Q5 LONG ANSWER 10M ★ High-yield

Describe the metabolic bone diseases. Add notes on osteomyelitis and the classification and features of bone tumours.

Pathology · 2nd Professional — Para-Clinical

Metabolic Bone Disease

Disease	Defect	Biochemistry	Features
Osteoporosis	Reduced bone mass with normal mineralisation; bone that is normal in quality but deficient in quantity	Calcium, phosphate and alkaline phosphatase all normal	Fractures of the vertebrae (crush), neck of femur and distal radius (Colles); loss of height and kyphosis. Post-menopausal (oestrogen deficiency, trabecular bone) and senile (cortical bone)
Osteomalacia and rickets	Defective mineralisation of normal osteoid; osteoid seams are widened	Calcium low or normal, phosphate low, alkaline phosphatase raised, PTH raised, vitamin D low	Rickets in children — bowing of legs, rachitic rosary, widened epiphyses, craniotabes, Harrison sulcus. Osteomalacia in adults — bone pain, proximal myopathy, waddling gait, looser zones (pseudofractures)
Primary hyperparathyroidism	Excess PTH → osteoclastic resorption	Calcium high, phosphate low, alkaline phosphatase raised, PTH raised	Osteitis fibrosa cystica — "brown tumours" of osteoclasts, haemorrhage and fibrous tissue; subperiosteal resorption of the radial side of the middle phalanges; "pepper-pot" skull. "Stones, bones, abdominal groans and psychic moans"
PAGET disease of bone	Disordered, excessive bone turnover	Calcium and phosphate normal; alkaline phosphatase markedly raised	Three phases — osteolytic, mixed, then osteosclerotic; a chaotic "mosaic" pattern of cement lines. Bone pain, deformity, increasing hat size, deafness, high-output cardiac failure; risk of osteosarcoma in about 1%

CLINICAL PEARL

The biochemical pattern identifies the disease before any radiograph.
Osteoporosis — everything normal.
Osteomalacia — low calcium and phosphate, high alkaline phosphatase.
Hyperparathyroidism — high calcium with low phosphate.
Paget — normal calcium and phosphate with a strikingly high alkaline phosphatase. Learning the four patterns is worth more than any list of features.

Osteomyelitis

Routes — haematogenous (commonest in children), direct spread from adjacent infection, and direct implantation after trauma or surgery
Organisms — staphylococcus aureus in 80–90%; salmonella characteristically in sickle cell disease; Pseudomonas in drug users; group B streptococcus and E. Coli in neonates
Site — the metaphysis of long bones in children, because blood flow there is sluggish in the looped capillaries
Morphology — suppuration raises the periosteum and compromises the blood supply; sequestrum is the resulting fragment of dead bone; involucrum is the shell of reactive new bone formed around it; cloaca is the opening through which pus discharges
BRODIE abscess — a walled-off subacute intraosseous abscess
Chronic osteomyelitis may lead to sinus formation, pathological fracture, AA amyloidosis, and squamous cell carcinoma in a long-standing sinus tract
Tuberculous osteomyelitis is important in India — particularly POTT disease of the spine, with caseation, vertebral collapse producing a gibbus, and a cold (paravertebral) abscess that may track along the psoas sheath

Bone Tumours — Classification

Tissue	Benign	Malignant
Bone-forming	Osteoma, osteoid osteoma, osteoblastoma	Osteosarcoma
Cartilage-forming	Osteochondroma (the commonest benign bone tumour), chondroma, chondroblastoma	Chondrosarcoma
Unknown origin	Giant cell tumour (osteoclastoma) — locally aggressive	EWING sarcoma
Marrow	—	Myeloma, lymphoma
Metastatic	—	Far commoner than all primary bone tumours combined

The Important Malignant Tumours

Feature	Osteosarcoma	EWING sarcoma	Giant cell tumour
Age	10–20 (bimodal; second peak in the elderly with Paget disease)	5–20	20–40, after epiphyseal fusion
Site	Metaphysis of long bones — around the knee (distal femur, proximal tibia) in 60%	Diaphysis of long bones; also pelvis and ribs	Epiphysis, extending to the articular surface; distal femur and proximal tibia
Radiology	"sunburst" or "sun-ray" spiculation; CODMAN triangle of reactive periosteal bone; mixed lytic and sclerotic	"onion-skin" layered periosteal reaction; permeative moth-eaten lysis	"soap bubble" eccentric lytic lesion
Histology	Malignant cells producing osteoid — the defining feature	Sheets of small round blue cells; PAS-positive glycogen; HOMER–WRIGHT rosettes; t(11;22) EWSR1–FLI1	Multinucleate osteoclast-like giant cells in a background of mononuclear stromal cells, which are the true neoplastic component
Behaviour	Early haematogenous spread to lung	Aggressive; may present with fever and leucocytosis, mimicking osteomyelitis	Locally aggressive, recurs; about 5% metastasise to lung despite benign histology

