphylococcus species and increase in Lactobacillus, Streptococcus and Eubacterium species. In the GLM group Bifidobacterium tended to increase and Enterococcus and yeast species to decrease. The GS-treated group demonstrated a trend towards a decrease in Bacteroides and an increase in yeasts and Coliforms species, most notably Escherichia coli. We further confirm significant improvement (p < 0.05) in all OA outcome measures from T ₀ to T ₁₂ weeks for both the GLM and GS groups. The GSRS scores indicated that GIT function significantly improved over the 12 weeks duration with GLM and GS supplementation.

Conclusion

Both GLM and GS reduced OA symptoms and non-significantly altered the gut microbiota profile from baseline. Changes in the microbiota profiles occurred in both treatment groups; the most notable being a reduction in the Clostridia sp. This study suggests that nutritional supplements such as GLM and GS may regulate some of the metabolic and immunological activities of the GIT microbiota. The decrease in Clostridia, a potent modulator of colonic Th17 and CD4+ regulatory T cells, was consistent with a decrease in inflammation; improved GSRS scores and OA symptoms for these OA participants. The GIT microbiota may be important factor in the first-pass metabolism of these nutraceuticals.     

Safety and efficacy of Curcuma longa extract in the treatment of painful knee osteoarthritis: a randomized placebo-controlled trial

Curcuma longa Linn. is widely used for the treatment of disorders associated with inflammation and was evaluated for its safety and efficacy in the treatment of painful knee osteoarthritis (OA). This was a randomized, single blind, placebo-controlled trial. Total of 120 patients (37 males and 83 females) with primary knee OA received either placebo (400 mg twice daily) or NR-INF-02 (500 mg twice daily) or glucosamine sulphate (GS) (750 mg twice daily) alone or combination of NR-INF-02 and GS for 42 days. The efficacy was assessed during treatment period, on day 21 and day 42. The decrease in severity of pain symptom and function of affected knee as primary efficacy outcome measure was assessed by Visual Analog Scale (VAS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scale, respectively. The clinical examination of affected joint was measured by an orthopaedic specialist and using a Clinician Global Impression Change (CGIC) scale. The analysis of post-treatment scores following administration of NR-INF-02 using VAS, WOMAC, and CGIC at each clinical visit showed significant decrease (p < 0.05) compared to placebo. NR-INF-02 treated group showed a significant (p < 0.01) decrease in use of rescue medication, along with clinical and subjective improvement compared to placebo. The tolerability and acceptability profile of NR-INF-02 was better during the trial period. The study demonstrates safety and efficacy of NR-INF-02 as a useful treatment option for patients with primary painful knee OA.     

'Natural remedies' in the treatment of osteoarthritis

Osteoarthritis (OA) is a common, chronic and painful condition. It is the most common of all rheumatic disorders and is destined to become one of the most prevalent and costly diseases in our society. The conventional therapeutic options employed in the management of OA are simple analgesics and NSAIDs, but these options frequently produce sub-optimal benefit and are associated with an adverse-safety profile. Unsurprisingly patients are looking to alternative and complementary medicine. The aim of this article was to review the available literature on the effectiveness and safety of 'natural remedies' for the treatment of OA. Computerised literature searches were carried out for systematic reviews and randomised controlled trials examining the role of 'natural remedies' in the treatment of OA. There have been few randomised controlled trials of 'natural remedies' that have satisfied the internationally agreed standards. There was, however, evidence of efficacy for glucosamine, chondroitin sulfate and possibly avocado/soybean unsaponifiables for the symptomatic relief of OA. To date, it is not established whether any of the 'natural remedies' are capable of chondroprotection. Even if 'natural remedies' are only modestly effective, they are widely available and well tolerated, suggesting that they may play a significant role in the management of OA in the elderly.     

