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Title: Osteopetrosis  
Author: World Heritage Encyclopedia
Language: English
Subject: Achondroplasia, Osteosclerosis, Tartrate-resistant acid phosphatase, Jansen's metaphyseal chondrodysplasia, Antley–Bixler syndrome
Collection: Genetic Disorders by System, Rare Diseases
Publisher: World Heritage Encyclopedia


Osteopetrosis (malignant)
X-ray of the pelvis of a patient with osteopetrosis, adult onset form (Albers-Schönberg disease). Note the dense bones.
Classification and external resources
ICD-10 Q78.2
ICD-9-CM 756.52
OMIM 166600 259700
DiseasesDB 9377
eMedicine med/1692
MeSH D010022

Osteopetrosis, literally "stone bone", also known as marble bone disease and Albers-Schönberg disease, is an extremely rare inherited disorder whereby the bones harden, becoming denser, in contrast to more prevalent conditions like osteoporosis, in which the bones become less dense and more brittle, or osteomalacia, in which the bones soften. Osteopetrosis can cause bones to dissolve and break.[1]

It can cause osteosclerosis.[2] The cause of the disease is understood to be malfunctioning osteoclasts. Radiological findings will show a bone-in-bone appearance.[3]


  • Signs and symptoms 1
  • Pathogenesis 2
  • Variations 3
  • Differential diagnosis 4
  • Treatment 5
  • Prevalence 6
  • Notable cases 7
  • See also 8
  • References 9
  • External links 10

Signs and symptoms

A 17-year-old male with osteopetrosis tarda: Typical cranial deformity and thoracic scoliosis

Despite this excess bone formation, people with osteopetrosis tend to have bones that are more brittle than normal. Mild osteopetrosis may cause no symptoms, and present no problems. However, serious forms can result in stunted growth, deformity, and increased likelihood of fractures; also, patients suffer anemia, recurrent infections, and hepatosplenomegaly due to bone expansion leading to bone marrow narrowing and extramedullary hematopoiesis. It can also result in blindness, facial paralysis, and deafness, due to the increased pressure put on the nerves by the extra bone.[4]

Comparison of bone pathology
Condition Calcium Phosphate Alkaline phosphatase Parathyroid hormone Comments
Osteopenia unaffected unaffected normal unaffected decreased bone mass
Osteopetrosis unaffected unaffected elevated unaffected thick dense bones also known as marble bone
Osteomalacia and rickets decreased decreased elevated elevated soft bones
Osteitis fibrosa cystica elevated decreased elevated elevated brown tumors
Paget's disease of bone unaffected unaffected variable (depending on stage of disease) unaffected abnormal bone architecture


Normal bone growth is achieved by a balance between bone formation by osteoblasts and bone resorption (breakdown of bone matrix) by osteoclasts. In osteopetrosis, the number of osteoclasts may be reduced, normal, or increased. Most importantly, osteoclast dysfunction mediates the pathogenesis of this disease.

Osteopetrosis is caused by underlying mutations that interfere with the acidification of the osteoclast resorption pit, for example due to a deficiency of the carbonic anhydrase enzyme encoded by the CA2 gene.[5] Carbonic anhydrase is required by osteoclasts for proton production. Without this enzyme hydrogen ion pumping is inhibited and bone resorption by osteoclasts is defective, as an acidic environment is needed to dissociate calcium hydroxyapatite from the bone matrix. As bone resorption fails while bone formation continues, excessive bone is formed.[6]


The several forms are:

Name OMIM Gene
OPTA1 607634 LRP5
OPTA2 166600 CLCN7
OPTB1 259700 TCIRG1
OPTB2 259710 TNFSF11
OPTB3 259730 CA2 (renal tubular acidosis)
OPTB4 611490 CLCN7
OPTB5 259720 OSTM1
OPTB6 611497 PLEKHM1
OPTB7 612301 TNFRSF11A

Differential diagnosis

The differential diagnoses include other disorders which can cause diffuse osteosclerosis, such as hypervitaminosis D and hypoparathyroidism, Paget's disease, diffuse bone metastasis of breast or prostate cancer (which tend to be osteoblastic, while most metastases are osteolytic), intoxication with fluoride, lead or beryllium, and hematological disorders such as myelofibrosis, sickle cell disease, and leukemia.


The only durable cure for osteopetrosis types affecting the osteoclasts (most types) is bone marrow transplant.[7]

If complications occur in children, patients can be treated with vitamin D. Gamma interferon has also been shown to be effective, and it can be associated to vitamin D. Erythropoetin has been used to treat any associated anemia. Corticosteroids may alleviate both the anemia and stimulate bone resorption. Fractures and osteomyelitis can be treated as usual.


There is 1 diseased for 100—200 thousands of newborns, but the chance to be diseased is greater in russian regions Chuvashia (1 diseased for 3500—4000 newborns) and Mari El (1 diseased for 14000 newborns) due to ethnogeny features of chuvash people и mari people.[8][9]

Notable cases

See also


  1. ^ "Marble Bone Disease: A Review of Osteopetrosis and Its Oral Health Implications for Dentists". Retrieved 2013-10-17. 
  2. ^ Lam DK, Sándor GK, Holmes HI, Carmichael RP, Clokie CM (2007). "Marble bone disease: a review of osteopetrosis and its oral health implications for dentists". J Can Dent Assoc 73 (9): 839–43.  
  3. ^ Horvai, Andrew (2012). Bone and Soft Tissue Pathology. Elsevier Health Sciences. p. 17.  
  4. ^ Robins basic pathology
  5. ^ Askmyr MK et al.: Towards a better understanding and new therapeutics of osteopetrosis. Br J Haematol 140:597, 208
  6. ^ Robbins Basic Pathology by Kumar, Abbas, Fausto, and Mitchell, 8th edition
  7. ^ Tolar J, Teitelbaum S, Orchard PJ (2004). "Osteopetrosis". New England Journal of Medicine 351 (27): 2839–49.  
  8. ^ Центр Молекулярной Генетики
  9. ^ Медицинская генетика Чувашии
  10. ^ Maddan, Heather (2007-09-23). "Marin County artist Laurel Burch dead at 61 of rare bone disease". The San Francisco Chronicle. Retrieved 2007-12-23. 
  11. ^ "The Story of Lil BUB". YouTube. Retrieved 2013-10-17. 

External links

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