Efficacy of a Treatment for Gonarthrosis Based on the Sequential Intra-Articular Injection of Linear and Cross-Linked Hyaluronic Acids

Abstract

Background. This study evaluates the clinical and biochemical effects of sequential intra-articular (IA) injections of linear (LHA) and cross-linked hyaluronic acid (CLHA) in patients with Gonarthrosis (GA). Methods. Thirty-nine (39) patients (age 64.89 ± 8.83) received first the LHA injection (0.8-1.2 MDa, 32mg/2ml) and after 1 week the CLHA (1.0 MDa and 2.0 MDa, 75mg/3ml) one; this round was repeated after 6 months. Clinical assessments-i.e. ultrasonography, visual analogic scale (VAS) for pain, range of motion (ROM) and Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index-were performed at baseline and at specific time points up to 12 months. Relevant markers were determined in blood and synovial fluid (SF) at selected intervals. SF from patients with recurrent effusion was subjected to proteomic analysis. Results. This schedule improved joint pain and function, and promoted a reduction of inflammatory cytokines (IL-1β, IL-9 and IL-17) in plasma and SF; cartilage thickness increased at 12 months and the increase negatively correlated with the baseline levels of C-telopeptide of type II collagen (CTX-II). SF proteomic revealed that proteins associated with inflammation (Apolipoprotein A-1, α-1 antitrypsin and IgK) decreased, while the IL-1 inhibitor Transthyretin increased. Conclusions. This schedule represents an effective treatment whose benefits persist up to 12 months after baseline.

Treatment of Achilles Tendinopathy in Recreational Runners with Peritendinous Hyaluronic Acid Injections: A Viscoelastometric, Functional, and Biochemical Pilot Study

“…Our data are in agreement with the finding of Wu et al [ 24 ], who showed that high-molecular-weight HA attenuated tendinopathy by down regulating MMP-1 and -3 expression via CD44. Indeed, HA, beyond its physical and lubricating properties, is actively involved in regulating inflammatory responses mediated through the interactions with different substrates and receptors, among which CD44 represents a primary target [ 32 ] and has HA also effectively mitigated chondropathy and tendinopathy in clinical practice [ 33 ].…”

“…The HA utilized in this pilot study is a blend of different MW linear-HA similar in composition to that exhibiting a strong and prompt anti-inflammatory activity in a previous study on osteoarthrosis (OA) from a previous study of our group [ 33 ]. Although completely different from each other, a common trait linking the two pathologies is the need to reduce the inflammatory process and its consequences, an effect that both the blends of HA proved to afford.…”

“…Indeed, in strict analogy with previous data on OA, here, we found that the AT-inflammatory hallmarks IL-1β and MMP-3 were rapidly and strongly reduced immediately after the first injection. Differently from OA, where very high MW HA is required—and usually included in injectable preparations—to afford viscosupplementation within the joint [ 33 ], in AT is unneeded. Rather, it is important that HA has some chance to diffuse around and through the paratenon sheath to reach the surrounding inflammation sites, a feature which is inversely related to MW; secondarily, some positive mechanical effect may derive from the lubrication of injured tendon, a property which is retained by the heavier HA fraction around 1.000 KDa.…”

A Single-blind Randomised Trial of Intra-Articular Hyaluronic Acid, Hypertonic Saline, and Physiotherapy in Knee Osteoarthritis

“…The main difference between the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the KOOS is the inclusion of two additional domains, a five-item sport and recreation function domain, and a four-item QOL domain. Also, the pain domain and stiffness domain were changed to a seven-item symptom domain with more detailed questions (29). For each domain, scores were normalized on a "0-100" scale; zero for the worst result and 100 for the best result.…”

Randomized Trial of Hymovis® versus Synvisc® on Matrix Metalloproteinases in Knee Osteoarthritis

“…Previous in vitro studies have shown that HA exerts an inhibitory effect on several MMPs (12,13) and HA treatment has been recently shown to reduce MMP-2 levels in SF of patients affected by knee OA (14). However, the effects of HA preparations may differ depending on method of production, treatment schedule, molecular weight, half-life within the joint, rheological properties and pharmacodynamics (15). Hymovis ® , a CE-marked and FDA-approved viscosupplementation preparation for intra-articular injection in OA patients is a gel made of linear HA partially chemically modified with an alkyl chain.…”