Osteoarthritis Part 1

Osteoarthritis in pets, description and causes


Synonyms of OA are arthritis and degenerative joint disease (DJD). Osteoarthrosis is also considered a synonym to OA or DJD. However, because OA is always associated with some degrees of inflammation, it is perhaps best to label those cases of joint disease that lack inflammation as osteoarthrosis.

OA is any disease process that involves synovial joint inflammation. It is a common, global, pathologic, ubiquitous, chronic (can be acute in experimental settings), degenerative, and inflammatory joint disease.

OA is characterized by joint function loss, lameness, stiffness, severe/chronic pain, disability, articular cartilage destruction/deterioration, bone deterioration, subchondral bone disease, and chondrocyte loss, all due to aberrant repair and eventual degradation of articular cartilage, with the final outcome being a failed joint.

OA is associated with an increase in prostaglandins and inflammatory cytokines, alterations in articular cartilage, subchondral bone metabolism & architecture, periarticular osteophytosis, fibrosis, enthesophytosis, synovitis, & synovial fibrosis.       

OA requires a multimodal therapeutic approach to the alleviation of clinical signs and improvement in overall quality of life.



Approximately 20% of the adult canine pet population spontaneously develop OA, translating to at least 11 to 15 million dogs in the United States and 5 million dogs in Europe, making it the most common form of arthritis in dogs. OA is the most common form of arthritis in cats as more than 60% of adult cats show radiographic evidence of appendicular skeletal OA.

Annual period prevalence estimates, identified from a population of 455,557 dogs, were the highest for dental disease (76% of dogs), OA (82%), and being overweight/obese (70%). The estimated annual period prevalence of appendicular OA was 2.5% in the United Kingdom (equating to around 200,000 affected dogs annually). Duration calculation trials suggest OA affects 11.4% of affected individuals’ lifespan, providing further evidence for substantial impact of OA on canine welfare at the individual & population level.



OA can be considered idiopathic/primary (which may be the more common cause in cats) or secondary, which is the most common cause in dogs. Secondary OA is due to developmental disease, joint instability, or trauma. Further classification of OA based on etiology is as follows:          


  • OA – primary versus secondary
  • Traumatic arthritis
  • Coagulopathic arthritis



  • Immune-mediated
  • Erosive (rheumatoid & periosteal proliferative polyarthritis)
  • Nonerosive (idiopathic type I, II, III, IV, systemic lupus erythematosus, drug                                       reactions, breed-associated immune-mediated polyarthropathy)


  • Bacterial, borrelial, fungal, mycobacterial, mycoplasmal, protozoal
  • Crystal-induced
  • Hydroxyapatite
  • Calcium pyrophosphate (pseudogout)
  • Sodium urate (gout)



Both internal and external patient factors play a role in the development of OA. Internal factors relate to an individuals susceptibility to the predisposition to OA development. These include age, genetics, & systemic factors. External patient factors include Joint developmental disease or abnormalities, joint trauma or injury, joint instability, joint overload, socioeconomic factors, comorbidities exercise, diet, & housing.

Internal and external factors lead to a predisposition to OA & affect joint mechanics (altering biochemical pathways). With time these factors affect the severity, the continuation of the inciting cause, & cause pain/disability. Clinical signs are especially obvious after prolonged activity. Expansion of the above predisposing internal and external patient factors are described below.





 Being older than eight years of age is a risk factor for OA in the United Kingdom. As chondrocytes age, they synthesize smaller and fewer aggrecan molecules, and less functional link proteins. Mitotic and synthetic activities decline along with their responsiveness to anabolic mechanical stimuli and growth factors.

An accumulation of advanced glycation end products within the type II collagen network (age-related collagen cross-links) results in a decrease in collagen network turnover. Aggrecan molecules length and uniformity lessens with age; C-terminal truncation occurs via matrix metalloproteinase (MMP) and aggrecanase activity. Shorter molecules contain fewer chondroitin sulfate side-chains and increased keratan sulfate, which results in a decreased ability to imbibe water into the tissue, thus reducing compressive stiffness.

Abnormal cellular activity, cellular responsiveness, repair mechanisms, and extracellular matrix features translate to tissue loss. This is seen with canine cranial cruciate ligament disease as there is an association between advanced glycation end-products and increased OA severity; this may explain why the treatment for cranial cruciate ligament surgery in older dogs is not as good. An online telemedicine veterinary session, specifically with Dr. Shadi Ireifej, a board-certified veterinary surgeon, via VetTriage.com will be helpful in cases whereby surgery was recommended but more information is sought regarding older pets.



