- Osteopetrosis
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Osteopetrosis (Malignant) Classification and external resources 
X-ray of the pelvis of a patient with osteopetrosis, adult onset form (Albers-Schonberg disease). Note the dense bones.ICD-10 Q78.2 ICD-9 756.52 OMIM 166600 259700 DiseasesDB 9377 eMedicine med/1692 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.
It can cause osteosclerosis.[1]
Contents
Pathogenesis
Normal bone growth is achieved by a balance between bone formation by osteoblasts and bone resorption (break down 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.[2]
Symptoms
A 17-year-old male with osteopetrosis tarda. Typical cranial deformity, 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 suffers 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.[3]
Comparison of bone pathology Phosphate Alkaline phosphatase Parathyroid hormone Comments Osteoporosis unaffected unaffected variable unaffected decreased bone mass Osteopetrosis unaffected unaffected elevated unaffected thick dense bones also known as marble bone Osteomalacia and rickets decreased decreased variable 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 Variations
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.
Treatment
The only durable cure for osteopetrosis types affecting the osteoclasts (most types) is bone marrow transplant.[4]
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
References
- ^ 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. http://www.cda-adc.ca/jcda/vol-73/issue-9/839.html.
- ^ Robbins Basic Pathology by Kumar, Abbas, Fausto, and Mitchell, 8th edition
- ^ Robins basic pathology
- ^ Tolar J, Teitelbaum S, Orchard PJ (2004). "Osteopetrosis". New England Journal of Medicine 351 (27): 2839–49. doi:10.1056/NEJMra040952. PMID 15625335.
- ^ Maddan, Heather. "Marin County artist Laurel Burch dead at 61 of rare bone disease". The San Francisco Chronicle. http://www.sfgate.com/cgi-bin/article.cgi?f=/c/a/2007/09/23/BAH2S9B1N.DTL. Retrieved 2007-12-23.
External links
- International Osteopetrosis Association
- GeneReviews/NCBI/NIH/UW entry on CLCN7-Related Osteopetrosis
- http://www.rarediseases.org/search/rdbdetail_abstract.html?disname=Osteopetrosis
Osteochondrodysplasia (Q77–Q78, 756.4–756.5) Osteodysplasia/
osteodystrophyOther/ungroupedFLNB (Boomerang dysplasia) · Opsismodysplasia · Polyostotic fibrous dysplasia (McCune-Albright syndrome)Chondrodysplasia/
chondrodystrophy
(including dwarfism)enchondromatosis (Ollier disease, Maffucci syndrome)Other dwarfismFibrochondrogenesis · Short rib-polydactyly syndrome (Majewski's polydactyly syndrome) · Léri-Weill dyschondrosteosisGenetic disorder, membrane: ATPase disorders ATP1 ATP2 ATP2A1 (Brody myopathy) · ATP2A2 (Darier's disease, Acrokeratosis verruciformis) · ATP2C1 (Hailey–Hailey disease)ATP7 ATP13 ATP13A2 (Kufor-Rakeb syndrome)Other Osteopetrosis B1Genetic disorder, membrane: Channelopathy Calcium channel CACNA1A (Familial hemiplegic migraine 1, Episodic ataxia 2, Spinocerebellar ataxia type-6) · CACNA1C (Timothy syndrome, Brugada syndrome 3, Long QT syndrome 8) · CACNA1F (Ocular albinism 2, CSNB2A) · CACNA1S (Hypokalemic periodic paralysis 1, Thyrotoxic periodic paralysis 1) · CACNB2 (Brugada syndrome 4)Ligand gatedSodium channel Voltage-gatedSCN1A (Familial hemiplegic migraine 3, GEFS+ 2, Febrile seizure 3A) · SCN1B (Brugada syndrome 6, GEFS+ 1) · SCN4A (Hypokalemic periodic paralysis 2, Hyperkalemic periodic paralysis, Paramyotonia congenita, Potassium-aggravated myotonia) · SCN4B (Long QT syndrome 10) · SCN5A (Brugada syndrome 1, Long QT syndrome 3) · SCN9A (Erythromelalgia, Febrile seizure 3B, Paroxysmal extreme pain disorder, Congenital insensitivity to pain)Potassium channel KCNA1 (Episodic ataxia 1) · KCNA5 (Familial atrial fibrillation 7) · KCNC3 (Spinocerebellar ataxia type-13) · KCNE1 (Jervell and Lange-Nielsen syndrome, Long QT syndrome 5) · KCNE2 (Long QT syndrome 6) · KCNE3 (Brugada syndrome 5) · KCNH2 (Short QT syndrome) · KCNQ1 (Jervell and Lange-Nielsen syndrome, Romano-Ward syndrome, Short QT syndrome, Long QT syndrome 1, Familial atrial fibrillation 3) · KCNQ2 (BFNS1}KCNJ1 (Bartter syndrome 2) · KCNJ2 (Andersen-Tawil syndrome, Long QT syndrome 7, Short QT syndrome) · KCNJ11 (TNDM3) · KCNJ18 (Thyrotoxic periodic paralysis 2)Chloride channel CFTR (Cystic fibrosis, Congenital absence of the vas deferens) · CLCN1 (Thomsen disease, Myotonia congenita) · CLCN5 (Dent's disease) · CLCN7 (Osteopetrosis A2, B4 · BEST1 (Vitelliform macular dystrophy) · CLCNKB (Bartter syndrome 3)TRP channel Connexin GJA1 (Oculodentodigital dysplasia, Hallermann–Streiff syndrome, Hypoplastic left heart syndrome) · GJB1 (Charcot–Marie–Tooth disease X1) · GJB2 (Keratitis–ichthyosis–deafness syndrome, Ichthyosis hystrix, Bart–Pumphrey syndrome, Vohwinkel syndrome) · GJB3/GJB4 (Erythrokeratodermia variabilis, Progressive symmetric erythrokeratodermia) · GJB6 (Clouston's hidrotic ectodermal dysplasia)Porin Categories:- Genetic disorders by system
- Rare diseases
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