The word osteoarthritis (OA) comes from the Greek words for bone, joint and inflammation and it represents a progressive condition caused by gradual loss of articular cartilage usually with concomitant changes in the subchondral bone and synovium. OA is also known as degenerative joint disease and osteoarthrosis. 

A synovial joint consists of apposing hyaline articular cartilage covered surfaces resting on compliant subchondral bone plates that are in turn supported by cancellous bone. The synovial cavity is lined with synovium and held in place by the fibrous joint capsule and supporting ligaments. Microscopically hyaline articular cartilage is composed of water (~75%), type II collagen (~15%), proteoglycans (~10%) and chondrocytes (only 2%).

The proteoglycans in cartilage draw water into the extracellular matrix and provide compressive stiffness and the arrangement of collagen fibrils provides tensile stiffness. The extracellular matrix of cartilage is constantly being remodelled to allow for growth and regeneration. Degradation is facilitated by matrix metalloproteinase (MMPs) enzymes and their proteolytic action is controlled by tissue inhibitors of metalloproteinases (TIMPs). These enzymes exist in a state of dynamic equilibrium, long term disruption of this balance between MMPs and TIMPs will have pathological consequences and lead to osteoarthritis. 

The osteoarthritic disease process can originate from various causes with trauma and synovitis being the most common as a result of overuse or poor conformation (metacarpophalangeal varus has been associated with an increased incidence of metacarpophalangeal OA) leading to abnormal forces on normal cartilage. The alternative situation is normal forces on abnormal cartilage (young horses with osteochondrosis) resulting in OA. Macroscopic changes of the articular surface indicative of osteoarthritis include fibrillation, wear lines and erosion of the shiny, white to translucent hyaline cartilage eventually down to subchondral bone in severe cases. Microscopic changes to the articular cartilage include chondrocyte necrosis, chondrone formation, fibrillation, focal loss of Safranin-O staining (=loss of proteoglycans) and focal cell loss. The synoval membrane can show intimal hyperplasia, oedema and fibrosis. The subchondral bone can become remodelled with the presence of osteochondral lesions and osteochondral splitting. These macroscopic and microscopic changes result from disruption to the normal equilibrium of the proteolytic MMPs and TIMPs. Pro-inflammatory cytokines IL-1β and TNFα result in increased expression of MMP-1, MMP-3 and MMP-13 (stromelysins that breakdown collagen) and ADAMPTS-4 and ADAMPTS-5 (aggrecanases that breakdown proteoglycan) that lead to matrix destruction. 

Osteoarthritis may be the most common cause of lameness in equine athletes of all types. Articular cartilage is devoid of sensory innervation and as a result pain and lameness resulting from OA are typically attributed to the periarticular soft tissues and bone. Limited range of motion is a common feature of equine OA of either high or low motion joints. Joint effusion is a common feature of OA in high motion joints but not low motion joints. Reduced synovial fluid viscosity is also a frequent finding in horses with OA of either high or low motion joints. Inconsistent lameness among horses with similar radiological signs parallels the weak correlation between pain and early OA in people. 

•   Periarticular osteophyte formation

•   Joint space narrowing

•   Subchondral bone sclerosis

•   Subchondral bone lysis 

0. MEDICAL MANAGEMENT OF OSTEOARTHRITIS 

0. Once hyaline articular cartilage is damaged is it not capable of regeneration, deep cartilage lesions heal spontaneously by a progression from granulation to fibrous tissue that is remodelled to fibrocartilage. At 12 months post injury the type II collagen approaches normal but the proteoglycan levels are only about half that of normal. There are 2 types of drugs that are used to manage OA

1. Palliative drugs that reduced the pain and inflammation

2. Disease modifying osteoarthritis drugs (DMOADs) that have a chondroprotective function

   so acting to slow the progression of disease. 

Non-steroidal anti-inflammatory drugs (NSAID) therapy for OA  

NSAIDs have been administered to treat joint disease for over 100 years since the introduction of salicyclic acid. NSAID refers to anti-inflammatory agents that inhibit some component of the enzyme system that converts arachidonic acid into prostaglandins and thromboxanes. Arachidonic acid resides in the phospholipid cell membrane and is oxidised by cyclo-oxygenase (COX) or 5-lipoxygenase (LOX) to form prostaglandins and leukotrienes, respectively. NSAIDs primarily act to inhibit COX and reduce prostaglandin production. There are many forms of COX enzyme; the most well studied are COX-1 (the constitutive/ housekeeping enzyme) and COX-2 (the inducible form primarily responsible for inflammatory responses). Some NSAIDs equally inhibit COX-1 and COX-2, while others seems to inhibit COX-2 more than COX-1. NSAIDs have been shown to inhibit proteoglycan synthesis experimentally. In the clinical setting side effects include gastric ulceration, right dorsal colitis and renal papillary necrosis. The most widely used NSAIDs in the equine industry are phenylbutazone (PBZ), flunixin meglumine, carprofen, meloxicam and ketoprofen. PBZ is commonly used orally because it is efficacious and affordable, it can be given intravenously but is very irritant if given perivascularly. 

Intra-articular corticosteroids therapy for OA  

Corticosteroids are potent anti-inflammatory agents and they inhibit inflammation at all levels. Pain relief is attributed to inhibition of prostaglandin synthesis specifically by inhibiting the enzyme phosphor lipase A2. Other anti-inflammatory effects are mediated through cytoplasmic receptors and the nuclear factor NF-κB that enhances inflammatory cytokine expression. Additionally corticosteroids reduce capillary dilatation, white blood cell migration and inhibit the cytokines IL- 1β and TNFα. The 2 widely available corticosteroids for intra-articular injection are triamcinolone (TA) and methyl prednisolone acetate (MPA). Experimental studies have shown that triamcinolone is less chondrocyte toxic than MPA and therefore is recommended for use in high motion joints. Intra-articular corticosteroids have been associated with several complications; laminitis; good evidence linking laminitis to corticosteroid use is lacking; catastrophic fracture; again evidence is lacking (McIlwraith 2010). As with any intra-articular injection there is a potential risk of introducing infection to the joint therefore strict aseptic technique (clipping and surgically preparing the joint to be injected) is important. 

