Effect of Intra-articular Hyaluronic Acid on Articular Cartilage Morphology and Composition in Mild to Moderate Knee Osteoarthritis

Introduction:

The medical management of knee osteoarthritis (OA performing intra-articular treatment with hyaluronic acid (HA) has recently become more widely accepted. The effectiveness of HA regarding the improvement of pain and function - also compared to placebo - has been shown by in vitro and clinical studies. However, most in vivo studies are based on patient well being, clinical scores and plain radiographs, which have however been shown neither to be an efficient way of monitoring OA progression nor to analyze the effect of HA on cartilage changes (1, 2).

Recently MRI has gained increasing importance as imaging modality for assessing cartilage changes in general but especially regarding degenerative changes in case of OA. Quantitative MRI (qMRI) studies were used to assess cartilage volume and thickness in patients with OA. In a longitudinal study Eckstein et al. (3) found an approximated annual loss of cartilage between 4 to 6%. Moreover, the effect of treatment on morphologic parameters can be evaluated objectively in-vivo which has been the major limitation of the validation process of drug therapy in OA so far. However, until now only three studies in the recent literature have used MRI to evaluate the effect of intraarticular HA on the articular cartilage of the knee joint. While Ozturk et al. (4) and Cubukçu et al. (5) evaluated the articular cartilage using a semiquantitative grading only Anandacoomarasamy et al. (6) have utilized validated techniques to assess cartilage defects and cartilage volume quantitatively for a follow-up period of six months. The so far published analyses have focused on entire cartilage plates, although it is likely that certain subregions of these plates are stronger affected by cartilage loss than others. Wirth et al. (7) demonstrated that cartilage loss can be measured in subregions (i.e., central, internal, external) of the femoro-tibial cartilage plates which allows for additional insight into the spatial distribution of tissue loss throughout the cartilage plates in OA (7, 8). Assuming that cartilage is not homogeneously lost throughout the plates, this approach may be used to identify subregions with a higher rate of and sensitivity to change, which may, in turn, permit a reduction of sample size and follow up periods in clinical studies to be able to demonstrate structure modifying effects of pharmaceutical compounds on disease progression (7-9).

The T2 relaxation time, another MRI based quantitative parameter, on the other hand is sensitive to tissue hydration and organizational properties of the collagen fiber matrix. It is thus considered to reflect compositional and architectural aspects as a surrogate parameter for cartilage matrix quality in cartilage degeneration (10). In mild OA of the knee, the mean cartilage T2 values, the standard deviation and the entropy were increased, indicating that in mild OA the T2 values are not only elevated but also are more heterogeneous as compared to healthy cartilage (11). It is generally assumed that changes of cartilage volume and thickness appear later and may also occur at a slower rate than T2 changes of cartilage in OA. Hence, the T2 relaxation properties of cartilage may be useful as non invasive parameters to analyse the impact of HA, especially with respect to the - in most cases - relatively short follow up periods available.

Therefore the aim of this study was to assess the impact of intraarticular hyaluronic acid on clinical outcome and on volumetric (including subregions) and T2 relaxation based changes of articular cartilage in patients with moderate knee OA.