Role of interleukin-1 inhibitors in osteoarthritis: an evidence-based review

Osteoarthritis (OA), the most common chronic musculoskeletal disease, represents a leading cause of disability in the elderly population worldwide. At present, there is no aetiological treatment for OA patients. Also, current therapeutic regimens for OA are only partially effective, and that is the main reason for most physicians' complaints. Therefore, one of the biggest challenges in the future will be to find the most appropriate therapy or therapies for OA. Currently, there are three basic modalities of treatment: nonpharmacological, pharmacological and surgical. Regarding pharmacological treatment, numerous molecular pathways involved in the pathophysiology of OA have been investigated as potential therapeutic targets. In preclinical and clinical trials, many compounds and agents have been tested, and some of them have already shown positive effects on the progression of knee and/or hip OA. One such possible pharmacological treatment of OA is anticytokine therapy. Interleukin-1 (IL-1), as a main inflammatory and catabolic cytokine in the pathophysiology of OA, represents one of the possible treatment targets. For specific inhibition of IL-1 production or activity, various treatment strategies could be used. These include the inhibition or modification of IL-1 action through the application of IL-1 receptor antagonist proteins, soluble IL-1 receptors, monoclonal antibodies against IL-1 or against IL-1 receptor I, blocking the formation of active IL-1β, blocking the IL-1 cellular signalling pathways, or using gene therapy. All the above mentioned treatment strategies for specific inhibition of IL-1 production or activity have been investigated in numerous preclinical and clinical studies. Some of these investigations led to the discovery of new potential drugs for the treatment of OA. However, the results of treatment with these drugs were not entirely satisfactory, and further research is required to achieve the desired goals of therapy.     

Glucosamine: a review of its use in the management of osteoarthritis

Glucosamine occurs naturally in all human tissues. It stimulates the synthesis of glycosaminoglycan, proteoglycan and hyaluronic acid, although the precise mechanism of action remains to be established. Formulated as glucosamine sulphate (Dona) and various others), glucosamine has been evaluated for its efficacy in relieving the symptoms of osteoarthritis and its disease-modifying potential.In two large randomised, double-blind, multicentre studies in patients with osteoarthritis, oral or intramuscular glucosamine for 4-6 weeks was associated with a greater decrease in symptom severity (as assessed by the Lequesne index) than placebo. In addition, there was a greater proportion of responders (defined as patients with a >or=3-point reduction in the Lequesne index, along with a positive overall assessment by the investigator) at the end of the treatment period with glucosamine than with placebo. In two large 4-week trials, oral glucosamine produced similar improvements to ibuprofen in the Lequesne index in one study and in articular pain scores in the other study. In a smaller 8-week comparative trial, oral glucosamine therapy achieved a significantly greater improvement in articular pain score than ibuprofen, and the investigators rated treatment efficacy as 'good' in a significantly greater proportion of glucosamine than ibuprofen recipients. In comparison with piroxicam, glucosamine significantly improved arthritic symptoms after 12 weeks of therapy and remained effective 8 weeks after treatment was discontinued. Beneficial effects of long-term oral glucosamine therapy in preventing joint space narrowing and improving symptoms were shown in two 3-year placebo-controlled trials in a total of 414 patients with osteoarthritis. Statistically significant differences favouring glucosamine were noted in the per-protocol and intention-to-treat analyses for the primary endpoints for both joint structural changes and symptom modification. Glucosamine has a tolerability profile similar to that of placebo and is better tolerated than ibuprofen or piroxicam. In particular, glucosamine recipients had a markedly lower incidence of gastrointestinal disturbances than those receiving ibuprofen. Other adverse events reported in both glucosamine and ibuprofen recipients were pruritus or skin reactions, flushing and fatigue. In general, a lower incidence of withdrawal from clinical trials was reported for glucosamine recipients than either ibuprofen or piroxicam recipients.CONCLUSION: In short-term clinical trials, glucosamine provided effective symptomatic relief for patients with osteoarthritis of the knee. In addition, glucosamine has shown promising results in modifying the progression of arthritis over a 3-year period. Glucosamine may therefore prove to be a useful treatment option for osteoarthritis.     

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.     

The influence of experimental therapy on the dynamics of endogenous glucosamine content in laboratory animals with nephropathy

The effects of glucosamine hydrochloride, glucosamine sulfate, N-acetylglucosamine, glucosamine pentaacetate, and combinations of glucosamine hydrochloride and N-acetylglucosamine with diclofenac sodium on the endogenous glucosamine (aminosugar) content in the blood and kidney of rats with experimental nephropathy have been studied. The development of inflammatory and destructive processes in kidneys is accompanied by an increase in the aminosugar content in the blood serum and the corresponding decrease in renal tissues. This fact can be used as a nonspecific diagnostic criterion for the level of kidney damage and for the efficacy of pharmacotherapy. Normalization of these indices in the case of successful therapy was observed, which was most pronounced upon the administration of glucosamine hydrochloride, N-acetylglucosamine, and their combinations with diclofenac sodium.