Albers-Schonberg disease

Osteopetrosis (Malignant)
Classification and external resources
10 9 OMIM DiseasesDB eMedicine MeSH D010022

Osteopetrosis, literally "stone bone", also known as marble bone disease and Albers-Schonberg 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.


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.

The exact mechanism is unknown. However, deficiency of carbonic anhydrase in osteoclasts is noted. The absence of this enzyme causes defective hydrogen ion pumping by osteoclasts and this in turn causes defective bone resorption by osteoclasts, as an acidic environment is needed for dissociation of calcium hydroxyapatite from bone matrix. Hence, bone resorption fails while its formation persists. Excessive bone is formed.[3]


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, 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
Osteoporosis 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


There are several forms:

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.[5]

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.

Notable cases

See also


External links

  • GeneReviews/NCBI/NIH/UW entry on CLCN7-Related Osteopetrosis

Template:ATPase disorders

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