Arthritis and metabolic bone disease
Arthritis, rheumatic disease and metabolic bone disease: patterns, mechanisms, X-rays
Arthritis and metabolic bone disease for FCPS Part 1: joint patterns, erosions, crystals, neuropathic joints, PVNS, bone infarcts and biochemistry. Each radiographic sign is explained by its mechanism.
Arthritis patterns
| Disease | Joints | Radiograph |
|---|---|---|
| Osteoarthritis | Weight-bearing joints, DIP, first CMC | Asymmetric narrowing, osteophytes, sclerosis, subchondral cysts |
| Erosive OA | PIP and DIP | Central erosions, gull-wing |
| Rheumatoid arthritis | Symmetric MCP, PIP, wrist, MTP | Periarticular osteopenia, marginal erosions, uniform narrowing |
| SLE | Hands | Deformities that correct (Jaccoud), no erosions |
| Psoriatic | DIP, dactylitis | Pencil-in-cup, new bone; nail pitting |
| Gout | First MTP | Punched-out erosions with overhanging edges, tophi, preserved joint space |
| CPPD | Knee, wrist | Chondrocalcinosis |
| Haemochromatosis | 2nd and 3rd MCP | Hook-like osteophytes, chondrocalcinosis |
| Neuropathic (Charcot) | Shoulder, foot, knee | Destruction, debris, sharp cut-off |
- Osteoarthritis is the commonest arthritis overall: a disease of cartilage (chondrocyte failure, loss of proteoglycan), not primarily of inflammation.
- Aspirin and NSAIDs relieve arthritic pain by inhibiting cyclooxygenase, decreasing prostaglandin synthesis.
Rheumatoid arthritis
- Autoimmune synovitis linked with HLA-DR4 (shared epitope). Pannus erodes bone at the joint margins (bare areas) where cartilage does not cover it.
- Anti-CCP is the most specific antibody; rheumatoid factor (IgM against IgG Fc) is less specific. ANA is often negative.
- Atlantoaxial subluxation: check before intubation.
- Rheumatoid nodule: central fibrinoid necrosis with palisading histiocytes. Caplan syndrome: lung nodules in coal miners with RA. Felty syndrome: RA, splenomegaly, neutropenia.
- AA amyloidosis: the precursor is serum amyloid A, an acute phase protein made by hepatocytes under IL-6; it stains red with Congo red and shows apple-green birefringence; kidney is commonly involved.
- Anaemia of chronic disease through hepcidin.
SLE and Jaccoud arthropathy
- Lupus arthritis is non-erosive. Jaccoud arthropathy: ulnar deviation and swan-neck deformities that correct passively, because the cause is lax joint capsules, ligaments and tendons, not bone or cartilage destruction; radiographs show deformity without erosions or narrowing.
Seronegative spondyloarthritis
- HLA-B27; inflammatory back pain (morning stiffness, better with exercise), anterior uveitis, enthesitis.
- Ankylosing spondylitis: earliest change at the sacroiliac joints (bilateral sacroiliitis); enthesitis gives shiny corners and squared vertebrae, then syndesmophytes from ossified outer annulus, giving a bamboo spine. The fused spine fractures easily; aortitis causes aortic regurgitation; apical lung fibrosis.
- Reactive arthritis: after dysentery or urethritis; arthritis, conjunctivitis, urethritis (HLA-B27).
Crystals, blood and synovium
- Gout: needle-shaped, negatively birefringent urate crystals; high cell turnover (polycythaemia vera, chemotherapy) raises urate.
- Dual-energy CT scans at two tube voltages: urate and calcium attenuate X-rays differently at the two energies, so software colour-codes urate deposits even when no fluid can be aspirated. Small or new deposits can be missed.
- Pseudogout: rhomboid, weakly positively birefringent calcium pyrophosphate; associated with hyperparathyroidism, haemochromatosis, hypomagnesaemia.
- Haemophilic arthropathy: repeated bleeds; enlarged epiphyses, wide intercondylar notch, squared patella.
- Pigmented villonodular synovitis: recurrent blood-stained effusions in one joint (knee) of a young adult with normal clotting; nodular synovium dark on T1 and T2 that blooms on gradient echo because of haemosiderin, with erosions on both sides of the joint. Image with MRI rather than repeatedly draining it.
