Serum hyaluronan levels are associated with disability for activity of daily living in patients with knee osteoarthritis regardless of the radiographic severity of the disease

Abstract

Purpose: Osteoarthritis (OA) is an age-related progressive joint disease, which is primarily characterized by cartilage degradation. OA of the knee is one of the major causes of morbidity and disability for activity of daily living (ADL) especially for elderly. Although plain radiographs are commonly used to detect OA in the clinical practice, it is hard to detect the essentials of the disease using plain radiographs. Biomarkers have characteristics which can be objectively measured and evaluated as indicators of normal biological processes, pathogenic processes, or pharmacologic responses to therapeutic interventions. Biomarkers have been developed to aid for diagnosing early-stage knee OA, predicting OA progression, and assessing therapeutic response. The availability of biomarkers, in addition to imaging technologies, e.g. magnetic resonance imaging (MRI), could dramatically improve diagnosis and treatment of OA. Hyaluronic acid and interleukin-6 in serum (sHA and sIL-6, respectively) are the potential candidates for biomarkers in knee OA. sHA was shown to be associated with pain of the patients with knee OA. sHA and sIL-6 were also shown to be predictors for the radiographic progression of knee OA. We also reported that sHA levels were associated with the severity of knee OA (BMC Musculoskelet Disord 2013) and sIL-6 levels were associated with pain (Osteoarthritis Cartilage 2013) and depressive state (Clin Rheum 2017) of the patients with knee OA. However, it has not been examined that whether sHA and sIL-6 were associated with disability for ADL in patients with knee OA. In this study, we examined the associations between sHA as well as sIL-6 levels and disability for ADL in patients with knee OA. Methods: One-hundred and fifteen postmenopausal women who attended our clinic with a main complaint of knee pain, showed radiographic knee OA (Kellgren-Lawrence [K/L] grade ≥2) and provided informed consent to participate in this study were enrolled. Patients with a history of hepatic diseases were excluded. The subjects were divided into two groups according to the radiographic severity of the disease: early stage group (K/L grade 2) and advanced stage group (K/L grades 3/4). Correlations between the subcategory of ADL of the Japanese Knee Osteoarthritis Measure (JKOM) or pain visual analog scale (VAS) and sHA or sIL-6 were calculated using Pearson's correlation coefficient. Results: When all the patients (early- and advanced-groups) were included, ADL was correlated with pain VAS of the patients (r = 0.58, P < 0.01). sHA was correlated with sIL-6 of all the patients (r = 0.26, P = 0.01). Disability of ADL was correlated with both sHA (r = 0.31, P < 0.01) and sIL-6 (r = 0.33, P < 0.01) of all the patients. Pain VAS was also correlated with both sHA (r = 0.26, P < 0.01) and sIL-6 (r = 0.25, P = 0.01) of all the patients. In the early stage knee OA group, ADL was also correlated with pain VAS of the patients (r = 0.53, P < 0.01). However, sHA was not correlated with sIL-6 of the early stage knee OA patients (r = 0.08, P = 0.56). Disability of ADL was correlated with both sHA (r = 0.50, P < 0.01) and sIL-6 (r = 0.30, P = 0.03) of the early stage knee OA patients. Pain VAS was correlated with sIL-6 (r = 0.31, P = 0.02) of the early stage knee OA patients, while it was not correlated with sHA (r = 0.27, P = 0.06). In the advanced stage knee OA group, ADL was also correlated with pain VAS of the patients (r = 0.64, P < 0.01). sHA was correlated with sIL-6 of the advanced knee OA patients (r = 0.31, P = 0.01). Disability of ADL was correlated with sHA of the advanced knee OA patients (r = 0.32, P = 0.01), while it was not correlated with sIL-6 (r = 0.20, P = 0.12). Pain VAS was also correlated with sHA (r = 0.31, P = 0.01), but not with sIL-6 (r = 0.19, P = 0.14), of the advanced knee OA patients. Conclusions: sHA is considered to be associated with synovitis in patients with knee OA. In our previous study, synovitis detected by the non-enhanced MRI was associated with both disability of ADL and subchondral bone pathologies detected by MRI of the patients with end stage knee OA (Osteoarthritis Cartilage 2015). Although further study is needed, the association between sHA, synovitis and subchondral bone pathologies detected by MRI is suggested in patients with knee OA.In conclusion, sHA was correlated with disability of ADL in patients with knee OA regardless of the radiographic severity of the disease.