Reference work entry

Osteopetrosis is a heterogeneous group of sclerosing bone diseases due to impaired bone and cartilage resorption, resulting from absence or defective function of osteoclasts (Steward 2003). The overall incidence of these conditions is difficult to estimate, but autosomal recessive osteopetrosis has an incidence of 1 in 250,000 births, and autosomal dominant osteopetrosis has an incidence of 1 in 20,000 births (Stark and Savarirayan 2009).

Synonyms and Related Disorders

Albers-Schonberg disease; Infantile malignant osteopetrosis; Ostoclast-poor osteopetrosis

Genetics/Basic Defects

  1. 1.
    Inheritance of recognized subtypes of human osteopetrosis (Stark and Savarirayan 2009; Steward 2003, 2010)
    1. a.
      Autosomal recessive osteopetrosis
      1. i.

        Classic (infantile malignant osteopetrosis): Vacuolar proton pump deficiency (ATP6i/TCIRG1) (locus 11q13.3-q13.5)

      2. ii.

        Neuropathic (osteopetrosis and infantile neuroaxonal dystrophy): CLC-7 chloride pump deficiency (loss of function CLCN7mutations) (locus...


Pulmonary Arterial Hypertension Optic Atrophy Renal Tubular Acidosis Ectodermal Dysplasia Common Variable Immune Deficiency 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Abinun, M., Newson, T., Rowe, P. W., et al. (1999). Importance of neurological assessment before bone marrow transplantation for osteopetrosis. Archives of Disease in Childhood, 80, 273–274.PubMedCrossRefGoogle Scholar
  2. Armstrong, D. G., Newfield, J. T., & Gillespie, R. (1999). Orthopedic management of osteopetrosis: Results of a survey and review of the literature. Journal of Pediatric Orthopaedics, 19, 122–132.PubMedCrossRefGoogle Scholar
  3. Askmyr, M. K., Fasth, A., & Richter, J. (2008). Towards a better understanding and new therapeutics of osteopetrosis. British Journal of Haematology, 140, 597–609.PubMedCrossRefGoogle Scholar
  4. Bénichou, O. D., Benichou, B., Copin, H., et al. (2000). Further evidence for genetic heterogeneity within type II autosomal dominant osteopetrosis. Journal of Bone and Mineral Research, 15, 1900–1904.PubMedCrossRefGoogle Scholar
  5. Bénichou, O., Cleiren, E., Gram, J., et al. (2001). Mapping of autosomal dominant osteopetrosis type II (Albers-Schonberg disease) to chromosome 16p13.3. American Journal of Human Genetics, 69, 647–654.PubMedCrossRefGoogle Scholar
  6. Bénichou, O. D., Laredo, J. D., & de Vernejoul, M. C. (2000). Type II autosomal dominant osteopetrosis (Albers-Schonberg disease): Clinical and radiological manifestations in 42 patients. Bone, 26, 87–93.PubMedCrossRefGoogle Scholar
  7. Campos-Xavier, A. B., Saraiva, J. M., Ribeiro, L. M., et al. (2003). Chloride channel 7 (CLCN7) gene mutations in intermediate autosomal recessive osteopetrosis. Human Genetics, 112, 186–189.PubMedGoogle Scholar
  8. Carolino, J., Perez, J. A., & Popa, A. (1998). Osteopetrosis. American Family Physician, 57, 1293–1296.PubMedGoogle Scholar
  9. Cheow, H. K., Steward, C. G., & Grier, D. J. (2001). Imaging of malignant infantile osteopetrosis before and after bone marrow transplantation. Pediatric Radiology, 31, 869–875.PubMedCrossRefGoogle Scholar
  10. Cleiren, E., Benichou, O., Van Hul, E., et al. (2001). Albers-Schonberg disease (autosomal dominant osteopetrosis, type II) results from mutations in the ClCN7 chloride channel gene. Human Molecular Genetics, 10, 2861–2867.PubMedCrossRefGoogle Scholar