- Haemochromatosis: arthritis with cardiomyopathy and raised ferritin: check transferrin saturation and HFE genotype.
Neuropathic joints
| Joint | Usual cause |
|---|---|
| Shoulder, elbow | Cervical syringomyelia |
| Foot and ankle | Diabetes mellitus |
| Knee | Tabes dorsalis |
- Loss of pain and proprioceptive protection lets repeated injury destroy the joint. Syringomyelia expands in the central cord and interrupts crossing spinothalamic fibres first, giving dissociated sensory loss (pain and temperature lost, touch kept) in a cape over shoulders and arms. A swollen, nearly painless shoulder with a vanished humeral head, sharp cut-off and debris is neuropathic; image the cervical cord.
Bone infarct and avascular necrosis
- Medullary bone infarct: steroids, alcohol, sickle cell, caisson disease. MRI shows a geographic area of fatty marrow with a serpiginous rim dark on T1 and a double line on T2 (granulation tissue inside sclerosis). Rarely a sarcoma arises in an old infarct.
- Avascular necrosis of the femoral head follows the same causes; the same double line appears at the subchondral bone.
Metabolic bone disease
| Disease | Calcium | Phosphate | ALP | PTH | Key sign |
|---|---|---|---|---|---|
| Osteoporosis | Normal | Normal | Normal | Normal | Fragility fractures; T-score ≤ −2.5 |
| Osteomalacia / rickets | Low or normal | Low | High | High | Looser zones; cupping and fraying |
| X-linked hypophosphataemic rickets | Normal | Very low | High | Normal | High FGF23 |
| Primary hyperparathyroidism | High | Low | High | High | Subperiosteal resorption (radial middle phalanges), pepper-pot skull, brown tumours |
| Paget disease | Normal | Normal | Very high | Normal | Enlarged, thick, coarse bone |
- Osteoporosis: oestrogen loss raises RANKL and lowers osteoprotegerin; steroids mainly suppress osteoblasts. Causes to seek in a fragility fracture: menopause, steroids, hyperthyroidism, hypogonadism, myeloma.
- Osteitis fibrosa cystica: severe hyperparathyroidism replaces bone with fibrous tissue and haemorrhagic cysts (brown tumours, full of osteoclast-like giant cells and haemosiderin).
- Renal osteodystrophy: secondary hyperparathyroidism; rugger-jersey spine.
- Paget disease: chaotic remodelling; bone is thick but weak (fractures), deafness, high-output heart failure (arteriovenous shunting in vascular bone), rare osteosarcoma.
- Scurvy: subperiosteal haemorrhage from weak collagen.
Osteomyelitis
- Staphylococcus aureus overall; Salmonella in sickle cell disease.
- Haematogenous infection settles in the metaphysis (sluggish flow in looping vessels).
- Infant septic hip: in the hip (and shoulder, elbow, ankle) the metaphysis lies inside the joint capsule, so pus from metaphyseal osteomyelitis bursts straight into the joint; in infants, vessels also cross the physis. A baby holding a leg still and flexed needs early ultrasound.
- Sequestrum, involucrum, cloaca; Brodie abscess is subacute and localised.
Bone tumours
| Tumour | Age and site | Imaging |
|---|---|---|
| Osteosarcoma | Teenager, metaphysis around the knee | Sunburst, Codman triangle |
| Ewing sarcoma | Child, diaphysis | Onion-skin; t(11;22) |
| Giant cell tumour | Adult, epiphysis after physeal closure | Eccentric lytic; neoplastic mononuclear stromal cells |
| Chondroblastoma | Adolescent, epiphysis, open physis | Lytic with stippled calcification |
Remember Erosions at the margin mean rheumatoid; erosions with overhanging edges mean gout; erosions in the centre mean erosive osteoarthritis.
Exam trap Severe hand deformity without erosions suggests lupus (Jaccoud), not rheumatoid arthritis.
Exam trap Brown tumours of hyperparathyroidism contain giant cells too; check calcium and PTH before calling a giant cell tumour.
How FCPS asks about this
- HLA linked with rheumatoid arthritis: HLA-DR4; most specific antibody anti-CCP.
- Precursor of amyloid in long-standing RA: serum amyloid A (AA amyloid).
- Destroyed painless shoulder with cape-like pain and temperature loss: cervical syringomyelia.
