Intra-articular injection in horses involves the administration of therapeutic agents directly into a joint space. This technique is used to manage joint diseases, such as osteoarthritis, by delivering medications like corticosteroids, hyaluronic acid, or biologic therapies directly to the affected area. The procedure aims to reduce inflammation, alleviate pain, and improve joint function. Intra-articular injections are commonly performed under sterile conditions to minimize the risk of infection. This page compiles peer-reviewed research studies and scholarly articles that explore the methods, efficacy, and safety of intra-articular injections in equine medicine, as well as their impact on joint health and performance in horses.
Vishwanath K, McClure SR, Bonassar LJ.Intra-articular injections of hyaluronic acid have been a mainstay of osteoarthritis treatment for decades. However, controversy surrounds the mechanism of action and efficacy of this therapy. As such, there has been recent interest in developing synthetic lubricants that lubricate cartilage. Recently, a synthetic 4 wt% polyacrylamide (pAAm) hydrogel was shown to effectively decrease lameness in horses. However, its mechanism of action and ability to lubricate cartilage is unknown. The goal of this study was to characterize the lubricating ability of this hydrogel and determine its efficacy ...
Klein CE, Bramlage LR, Stefanovski D, Ruggles AJ, Embertson RM, Hopper SA.To compare 3 different methods for treatment of medial femoral condyle (MFC) subchondral cystic lesions in Thoroughbred horses <24 months old based on the criterion of ability to race post-treatment. Methods: Retrospective cohort study. Methods: Thoroughbreds (n = 107, age < 24 months) diagnosed with MFC subchondral cystic lesions. Methods: Medical records between January 2004 and December 2017 were reviewed. Three treatment methods were used in these horses during that time frame: arthroscopic debridement, intralesional autologous mesenchymal stem cell (MSC) injection, and int...
Abd El-Rahman SS, Amer MS, Hassan MH, Fahmy HM, Shamaa AA.Lyophilized equine platelet derived growth factors (LGF) is a novel advanced platelet rich protein growth factor. It has been successfully applied in various fields of regenerative medicine to treat a variety of inflammatory and degenerative musculoskeletal conditions. Our study aimed to evaluate the efficacy of intraarticularly injected LGF for the remedy of articular cartilage injury, commonly characterized by progressive pain and loss of joint function in osteoarthritic rabbits. Full-thickness cylindrical cartilage defects were generated in both femoral condylar articular surfaces in twenty...
Schroeder EL, Gardner AK, Mudge MC.Cecal or colonic gas tympany of any cause may result in increased intraabdominal pressure, causing a significant decrease in venous return and cardiac output. Trocarization of the large colon or cecum in the event of large intestinal tympany may resolve gas distension and accompanying increased intraabdominal pressures sufficiently enough to promote resolution of a displaced large colon. Furthermore, trocarization of the medical colic may decrease morbidity and mortality associated with severe intraabdominal hypertension. Methods: This how-to description details the technique of transcutaneous...
Beck AA, Paz LB, Frank MI, Engelmann AM, Krause A, Côrte FD.Botulinum toxin type A (BoNT-A) is a promising alternative for patients suffering from chronic joint pain. The aim of this study was to investigate whether a single injection of BoNT-A would produce adverse effects on clinical parameters and synovial parameters as well as lameness. One randomly selected radiocarpal joint was treated with 50 U of BoNT-A in eight horses, and the contralateral joint received saline solution. All horses received injections at day 0 and were re-evaluated twice daily for 7 days for heart rate (HR), respiratory rate (RR), rectal temperature (RT), mucous membrane colo...
Westendorf J, Wobeser B, Epp T.Inter- and intra-rater variability negatively affects the reliability of various histopathology grading scales used as prognostic aids in human and veterinary medicine. The Kenney-Doig categorization (grading) scale, which is used to associate equine endometrial histologic lesions with prognostic estimation of a broodmare's reproductive potential, has not been evaluated for inter- or intra-rater variability, to our knowledge. To assess whether the Kenney-Doig system produces reliable results among observers, 8 pathologists, all with American College of Veterinary Pathologists certification, we...
Pimentel KL, Carmalt JL. There is conflicting evidence regarding communication between the two compartments of the equine temporomandibular joint (TMJ). Understanding the inter-relationship between TMJ compartments is critical for diagnostic and clinical management purposes. To determine the frequency of communication between the discotemporal joint (DTJ) and the discomandibular joint (DMJ) of the equine TMJ in horses free of overt disease. A randomized, blinded, controlled cadaveric study. Equine cadaver heads ( = 20), with no reported history of potential TMJ disease, were collected and stored frozen until use. ...