In terms of gender, ovariectomy results in biomechanical, compositional, and histological cartilage changes, but with no consistent association to OA.

Boxer dogs with pelvic limb lameness due to canine hip dysplasia who were neutered at a mean age of 3 years have a 1.5-times likelihood of developing clinical hip dysplasia versus sexually intact dogs. There is an increased risk of cranial cruciate ligament rupture in neutered male and female dogs, and a risk for OA development with being neutered in dogs of the United Kingdom.

Males are 1.8-times more likely to develop elbow OA than female dogs. Female dogs have a higher risk of developing stifle joint OA.



Systemic factors include obesity, genetics (bodyweight), and comorbidities.



 Obesity is defined as excess body fat accumulation resulting in adverse effects to health. Obese patients have increased mechanical loading. Nutrient excess, which leads to obesity, may result in lipotoxicity; different fatty acid types have distinct effects on inflammation.

Perhaps the best study displaying this is the Labrador Retriever study. This showed that of control-fed dogs, by 2 years of age, 42% had radiographic evidence of hip OA versus 4% of dogs with diet restriction. At 5 years of age OA was observed in 52% of control-fed versus 13% of dogs with the restricted diet, and bodyweight correlated with hip OA severity. At the end of the study 83% of control-fed had OA, 50% of restricted diet dogs had OA, and the restricted-fed exhibited a longer median lifespan. With regard to stifle & elbow joints; OA present in 2 or more joints was seen in 77% of control-fed and only 10% of restricted-fed by 8 years of age.



With regard to genetics/bodyweight, increased bodyweight results in an increased OA initiation risk. It is also associated with increased clinical signs in dogs with canine hip dysplasia, in those developing cranial cruciate ligament disease, and in those with elbow dysplasia. Dogs weighing over 10 kg have a higher risk of developing stifle joint OA. Risk factors associated with OA diagnosis in the United Kingdom include larger body weight and specific breeds (Labrador & Golden Retrievers).



Comorbidities such as hyperadrenocorticism & diabetes mellitus are external factors that also may increase the propensity for OA development.



The external factor of joint developmental disease or abnormality is perhaps best seen with non-chondrodystrophic breeds. Non-chondrodystrophic dog breeds are more susceptible than chondrodystrophic dog breeds. The latter are those dogs whose chondrodystrophy is associated with the fibroblast growth factor 4 (FGF4) retrogene as identified by a higher release of glycosaminoglycans, DNA content, cyclooxygenase 2 (COX-2) expression, and higher DKK3 protein expression (which directly transdifferentiates fibroblasts into endothelial cells).



Joint trauma/injury, joint instability, & joint overload are external factors that result in biomechanical joint alterations. Canine stifle joint OA development is at a higher risk in cases of ruptured cranial cruciate ligaments or patella luxation.



Socioeconomic factors have been stated as an external factor to OA development. An example is dogs who are insured in the United Kingdom have an increased risk of OA development.



With regard to exercise, diet, & housing, there is an increased incidence of hip dysplasia or hip OA in Boxer dogs who grew up on slippery” floors. There is also an increased risk factor for hip & elbow dysplasia development in Labrador Retrievers between 1 and 2 years of age who exercised by running after balls and sticks thrown by the owner. OA associated with hip dysplasia is one of the most common orthopedic abnormalities in dogs, with an incidence of up to 40% in some breeds.



Cartilage alterations, specifically with articular cartilage, are a monumental part of OA. Loss of compressive stiffness, loss of tensile strength, surface fibrillation, and erosion and ulceration of the articular cartilage occur.

Molecular degradation of the extracellular matrix (ECM), increased water level content, decreased tissue aggrecan molecule size, and damaged collagen network structure occur. This translates to reduced cartilage stiffness. Enhanced chondrocyte proliferation and metabolism occurs over months to years. Exhaustion of chondrocyte repair and cartilage tissue loss occurs.

There is an anabolic and catabolic process imbalance with the upregulation of degradation and synthesis. This occurs in the short to medium term: 1 to 3 years. Cartilage thickness becomes increased, with more cells translating to more ECM and tissue swelling.