HA is a large non-sulphated glycosaminoglycan component of synovial fluid responsible for viscoelasticity, boundary lubrication and steric hindrance, it also is an important component of proteoglycan in the cartilage matrix providing compressive stiffness. The exact mechanism of action at a cellular level is unknown. Thought to reduce neutrophil chemotaxis and phagocytosis, Reduce PGE, IL-1 and bradykinin production and scanvenge free radicals. All of these properties have been demonstrated in vitro. Modest analgesic, mostly anti-inflammatory through steric hindrance or pharmacological through inhibition of inflammatory mediators. HA can be administered both intravenously and intra-articularly. There is still controversy over whether high or low molecular weight HA is more efficacious. HA resulted in significantly less cartilage fibrillation in a recent experimental study (Frisbie et al. 2009). HA can be combined with corticosteroids for intra-articular injection to provide anti-inflammatory and chondroprotective effects. 

Polysulphatedglycosaminoglycans (PSGAGs) for therapy of OA  

AdequanTM is the commercial product licensed for intra-articular and intra-muscular use in the horse. It contains PSGAGs manufactured from an animal source (chondroitin sulphates extracted from bovine trachea). PSGAGs have been shown to promote chondrocyte metabolic activity and inhibit the effects of cytokines and prostaglandins on cartilage and are therefore classed as DMOADs. PSGAGs have been shown to potentiate the subinfective dose of Staph aureus and therefore intra-articular administration should be combined with concurrent intra-articular antibiotic administration. Synovial vascularity and subintimal fibrosis was reduced experimentally in horses given PSGAGs compared to controls (Frisbie et al. 2009). One study has shown that 67% of horses receiving intra-articluar PSGAGs had a successful outcome (Kristiansen and Kold 2007). 

Pentosan polysulphate therapy for OA  

This is a PSGAG extracted from plants that is licensed for intra-muscular use in horses and has been shown to achieve therapeutic levels in synovial fluid following intra-muscular injection. It should be noted that pentosan polysulphate increases activated partial thromboplastin time in a dose dependant manner and therefore should not be administered within 24 hours of high stress activities or where physical injury may occur. 

Oral neutraceuticals: Chondroitin sulphate and Glucosamine therapy for OA 

Oral nutraceuticals contain the component of cartilage and the precursor molecules chondriotin sulphate and glucosamine hydrochloride. There is still no conclusive data demonstrating absorption or bioavailability at the joint in the horse (Pearson and Lindinger 2009). These drugs have an excellent safety profile and there are several multicentre placebo controlled blinded studies in the human field demonstrating reduced OA pain with glucosamine and chodroitin sulphate use. The oral nutraceutical industry is not regulated and therefore there is no monitoring of what exactly is in a particular product. The 2 veterinary marketed products contain the highest concentrations of chondroitin sulphate and glucosamine but are also the most expensive. 

Bisphosphonates therapy for OA  

Tiludronate (Equidronate in UK, Tildren in USA; CEVA) and clodronate disodium (Osphos, Dechra) are bisphosphonates that that regulate bone remodelling through inhibition of bone resorption (specifically osteoclastic resorption) and it is therefore it is postulated it should ameliorate the remodelling processes active in OA and navicular disease. One clinical study has shown efficacy of tiludronate in combination with a controlled exercise programme for the treatment of distal tarsal OA (Gough et al. 2010). 

Autologous conditioned serum therapy for OA 

Autologous conditioned serum (ACS) is generated from 50ml of the horses’ blood that is incubated overnight at 37oC in a special syringe containing chromium coated glass spheres. The chromium spheres stimulate white blood cells to produce anti-inflammatory cytokines (interleukin- 1 receptor antagonist, IL-4, IL-10, IL-13). The serum is aspirated the following day in an aseptic manner and stored (frozen) in 2 ml aliquots until used. One experimental OA study in horses showed reduced synovial membrane hyperplasia compared to control horses (Frisbie et al. 2007). The same study found no clinical reduction in pain scores with administration of ACS. A recent report in humans documented increased production of the pro-inflammatory cytokines (IL-1β and TNFα) (Rutgers et al 2010). 

SURGICAL MANAGEMENT OF OSTEOARTHRITIS 

Arthroscopic debridement of meniscal or ligamentous injuries 

Minimally invasive surgery is increasingly available in equine practice and purports significant advantages over arthrotomy including reduced morbidity and convalescent time. Consequently debridement of intra-articular ligamentous or meniscal injuries in widely practiced. Exposure of collagen fibrils within the synovial environment is thought to potentiate inflammation and predispose to OA hence debridement and reduction of fibrillated ligament or meniscus is thought to be beneficial. 

Surgical arthrodesis 

Surgical arthrodesis of a joint is essentially facilitated ankylosis or fusing of the joint to obliterate any joint movement and therefore reduce pain. The low motion joints such as the proximal interphalangeal joint (Knox and Watkins 2006) and the tarsmetatarsal joint are amenable to surgical arthrodesis in the horse and return to mild athletic activity. The high motion joints; the metacarpophalangeal joint and the carpus can be surgically arthrodesed if the goal of surgery is pasture soundness.