How bone disorders are tested on Step 1

Use the four labs to sort metabolic bone disease.

DisorderCalciumPhosphateAlkaline phosphatasePTH
OsteoporosisNormalNormalNormalNormal
Osteomalacia or rickets↓↓↑↑
Paget diseaseNormalNormal↑↑Normal
Primary hyperparathyroidism (osteitis fibrosa cystica)↑↓↑↑
OsteopetrosisNormal or ↓NormalNormalNormal or ↑

Alkaline phosphatase reflects osteoblast activity.

Osteoporosis↓ Bone mass, normal mineralPostmenopause, steroids, inactivityVertebral, hip, wrist fracturesNormal labsBisphosphonates, calcium, vitamin DOsteomalaciaPoorly mineralized osteoidVitamin D deficiency, malabsorptionBone pain, weakness, pseudofracturesLow Ca²⁺ and phosphate; high ALPVitamin D and calciumvs
Osteoporosis vs osteomalacia. Rickets in children adds bowed legs, rachitic rosary, and craniotabes.

Paget disease and osteopetrosis

Abnormal remodeling or failed resorption.

  • Paget disease of bone: excess osteoclast activity, then disorganized new bone ("mosaic" pattern). Skull, pelvis, and spine; headaches, hearing loss, bone pain, high-output heart failure from vascular bone; increased risk of osteosarcoma. Treat with bisphosphonates.
  • Osteopetrosis: osteoclasts cannot resorb bone (for example, carbonic anhydrase II deficiency); dense but brittle bone, marrow failure, cranial nerve compression.

Genetic bone disorders

Collagen and growth plate defects.

  • Osteogenesis imperfecta: COL1A1 or COL1A2 mutations (usually autosomal dominant); fractures with minor trauma, blue sclerae, hearing loss, dental problems.
  • Achondroplasia: FGFR3 gain of function inhibits cartilage growth at the growth plate; short limbs, large head, normal intelligence; risk rises with advanced paternal age.

Bone tumors

Location within the bone and the patient's age are the main clues.

OsteochondromaMost common benign; bony stalk with cartilage cap;metaphysisGiant cell tumorAges 20–40; epiphysis near the knee; "soap bubble"X-rayOsteosarcomaTeens and older adults; metaphysis; Codman triangle,sunburstEwing sarcomaBoys; diaphysis; onion skin; small round blue cells;t(11;22)MetastasesMost common bone malignancy overall; breast,prostate, lung, kidney, thyroid
Bone tumors. Osteosarcoma risk rises with hereditary retinoblastoma, Li-Fraumeni syndrome, Paget disease, and prior radiation.

Worked example

Use an isolated lab abnormality.

functions Worked example — bone pain and a bigger hat

A 70-year-old man has hip pain, new hearing loss, and notices his hats no longer fit. Calcium, phosphate, and PTH are normal; alkaline phosphatase is markedly elevated. X-ray shows thickened, coarse bone. What is the diagnosis?

  1. Normal calcium, phosphate, and PTH argue against parathyroid disease and osteomalacia.
  2. A very high alkaline phosphatase alone means intense osteoblast activity.
  3. Skull enlargement and hearing loss (bony compression of the auditory apparatus) fit abnormal remodeling.
  4. This is Paget disease of bone, treated with bisphosphonates.

Answer. Paget disease of bone.