  11. Cournot, G., Trubert-Thil, C. L., Petrovic, M., et al. (1992). Mineral metabolism in infants with malignant osteopetrosis: Heterogeneity in plasma 1,25-dihydroxyvitamin D levels and bone histology. Journal of Bone and Mineral Research, 7, 1–10.PubMedCrossRefGoogle Scholar
  12. de Vernejoul, M. C., & Benichou, O. (2001). Human osteopetrosis and other sclerosing disorders: Recent genetic developments. Calcified Tissue International, 69, 1–6.PubMedCrossRefGoogle Scholar
  13. Driessen, G. J., Gerritsen, E. J., Fischer, A., et al. (2003). Long-term outcome of haematopoietic stem cell transplantation in autosomal recessive osteopetrosis: an EBMT report. Bone Marrow Transplantation, 32, 657–663.PubMedCrossRefGoogle Scholar
  14. Eapen, M., Davies, S. M., Ramsay, N. K., et al. (1998). Hematopoietic stem cell transplantation for infantile osteopetrosis. Bone Marrow Transplantation, 22, 941–946.PubMedCrossRefGoogle Scholar
  15. El-Tawil, T., & Stoker, D. J. (1993). Benign osteopetrosis: A review of 42 cases showing two different patterns. Skeletal Radiology, 22, 587–593.PubMedCrossRefGoogle Scholar
  16. Felix, R., Hofstetter, W., & Cecchini, M. G. (1996). Recent developments in the understanding of the pathophysiology of osteopetrosis. European Journal of Endocrinology, 134, 143–156.PubMedCrossRefGoogle Scholar
  17. Frattini, A., Pangrazio, A., Susani, L., et al. (2003). Chloride channel ClCN7 mutations are responsible for severe recessive, dominant, and intermediate osteopetrosis. Journal of Bone and Mineral Research, 18, 1740–1747.PubMedCrossRefGoogle Scholar
  18. Gerritsen, E. J., Vossen, J. M., van Loo, I. H., et al. (1994). Autosomal recessive osteopetrosis: variability of findings at diagnosis and during the natural course. Pediatrics, 93, 247–253.PubMedGoogle Scholar
  19. Guerrini, M. M., Sobacchi, C., Cassani, B., et al. (2008). Human osteoclast-poor osteopetrosis with hypogammaglobulinemia due to TNFRSF11A (RANK) mutations. American Journal of Human Genetics, 83, 64–76.PubMedCrossRefGoogle Scholar
  20. Jacquemin, C., Mullaney, P., & Svedberg, E. (1998). Marble brain syndrome: Osteopetrosis, renal acidosis and calcification of the brain. Neuroradiology, 40, 662–663.PubMedCrossRefGoogle Scholar
  21. Kapelushnik, J., Shalev, C., Yaniv, I., et al. (2001). Osteopetrosis: A single centre experience of stem cell transplantation and prenatal diagnosis. Bone Marrow Transplantation, 27, 129–132.PubMedCrossRefGoogle Scholar
  22. Key, L., Carnes, D., Cole, S., et al. (1984). Treatment of congenital osteopetrosis with high dose calcitriol. The New England Journal of Medicine, 310, 409–415.PubMedCrossRefGoogle Scholar
  23. Key, L. L., Jr., Rodriguiz, R. M., Willi, S. M., et al. (1995). Long-term treatment of osteopetrosis with recombinant human interferon gamma. The New England Journal of Medicine, 332, 1594–1599.PubMedCrossRefGoogle Scholar
  24. Kilic, S. S., & Etzioni, A. (2008). The clinical spectrum of leukocyte adhesion deficiency (LAD) III due to defective CalDAG-GEF1. Journal of Clinical Immunology, 29, 117–122.PubMedCrossRefGoogle Scholar
  25. Kocher, M. S., & Kasser, J. R. (2003). Osteopetrosis. The American Journal of Orthopedics, 32, 222–228.PubMedGoogle Scholar
  26. Kornak, U., Kasper, D., Bosl, M. R., et al. (2001). Loss of the ClC-7 chloride channel leads to osteopetrosis in mice and man. Cell, 104, 205–215.PubMedCrossRefGoogle Scholar
