Osteopetrosis

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Osteopetrosis (Malignant)
Classification and external resources
Osteopetrosis pelvis X-ray.png
X-ray of the pelvis of a patient with osteopetrosis, adult onset form (Albers-Schonberg disease). Note the dense bones.
ICD-10Q78.2
ICD-9756.52
OMIM166600 259700
DiseasesDB9377
eMedicinemed/1692
MeSHD010022
 
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Osteopetrosis (Malignant)
Classification and external resources
Osteopetrosis pelvis X-ray.png
X-ray of the pelvis of a patient with osteopetrosis, adult onset form (Albers-Schonberg disease). Note the dense bones.
ICD-10Q78.2
ICD-9756.52
OMIM166600 259700
DiseasesDB9377
eMedicinemed/1692
MeSHD010022

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.

Pathogenesis[edit]

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]

Symptoms[edit]

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, 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
ConditionCalciumPhosphateAlkaline phosphataseParathyroid hormoneComments
Osteoporosisunaffectedunaffectednormalunaffecteddecreased bone mass
Osteopetrosisunaffectedunaffectedelevatedunaffectedthick dense bones also known as marble bone
Osteomalacia and ricketsdecreaseddecreasedelevatedelevatedsoft bones
Osteitis fibrosa cysticaelevateddecreasedelevatedelevatedbrown tumors
Paget's disease of boneunaffectedunaffectedvariable (depending on stage of disease)unaffectedabnormal bone architecture

Variations[edit]

There are several forms:

NameOMIMGene
OPTA1607634LRP5
OPTA2166600CLCN7
OPTB1259700TCIRG1
OPTB2259710TNFSF11
OPTB3259730CA2 (renal tubular acidosis)
OPTB4611490CLCN7
OPTB5259720OSTM1
OPTB6611497PLEKHM1
OPTB7612301TNFRSF11A

Differential diagnosis[edit]

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.

Treatment[edit]

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[edit]

See also[edit]

References[edit]

  1. ^ "Marble Bone Disease: A Review of Osteopetrosis and Its Oral Health Implications for Dentists". Cda-adc.ca. 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. PMID 18028760. 
  3. ^ Robbins Basic Pathology by Kumar, Abbas, Fausto, and Mitchell, 8th edition
  4. ^ Robins basic pathology
  5. ^ Tolar J, Teitelbaum S, Orchard PJ (2004). "Osteopetrosis". New England Journal of Medicine 351 (27): 2839–49. doi:10.1056/NEJMra040952. PMID 15625335. 
  6. ^ Maddan, Heather. "Marin County artist Laurel Burch dead at 61 of rare bone disease". The San Francisco Chronicle. Retrieved 2007-12-23. 
  7. ^ "The Story of Lil BUB". YouTube. Retrieved 2013-10-17. 

External links[edit]