Osteoarthritis — Pathogenesis, Diagnosis and Treatment

Osteoarthritis is a whole-joint disease characterised by focal hyaline cartilage destruction with joint space loss, subchondral sclerosis and osteophyte formation, together with synovial hypertrophy, capsular and ligamentous change and peri-articular muscle weakness.

It is the most common joint disease among older adults and the major cause of knee, hip and back pain. Almost 60% of Americans aged 65 and over report arthritis or chronic joint symptoms, and musculoskeletal disorders are the commonest cause of disability in old age.

In India, symptomatic knee osteoarthritis affects roughly 25–30% of adults over 60, with a female preponderance; deep squatting, floor-sitting, stair use in unlifted buildings and manual labour are important local contributors.

OA is not by definition inflammatory, although synovial hypertrophy and joint effusions are typical — a key distinction from rheumatoid arthritis.

Systemic: age, female sex (especially post-menopause), obesity, genetic predisposition, and metabolic syndrome (the “metabolic OA” phenotype).

Local and mechanical: previous joint injury or surgery (meniscectomy), malalignment (varus knee), joint dysplasia, occupational kneeling, squatting and lifting, quadriceps weakness, and proprioceptive loss.

OA is not simply “wear and tear”. Progression revolves around a complex interplay of chondrocyte dysregulation of the extracellular matrix, genetic influences, local mechanical factors and inflammation.

Abnormal mechanical loading activates chondrocytes to release matrix metalloproteinases (especially MMP-13) and aggrecanases (ADAMTS-4 and -5), which degrade type II collagen and aggrecan faster than they can be resynthesised.

IL-1β, TNF-α, IL-6, nitric oxide and prostaglandin E2 from chondrocytes and synovium amplify catabolism; adipokines such as leptin link obesity to cartilage damage beyond simple mechanical load.

Subchondral bone shows increased turnover, sclerosis, bone marrow lesions and cysts; osteophytes form at the joint margin by endochondral ossification, representing an attempted repair response.

Pain in established OA is mixed — nociceptive from subchondral bone, synovium, capsule and entheses (cartilage itself is aneural), plus peripheral and central sensitisation. This explains the poor correlation between radiographic severity and symptoms.

A vicious cycle operates in older people: joint pain → activity avoidance → muscle weakness and joint instability → further injury and pain → loss of cardiorespiratory fitness → an unfit, inactive, arthritic person with compromised independence.

Diagnosis is clinical: activity-related joint pain, morning stiffness lasting minutes rather than hours, gelling after inactivity, crepitus, restricted range of movement, bony enlargement, and minimal warmth or erythema.

Distinguishing OA from inflammatory arthritis: Clinical feature Osteoarthritis Inflammatory arthritis Duration of stiffness Minutes Hours Pain Usually with activity Occurs even at rest and at night Fatigue Unusual Common Swelling Common, little synovial reaction Very common, with synovial proliferation and thickening Erythema and warmth Unusual Common

Typical joints: knees, hips, first carpometacarpal joint, distal interphalangeal (Heberden’s nodes) and proximal interphalangeal (Bouchard’s nodes), first metatarsophalangeal joint (hallux rigidus), midfoot, and cervical and lumbar facet joints.

Foot OA affects one in six people over 50, with two phenotypes: isolated first MTP joint OA (hallux rigidus) — localised pain, stiffness and a dorsal exostosis — and a polyarticular midfoot form presenting as dorsal foot pain worse on prolonged standing and walking on uneven ground.

Plain radiography remains the main modality — joint space narrowing, subchondral sclerosis, osteophytes and subchondral cysts (Kellgren–Lawrence grades 0–4). MRI and ultrasound are more accurate and comprehensive measures of joint change but are rarely needed for diagnosis.

Blood tests are normal. ESR, CRP, rheumatoid factor and anti-CCP are used only to exclude alternatives. Aspirate the joint if there is an effusion with warmth, to exclude sepsis or crystal arthropathy — remember that gout and pseudogout commonly coexist with OA in the elderly.

Non-pharmacological management should be the focus of intervention: patient education and self-management, weight loss, land-based and aquatic exercise, quadriceps strengthening, daily range-of-motion exercise, local ice and heat, and acupuncture. Group exercise improves poor compliance by adding a social component.

Assistive devices and biomechanics: a cane held in the contralateral hand reduces load on an arthritic hip; cane length should equal the distance from the wrist crease to the floor, and stick rubbers must be checked and replaced to avoid falls. For knee pain the patient should experiment with the cane in either hand. Moulded splints protect arthritic hand joints; foot orthoses and shoe-stiffening inserts are effective for first MTP and midfoot OA.

Time analgesia before activity — OA pain is exacerbated by exercise, so medication is best given beforehand rather than afterwards.

Pharmacological therapy is symptomatic: topical NSAIDs first for knee and hand OA in older adults (best benefit-to-risk ratio); paracetamol has modest effect; oral NSAIDs at the lowest dose for the shortest duration, with PPI cover and careful attention to renal, cardiac, GI and Beers-criteria risk.

Intra-articular corticosteroid gives short-term relief of a flare (weeks). Viscosupplementation with hyaluronic acid and nutraceuticals (glucosamine, chondroitin) have not shown significant pain benefit beyond placebo, and vitamin D neither reduces pain nor repairs structural damage.

Duloxetine is useful where central sensitisation dominates. Avoid long-term opioids in older adults. Refractory pain is best managed by a multidisciplinary pain team with anaesthetic, psychological and physiotherapy input.

Surgery: total knee or hip arthroplasty is reserved for severe symptomatic disease failing conservative treatment; patients should be medically stable, encouraged to lose weight and strengthen relevant muscles before operation. Arthroscopic lavage and debridement have little evidence of efficacy and are not recommended for degenerative knee disease.

Optimal management usually requires several modalities combined, and the best combination varies from patient to patient — a genuinely individualised, function-focused approach.