🦴 Normal bone

  • Organic matrix – type I collagen (90%), osteocalcin, glycoproteins, proteoglycans
  • Inorganic matrix – calcium hydroxyapatite [Ca₁₀(PO₄)₆(OH)₂], Mg, K, Cl, Na, F
  • Osteoblasts
    • Produce osteoid (unmineralized bone)
    • High alkaline phosphatase; PTH receptors
    • Modulate osteoclast activity
  • Osteocytes – mature osteoblasts embedded in matrix; maintain bone
  • Osteoclasts
    • Bone resorption in Howship's lacunae
    • Rich in acid phosphatase & collagenase
  • Remodeling – balanced resorption/formation; key hormones: PTH, calcitonin, vitamin D, estrogen, thyroid hormone, cortisol, GH
  • Intramembranous ossification – direct bone formation (flat bones: cranium, clavicle, vertebrae, wrist/ankle)
  • Endochondral ossification – cartilage model → long bones (femur, humerus, tibia, fibula)
  • Osteoid is unmineralized bone matrix; alkaline phosphatase reflects osteoblast activity.

🧬 Hereditary skeletal disorders

  • Achondroplasia – AD mutation in FGFR3
    • ↓ endochondral bone formation, premature growth plate ossification
    • Short, thick long bones; normal cranium/vertebrae; normal intelligence & lifespan
  • Osteogenesis imperfecta – abnormal type I collagen
    • Recurrent fractures, osteopenia, blue sclerae, joint hypermobility, deafness, dentinogenesis imperfecta, thin skin/easy bruising
    • Supportive treatment only
  • Fibrous dysplasia – GNAS mutation → fibrous tissue instead of bone
    • Pain, swelling, pathologic fractures (ribs, femur, cranium)
    • Microscopy: irregular bony trabeculae in fibrous stroma
  • Osteopetrosis – ↓ osteoclast function → thick sclerotic bones
    • AR (malignant): infants, early death from anemia/infection/hemorrhage
    • AD (benign): adults, fractures, anemia, cranial nerve palsies
    • “Erlenmeyer flask” deformity; myelophthisic anemia; hydrocephalus
    • Treatment: hematopoietic stem cell transplant
  • Osteopetrosis = marble bone disease; bone is dense but brittle, marrow failure is a key complication.

⚖️ Metabolic bone disorders

  • Paget disease – localized disorder, excessive resorption → disorganized replacement
    • Age >40, European ancestry; skull, pelvis, femur, vertebrae
    • Stages: osteolytic → mixed → osteosclerotic (burnout)
    • ↑ alkaline phosphatase, ↑ urinary hydroxyproline; X-ray: lytic/sclerotic enlargement
    • Complications: high-output cardiac failure (AV shunts), osteosarcoma (rare)
    • Microscopy: mosaic pattern of cement lines
  • Osteoporosis – decreased bone mass, thin fragile bones
    • Most common bone disorder; postmenopausal Caucasian women, elderly
    • Primary: estrogen deficiency, genetics, inactivity, age, nutrition
    • Secondary: immobilization, Cushing, thyrotoxicosis, corticosteroids, alcohol, smoking
    • Fractures: vertebrae (compression), femoral neck, Colles (distal radius)
    • DEXA measures BMD; labs usually normal (Ca, P, ALP)
    • Treatment: weight-bearing exercise, Ca + vitamin D, bisphosphonates, calcitonin
  • Paget = ↑ ALP with normal Ca/P; osteoporosis = normal ALP, Ca, P.

🥚 Mineralization defects

  • Osteomalacia (adults) – impaired mineralization of osteoid
    • Causes: vitamin D deficiency, malabsorption, renal/liver disease
    • Bone pain, fractures; Looser zones (transverse lucencies) on X-ray
    • Labs: ↓ Ca, ↓ P, ↑ alkaline phosphatase
  • Rickets (children) – undermineralized growth plate & bone
    • Craniotabes (softening), frontal bossing, rachitic rosary, pectus carinatum, bowing of legs
    • Treatment: vitamin D + calcium
  • Osteitis fibrosa cystica – primary hyperparathyroidism → ↑ osteoclast activity
    • Bone pain, deformities, fractures; “brown tumors” (cystic fibrous masses)
    • Micro: ↑ osteoclasts, marrow fibrosis, cystic spaces (dissecting osteitis)
    • Resolves with treatment of hyperparathyroidism
  • Osteomalacia = low Ca/P, high ALP; osteoporosis = normal Ca/P/ALP.