Osteosarcoma predisposing factors — PAGET disease, previous radiation, and hereditary retinoblastoma (RB gene); serum alkaline phosphatase is raised
Ewing sarcoma responds well to chemotherapy and survival has improved greatly; it must be told apart from osteomyelitis, which it closely mimics

Benign Bone Tumours and Tumour-like Lesions

Lesion	Features
Osteochondroma (exostosis)	The commonest benign bone tumour; a cartilage-capped bony outgrowth at the metaphysis, pointing away from the joint; multiple in hereditary multiple exostoses, which carries a risk of chondrosarcoma
Osteoid osteoma	Under 2 cm; a radiolucent nidus with surrounding sclerosis; severe night pain characteristically relieved BY aspirin, because the nidus produces prostaglandins
Osteoblastoma	Over 2 cm; vertebrae; pain not relieved by aspirin
Enchondroma	Cartilage within the medulla, typically of the small bones of the hand; multiple in OLLIER disease and maffucci syndrome (with haemangiomas)
Fibrous dysplasia	Medullary bone replaced by fibrous tissue with "chinese letter" trabeculae of woven bone; GSAS1 mutation. McCUNE–albright syndrome adds cafe-au-lait spots and precocious puberty
Simple and aneurysmal bone cyst	Lytic lesions presenting with pathological fracture in children and adolescents

Applied Aspects

Metastases are far commoner than primary bone tumours — from breast, prostate, lung, kidney and thyroid. Most are osteolytic; prostate is characteristically osteoblastic. In an adult over 40 with a bone lesion, a metastasis is the most likely diagnosis
Diagnosis of a bone tumour requires clinical, radiological and pathological correlation together — histology alone can be seriously misleading, and the age and site narrow the differential more than anything else
Biopsy must be planned by the surgeon who will resect the tumour, since a badly placed tract contaminates compartments and may convert a limb-sparing operation into an amputation
Vitamin D deficiency is extremely common in India despite abundant sunlight — from skin pigmentation, covering clothing, indoor living, air pollution and low dietary intake; rickets and osteomalacia remain frequent and are cheaply prevented
Osteoporosis is diagnosed by DEXA — a T-score at or below −2.5; prevention by calcium, vitamin D, weight-bearing exercise and avoidance of smoking and excess alcohol
Suspect myeloma in an older patient with lytic lesions, anaemia and a very high ESR, and remember that its lesions do not show on isotope bone scans because osteoblasts are suppressed
Chronic osteomyelitis in India is frequently tuberculous, and a discharging sinus over a bone should prompt staining and culture for acid-fast bacilli as well as pyogenic organisms
Pott disease may present with a cold abscess or with paraplegia before any spinal deformity is obvious, and early treatment prevents permanent neurological damage
Osteosarcoma survival has improved from about 20% to over 60% with neoadjuvant chemotherapy followed by limb-sparing surgery — a major advance within living memory
Persistent bone pain that is worse at night and not related to activity is the classical warning symptom of a bone tumour, and deserves a radiograph rather than reassurance
Fluorosis is an important cause of skeletal disease in parts of India — excess fluoride in groundwater causes dense sclerotic bone with ligamentous calcification and mottled teeth
Avascular necrosis of the femoral head follows fracture, steroids, sickle cell disease, alcohol and caisson disease, and presents with hip pain long before radiographic change
Renal osteodystrophy combines osteomalacia, osteitis fibrosa and osteosclerosis in one patient, and is managed by controlling phosphate and giving active vitamin D
A raised alkaline phosphatase with normal calcium in an elderly patient should prompt consideration of Paget disease, and is often the way it is first found
Sudden increase in pain or a new mass in Paget disease suggests sarcomatous transformation, which carries a very poor prognosis
Bone biopsy should be the last step, not the first — age, site and radiographic pattern together narrow the differential more than histology alone can

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