Evaluation of the inflammatory response to two intra‐articular hyaluronic acid formulations in normal equine joints

Abstract

Intra‐articular (IA) hyaluronic acid (HA) is commonly used to treat equine arthritis. Inflammatory response or “joint flare” is a recognized potential side effect. However, the incidence and severity of inflammation following IA HA injection in horses is not well documented. This study compared the effects of two IA HA formulations of different molecular weight (MW) and a saline control on clinical signs and synovial fluid markers of inflammation in normal equine joints. Eight adult horses each had three healthy fetlock joints randomly assigned to treatment with either 1.4 mega Dalton HA, 0.8 mega Dalton HA or saline control once weekly for three weeks. Clinical evaluation and synovial fluid analysis were performed by blinded assessors. Outcomes of interest were lameness score, joint effusion score and synovial fluid white cell count and differential, total protein, viscosity and serum amyloid A. Joints injected with HA developed significant mild‐to‐moderate inflammatory responses often associated with lameness and joint effusion compared with saline control joints. The higher MW HA formulation elicited a significantly greater inflammatory response than the lower MW HA after the first injection. In HA injected joints, viscosity remained poor for the entire study. Both IA HA formulations in this study induced an inflammatory response in healthy equine joints. This may have implications for the use of HA in equine joints. The findings in this study are limited to the two HA formulations used. Further investigation of different HA formulations and the use of HA in normal and arthritic equine joints is warranted.

Effects of intra‐articular injection of an acellular equine liquid amniotic allograft in healthy equine joints

“…Neither SLS nor force‐plate analysis indicated an increase in lameness in any study horse on any observation day postinjection. Studies investigating various joint injection formulations have had variable results ranging from no change to substantial lameness 16,17,23–27 . Due to the variation in reported incidence of lameness after IA injection, it should be recognized that, although none of the 8 study horses displayed an increase in lameness following ELAA injection, this may be a possible side effect.…”

“…Horses displaying an acute reactive synovitis (joint flare), generally characterized by clinical signs of lameness ranging from mild to severe within 24‐48 h of an IA injection with any preparation, is a recognized side effect by equine practitioners and researchers 16,1716,17 . It is noteworthy that the treatment is decellularized; some studies have reported that acellular preparations of mesenchymal stem cell (MSC) content are less likely to induce an adverse immunologic event than cell‐containing counterparts 18,19 .…”

“…Horses displaying an acute reactive synovitis (joint flare), generally characterized by clinical signs of lameness ranging from mild to severe within 24-48 h of an IA injection with any preparation, is a recognized side effect by equine practitioners and researchers. 16,1716,17 It is noteworthy that the treatment is decellularized; some studies have reported that acellular preparations of mesenchymal stem cell (MSC) content are less likely to induce an adverse immunologic event than cellcontaining counterparts. 18,19 In studies evaluating decellularized extracellular matrix scaffolds of various tissues including cartilage, skin, pericardium, and small intestinal mucosa from various species, it is reported that the presence of intact cells elicit a stronger proinflammatory response.…”

In vivo joint synovial fluid disposition of a novel sustained‐release formulation of diclofenac and hyaluronic acid in horses

“…Consequently, it cannot be concluded from the data presented here that intra‐articular administration of SYN321 induces lameness. It has been shown previously that joints injected with HA can develop significant mild‐to‐moderate inflammatory responses, often associated with lameness and joint effusion, compared with saline control joints (Johnston et al, 2020). This is consistent with our findings of swelling and potential lameness by subjective and objective lameness measures of the control limb.…”

Sustained Intra-Articular Release and Biocompatibility of Tacrolimus (FK506) Loaded Monospheres Composed of [PDLA-PEG1000]-b-[PLLA] Multi-Block Copolymers in Healthy Horse Joints

“…Similar responses have been reported after the injection of (sterile) lipopolysaccharide (LPS) and, also, to a lesser extent, as a transient reaction to the injection of saline. They are likely a more general response of some individuals to the arthrocentesis itself and the injection of (any) material into the joint [ 32 , 52 , 53 , 54 ]. For HA, this inflammatory response can be quite severe and was, in this case, still detectable after 6 weeks, as shown by the mild increase in synovial grading score.…”