🔥 Inflammatory bone disease

  • Pyogenic osteomyelitis – bacterial bone infection
    • Hematogenous spread (most common) → metaphysis
    • Pathogens: S. aureus (most common), E. coli, Salmonella (sickle cell), Pseudomonas (IVDU/diabetes)
    • Fever, leukocytosis, localized pain/erythema/swelling
    • X-ray: normal for 2 weeks → periosteal elevation → lytic focus + sclerosis
    • Sequestrum (necrotic bone) & involucrum (new bone formation)
    • Treatment: antibiotics ± surgical drainage
    • Complications: Brodie abscess, sinus tract, squamous cell carcinoma, secondary amyloidosis
  • Tuberculous osteomyelitis – 1% of TB cases
    • Pott disease (thoracic/lumbar vertebrae), caseating granulomas
    • Fever, night sweats, weight loss; complications: compression fracture, psoas abscess
  • Osgood-Schlatter – traction apophysitis at tibial tuberosity (adolescents)
  • In osteomyelitis, MRI is more sensitive than X-ray; blood cultures and bone biopsy are diagnostic.

🔄 Avascular necrosis & hypertrophic osteoarthropathy

  • Avascular necrosis – ischemic necrosis of bone marrow
    • Causes: trauma/fracture (most common), steroids, sickle cell, Gaucher, caisson disease
    • Complications: osteoarthritis, pathologic fracture
  • Hypertrophic osteoarthropathy – painful swelling of wrists/fingers/ankles
    • Associated with bronchogenic carcinoma (paraneoplastic), chronic lung disease, cyanotic CHD, IBD
    • Periosteal new bone formation → digital clubbing, arthritis
    • May regress with treatment of underlying disease

🩻 Benign bone tumors

  • Osteoma – skull/facial bones; Gardner syndrome; no malignant transformation
  • Osteoid osteoma – diaphysis (tibia/femur), males 5–25; night pain relieved by aspirin; radiolucent nidus with sclerotic rim
  • Osteoblastoma – >2 cm, vertebrae; similar to osteoid osteoma
  • Osteochondroma – metaphyseal cartilage-capped exostosis; adolescent males; malignant transformation rare; multiple = osteochondromatosis
  • Enchondroma – medullary cartilage (hands/feet); solitary; multiple in Ollier (unilateral) or Maffucci (with hemangiomas) – risk of malignant transformation
  • Giant cell tumor (osteoclastoma) – females 20–50, epiphysis around knee; “soap bubble” X-ray; locally aggressive, 40–60% recurrence, ~2% pulmonary metastasis
  • Giant cell tumor is benign but can metastasize; high recurrence rate.

🧪 Malignant bone tumors

  • Osteosarcoma – most common primary malignant bone tumor
    • Teenagers (10–25), males; metaphysis around knee
    • Pain, swelling; Codman triangle, sunburst pattern on X-ray
    • Secondary: Paget disease, irradiation, chronic osteomyelitis (elderly)
    • Poor prognosis; metastases to lung (hematogenous)
  • Chondrosarcoma – malignant chondroblasts
    • Age 30–60, males; pelvis, spine, shoulder girdle
    • Popcorn calcification; prognosis depends on histologic grade
  • Ewing sarcoma – undifferentiated small round blue cells
    • Age 5–20, males; diaphysis (femur, pelvis, tibia)
    • t(11;22) EWS-FLI1 fusion; onion-skin periosteal reaction
    • Homer Wright pseudorosettes; 75% 5-year survival with chemo/radiation/surgery
  • Metastatic bone tumors – more common than primary
    • Prostate (osteoblastic), breast, lung, thyroid, kidney
  • Ewing: t(11;22); osteosarcoma: sunburst + Codman; chondrosarcoma: popcorn calcification.