Does hyaluronic acid injection prevent the progression of knee Osteoarthritis ?

Abstract

Purpose: Intra-articular injection of hyaluronic acid (HA) is performed as a conservative treatment for knee osteoarthritis (OA). HA has diverse pharmacological actions. In addition to increased lubrication of joint surfaces, its actions have been reported to include inhibition of the release of inflammatory cytokines and promotion of endogenous HA production. While many reports have suggested that injection of HA is clinically effective for knee OA, the actual improvement only seems to be modest. It has also been reported that injection of HA did not prevent the progression of knee OA, but rather promoted it. Thus, there are many unanswered questions about intra-articular HA therapy. The purpose of this study is imaging evaluation of patients who received long-term treatment with intra-articular HA for knee OA was conducted. Methods: This study was conducted in accordance with all applicable requirements of our university (including IRB approval). The subjects were 42 patients/64 knees (male: 17, female: 25) who received long-term intra-articular injection of HA for knee OA at the outpatient clinic of our university. Their mean age was 74.0 years, and the mean observation period was 4 years and 7 months. Knee radiographs were assessed by the Kellgren-Lawrence (K-L) classification, and the joint space was measured on frontal and lateral views obtained with the patient in the standing semiflexion position. In addition, the height, body weight, body mass index (BMI), frequency of HA injections, and total dose of HA were evaluated. Radiographic disease progression was defined as an annual increase of at least 1 grade in the K-L score or a decrease of > 0.2 mm in knee joint cartilage thickness annually. Results: Knee OA progression was seen in 24/64 knees (37.5%), while OA did not progress or the joint space increased in 40/64 knees (62.5%) (Fig 1). Approximately half of the knees with progression of knee OA were in K-L grade 3 or higher (45.8% * χ2 test), while all grade 1 or 2 patients who showed progression were obese with a BMI ≥27 kg/m2. On the other hand, in the group without knee OA progression, more than three-fourths of the knees were K-L grade 1 and 2 (77.5% * unpaired t-test). The interval between HA injections was shorter in patients without progression of knee OA, and the total dose was larger than in patients with progression (Table 1). Conclusions: Our previous study in OA animal models indicated that intra-articular injection of HA has both symptom-modifying and disease-modifying effects. In this study, the aim was to determine whether HA has these effects in human knees, as well as to determine the long-term treatment course with intra-articular injection of HA. In the OARSI guidelines, the strength of the recommendation for intra-articular injections of HA is 64, which is lower than for intra-articular injection of corticosteroids. In the previous research, HA treatment is well tolerated and produces statistically and clinically significant improvement of symptoms in patients with mild to moderate knee OA. In this study, 37.5% of the patients showed OA progression despite continuing HA injection. Converted to the annual OA progression ratio, 7.9% of the patients were shown to have knee disease progression annually. Comparing this ratio with the natural course of knee OA, 7% was reported by the Framingham study, with 3% reported by another study. It is difficult to compare this ratio because of the different populations and study designs. However, intra-articular injection of HA may not prevent OA progression. Approximately two-thirds of patients who received intra-articular injection of HA showed no progression or improvement of knee OA. Intra-articular injection of HA may not be effective in patients with K-L grade 3 or higher or BMI ≥27 kg/m2.View Large Image Figure ViewerDownload Hi-res image Download (PPT)