Martinez RE, Leatherwood JL, Arnold CE, Glass KG, Walter KW, Valigura HC, Norton SA, White-Springer SH.Dietary intervention may be a valuable strategy to optimize the intra-articular environment in young horses to prolong their performance career. To test the hypothesis that dietary supplementation of a Saccharomyces cerevisiae fermentation product would reduce markers of joint inflammation and increase markers of cartilage metabolism following a single inflammatory insult, Quarter Horse yearlings (mean ± SD; 9 ± 1.0 mo) were balanced by age, sex, body weight (BW), and farm of origin and randomly assigned to the following treatment groups: 1.25% BW/d (dry matter basis) custom-formulated conce...
de Clifford LT, Lowe JN, McKellar CD, McGowan C, David F.The purpose of this prospective double-blinded positive control study was to compare the efficacy of 2.5% polyacrylamide hydrogel (2.5% PAAG) in the management of middle carpal joint lameness in Thoroughbreds against treatments of triamcinolone acetonide (TA) or sodium hyaluronate (HA). A total of 31 flat-racing Thoroughbreds with lameness (grade 1-3/5) localized to the carpus by intra-articular analgesia were selected. Following a radiological assessment of the carpi confirming the absence of fragment/fracture, the horses were randomly assigned for intra-articular treatment with either 2 ml o...
Walters M, Skovgaard K, Andersen PH, Heegaard PMH, Jacobsen S.The role of resident cells such a synoviocytes and chondrocytes in intra-articular inflammation is well-characterized, however the in vivo gene expression patterns of cells (predominantly leukocytes) in the synovial fluid (SF) of an inflamed joint have never previously been investigated. The aim of this study was to investigate gene expression in SF leukocytes from the inflamed joint cavity after intra-articular lipopolysaccharide (LPS) injection in horses to improve our understanding of the temporal regulation of the intra-articular inflammatory response. Gene expression was investigated in S...
Pezzanite LM, Hendrickson DA, Dow S, Stoneback J, Chow L, Krause D, Goodrich L.Antibiotics have been injected intra-articularly by equine veterinarians for decades, either prophylactically when other drugs are administered for osteoarthritis or therapeutically to treat septic arthritis. This route of administration has also more recently gained attention in human orthopaedic clinical practice, particularly as an alternative to systemic antibiotic administration to treat infections following prosthetic arthroplasty. While the rationale for injecting antibiotics intra-articularly has been largely focused on achieving high local drug concentrations, there has been relativel...
Cokelaere SM, Groen WMGAC, Plomp SGM, de Grauw JC, van Midwoud PM, Weinans HH, van de Lest CHA, Tryfonidou MA, van Weeren PR, Korthagen NM.There is an increasing interest in controlled release systems for local therapy in the treatment of human and equine joint diseases, aiming for optimal intra-articular concentrations with no systemic side effects. In this study, the intra-articular tolerability and suitability for local and sustained release of tacrolimus (FK506) from monospheres composed of [PDLA-PEG1000]-b-PLLA multiblock copolymers were investigated. Unloaded and tacrolimus-loaded (18.4 mg tacrolimus/joint) monospheres were injected into the joints of six healthy horses, with saline and hyaluronic acid (HA) in the contralat...
Jiang Z, Haughan J, Moss KL, Stefanovski D, Ortved KF, Robinson MA.Gene therapy is currently prohibited in human and equine athletes and novel analytical methods are needed for its detection. Most in vivo products use non-integrating, recombinant viral vectors derived from adeno-associated virus (AAV) to deliver transgenes into cells, where they are transcribed and translated into functional proteins. Although the majority of wild-type AAV (WTAAV) DNA is removed from recombinant AAV (rAAV) vectors, some sequences are conserved. The goal of this study was to develop a quantitative polymerase chain reaction (QPCR) screening test targeting conserved AAV sequence...
Alsafy MAM, Elbakary RMA, Bassuoni NF.Joint diseases often represent the major part of equine clinician's caseloads. The current study aimed to document the normal anatomy of the donkey shoulder and elbow joints using computed tomography, cadaver sections, and radiography. Seven adult donkeys were used in this study. The current study proved there were no pouches of the donkey shoulder joint. Communication between the joint capsule and bicipital bursa was observed only in two limbs of four used in the present work. The joint was without pericapsular ligaments. The glenohumeral ligament was identified by the thickening of the artic...
Van Hecke L, Magri C, Duchateau L, Beerts C, Geburek F, Suls M, Da Dalt L, Patruno M, Saunders J, Broeckx SY, Depuydt E, Spaas JH.The use of mesenchymal stem cells (MSCs) for the treatment of equine joint disease is widely investigated because of their regenerative and immunomodulatory potential. Allogeneic MSCs provide a promising alternative to autologous MSCs, since the former are immediately available and enable a thorough donor screening. However, questions have been raised concerning the immunogenic potential of allogeneic MSCs, especially after repeated administration. Methods: Current retrospective study assessed the cellular and humoral immunogenicity of ten jumping and dressage horses with naturally occurring d...
