Palmieri Beniamino, Rottigni Valentina, Iannitti Tommaso
Department of General Surgery and Surgical Specialties, University of Modena and Reggio Emilia Medical School, Surgical Clinic, Modena, Italy.
Drug Des Devel Ther. 2013;7:7-12. doi: 10.2147/DDDT.S37330. Epub 2013 Jan 7.
Hyaluronic acid has been extensively used for treatment of knee osteoarthritis due to its anti-inflammatory properties and its ability to act as a synovial lubricant. Furthermore, it has found application in combination with other drugs in the dermatological field and in pre-clinical studies in animal models of osteoarthritis. Experimental evidence suggests that a combination of this macromolecule with other drugs may act as a slow-release depot. However, to date, to the best of our knowledge, no one has tested local intra-articular delivery of highly cross-linked hyaluronic acid combined with bisphosphonate or nonsteroidal anti-inflammatory drugs for management of knee osteoarthritis pain in the clinical setting. The aim of the present randomized double-blind study was to investigate, for the first time, the effect of a highly cross-linked hyaluronic acid, Variofill(®), alone or in combination with diclofenac sodium or sodium clodronate, for management of bilateral knee osteoarthritis-related pain.
Sixty-two patients with symptomatic bilateral medial tibiofemoral knee osteoarthritis (Kellgren-Lawrence grade II and III) and pain in both knees corresponding to a daily visual analog scale (VAS) score ≥ 30 in the month before the beginning of the study were included in this investigation. Patients were divided into three groups: group 1, treated with an injection of hyaluronic acid alone (66 mg) into each knee; group 2, treated with an injection of hyaluronic acid (49.5 mg) plus diclofenac sodium (5 mg) into each knee; group 3, treated with an injection of hyaluronic acid (49.5 mg) plus sodium clodronate (5 mg) into each knee. Patients also underwent blood tests for measurement of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) immediately before and at 6-month follow-up.
Hyaluronic acid alone and in combination with sodium clodronate or diclofenac sodium produced a significant improvement in mean VAS pain score at 3 and 6-month follow-up. At 6-month follow-up, therapy with hyaluronic acid plus sodium clodronate was the most beneficial in terms of percentage improvement in VAS pain score. A significant improvement in ESR and CRP was observed at 6-month follow-up in each treatment group. No significant difference was observed when the percentage change from baseline related to these parameters was compared among the groups. No dropout was observed in any group. No serious adverse events were observed.
Further studies are necessary to determine the effect of a therapy based on hyaluronic acid combined with diclofenac sodium or sodium clodronate in larger cohorts of patients affected by knee osteoarthritis and in longer-term follow-up.
透明质酸因其抗炎特性以及作为滑膜润滑剂的能力，已被广泛用于治疗膝关节骨关节炎。此外，它还在皮肤科领域与其他药物联合应用，并在骨关节炎动物模型的临床前研究中有所应用。实验证据表明，这种大分子与其他药物联合使用可能起到缓释储库的作用。然而，据我们所知，迄今为止，尚未有人在临床环境中测试高交联透明质酸与双膦酸盐或非甾体抗炎药联合进行关节内局部给药对膝关节骨关节炎疼痛的治疗效果。本随机双盲研究的目的是首次调查高交联透明质酸Variofill®单独使用或与双氯芬酸钠或氯屈膦酸钠联合使用对双侧膝关节骨关节炎相关疼痛的治疗效果。
本研究纳入了62例有症状的双侧胫股内侧膝关节骨关节炎（Kellgren-Lawrence分级II级和III级）患者，且在研究开始前一个月双膝疼痛对应的每日视觉模拟量表（VAS）评分≥30分。患者被分为三组：第1组，每膝注射单独的透明质酸（66mg）进行治疗；第2组，每膝注射透明质酸（49.5mg）加双氯芬酸钠（5mg）进行治疗；第3组，每膝注射透明质酸（49.5mg）加氯屈膦酸钠（5mg）进行治疗。患者在治疗前及随访6个月时还接受了血液检查以测量红细胞沉降率（ESR）和C反应蛋白（CRP）。
单独使用透明质酸以及与氯屈膦酸钠或双氯芬酸钠联合使用，在随访3个月和6个月时均使平均VAS疼痛评分有显著改善。在随访6个月时，就VAS疼痛评分的改善百分比而言，透明质酸加氯屈膦酸钠治疗最为有益。每个治疗组在随访6个月时ESR和CRP均有显著改善。比较各组这些参数相对于基线的变化百分比时，未观察到显著差异。任何组均未出现退出情况。未观察到严重不良事件。
有必要进行进一步研究，以确定基于透明质酸与双氯芬酸钠或氯屈膦酸钠联合治疗对更大规模膝关节骨关节炎患者群体及更长随访期的效果。