- Recurrent bloody knee effusions, normal clotting, blooming synovium: PVNS.
- Correctable deformities without erosions in SLE: Jaccoud arthropathy from lax capsules.
- Why septic arthritis follows infant hip osteomyelitis: the metaphysis is intracapsular.
- How dual-energy CT detects urate: different attenuation at two energies.
Test yourself on this topic
5 of the 52 questions in our bank on this topic. Choose an answer to see why every option is right or wrong.
A 55-year-old man has a hot, swollen first metatarsophalangeal joint after a weekend of heavy eating and drinking. Fluid aspirated from the joint is examined under polarised light. What is most likely to be seen?
Answer: Needle-shaped, negatively birefringent crystals
Gout is caused by deposition of monosodium urate crystals. Under compensated polarised light microscopy these are needle-shaped and strongly negatively birefringent, appearing yellow when parallel to the axis of the compensator. The crystals are phagocytosed by neutrophils and activate the NLRP3 inflammasome, releasing IL-1 and causing intense inflammation. Calcium pyrophosphate crystals of pseudogout are rhomboid and weakly positively birefringent and usually affect the knee or wrist of older people.
Crystal arthropathy
- Gout: needle, negative birefringence
- CPPD: rhomboid, weakly positive
- Crystals trigger IL-1 release
- First MTP: podagra
Remember Needles are negative: gout.
Exam trap Crystals and infection can occur together, so send the fluid for Gram stain and culture as well.
Why the other options are wrong
- Rhomboid, weakly positively birefringent crystals These are calcium pyrophosphate crystals of pseudogout, usually in the knee or wrist.
- Cholesterol plates with notched corners Seen in chronic effusions such as rheumatoid joints, not acute gout.
- Gram-positive cocci in clusters Septic arthritis can coexist, but this picture is classic acute gout.
- Calcium oxalate envelope-shaped crystals Seen in oxalosis in renal failure, not in typical gout.
A 19-year-old man has had repeated episodes of a hot, swollen right knee since childhood, often after minor knocks. His maternal uncle had the same problem. Platelet count and prothrombin time are normal, but the APTT is prolonged. What is the most likely cause of his knee disease?
Answer: Haemophilic arthropathy
Haemophilia A and B are X-linked, so affected males often have affected maternal uncles; both prolong the APTT with a normal prothrombin time and platelet count. Recurrent bleeding into a joint leaves haemosiderin in the synovium, which becomes hypertrophied and inflamed and releases enzymes that damage cartilage. Chronic hyperaemia during growth causes epiphyseal overgrowth, widening of the intercondylar notch and squaring of the patella. The knee, elbow and ankle are the commonest target joints.
Haemophilic arthropathy
- X-linked; APTT prolonged
- Repeated haemarthroses
- Haemosiderin drives synovitis
- Hyperaemia: epiphyseal overgrowth
Remember Recurrent knee bleeds in a boy with a long APTT: haemophilic joint.
Exam trap Women carriers can also have low factor levels and bleeding symptoms, so a normal mother does not exclude the diagnosis.
Why the other options are wrong
- Juvenile idiopathic arthritis Can cause epiphyseal overgrowth, but would not prolong the APTT or run in maternal uncles.
- Tuberculous arthritis Usually gives a chronic single swollen joint with systemic symptoms, not bleeds after knocks.
- Osteochondritis dissecans A focal fragment of subchondral bone, usually of the medial femoral condyle, without recurrent bleeds.
- Septic arthritis An acute febrile illness, not repeated swelling since childhood.
A 15-year-old boy with open growth plates has shoulder pain from a small tumour in the epiphysis of the proximal humerus. Biopsy shows sheets of round to polygonal cells with grooved nuclei, scattered giant cells and fine lace-like (chicken-wire) calcification around individual cells. What is the most likely diagnosis?
Answer: Chondroblastoma
Chondroblastoma is a benign cartilage tumour that arises in the epiphysis or apophysis of a skeletally immature patient, typically in the proximal humerus, distal femur or proximal tibia. Histology shows sheets of chondroblasts with grooved ('coffee bean') nuclei, osteoclast-like giant cells, islands of pink chondroid matrix and pericellular 'chicken-wire' calcification. Most carry an H3F3B histone mutation. Giant cell tumour also reaches the joint surface but occurs after physeal closure and lacks chondroid matrix and chicken-wire calcification.