Krause DM, Pezzanite LM, Griffenhagen GM, Hendrickson DA.Frequency of synovial sepsis in horses following intrasynovial injection has been reported, but not compared with respect to the environment in which the injection was performed. Objective: To describe occurrence of synovial sepsis following intrasynovial injections performed in ambulatory vs hospital settings. Methods: Retrospective cohort study. Methods: Records from the Colorado State University were evaluated (2014-2018) and horses receiving intrasynovial injections were identified. Patients presenting for septic synovial structures were excluded. Patient signalment, primary supervising se...
Gaesser AM, Underwood C, Linardi RL, Even KM, Reef VB, Shetye SS, Mauck RL, King WJ, Engiles JB, Ortved KF.Autologous protein solution (APS) has been used anecdotally for intralesional treatment of tendon and ligament injuries, however, its use in these injuries has never been studied . Our objective was to evaluate the effect of APS on tendon healing in an equine superficial digital flexor (SDF) tendonitis model. We hypothesized intralesional injection of APS would result in superior structural and biomechanical healing. SDF tendonitis was induced in both forelimbs of eight horses using collagenase injection. One forelimb was randomly assigned to receive an intralesional injection of APS, while th...
Zanotto GM, Frisbie DD.Osteoarthritis is a common clinical condition in the performance horse. In the last 10 years, there has been substantial growth in understanding of the disease and in the development of novel therapies. Objective: To document changes in clinical use of joint therapies over the past 10 years. We also aimed to understand how newly developed therapies have been added to routine clinical practice. Methods: Survey of veterinary professionals. Methods: We administered an electronic survey to members of the American Association of the Equine Practitioners. Questions from a similar survey in 2009 we...
Beaulieu A, Nykamp S, Phillips J, Arroyo LG, Koenig J, Zur Linden A.Intra-articular injections are routinely performed to alleviate pain and inflammation associated with osteoarthritis in horses. Intra-articular injections require accurate needle placement to optimize clinical outcomes and minimize complications. This study's objectives were to develop and validate a three-dimensional (3D) printed model of an equine cervical articular process joint to teach ultrasound-guided injections. Five identical models of an equine cervical articular process joint were 3D printed and embedded in 10% ballistic gelatin. Experts' and novices' ability to successfully insert ...
Mocchi M, Grolli S, Dotti S, Di Silvestre D, Villa R, Berni P, Conti V, Passignani G, Brambilla F, Bue MD, Catenacci L, Sorrenti M, Segale L, Bari E....In the last decades, it has been demonstrated that the regenerative therapeutic efficacy of mesenchymal stromal cells is primarily due to the secretion of soluble factors and extracellular vesicles, collectively known as secretome. In this context, our work described the preparation and characterization of a freeze-dried secretome (Lyosecretome) from adipose tissue-derived mesenchymal stromal cells for the therapy of equine musculoskeletal disorder. An intraarticular injectable pharmaceutical powder has been formulated, and the technological process has been validated in an authorized facility...
Hendesi H, Stewart S, Gibison ML, Guehring H, Richardson DW, Dodge GR.Posttraumatic osteoarthritis is a disabling condition impacting the mostly young and active population. In the present study, we investigated the impact of intra-articular sprifermin, a recombinant truncated fibroblast growth factor 18, on the outcome of microfracture treatment, a widely used surgical technique to enhance cartilage healing at the site of injury. For this study, we created a cartilage defect and performed microfracture treatment in fetlock joints of 18 horses, treated joints with one of three doses of sprifermin (10, 30, or 100 μg) or with saline, hyaluronan, and evaluated a...
Cruz-Sanabria JA, Gaschen L, Bragulla HH, Mitchell M, Leise BS.To develop an ultrasound-guided cervical perineural injection technique for horses and to evaluate and compare the distribution of contrast agent among perineural, intra-articular and periarticular injections. Methods: Prospective, experimental cadaveric study. Methods: A total of 14 equine cadaveric necks. Methods: Bilateral ultrasound-guided perineural injection technique for the caudal cervical spinal nerve roots (CSNRs 5-7) was developed. Paramagnetic or iodinated contrast was injected and the distribution of contrast was evaluated using magnetic resonance (MR) or computed tomography (CT) ...
Lapjit C, Charoenchanikran P, Petchkaew P, Sukpipattanamongkol S, Yodsheewan R, Theerapan W, Chanda M.The fetlock joint is a high mobility structure that accommodates enormous loading during locomotion. An injury of the superficial constituent such as subtendinous bursitis may occur due to repeated trauma. An 8-year old school riding horse was presented with dorsomedial distension in the left hindlimb fetlock region. The lesion was noted following routine exercise. The horse demonstrated no lameness and a negative response to the fetlock flexion test. Radiographic findings revealed a smooth surface cortical thickening on the medial aspect of the distal third metatarsal bone. Furthermore, the u...
