Topic updated on 09/19/15 12:45pm
  • A metabolic bone disease caused by defective osteoclastic resorption of immature bone 
  • Pathophysiology
    • inability of the osteoclast to acidify Howship's lacuna 
    • leads to dense bone and obliterated medullary canal
    • may be linked to a defect in the thymus
  • Genetics
    • see classification
  • Associated conditions 
    • cranial nerve palsies
      • from overgrowth of skull foramina
      • optic > auditory > trigeminal > facial
    • osteomyelitis
      • lack of marrow vascularity and impaired WBC function
    • long bone fractures (tension failure)
    • coxa vara
      • from femoral neck fracture nonunion or repeated stress fractures
  • Prognosis
    • autosomal recessive is lethal and often causes death in infancy
    • autosomal dominant is compatible with life but associated with morbidity (see below)
Genetic Forms
Autosomal Recessive Form
Infantile or "malignant" form
Fatal in the first few years of life if untreated
Mapped to chromosome 11q13
Autosomal Dominant Form
Known as Albers-Schonberg disease
Mutations causing deactivation in 3 genes have been found:
  1. carbonic anhydrase II   
  2. alpha 3 subunit of vacuolar proton pump
  3. chloride channel 7

  • Autosomal recessive form
    • symptoms
      • frequent fractures
      • progressive deafness and blindness
      • severe anemia (caused by encroachment of bone on marrow) beginning in early infancy or in utero
    • physical exam
      • macrocephaly
      • hepatosplenomegaly (caused by compensatory extramedullary hematopoiesis)
      • dental abscesses and osteomyelitis of the mandible
  • Autosomal dominant form
    • symptoms
      • often not discovered until adulthood
      • may present with pathologic fracture
      • anemia (fatigue)
    • physical exam
      • generalized osteosclerosis
      • cranial nerve palsy
  • Radiographs
    • recommended views
      • AP and lateral of bone of interest
    • findings
      • "erlenmeyer flask" proximal humerus and distal femur
      • "rugger jersey spine" with very dense bone 
      • loss of medullary canal "bone within a bone" appearance
      • block femoral metaphysis 
  • Histology
    • see defective osteoclasts  
    • osteoclasts lack ruffled border and clear zone
    • islands of calcified cartilage within mature trabeculae
    • empty lacunae and plugging of the haversian canals also seen
  • Nonoperative
    • high dose calcitriol (1,25 dihydroxy vitamin D), bone marrow transplant
      • indications
        • autosomal recessive (infantile-malignant) form
    • interferon gamma-1beta
      • indications
        • autosomal dominant form


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Qbank (7 Questions)

(OBQ12.58) Which of the following most accurately describes the cause of osteopetrosis? Topic Review Topic

1. Decreased expression of type I collagen
2. Decreased mineralization of osteoid matrix
3. Loss-of-function of GS alpha protein gene
4. Loss-of-function of carbonic anhydrase II gene
5. Mutation of FGFR3

(OBQ11.139) An enzymatic mutation leading to abnormal carbonic anhydrase function in osteoclasts would lead to a condition best illustrated by which of the following radiographs in Figures A thru E. Topic Review Topic
FIGURES: A   B   C   D   E  

1. Figure A
2. Figure B
3. Figure C
4. Figure D
5. Figure E

(OBQ08.110) A 22-year-old male sustained a distal radius fracture following a fall down the stairs. The emergency room physician noticed abnormal bone appearance on the radiographs and referred him for skeletal survey and further orthopaedic evaluation. Pelvis and spine radiographs are provided in Figures A and B. Which of the following best describe the etiology of the bony disease? Topic Review Topic
FIGURES: A   B        

1. Defect in renal 25-(OH)-vitamin D1 alpha-hydroxylase
2. Defective osteoclast function
3. Autosomal dominant inheritance of altered fibroblast growth factor receptor 3 (FGFR3)
4. Alteration in osteoblast differentiation
5. Inability of proximal tubules to reabsorb phosphate

(OBQ07.260) A 5-year-old boy has sustained multiple fractures since birth. A pelvis radiograph taken 4 years ago is shown in Figure A. A current spine radiograph is shown in Figure B. Which of the following describes the mode of inheritance of this disease? Topic Review Topic
FIGURES: A   B        

1. Autosomal dominant
2. Autosomal recessive
3. X-linked dominant
4. X-linked recessive
5. Trinucleotide repeat

(OBQ06.123) What is the cellular mechanism responsible for osteopetrosis (Albers-Schönberg Disease)? Topic Review Topic

1. Inactive osteoclast Gs alpha subunit of the G-protein coupled receptor
2. Inactive osteoclast carbonic anhydrase
3. Inactive osteoclast mitochondria
4. Overactive osteoblast ruffled border
5. Overactive osteoblast RunX2

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HPI - Pain and inability to weight bear on RIGHT hip after simple fall.
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