The end-stage is characterized by cartilage ulceration and subchondral bone eburnation. Once damaged, the articular cartilage seldom undergoes spontaneous repair because of its avascular, aneural, and alymphatic state.

Inflammatory mediators play an important role in the pathogenesis of OA. Below is an abbreviated version of this complex process.



 Chondrocytes produce interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) in an autocrine and paracrine fashion. IL-1, IL-17, IL-18, and TNF-alpha upregulate matrix MMP synthesis and other proteolytic enzymes, and they decrease the synthesis of their inhibitors (tissue inhibitors of metalloproteinases, TIMP).

MMP-1 downregulation along with MMP-13 & disintegrin upregulation results in MMP-13 aggrecan degradation. MMP-1 and -13 (perhaps MMP-8 & -14 as well) degrade collagen type II. IL-1beta and TNF-alpha promote chondrocyte nitric oxide (NO) formation from the inducible isoform of nitric oxide synthase (iNOS), which is catabolic, resulting in matrix synthesis inhibition, MMP activation, and apoptosis.

OA cartilage expresses COX-2 and produce prostaglandin E2 (PGE2). PGE2 decreases proteoglycan synthesis and enhances degradation of aggrecan and type II collagen. Prostaglandins are considered pro-inflammatory lipid metabolites.

Aggrecanases ADAMTS-4 and ADAMTS-5 cleave aggrecan molecules.

Reactive oxygen species (superoxide anion, hydrogen peroxide, & hydroxyl radicals) promote chondrocyte apoptosis.          

Anabolic changes resulting in cartilage matrix molecule synthesis (aggrecan molecules & collagen synthesis) are dictated by growth factors insulin-like growth factors (IGF-1 and -2), and TGF-beta. Decreased IGF in circulation and locally result in decreased binding proteins availability and TGF-beta expression reduction.

In canine cultured chondrocytes IL-1β increases the expression of inflammatory genes and mediators, & TGF-β largely attenuates the IL-1β-mediated inflammatory response. Therefore, TGF-β might be a novel target for use in the prevention and treatment of cartilage breakdown in dogs with OA. The TGF-beta superfamily promotes osteophyte/osteochondrophyte formation from the periosteum that overlies the bone. These originate from mesenchymal stem cells present in the periosteum and synovial lining at the cartilage-bone junction. Subchondral bone sclerosis is the end result of subchondral bone plate thinning and increased porosity. 



The joint is comprised of the ECM, bone, cartilage, central nervous system, fat, ligament, synovial fluid, synovium.

The stabilization of the ECM components are significant in maintaining a normal healthy joint environment. In OA, ECM components are altered and indicate disease progression. The joint ECM is composed of proteoglycans (aggrecan, perlecan, inter α-trypsin inhibitor), glycoproteins (fibronectin, lubricin, COMP) and collagen types (most abundantly collagen type II) which represent structural and functional transformation during disease advancement.

The synovial membrane lining the joint capsule is composed of a discontinuous fibroblast-like and macrophage-like cell layer. Histological changes include synovial hypertrophy, hyperplasia, and lymphocyte infiltration of the sublining tissue. Mechanical and enzymatic action of cartilage breakdown products provokes collagenase and other hydrolytic enzyme production by macrophages and synovial cells. The macrophages release IL-1beta and TNF-alpha. The synovium also is the origin of OA-associated pain. The stifle’s joint fibrous capsule contains the synovial membrane, which produces cartilage nutrients. There is good diagnostic agreement between synovial fluid effusion and osteophytosis when dealing with stifle joint OA.

Pain sensitization is characterized by a dull and aching, poorly localized sensation. The joint nerves include the A-beta fibers of ligaments and fibrous joint capsule. The A-delta, C-fibers, and free nerve endings are present in all aspects of the joint except for normal articular cartilage. Conscious sensations are evoked from the ligaments, fibrous capsule, adipose tissue, meniscus, periosteum, and synovial layer, but not cartilage. Mechanical stimulation of the primary afferent fibers occurs via inflammatory mediators. TNF-alpha, IL-6, bradykinin, PGE2, prostacyclin (PGI2), serotonin, substance P, galanin neuropeptide, & neuropeptide Y contribute to nociception. Central sensitization may be due to COX & NO-induced cell death.



 Additional information can be found with this online veterinarian YouTube video:

 Osteoarthritis: Listen to this YouTube video for more information: https://youtu.be/Lt_NbsIvc2A