Van de Water E, Oosterlinck M, Korthagen NM, Duchateau L, Dumoulin M, van Weeren PR, Olijve J, van Doorn DA, Pille F.An established lipopolysaccharide (LPS) model previously described in Warmbloods, was inconsistent in Standardbred horses, where lameness was not detected despite the presence of synovitis. The present study aimed to determine the dose of LPS from E. coli O55:B5 required to induce mild to moderate lameness following middle carpal joint injection in Standardbred horses and to quantitate the induced lameness over time, with and without anti-inflammatory pre-treatment. In a baseline trial, eight healthy, clinically sound Standardbred horses were used in a rule-based dose-escalation design trial, ...
Frydendal C, Nielsen KB, Berg LC, van Galen G, Adler DMT, Andreassen SM, Jacobsen S.To investigate neutrophil gelatinase-associated lipocalin (NGAL) concentrations in serum and synovial fluid (SF) from horses with joint inflammation. Methods: Experimental studies and retrospective clinical study. Methods: Serum and SF samples were available from healthy horses (n = 19), clinical cases, and horses with experimental joint inflammation. Clinical cases included horses with (n = 10) or without (n = 10) septic arthritis. Experimental intra-articular inflammation was induced by lipopolysaccharide (LPS; n = 7, severe inflammation), lidocaine (n = 6, moderate inflammation), or mepivac...
Kearney CM, Korthagen NM, Plomp SGM, Labberté MC, de Grauw JC, van Weeren PR, Brama PAJ.Intra-articular triamcinolone acetonide is a widely used treatment for joint inflammation despite limited scientific evidence of its efficacy. Objective: To investigate if intra-articular triamcinolone acetonide has sustained anti-inflammatory effects using an equine model of repeated joint inflammation. Methods: Randomised controlled experimental study. Methods: For three consecutive cycles 2 weeks apart, inflammation was induced in both middle carpal joints of eight horses by injecting 0.25 ng lipopolysaccharide (LPS). After the first LPS injection only, treatment with 12 mg triamcinolone...
Di Salvo A, Chiaradia E, Nannarone S, Della Rocca G.Joint pain is a major cause of lameness in animals such as horses and dogs, and it may affect their athletic performance and quality of life. The intra-articular administration of analgesic/antinflammatory drugs is a common practice in veterinary medicine, for both lameness diagnosis and joint pain management. It is used either perioperatively, such as in animals undergoing arthroscopy/arthrotomy, and in osteoarthritic animals. However, evidence regarding efficacy and safety of each drug is limited, and controversies persist in these areas. In particular, it is often uncertain whether a define...
Rowland AL, Miller D, Berglund A, Schnabel LV, Levine GJ, Antczak DF, Watts AE.Allogeneic mesenchymal stromal cells (MSCs) have been used clinically for decades, without cross-matching, on the assumption that they are immune-privileged. In the equine model, we demonstrate innate and adaptive immune responses after repeated intra-articular injection with major histocompatibility complex (MHC) mismatched allogeneic MSCs, but not MHC matched allogeneic or autologous MSCs. We document increased peri-articular edema and synovial effusion, increased synovial cytokine and chemokine concentrations, and development of donor-specific antibodies in mismatched recipients compared wi...
Haseler CJ, Jarvis GE, McGovern KF.Intrasynovial corticosteroid injections are commonly used in the treatment of equine orthopaedic disease, but corticosteroid administration is widely considered a risk factor for the development of laminitis. Despite a list of putative mechanisms and a number of case reports of steroid-induced laminitis, no case-control or cohort studies investigating the association between use of intrasynovial corticosteroids and acute laminitis have been published. Objective: To quantify the risk of laminitis posed by intrasynovial triamcinolone acetonide (TA) administration in a mixed population of horses....
da Silva Xavier AA, da Rosa PP, de Brum Mackmill L, Roll VFB.For several years, hyaluronic acid (HyA) and, more recently, polyacrylamide hydrogel (PHyd) have been used to reduce lameness and pain caused by osteoarthritis. However, there is still a lack of scientific evidence of the efficacy of these substances to allow veterinary experts to make decisions about their use in horses. The objective of this study was to evaluate, through a systematic review and network meta-analysis (NMA), the efficacy of HyA, associated or not with other drugs, and PHyd in relieving lameness in horses with osteoarthritis. The searches for primary studies were conducted on ...
