University Hospitals Leuven, Department of Orthopaedic Surgery, Pellenberg, Belgium.
BioDrugs. 2012 Aug 1;26(4):257-68. doi: 10.2165/11632580-000000000-00000.
Although accepted as a conservative treatment option for knee osteoarthritis, the debate about the effectiveness of intra-articular treatment with hyaluronic acid (HA) is still ongoing because of contrasting outcomes in different clinical studies. Several well designed clinical studies showed a significant improvement in pain at follow-up compared with baseline but no significant improvement comparing the efficacy of HA with placebo (saline) or with other conservative treatment options. Notwithstanding the effectiveness of different types of intra-articular HA products, the question of whether one HA product is better than another is still unanswered. In this systematic review we compare the effects of intra-articularly administered HA with intra-articularly administered placebo in general and, more specifically, the effects of individual HA products with placebo. We also compare the efficacy of different HA products.
A systematic review of randomized controlled trials (RCTs) was conducted using databases including MEDLINE, Cochrane Database of Systematic Reviews, Cochrane Clinical Trial Register and EMBASE.
Seventy-four RCTs were included in this systematic review. HA improves pain by approximately 40-50% compared with baseline levels. However, when compared with saline the difference in efficacy is not that large. Due to a large 'placebo effect' of saline (approximately 30% pain reduction, persisting for at least 3 months) we determined a weighted mean difference between the efficacy of HA and saline of just 10.20 using the visual analog scale for pain. It is debatable whether this difference reaches the minimum clinically important difference. Comparing the different HA products, which vary in the molecular weight, concentration, and volume of HA, we were not able to conclude that one brand has a better efficacy than another due to the heterogeneity of the studies and outcomes.
In the future it will be important to determine the exact mechanism of action of placebo as this may give us an idea of how to treat osteoarthritis more efficiently. Due to the limitations of this review (follow-up of just 3 months and large heterogeneity of the included studies), it is also important to compare the different HA products to determine which product(s), or which molecular weight range, concentration, or volume of HA is the best option to treat osteoarthritis. Our recommendation is to start large (multicenter) RCTs to give us more evidence about the efficacy of the different HA products.
尽管关节内注射透明质酸（HA）被认为是治疗膝骨关节炎的保守治疗选择，但由于不同临床研究结果的差异，关于其疗效的争论仍在继续。几项精心设计的临床研究表明，与基线相比，随访时疼痛明显改善，但与安慰剂（盐水）或其他保守治疗相比，HA 的疗效并无显著改善。尽管不同类型的关节内 HA 产品都有疗效，但一种 HA 产品是否优于另一种产品的问题仍未得到解答。在这项系统评价中，我们比较了关节内注射 HA 与关节内注射安慰剂的效果，更具体地说，比较了不同 HA 产品与安慰剂的效果。我们还比较了不同 HA 产品的疗效。
使用包括 MEDLINE、Cochrane 系统评价数据库、Cochrane 临床试验注册中心和 EMBASE 在内的数据库进行了系统评价的随机对照试验（RCT）。
本系统评价共纳入 74 项 RCT。HA 可使疼痛较基线水平改善约 40-50%。然而，与生理盐水相比，疗效差异并不那么大。由于生理盐水的“安慰剂效应”较大（约 30%的疼痛减轻，至少持续 3 个月），我们使用视觉模拟量表评估疼痛，得出 HA 与生理盐水之间的疗效差异仅为 10.20。这种差异是否达到最小临床重要差异值得商榷。比较不同 HA 产品，这些产品在 HA 的分子量、浓度和体积上有所不同，由于研究和结果的异质性，我们无法得出哪个品牌的疗效更好。
未来，确定安慰剂的确切作用机制将很重要，因为这可能使我们了解如何更有效地治疗骨关节炎。由于本综述的局限性（仅随访 3 个月，纳入研究的异质性较大），比较不同的 HA 产品以确定哪种产品（或哪种分子量范围、浓度或 HA 体积）是治疗骨关节炎的最佳选择也很重要。我们的建议是开展大型（多中心）随机对照试验，以提供更多关于不同 HA 产品疗效的证据。
