• Osteoarthritis (OA) is a non-inflammatory degenerative disease affecting joints with degradation and destruction of articular cartilage and the underlying subchondral bone. It is often progressive and is the most common joint disorder in the world.

Primary

• No clear underlying cause
• Genetic factors
• More common in women 

Secondary

• There is a pre-existing joint abnormality which may be due to:

• Mechanical causes including slipped upper femoral epiphysis, Perthes disease, post-traumatic and skeletal dysplasia
• Metabolic causes
• Post-inflammatory causes such as joint infection (septic arthritis), gout and rheumatoid arthritis

• Classically OA has been considered a “wear and tear” degenerative condition of joints. However, OA is a systemic disease that affects the whole joint, including cartilage, subchondral bone, synovium, tendons and muscles.
• The disease is characterised by degeneration of articular cartilage, low grade synovial inflammation (synovitis), and alterations in peri-articular soft tissues and subchondral bone.

 Osteoarthritic cartilage^1,2

• OA is not an inevitable consequence of aging and osteoarthritic cartilage is chemically different to normal cartilage of the same age. 
• Changes seen in osteoarthritic cartilage include changes in the matrix composition, with loss of proteoglycans and increased water content that will stimulate chondrocytic synthetic and proliferative response in an attempt to restore and maintain the cartilage.
• Commonly, aging non-arthritic cartilage will demonstrate fibrillation of the joint surface, which is usually entirely asymptomatic. Changes seen within the matrix include decreased water composition, increased collagen cross-linking and smaller proteoglycan aggregates (due to alteration in the function of aggrecans with age). It is presumed that these changes in composition and organisation of the matrix will adversely affect the mechanical properties of cartilage over time.
• Although these two processes are entirely different, one is not exclusive of the other and aging cartilage may eventually lead to osteoarthritic changes within a joint.
• Cartilage degeneration and development of osteoarthritis is not simply the result of age and long-term mechanical wear. Degeneration of cartilage in osteoarthritis occurs through characteristic stages, the understanding of which can aid cartilage restoration interventions.
• Early observations that adult articular cartilage does not have the capacity to repair any structural damage due to injury or disease supported the view that adult articular cartilage is an inert bearing structure. This view implied that degeneration of the articular surface is potentially inevitable with aging and prolonged mechanical wear and that, other than altering joint loading, little could be done to prevent or reverse its occurrence. Buckwalter and Mankin challenge this view using evidence obtained from their own extensive work on articular cartilage as well as that of other researchers.³
• The authors review and outline the differences between cartilage changes due to aging and due to osteoarthritis degeneration (Table1) and demonstrate that the two are distinct processes. Three stages of degeneration in osteoarthritis (Table 2) and the associated reparative attempts of cartilage under these conditions were presented:

• Disruption or alteration of the cartilage matrix
• The chondrocytic response to tissue damage
• The decline of the chondrocytic synthetic response and the progressive loss of tissuTable 1. Differences between aging and osteoarthritic cartilage

Table 1. Differences between aging and osteoarthritic cartilage

Table 2. Stages in the development and progression of degeneration of articular cartilage in osteoarthrosis

• There is mechanical failure of the articular cartilage with progressive cartilage loss and subsequent new bone and cartilage formation at the joint margins.

• The process can be divided into three overlapping stages:

• Cartllage matrix damage or alteration
• Chondrocyte response to tissue damage
• Decline of chondrocyte synthetic response and progressive loss of tissue
• Initially the collagen network becomes damaged and disorganised. The cartilage structure becomes more permeable to water and proteoglycans are lost from the extracellular matrix with a change in the ratio of chondroitin to keratin (chondroitin is lost). These changes lead to increased water content with consequent swelling of the cartilage.
• Increased water content changes the mechanical properties of cartilage, leading to decreased stiffness, resulting in a weaker structure that is more prone to damage. Chondrocyte damage releases IL-1 into the synovial fluid that stimulates metalloproteinases and collagenase that breaks down collagen. The synovial fluid also changes, with decreased hyaluronic acid concentration resulting in thicker fluid with diminished lubricant properties.
• Attempts at repair result in a hypermetabolic state within the cartilage. The dysfunctioning cartilage allows greater forces to be transmitted to the subchondral bone, leading to bone remodeling and the sclerosis that is seen on X-rays. Microfractures or small areas of focal avascular necrosis within this subchondral bone allow synovial fluid to be pumped into the supporting bone, resulting in cyst formation. Abnormal stresses in the joint stimulate an attempt at healing, resulting in the formation of bone and cartilage “osteophytes,” which increase the joint surface area (to load share).
• Chondral changes include cartilage fragmentation (fibrillation), cartilage degradation and loss of type II collagen and proteoglycans, chondrocyte apoptosis (hypocellularity) and matrix mineralisation.
• Synovial changes in OA include inflammation, synovial hypertrophy, recruitment and activation of T cells, macrophages and fibroblasts, production of matrix metalloproteinases (MMPs) and reactive oxygen species (ROS).
• Synovial fluid alterations in OA include accumulation of MMPs and ROS, release of IL-1β, TNFα and other pro-inflammatory cytokines (IL-6, IL-8), release of inflammatory pain mediators such as prostaglandin E2 (PGE₂), formation of degradative products and microcrystals.
• Subchondral alterations in OA include subchondral sclerosis (i.e.eburnation), osteoblast-mediated subchondral bone formation, proteolysis (degradation) of IGF-I and IGF-I binding proteins (IGFBPs), increased production of some growth factors and cytokines including transforming growth factor β (TGFβ), PGE₂and interleukin 6 (IL-6).