Ma TW, Li Y, Wang GY, Li XR, Jiang RL, Song XP, Zhang ZH, Bai H, Li X, Gao L.The study aimed to clarify the changes in the concentration of inflammatory mediators, proteases, and cartilage degradation biomarkers in the synovial fluid of joints in an equine osteoarthritis model. Methods: Osteoarthritis was induced in eight Mongolian horses by a sterile intra-articular injection of amphotericin B, which was injected into the left carpal joint in a dose of 2 mL (25 mg/mL). The control group comprised five horses which were injected with an equal dose of sterile physiological saline into the left carpal joint. Synovial fluid was obtained at baseline and every week after in...
Whithair KJ, Bowersock TL, Blevins WE, Fessler JF, White MR, Van Sickle DC.Septic arthritis was induced in one antebrachiocarpal joint of seven horses by the intra-articular injection of 1 mL Staphylococcus aureus suspension containing a mean of 10(5) colony-forming units. Twenty-four hours after inoculation, four horses were treated by regional perfusion with 1 g of gentamicin sulfate, and three horses received 2.2 mg/kg gentamicin sulfate intravenously (IV) every 6 hours. Synovial fluid was collected for culture and cytology at regular intervals, and the synovial membranes were collected for culture and histologic examination at euthanasia 24 hours after the first ...
Caron JP.Lameness remains an important source of reduced performance in many types of horses. Pain referable to joints is among the most common causes, and intra-articular injections remain a common and important means of addressing lameness referable to joints in horses.
Hawkins DL, MacKay RJ, Gum GG, Colahan PT, Meyer JC.In each of 4 horses, sterile synovitis was induced by intra-articular injection of 3 micrograms of Escherichia coli endotoxin (lipopolysaccharide, LPS) into one antebrachiocarpal joint; an equal volume (2 ml) of phosphate-buffered saline solution (PBSS) was injected into the opposite, control carpus. Blood and 1.5 ml of synovial fluid were obtained at postinjection hours (PIH) 0, 2, 4, 8, 12, 18, 42, 66, and 144. Synovial fluid sample collection was accomplished by use of an indwelling, intra-articular catheter through PIH 12, and by arthrocentesis subsequently. Joint fluid samples were analyz...
Kay AT, Bolt DM, Ishihara A, Rajala-Schultz PJ, Bertone AL.To assess analgesia, inflammation, potency, and duration of action associated with intra-articular injection of triamcinolone acetonide (TA), mepivacaine hydrochloride, or both in metacarpophalangeal (MCP) joints of horses with experimentally induced acute synovitis. Methods: 18 horses. Methods: Both forelimbs of each horse were injected with lipopolysaccharide (LPS) 3 times. After the first LPS injection, 1 forelimb of each horse was treated with intra-articular injection of mepivacaine (80 mg; n=6), TA (9 mg; 6), or mepivacaine with TA (same doses of each; 6) 12 hours after the initial LPS i...
Soma LR, Uboh CE, You Y, Guan F, Boston RC.To compare pharmacokinetics of triamcinolone acetonide (TA) following i.v., intra-articular (i.a.), and i.m. administration and determine its effect on plasma concentrations of hydrocortisone and cortisone. Methods: 6 Thoroughbreds. Methods: TA (0.04 mg/kg) was administered i.v., i.m., or i.a., and plasma TA, hydrocortisone, and cortisone concentrations were determined. Results: I.v. administration of TA was fitted to a 2-compartment model. Median distribution half-life was 0.50 hours (range, 0.24 to 0.67 hours); elimination half-life was 6.1 hours (range, 5.0 to 6.4 hours). Transfer half-life...
Christensen L, Camitz L, Illigen KE, Hansen M, Sarvaa R, Conaghan PG.Polyacrylamide hydrogel (PAAG) is a non-toxic, non-degradable synthetic product, used for years in the augmentation of soft tissues. Preliminary results in animals and humans have suggested long-lasting beneficial effects on symptoms of osteoarthritis (OA). The aim of this histopathological study was to investigate whether intra-articular injection of PAAG is integrated into synovial tissue in normal and OA animal joints, and if this integration is sustained. (A) A prospective, controlled, longitudinal study of normal knee joints injected with PAAG was performed in 10 rabbits, following the an...
Garrett KS, Bramlage LR, Spike-Pierce DL, Cohen ND.To determine the effects of treatment with platelet- and leukocyte-rich plasma (PRP) on future 2-, 3-, and 4-year-old racing performance of yearling Thoroughbreds with proximal sesamoid bone inflammation and associated suspensory ligament branch (SLB) desmitis. Methods: Randomized clinical trial. Methods: 39 yearling Thoroughbreds. Methods: Yearling Thoroughbreds with radiographic evidence of performance-limiting proximal sesamoid bone inflammation and ultrasonographic evidence of associated SLB desmitis were identified and randomly assigned to undergo PRP (treatment group) or saline (0.9% NaC...
