Tutorial 03: Bone and Joint Disease

Osteoarthritis (OA) is the most common joint disease worldwide. It is characterised by progressive loss of articular cartilage, subchondral bone changes, and periarticular new bone formation (osteophytes). OA was long considered simple "wear and tear" but is now understood to involve altered chondrocyte biology: in response to mechanical stress, chondrocytes increase production of matrix metalloproteinases (MMPs) and inflammatory cytokines (IL-1β, TNF-α) while reducing synthesis of proteoglycans and type II collagen. This imbalance leads to progressive proteoglycan depletion and cartilage degradation.

Gross pathological changes in OA include: surface fibrillation of cartilage (superficial splitting, the earliest change), progressive cartilage loss exposing subchondral bone (eburnation — the bone becomes polished and sclerotic from articulating directly against bone), subchondral cyst formation (synovial fluid forced into bone through articular surface defects), and marginal osteophyte formation (new bone at joint margins, visible on X-ray as "bony spurs"). OA characteristically affects weight-bearing joints (hip, knee), the distal interphalangeal joints (DIP; Heberden's nodes — osteophyte nodules), and the proximal interphalangeal joints (PIP; Bouchard's nodes). There is no effective disease-modifying therapy; management is symptomatic (analgesia, physiotherapy, joint replacement).

Rheumatoid arthritis (RA) is a systemic autoimmune disease causing symmetric erosive polyarthritis predominantly affecting small joints of hands and feet. It is 3× more common in women. The genetic predisposition involves HLA-DR4 and HLA-DR1. Autoantibodies include rheumatoid factor (RF, an IgM against the Fc portion of IgG) and anti-cyclic citrullinated peptide (anti-CCP) antibodies. Anti-CCP is more specific than RF and may precede clinical disease by years. The synovium becomes hyperplastic, forming a pannus — a destructive layer of granulation tissue that erodes into adjacent cartilage and bone. TNF-α, IL-1, and IL-6 drive synovial inflammation and systemic features (fever, anaemia of chronic disease, vasculitis, subcutaneous rheumatoid nodules). Treatment: DMARDs (disease-modifying antirheumatic drugs — methotrexate first-line) and biologics targeting TNF (infliximab, etanercept) or IL-6 (tocilizumab).

Gout is caused by deposition of monosodium urate (MSU) crystals in joints and soft tissues, resulting from chronic hyperuricaemia. Uric acid is the end-product of purine metabolism; hyperuricaemia results from overproduction (high purine diet, haematological malignancy, psoriasis) or underexcretion (renal impairment, thiazide diuretics). MSU crystals precipitate preferentially in cooler peripheral joints: first metatarsophalangeal joint (podagra), ankles, knees. Acute gout: neutrophils engulf crystals, triggering activation of the NLRP3 inflammasome → IL-1β release → intense acute inflammation. Synovial fluid microscopy shows needle-shaped negatively birefringent crystals under polarised light. Chronic gout: accumulation of crystal deposits (tophi) in soft tissues (helix of ear, tendons, subcutaneous tissue). Treatment: acute attack — colchicine (microtubule inhibitor, prevents neutrophil chemotaxis), NSAIDs, or corticosteroids; urate-lowering therapy — allopurinol (xanthine oxidase inhibitor).

Osteomyelitis is infection of bone. Haematogenous osteomyelitis in children typically seeds the metaphysis of long bones (where vascular loops slow blood flow). Staphylococcus aureus accounts for 80–90% of cases. Pus accumulates under the periosteum, stripping it from bone (periosteal elevation). Ischaemic necrosis of cortical bone produces a sequestrum (dead bone) surrounded by new periosteal bone (involucrum). Treatment requires prolonged antibiotics and surgical debridement. Septic arthritis (most commonly S. aureus) requires urgent surgical drainage to prevent chondrocyte death from neutrophil enzymes.