Blaine Theodore, Moskowitz Roland, Udell James, Skyhar Michael, Levin Robert, Friedlander Jeffrey, Daley Michael, Altman Roy
Brown Alpert Medical School, Rhode Island Shoulder and Elbow Service, University Orthopedics, 2 Dudley Street, Providence, RI 02901, USA.
J Bone Joint Surg Am. 2008 May;90(5):970-9. doi: 10.2106/JBJS.F.01116.
Presently, there are no approved nonoperative therapies for the ongoing treatment of persistent shoulder pain. Preliminary data suggest that intra-articular sodium hyaluronate injections may be beneficial for the treatment of persistent shoulder pain resulting from various etiologies. The present study evaluated the efficacy and safety of sodium hyaluronate (Hyalgan; molecular weight, 500 to 730 kDa) for these patients.
Six hundred and sixty patients with persistent shoulder pain and limitation resulting from glenohumeral joint osteoarthritis, rotator cuff tear, and/or adhesive capsulitis who had had a failure of conventional therapy were enrolled in this double-blind, randomized, phosphate-buffered saline solution-controlled study, and 456 patients completed twenty-six weeks of follow-up. Patients were randomized to receive either five weekly intra-articular injections of sodium hyaluronate, three weekly intra-articular injections of sodium hyaluronate followed by two weekly intra-articular injections of saline solution, or five weekly intra-articular injections of saline solution. The main outcomes were improvement in terms of shoulder pain on movement at thirteen weeks after the initiation of treatment (as assessed with use of a 100-mm visual analog scale) and the treatment effect throughout twenty-six weeks.
For the overall intent-to-treat population, patients who were managed with sodium hyaluronate had greater pain relief than controls did; significant differences were noted at Week 7 (for the five-injection hyaluronate group), Week 17 (for the three and five-injection hyaluronate groups), and Week 26 (for the three-injection hyaluronate group). Analysis of the stratified populations clearly established that this effect was due to benefits experienced by the patients with osteoarthritis. The treatment effect through twenty-six weeks was significant in patients with osteoarthritis in the three-injection (p = 0.003) and five-injection (p = 0.002) groups, with no significant difference for either regimen in patients without osteoarthritis. The safety profile was very favorable, with no product-related serious adverse effects and no between-group differences for any reported adverse event.
Although the primary end point of this study (that is, improvement in terms of shoulder pain at thirteen weeks) was not achieved, the overall findings, including secondary end points, indicate that sodium hyaluronate (500 to 730 kDa) is effective and well tolerated for the treatment of osteoarthritis and persistent shoulder pain that is refractory to other standard nonoperative interventions.
目前，尚无经批准用于持续治疗持续性肩部疼痛的非手术疗法。初步数据表明，关节腔内注射透明质酸钠可能有助于治疗由各种病因引起的持续性肩部疼痛。本研究评估了透明质酸钠（施沛特；分子量500至730 kDa）对这些患者的疗效和安全性。
660例因肩肱关节骨关节炎、肩袖撕裂和/或粘连性关节囊炎导致持续性肩部疼痛和活动受限且常规治疗失败的患者纳入了这项双盲、随机、磷酸盐缓冲盐溶液对照研究，456例患者完成了26周的随访。患者被随机分为三组，分别接受每周一次共五次的关节腔内注射透明质酸钠、每周一次共三次的关节腔内注射透明质酸钠随后每周一次共两次的关节腔内注射盐溶液，或每周一次共五次的关节腔内注射盐溶液。主要结局指标为治疗开始后13周时肩部活动时疼痛的改善情况（使用100 mm视觉模拟量表评估）以及整个26周的治疗效果。
对于总体意向性治疗人群，接受透明质酸钠治疗的患者比对照组疼痛缓解更明显；在第7周（五针透明质酸钠组）、第17周（三针和五针透明质酸钠组）和第26周（三针透明质酸钠组）观察到显著差异。分层人群分析明确表明，这种效果是由于骨关节炎患者所获得的益处。在三针组（p = 0.003）和五针组（p = 0.002）的骨关节炎患者中，26周的治疗效果显著，在无骨关节炎的患者中，两种治疗方案均无显著差异。安全性非常良好，未出现与产品相关的严重不良反应，任何报告的不良事件在组间也无差异。
尽管本研究的主要终点（即治疗13周时肩部疼痛的改善情况）未达到，但包括次要终点在内的总体研究结果表明，透明质酸钠（500至730 kDa）对于治疗骨关节炎以及对其他标准非手术干预无效的持续性肩部疼痛是有效且耐受性良好的。