Tulamo RM, Bramlage LR, Gabel AA.Infectious arthritis was induced experimentally in one tarsocrural joint of six horses by intra-articular injection of 1 ml Staphylococcus-saline suspension containing 9 x 10(4) to 3 x 10(6) organisms. The corresponding contralateral joint was injected with 1 ml of saline and served as a control. The progression of the induced infectious arthritis was assessed over a nine-day period by clinical examination and sequential synovial fluid analysis with pH and lactate measurements. Changes in synovial fluid were present before clinical signs of infectious arthritis were manifested. The diagnostic ...
Neuenschwander HM, Moreira JJ, Vendruscolo CP, Fülber J, Seidel SRT, Michelacci YM, Baccarin RYA.The intra-articular use of hyaluronic acid (HA) for the treatment of synovitis and osteoarthritis is still controversial. As a consequence, corticosteroids remain the most frequently employed therapeutic agents, despite their potential systemic and local deleterious effects. This study examined the anti-inflammatory, antioxidant, and chondroprotective activities of low and high molecular weight hyaluronic acid (LMW-HA and HMW-HA) on lipopolysaccharide (LPS)-induced synovitis in horses compared to triamcinolone acetonide (TA). LPS was injected in the metacarpophalangeal joints, which were treat...
Asheim A, Lindblad G.Forty-five race-horses with arthritis of non-in-fectious type in 54 joints were treated with sodium hyaluronate intra-articularly. All joints had previously been treated without lasting success by conventional methods, such as firing, blistering or intraarticular injection of cortisone. In most cases only 1 injection of 2 ml (20 mg) sodium hyaluronate was needed. To avoid subjective evaluation, the effects of the treatment were based on the joint’s capacity of withstanding extreme stress, which means that the horse should be able to train and race again. The treatment was concentrated on the...
Broeckx SY, Spaas JH, Chiers K, Duchateau L, Van Hecke L, Van Brantegem L, Dumoulin M, Martens AM, Pille F.The safety of the intra-articular use of mesenchymal stem cells (MSCs) is scarcely reported. Therefore, the goal of this study was to investigate the safety of a single intra-articular injection with allogeneic chondrogenic induced MSCs combined with equine plasma (=the investigational product: IVP) compared to a saline (0.9% NaCl) placebo control (=control product: CP). Sixteen healthy experimental horses were randomly assigned to receive a single intra-articular injection with either the IVP (n=8) or the CP (n=8) in the left metacarpophalangeal joint. All horses underwent a daily clinical as...
Vandeweerd JM, Zhao Y, Nisolle JF, Zhang W, Zhihong L, Clegg P, Gustin P.Intra-articular (IA) corticosteroids (CS) have been used in the treatment of osteoarthritis for many years, although their effects on articular cartilage are not fully understood. To identify whether previous animal studies have provided enough evidence about the effects of CS, we undertook a systematic review that identified 35 relevant in vivo animal experimental studies between 1965 and 2014 assessing the effects of CS on either normal cartilage, or in either induced osteoarthritis (OA) or synovitis. The quality of the methodology was assessed. Deleterious effects, both structural and bioc...
Kearney CM, Khatab S, van Buul GM, Plomp SGM, Korthagen NM, Labberté MC, Goodrich LR, Kisiday JD, Van Weeren PR, van Osch GJVM, Brama PAJ.Allogenic mesenchymal stem cell (MSC) secretome is a novel intra-articular therapeutic that has shown promise in and small animal models and warrants further investigation. Unassigned: To investigate if intra-articular allogenic MSC-secretome has anti-inflammatory effects using an equine model of joint inflammation. Unassigned: Randomized positively and negatively controlled experimental study. Unassigned: In phase 1, joint inflammation was induced bilaterally in radiocarpal joints of eight horses by injecting 0.25 ng lipopolysaccharide (LPS). After 2 h, the secretome of INFy and TNFα stimul...
Sladek S, Kearney C, Crean D, Brama PAJ, Tajber L, Fawcett K, Labberte MC, Leggett B, Brayden DJ.Polyelectrolyte nanoparticle constructs (NPs) comprising salmon calcitonin (sCT), chitosan (CS), and hyaluronic acid (HA) were previously established as having anti-inflammatory potential when injected via the intra-articular (i.a.) route to a mouse model. We attempted to translate the formulation to a large animal model, the lipopolysaccharide (LPS)-stimulated equine model of joint inflammation. The aim was to manufacture under aseptic conditions to produce sterile pyrogen-free NPs, to confirm physicochemical characteristics, and to test toxicity and efficacy in a pilot study. NP dispersions ...