Disruption or alteration of cartilage matrix

• Disruption or alteration of macromolecular framework of matrix associated with increase in concentration of water that may be caused by mechanical insults, degradation of matrix macromolecules, or alterations of chondrocyte metabolism. At first, concentration of type II collagen remains unchanged, but collagen meshwork may be damaged, and concentration of aggrecans and degree of proteoglycan aggregation decrease.

Response of chondrocytes to disruption or alteration of matrix

• When chondrocytes detect a disruption or alteration of their matrix, they can respond by increasing synthesis and degradation of the matrix and by proliferating. Their response may restore tissue, maintain tissue in an altered state, or increase volume of cartilage. They may sustain an increased level of activity for years.

Decline in response of chondrocytes

• Failure of chondrocytic response to restore or maintain tissue leading to loss of articular cartilage accompanied or proceeded by decline in chondrocytic response. Causes for this decline remain poorly understood, but they may partially result from mechanical damage to tissue, with injury to chondrocytes and downregulation of chondrocytic response to anabolic cytokines.

• OA can potentially affect any joint.
• Weight-bearing joints are most commonly affected – particularly the hip and knee.
• Also affected – fingers and thumb (first carpometacarpal joint), distal interphalangeal joint (DIP) and proximal interphalangeal joint (PIP), wrist, shoulder and spine.

• Pain – this is the chief presenting complaint. Classically: asymmetrical joint pain progressively worsening over a number of years. As the disease progresses, patients can get night pain disturbing their sleep. The pain is worse with movement/exercise and relieved by rest. NB. Pain may be referred to an adjacent joint, so hip pain can be referred to the knee.
• Stiffness – occurs after resting, therefore stiffness is usually worse in the morning but improves as the day progresses. But consider that early morning stiffness (predominantly affecting the hands and fingers) is classically also a feature of rheumatoid arthritis.
• Weakness – this is usually a result of muscle wasting due to pain inhibition and disuse.

• Activities of daily living – e.g. dressing, climbing stairs, cooking. It is important to determine what patients can and cannot do due to the OA.
• Mobility – use of walking aids, exercise tolerance, i.e. how far can patients walk and what makes them stop (is it joint pain or some other reason, e.g. breathlessness?).
• Home set-up – modifications to house (stair lifts), involvement of social services, help from any other agency (meals on wheels), family support.

• Inspection: swelling, erythema, muscle wasting, scars, contractures/fixed flexion deformities (a sign of advanced disease).
• Palpation: effusion (due to excess synovial fluid), joint tenderness with or without crepitus.
• Reduced range of movement.
• Examine the gait: use of walking aids. Is the patient limping?
• Classic OA signs:

• Heberden’s nodes = swelling of DIPs
• Bouchard’s nodes = swelling of PIPs

• ALWAYS examine the joint above and below (due to referred pain).
• ALWAYS examine the neurovascular system (i.e. check peripheral pulses and examine peripheral neurological system in relation to affected joint).

• Narrowing of joint space – due to cartilage loss.
• Subchondral sclerosis – thickened, new bone.
• Subchondral cysts – due to microfracture of sclerotic bone.
• Osteophytes – bony outgrowths at the joint margins (sign of advanced disease).

• There may be evidence of a pre-existing joint abnormality suggesting secondary OA, such as a previous fracture or congenital joint disease.

Conservative

• Lifestyle advice – weight loss, regular exercise, avoid excess load bearing and impact activities (e.g. heavy lifting, running).
• Physiotherapy – increases mobility and muscle strength and may result in improved gait and function.
• Walking aids.

Medical

• Regular analgesics – paracetamol, non-steroidal anti-inflammatory drugs (NSAIDS), codeine (ascending WHO pain ladder).
• Corticosteroid injections – may provide temporary symptomatic relief.
• Viscosupplement injections – synthetic hyaluronic acid is gaining in popularity but there is limited evidence of any benefit.
• Glucosamine – supplement widely taken but with limited evidence of any benefit.

Surgical

• Many options available if above measures have failed:
• Arthroscopic debridement – in selected cases, may be useful if mechanical symptoms are present, following an extended period of non-operative management (increasing scientific evidence suggests a “wash-out” does not provide any benefit).
• Osteotomy – correction of any angular deformity to offload the affected joint to improve symptoms and defer arthroplasty.
• Arthrodesis – joint fusion to relieve pain (e.g. spinal fusion, toes, ankle).
• Arthroplasty – commonly hip or knee but increasing availability for other joints. Excellent mid to long-term results for improving pain and function.

Figure 2. AP radiograph of a right knee demonstrating Total Knee Arthroplasty (or replacement)

 

 

Figure 3. AP radiograph demonstrating osteoarthritis of both hips. Note pelvic obliquity  (which may be as a result of spinal abnormality or muscular spasm)