Hyaluronan molecular weight distribution is associated with the risk of knee osteoarthritis progression

Abstract

summary Objective We investigated the relationship between the molecular weight (MW) distribution of hyaluronan (HA) in synovial fluid (SF) and risk of knee osteoarthritis (OA) progression. Methods HA MW was analyzed for 65 baseline knee SFs. At 3-year follow-up, knees were scored for change in joint space narrowing (JSN), osteophyte (OST) progression, or occurrence of total knee arthroplasty (TKA). HA MW distribution was analyzed using agarose gel electrophoresis (AGE), and its relationship to OA progression was evaluated using logistic regression. The association between HA MW and self-reported baseline knee pain was analyzed using Pearson's correlation coefficients. Results Knee OA was categorized as non-progressing (OST−/JSN−, 26 knees, 40%), or progressing based on OST (OST+/JSN−, 24 knees, 37%), OST and JSN (OST+/JSN+, 7 knees, 11%) or total knee arthroplasty (TKA, 8 knees, 12%). The MW distribution of HA in baseline SFs was significantly associated with the odds of OA progression, particularly for index knees. After adjusting for age, gender, BMI, baseline X-ray grade and pain, each increase of one percentage point in %HA below 1 million significantly increased the odds of JSN (odds ratios (OR) = 1.45, 95% CI 1.02–2.07), TKA or JSN (OR = 1.24, 95%CI 1.01–1.53) and the odds of any progression (OR = 1.16, 95% CI 1.01–1.32). HA MW distribution significantly correlated with pain. Conclusion These data suggest that the odds of knee OA progression increases as HA MW distribution shifts lower and highlight the value of reporting MW distribution rather than just average MW values for HA.

Compression-Assisted Arthrocentesis of the Knee as a Quality Improvement Intervention

“…A number of prior studies have focused on the need to accurately place the needle intraarticularly and completely aspirate as much effusion as possible prior to injection, and all have generally demonstrated improved joint injection outcomes [5,18,27-29]. In 2003 Weitoft et al demonstrated that complete aspiration of the knee prior to corticosteroid injection prolonged the time-to-flare, and thus, reduced the need for repetitive corticosteroid injection [5].…”

“…Extraction of joint fluid for biomarker analysis even in the dry (non-effusive) knee is presently an important area in arthritis research and may also be integral to future joint preservation strategies and therapies [6,22,29,30]. Similar to Bhavsar et al, Yaqub et al, and Meehan et al, but using a different study design, we found that mechanical compression permitted fluid extraction in a much greater proportion of osteoarthritic knees that presented clinically as dry, non-effusive knees (Figure 3) [7-9].…”

“…Similar to Bhavsar et al, Yaqub et al, and Meehan et al, but using a different study design, we found that mechanical compression permitted fluid extraction in a much greater proportion of osteoarthritic knees that presented clinically as dry, non-effusive knees (Figure 3) [7-9]. The failure of full synovial fluid extraction during conventional aspiration of both the effusive and non-effusive knee may be due to a combination of mistargeting of the needle, the complex intraarticular synovial compartments that trap viscous fluid, ineffective manual compression, resistance to movement of fluid due to the semi-solid gel-like properties of synovial fluid, and its non-Newtonian elasticity and viscosity [8,29-31]. A constant circumferential pressure as provided by a mechanical compressive brace dilates the joint space to be targeted (Figures 1 and 2) and takes advantage of the classic rheological properties of synovial fluid to permit linear non-turbulent fluid flow to the needle access point, enhancing fluid aspiration (Figure 3).…”

OARSI Clinical Trials Recommendations: Soluble biomarker assessments in clinical trials in osteoarthritis

“…Many of the existing OA-related biomarker assays have grown directly out of an understanding of joint tissue metabolism[8, 9] and reflect catabolism or anabolism of joint tissues. To the extent that many of the products of joint tissue metabolism can stimulate an innate immune response (for instance fibronectin and hyaluronan fragments)[10-13], and be detected in biospecimens[3, 14, 15], there is a potential to have some OA-related biomarkers that are directly involved in the pathophysiology of an OA disease outcome. This is an enviable scenario that has rarely been achieved in other disease areas but represents the holy grail of biomarker development.…”

Use of hyaluronic acid preparations in the combination therapy of osteoarthritis

“…Она входит и в состав синови-альной жидкости, определяя ее вязкоэластические свойства [9]. По мере прогрессирования ОА отмечается снижение молекулярной массы ГНК синовиальной жидкости, что мо-жет отрицательно повлиять на биомеханику сустава, хотя и не коррелирует с наличием артралгий [10].…”