Chondroblastoma
- Epiphysis of a teenager
- Grooved coffee-bean nuclei
- Chicken-wire calcification
- Closed physis instead: giant cell tumour
Remember Epiphysis plus chicken-wire calcification: chondroblastoma.
Exam trap Infection (Brodie abscess) can also involve the epiphysis in children, so an epiphyseal lesion is not always a tumour.
Why the other options are wrong
- Giant cell tumour Occurs after physeal closure; it has giant cells but no chondroblasts or chicken-wire calcification.
- Osteosarcoma A malignant tumour forming lace-like osteoid between pleomorphic cells, usually in the metaphysis.
- Simple bone cyst A fluid-filled cavity lined by thin fibrous tissue, not a cellular tumour.
- Enchondroma Lobules of mature hyaline cartilage, usually in the hands, not chondroblasts in the epiphysis.
A 28-year-old woman has a giant cell tumour of the distal radius, extending to the subchondral bone, with closed growth plates. Biopsy shows numerous osteoclast-like giant cells evenly scattered among mononuclear cells. She is treated with denosumab before surgery. Which cells are the true neoplastic population?
Answer: Mononuclear stromal cells
In giant cell tumour of bone, the neoplastic cells are the mononuclear stromal cells, which carry a characteristic H3F3A histone mutation and express RANK ligand. RANKL recruits and activates monocytes to fuse into the numerous osteoclast-like giant cells, which are reactive and cause the bone destruction. Denosumab, a monoclonal antibody against RANKL, therefore shrinks the tumour by removing the signal that drives giant cell formation. The tumour arises in the metaphysis and extends to the subchondral bone after the growth plate closes.
Giant cell tumour
- Neoplastic: mononuclear stromal cells
- Stromal cells make RANKL
- Giant cells are reactive osteoclasts
- Treatment: denosumab (anti-RANKL)
Remember The giant cells are recruits; the stromal cells give the orders.
Exam trap Other lesions such as brown tumours also contain giant cells, so check calcium and PTH before diagnosing GCT.
Why the other options are wrong
- Osteoclast-like giant cells These are reactive cells recruited by the stromal cells' RANKL; they give the tumour its name but are not neoplastic.
- Reactive macrophages Present but not the driving neoplastic cells.
- Osteoblasts lining trabeculae Osteoblasts are not the tumour cells in this lesion.
- Chondrocytes in a cartilage matrix A cartilage matrix suggests a chondroid tumour, not giant cell tumour.
A 26-year-old man has inflammatory back pain. The lateral lumbar radiograph shows small erosions at the anterior corners of several vertebral bodies, some healing with bright sclerosis, making the vertebrae look square. What process causes these corner changes?
Answer: Enthesitis at the vertebral body corners
In ankylosing spondylitis, the primary lesion is enthesitis: inflammation where the outer fibres of the annulus fibrosus attach to the vertebral corners. This causes small corner erosions (Romanus lesions), which heal with reactive sclerosis ('shiny corners') and loss of the normal anterior concavity, so the vertebrae look square. Later, the outer annulus ossifies to form thin vertical syndesmophytes that bridge the discs. MRI shows the active corner inflammation as bright signal on fluid-sensitive sequences.
Ankylosing spondylitis spine
- Primary lesion: enthesitis
- Corner erosions: Romanus lesions
- Healing: shiny corners, squaring
- Later: syndesmophytes, bamboo spine
Remember Shiny square corners: enthesitis of ankylosing spondylitis.
Exam trap Do not confuse thin vertical syndesmophytes with the thick horizontal osteophytes of degeneration.
Why the other options are wrong
- Disc herniation into the endplate A disc herniation into the endplate forms a Schmorl node in the middle of the endplate, not at the corners.
- Osteophytes from disc degeneration Degenerative osteophytes project horizontally from the endplate margins, without corner erosions.
- Infection spreading under the ligament Spinal infection destroys the disc and endplates rather than producing small healed corner erosions.
- Ischaemia of the central endplate Central endplate infarction gives the H-shaped vertebrae of sickle cell disease.
Where this sits in the CPSP syllabus
- Diagnostic Radiology, Paper 2: Musculoskeletal and endocrine disorders, Arthritis, rheumatic disease and metabolic bone disease
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