Osteopetrosis

Rare hereditary bone disorder where osteoclasts cannot resorb bone, leading to abnormally dense, brittle bones.

• The infantile form is often fatal by early childhood without treatment, whereas the adult form can be asymptomatic. Classic "bone-in-bone" x-ray findings and the contrast with osteoporosis make it a high-yield exam topic.

• Dense, sclerotic bones that paradoxically break easily (excess bone but poor quality). Marrow space narrowing leads to pancytopenia with extramedullary hematopoiesis (hepatosplenomegaly). Cranial nerve compression from skull thickening causes vision and hearing loss, facial paralysis. Teeth may erupt late due to dense bone.
• Infantile (malignant, AR): presents in infancy with failure to thrive, pathologic fractures, pancytopenia (infections, bleeding), cranial nerve palsies (blindness, deafness), and enlarged liver/spleen. Often fatal if untreated.
• Adult (benign, AD, Albers-Schönberg): usually milder. May be discovered incidentally in adolescence/adulthood with repeated fractures, sometimes cranial nerve issues or arthritis. No marrow failure (near-normal blood counts), so life expectancy is generally normal.

1. Identify osteosclerosis on imaging: diffuse bony thickening with classic "bone-in-bone" appearance confirms osteopetrosis.
2. Assess severity: check CBC for pancytopenia (marrow failure) and evaluate cranial nerve function (vision, hearing) in severe cases.
3. Consider genetic testing to identify the mutated gene (e.g., TCIRG1 in many AR cases, CLCN7 in most AD cases).
4. Infantile malignant osteopetrosis requires early hematopoietic stem cell transplant for survival. Adult benign osteopetrosis is managed supportively (fracture care, antibiotics for osteomyelitis, etc.).

1. Infantile (severe): early hematopoietic stem cell transplant (curative by providing functional osteoclasts).
2. Supportive care for complications: blood transfusions for anemia, antibiotics for osteomyelitis, adequate calcium/vitamin D intake, etc.
3. Interferon γ (Actimmune) can enhance bone resorption and immune function in severe cases, but transplant offers the best outcome.

• Osteopetrosis is basically the opposite of osteoporosis: bones are dense like marble but break like chalk.
• Carbonic anhydrase II mutation causes osteopetrosis with renal tubular acidosis (metabolic acidosis + kidney stones).
• Think marble bones: "stone bone" disease with cranial nerve palsies and pancytopenia from bone overgrowth.

1. Suspect osteopetrosis if X-ray shows diffuse osteosclerosis (e.g., bone-in-bone).
2. Check CBC (for pancytopenia) and assess cranial nerve function (vision, hearing).
3. If infantile form, arrange prompt HSCT evaluation; provide supportive care (transfusions, infection prophylaxis).
4. If adult form, manage conservatively (fracture prevention, treat complications).

• Infant with fractures, anemia, hepatosplenomegaly, cranial nerve deficits, and diffuse bone-in-bone sclerosis on X-ray → infantile (malignant) osteopetrosis.
• Adult with incidentally very dense bones on X-ray and history of multiple fractures → benign (adult) osteopetrosis (Albers-Schönberg disease).