Evaluation of the therapeutic effect of treatment with intra-articular hyaluronic acid in knees for Kashin-Beck disease: A meta-analysis

Objective: To assess the efficacy and safety of intra-articular hyaluronic acid (IAHA) injection in knee joints of patients with Kashin-Beck disease (KBD). Methods: We searched nine electronic databases as well as unpublished data from inception until November 30th 2013 using a combination of search terms for KBD and hyaluronic acid (HA). For dichotomous data, odds ratios (OR) and 95% confidence intervals (CI) were estimated. For continuous data, standard mean difference (SMD) was used for outcomes pooled on the difference scale using a "random-effects" or "fixed-effects" model. We also compared the mean and standard deviation of cytokine levels in post-treatment. Results: The seven eligible trials included 954 IAHA and 495 control patients. The methodological quality of included trials was low. The overall effectiveness of the IAHA group and control group were 93.7% and 62.9%, respectively. IAHA group resulted in very large treatment effects compared to pre-treatment values in 12 months, with SMD values ranging from 1.19-2.64 (all P<0.05). Compared to controls, SMDs in IAHA group ranged from 0.19-0.64 at 1 week to 1 month (all P>0.05) and 0.68-1.47 at 2 months to 12 months (all P<0.05). There was significant improved of HA, cluster of differentiation44 (CD44), keratan sulfate (KS), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and nitric oxide (NO) contents in serum compared with that in the post-treatment and healthy control in non-KBD area (all P<0.05). Conclusion: IAHA for the treatment of KBD was safe and efficacious at 12 months with low and transient adverse reactions. However, more high-quality randomized controlled trials (RCTs) are needed to confirm its therapeutic effect.