Efficacy of Intra-Articular Injection of Biofermentation-Derived High-Molecular Hyaluronic Acid in Knee Osteoarthritis: An Ultrasonographic Study

Abstract

Objective: The aim of this study is to evaluate the efficacy of intra-articular injection with HYAJOINT Plus, a biofermentation-derived, high-molecular hyaluronic acid (HA), on the progression of structural changes of cartilage in patients with knee osteoarthritis (OA) by using objectively promised ultrasonography (US) evaluation.

Design: In this prospective clinical trial, 56 OA patients completed the study. One single dose of injection of HYAJOINT Plus into the knee cavity was performed. The primary efficacy outcome measure for structural change of knee joint was evaluated by US using a semiquantitative grading system. Secondary efficacy outcome measures included Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total and subscale scores. All efficacy outcomes were measured at baseline and at first, third, and sixth month following treatment.

Results: There were significant US grade-improvement changes of cartilage between baseline and follow-up visits over medial femoral condyle and transverse overall evaluation at 3- and 6-month follow-ups, and over lateral femoral condyle, intercondylar notch, and medial longitudinal area at 6-month follow-up. The improved score change of WOMAC from baseline was significant at 1- and 3-month follow-ups in pain subscale, whereas score change from baseline was significant at 6-month follow-up in total score and all 3 subscale scores.

Conclusions: It was determined that significant improvement was found on cartilage by US after intra-articular injection with high-molecular weight, biological fermentation-derived HYAJOINT Plus. The semiquantitative grading system by US is a promising tool to identify the efficacy on cartilage band after interventions.

Keywords: articular cartilage; hyaluronic acid; knee; ultrasonography.

Figure 1.

Example of US change of cartilage band in follow-up. (A) At 0 months, the superficial margin of the cartilage band was not sharp and the clarity was blurred. The status was graded as 3. (B and C) In the first and third month, the clarity was clear but the superficial margin was still not sharp. The status was graded as 2. (D) In the sixth month, the superficial margin was sharp and the clarity was clear. The status was graded as 1. US = ultrasonography.

Figure 2.

WOMAC score during follow-up (N = 56). There was no significant change of WOMAC score at follow-up periods, including total score and subscale scores. WOMAC = Western Ontario and McMaster Universities Osteoarthritis Index.

Figure 3.

WOMAC score change from baseline (N = 56). Score change from baseline was significant at 1-month and 3-month follow-ups in pain subscale (–1.16, P = 0.002, and −1.50, P < 0.001 respectively). Score change from baseline was significant at 6-month follow-up in total score and pain/stiffness/function subscale scores (–4.36, P = 0.005; –1.59, P ≤ 0.001; –0.43, P = 0.013; –2.34, P = 0.044 respectively). WOMAC = Western Ontario and McMaster Universities Osteoarthritis Index. *P < 0.05. **P < 0.01. ***P < 0.001.