Robion FC, Doizé B, Bouré L, Marcoux M, Ionescu M, Reiner A, Poole AR, Laverty S.In vivo the effects of intra-articular (IA) corticosteroids on articular cartilage remain controversial. This study was designed to examine this issue using synovial fluid (SF) markers of cartilage metabolism. Paired radiocarpal joints, without clinical or radiographic signs of joint disease, were studied in 10 adult horses. Aseptic arthrocentesis was performed weekly for 13 weeks. IA injections of methylprednisolone acetate (MPA) into the treatment joint and the vehicle into the control joint were performed at weeks 3, 5 and 7. We used radioimmunoassays on SF samples which measure a keratan s...
Ishihara A, Bartlett JS, Bertone AL.Intra-articular gene therapy has potential for the treatment of osteoarthritis and rheumatoid arthritis. To quantify in vitro relative gene transduction, equine chondrocytes and synovial cells were treated with adenovirus vectors (Ad), serotype 2 adeno-associated virus vectors (rAAV2), or self-complementary (sc) AAV2 vectors carrying green fluorescent protein (GFP). Using 6 horses, bilateral metacarpophalangeal joints were injected with Ad, rAAV2, or scAAV2 vectors carrying GFP genes to assess the in vivo joint inflammation and neutralizing antibody (NAb) titer in serum and joint fluid. In vit...
Frisbie DD, Kawcak CE, Baxter GM, Trotter GW, Powers BE, Lassen ED, McIlwraith CW.To determine effects of intra-articularly administered 6alpha-methylprednisolone acetate (MPA) in exercised horses with carpal osteochondral fragmentation. Methods: 18 horses: 3 groups of 6 each. Methods: An osteochondral (chip) fragment was created in 1 randomly chosen middle carpal joint of each horse. Polyionic fluid (PF) was injected into both middle carpal joints of horses in the control group. In horses of the MPA-control group, MPA was injected into the middle carpal joint without an osteochondral fragment; a similar volume of PF was injected into the contralateral middle carpal joint. ...
Frisbie DD, Stewart MC.Joint disease is a major cause of wastage in performance horses. Arthritis can be challenging to treat because articular cartilage has little or no capacity for repair, therapeutic options are limited and are largely targeted at ameliorating clinical signs of joint disease. Cell-based therapies have potential to overcome the intrinsic constraints to articular cartilage repair. This article focuses on cell-based therapies for treatment of equine joint disease. Results from experimental model and human clinical studies are presented along with available data from equine studies.
DePuy T, Howard R, Keegan K, Wilson D, Kramer J, Cook JL, Childers MK.To test the hypothesis that botulinum toxin type A (BoNT-A) can attenuate lameness associated with acute synovitis in an equine model. Methods: Four horses 2-6 yrs of age with clinically normal carpi were studied for 15 days. Kinematic gait analysis and clinical measures of lameness were conducted before and after experimental interventions. Horses were randomly assigned to either placebo (saline) or treatment (BoNT-A) groups. On day 0 of the intervention, 50 units of BoNT-A or an equivalent volume of saline (0.09%) was given into the middle carpal joints. On day 14, acute synovitis was induce...
de Grauw JC, Visser-Meijer MC, Lashley F, Meeus P, van Weeren PR.Intra-articular (IA) injection of corticosteroids with or without hyaluronate (HA) has been used for decades in equine practice for treatment of noninfectious synovitis and osteoarthritis. However, to date, no large-scale randomised equine field trials have been reported that address the supposed superior clinical efficacy of the combination of corticosteroid + HA compared with IA injection of corticosteroid alone. Objective: To compare the clinical efficacy of IA triamcinolone acetonide (TA, 12 mg) compared with IA TA (12 mg) + high molecular weight HA (20 mg) in horses with clinical jo...
Van Hecke L, Magri C, Duchateau L, Beerts C, Geburek F, Suls M, Da Dalt L, Patruno M, Saunders J, Broeckx SY, Depuydt E, Spaas JH.The use of mesenchymal stem cells (MSCs) for the treatment of equine joint disease is widely investigated because of their regenerative and immunomodulatory potential. Allogeneic MSCs provide a promising alternative to autologous MSCs, since the former are immediately available and enable a thorough donor screening. However, questions have been raised concerning the immunogenic potential of allogeneic MSCs, especially after repeated administration. Methods: Current retrospective study assessed the cellular and humoral immunogenicity of ten jumping and dressage horses with naturally occurring d...
Trela JM, Spriet M, Padgett KA, Galuppo LD, Vaughan B, Vidal MA.Intra-arterial (i.a.) and intravenous (i.v.) regional limb perfusions (RLP) through the median artery and cephalic vein, respectively, have been previously investigated for administration of mesenchymal stem cells (MSCs) to the equine distal limb. Limitations due to thrombosis of the arteries after i.a. RLP and poor distribution of MSCs to the foot with i.v. RLP were observed. These techniques need to be modified for clinical use. Objective: Evaluate the distribution, uptake and persistence of radiolabelled MSCs after i.a. injection through the median artery without a tourniquet and after i.v....
