Detection of synovitis in early knee osteoarthritis by MRI and serum biomarkers in Japanese general population

Abstract

To investigate synovitis' influence on early knee osteoarthritis (EKOA) by serum biomarkers and magnetic resonance imaging (MRI) findings in Japanese women. We enrolled 255 women aged 30-70 without radiographic abnormalities (Kellgren-Lawrence grade ≥ 2). Knee injury, OA outcome scores (KOOS), clinical examinations, and standing radiograph were used for classification criteria of EKOA. Participants were classified into normal knee group and EKOA group. All participants underwent MRIs of their right knee. The amount of effusion-synovitis volume was quantified. We compared serum matrix metalloproteinases-3 levels (MMP-3), high-sensitivity C-reactive protein, interleukin-6, and adiponectin between the groups. The relationship between synovitis and EOKA was investigated using multiple linear regression. Fifty-four participants (21%) were classified as EKOA. Serum MMP-3 concentration and effusion-synovitis volume were higher in patients with EKOA (p = 0.025 and p = 0.001, respectively). Effusion-synovitis volume negatively correlated with all KOOS subscales and positively correlated with serum MMP-3 concentration. Serum MMP-3 concentration was associated with effusion-synovitis volume β = 0.60, p < 0.001). There was mildly active but definitive synovitis in EKOA. This was an observational study so that no conclusions can be drawn regarding cause-effect for synovitis and symptoms. Future studies should conduct follow-up of participants with synovitis to assess the progression of knee OA. Knee osteoarthritis (OA) is a major joint disease that causes chronic pain, stiffness, and disability, especially in the aging population 1,2. It requires high-cost treatment, such as arthroplasty, decreases productivity, and creates absence from work; therefore, knee OA imposes a substantial and growing burden on society 3. Although early intervention or preventive approaches are needed, the timing and identifying methodology are not established, as conventional standard diagnosis and assessment are conducted mainly based on the Kellgren-Lawrence (KL) grading on radiographs 4 , thus making it difficult to detect early and minute changes. Recently, new criteria for detecting early knee OA were proposed by the first international EKOA workshop (EKOA) without radiographic abnormalities 5 ; they allow identification of people with moderate knee symptoms who have same risk factors as those with definitive knee OA. EKOA prevalence was 9.5% in men and 15.0% in women, and the highest prevalence was noted in middle-aged females 6. Nevertheless, EKOA's etiology has not been well studied. Several biomarkers are frequently used to assess disease activity precisely and quantitatively. There are reports regarding the availability of serum biomarkers to evaluate synovitis at an early phase and to predict OA progression. Interleukin-6 (IL-6) and keratan sulfate levels increase in the early phase of knee OA accompanied by knee pain 7,8. Magnetic resonance imaging (MRI) is a useful imaging biomarker for assessing early phase of knee OA. The Framingham ...

Common Biochemical and Magnetic Resonance Imaging Biomarkers of Early Knee Osteoarthritis and of Exercise/Training in Athletes: A Narrative Review

“…In addition to the above-mentioned work of inflammatory biomarkers, the levels of CRP, IL-6, and TNF-α were reported in other studies. Although these biomarkers were found unchanged in early OA individuals [55,63,65], changes were observed in athletes. For marathoners, one study reported unchanged levels of TNF-α [67], others showed increased levels not only of TNF-α but also of CRP and IL-6 [66][67][68]70].…”

“…MMP-1 levels did not change in either early OA [72] or marathoners [52], while ADAMTS4 increased in early OA [72]. MMP-3 and -9 levels increased in early OA [65,73] and in marathoners [52,70], and MMP-9 in cyclists [71]. In one study [52], 36 ultramarathoners participated in a race comprising 64 running days without any days of rest.…”

“…All these joint tissues have been found to be involved in the OA pathological process. Moreover, meniscal extrusion, early ligamentous degeneration, and effusion/synovitis, were shown to precede the onset of radiographic knee OA in addition to increasing the risk for the development of accelerated knee OA [65,106,107]. Indicative of the OA incidence are the infrapatellar fat pad and the bone curvature and shape [103,105,[108][109][110][111].…”

Reduced serum levels of anti-Mullerian hormone is a putative biomarker of early knee osteoarthritis in middle-aged females at menopausal transition

“…Another interesting result in this study was that serum AMH concentration in the female population having knee OA was associated with serum inflammation markers. Systemic and focal inflammation in the synovium play an important role even in the early phase of knee OA 39 . Inflammation is generally induced by microfragments of cartilages or danger-associated molecular pattern (DAMPS) in synovial fluids and releases several proteases and cytokines, which accelerate the degeneration of articular tissues [40][41][42] .…”

Metabolomics with severity of radiographic knee osteoarthritis and early phase synovitis in middle-aged women from the Iwaki Health Promotion Project: a cross-sectional study

“…Osteoarthritis (OA), an age-related low-grade inflammatory disease of the synovial joints [1][2][3], is one of the costliest and most disabling forms of arthritis, being highly prevalent and posing a major public health burden [4,5]. Although prevention and an early diagnosis are prerequisites for a favorable outcome, the detailed etiology, pathophysiology, and metabolism of OA remain unclear [6].…”