Colbath AC, Dow SW, Hopkins LS, Phillips JN, McIlwraith CW, Goodrich LR.Allogeneic and autologous bone marrow-derived mesenchymal stem cells (BMDMSCs) have been administered in equine joints for their anti-inflammatory effects. However, allogeneic BMDMSC offer multiple clinical and practical advantages. Therefore, it is important to determine the relative effectiveness of allogeneic vs autologous BMDMSCs. Objective: The objective of the study was to compare the inflamed joint response to autologous vs allogeneic BMDMSCs injections, and to determine if either treatment generated an anti-inflammatory effect. Methods: Randomised controlled study. Methods: Bone marrow...
Bembo F, Eraud J, Philandrianos C, Bertrand B, Silvestre A, Veran J, Sabatier F, Magalon G, Magalon J.To assess the safety and potential efficacy of a standardized technique consisting of intra-articular injection of 10 cc of a homogeneous mixed product using autologous micro-fat and platelet rich plasma (PRP) (ratio 1:1) in the carpus or the fetlock joint of sport horses presenting degenerative joint disease (DJD). Methods: Eight sport horses with DJD confirmed by radiography and ultrasonography and causing lameness and the impossibility to compete were treated. PRP was prepared after a double centrifugation whereas micro-fat was harvested and purified using a closed system. The two products ...
Dabareiner RM, Cohen ND, Carter GK, Nunn S, Moyer W.To identify types of musculoskeletal problems associated with lameness or poor performance in horses used for barrel racing. Methods: Retrospective case series. Methods: 118 horses. Methods: Medical records were reviewed for information on signalment, history, physical and lameness examination findings, diagnostic tests performed, diagnosis, and treatment. Results: Most horses were examined because of lameness (n = 72 [61%]) rather than poor performance (46 [39%]), but owner complaint was not significantly associated with age or body weight of the horse. The most common performance change was ...
Pearson W, Orth MW, Lindinger MI.To evaluate inflammatory responses induced via intra-articular recombinant human interleukin (IL)-1beta treatment in horses receiving a dietary nutraceutical (DN; composed of mussel, shark cartilage, abalone, and Biota orientalis lipid extract) and assess the clinical effects of long-term DN administration. Methods: 22 healthy horses. Methods: 12 horses were fed 0, 15, 45, or 75 mg of DN (3 horses/treatment) daily for 84 days. General health and clinicopathologic variables were monitored at intervals. Ten other horses received 0 or 15 g of DN/d (5 horses/treatment) for 29 days (beginning day -...
Haughan J, Jiang Z, Stefanovski D, Moss KL, Ortved KF, Robinson MA.Gene therapy promotes the expression of missing or defective genes and can be curative following administration of a single dose. Gene therapy is prohibited in equine athletes by regulatory bodies due to the high potential for abuse and novel analytical methods are needed for detection. The goal of this study was to detect the administration of an experimental gene therapy: a recombinant adeno-associated viral vector (rAAV) carrying a transgene for the anti-inflammatory cytokine IL-10 (rAAV-IL10). Twelve horses were randomly assigned to receive an intra-articular injection of rAAV-IL10 or phos...
Soma LR, Uboh CE, Liu Y, Li X, Robinson MA, Boston RC, Colahan PT.This study investigated and compared the pharmacokinetics of intra-articular (IA) administration of dexamethasone sodium phosphate (DSP) into three equine joints, femoropatellar (IAS), radiocarpal (IAC), and metacarpophalangeal (IAF), and the intramuscular (IM), oral (PO) and intravenous (IV) administrations. No significant differences in the pharmacokinetic estimates between the three joints were observed with the exception of maximum concentration (Cmax ) and time to maximum concentration (Tmax ). Median (range) Cmax for the IAC, IAF, and IAS were 16.9 (14.6-35.4), 23.4 (13.5-73.0), and 46.9...
Nielsen JV, Berg LC, Thoefnert MB, Thomsen PD.Intra-articular facet joint injection is an established diagnostic procedure in human medicine but there are no reports on its reliability in equine practice. Objective: To investigate the accuracy of ultrasound-guided intra-articular injections of the cervical facet joints and to estimate factors influencing the accuracy. Methods: Sixty injections with blue dye were performed on the facet joints between 2nd and 7th cervical vertebra (C2-C7) on horses subjected to euthanasia for nonorthopaedic reasons. The facet joints were subsequently dissected to verify accuracy of deposition. Results: Seve...