  27. Kornak, U., Schulz, A., Friedrich, W., et al. (2000). Mutations in the a3 subunit of the vacuolar H(+)-ATPase cause infantile malignant osteopetrosis. Human Molecular Genetics, 9, 2059–2063.PubMedCrossRefGoogle Scholar
  28. Lam, D. K., Sándor, G. K. B., Holmes, H. I., et al. (2007). Marble bone disease: A review of osteopetrosis and its oral health implications for dentists. Journal of the Canadian Dental Association, 73, 839–843.PubMedGoogle Scholar
  29. Landa, J., Margolis, N., & Cesare, P. D. (2007). Orthopaedic management of the patient with osteopetrosis. Journal of the American Academy of Orthopaedic Surgeons, 15, 654–662.PubMedGoogle Scholar
  30. Luzzi, V., Consoli, G., Daryanani, V., et al. (2006). Malignant infantile osteopetrosis: Dental effects in paediatric patients. Case reports. European Journal of Paediatric Dentistry, 7, 39–44.PubMedGoogle Scholar
  31. Manusov, E. G., Douville, D. R., Page, L. V., et al. (1993). Osteopetrosis (“marble bone” disease). American Family Physician, 47, 175–180.PubMedGoogle Scholar
  32. Mazzolari, E., Forino, C., Razza, A., et al. (2009). A single-center experience in 20 patients with infantile malignant osteopetrosis. American Journal of Hematology, 84, 473–479.PubMedCrossRefGoogle Scholar
  33. Mory, A., Feigelson, S. W., Yarali, N., et al. (2008). Kindlin-3: A new gene involved in the pathogenesis of LAD-III. Blood, 112, 2591.PubMedCrossRefGoogle Scholar
  34. Oğur, G., Oğur, E., Celasun, B., et al. (1995). Prenatal diagnosis of autosomal recessive osteopetrosis, infantile type, by X-ray evaluation. Prenatal Diagnosis, 15, 477–481.PubMedCrossRefGoogle Scholar
  35. Pangrazio, A., Poliani, P. L., Megarbane, A., et al. (2006). Mutations in OSTM1 (grey lethal) define a particularly severe form of autosomal recessive osteopetrosis with neural involvement. Journal of Bone and Mineral Research, 21, 1098–1105.PubMedCrossRefGoogle Scholar
  36. Schulz, A. S., Classen, C. F., Mihatsch, W. A., et al. (2002). HLA-haploidentical blood progenitor cell transplantation in osteopetrosis. Blood, 99, 3458–3460.PubMedCrossRefGoogle Scholar
  37. Schulz, A., Kornak, U. (2007) CLCN7-related osteopetrosis. GeneReviews. Initial posting, February 12, 2007. Available at:
  38. Shalev, H., Mishori-Dery, A., Kapelushnik, J., et al. (2001). Prenatal diagnosis of malignant osteopetrosis in Bedouin families by linkage analysis. Prenatal Diagnosis, 21, 183–186.PubMedCrossRefGoogle Scholar
  39. Smahi, A., Courtois, G., Rabia, S. H., et al. (2002). The NF-kappaB signalling pathway in human diseases: From incontinentia pigmenti to ectodermal dysplasias and immune-deficiency syndromes. Human Molecular Genetics, 11, 2371–2375.PubMedCrossRefGoogle Scholar
  40. Sobacchi, C., Frattini, A., Guerrini, M. M., et al. (2007). Osteoclast-poor human osteopetrosis due to mutations in the gene encoding RANKL. Nature Genetics, 39, 960–962.PubMedCrossRefGoogle Scholar
  41. Sobacchi, C., Frattini, A., Orchard, P., et al. (2001). The mutational spectrum of human malignant autosomal recessive osteopetrosis. Human Molecular Genetics, 10, 1767–1773.PubMedCrossRefGoogle Scholar
  42. Srinivasan, M., Abinun, M., Cant, A. J., et al. (2000). Malignant infantile osteopetrosis presenting with neonatal hypocalcaemia. Archives of Disease in Childhood. Fetal and Neonatal Edition, 83, F21–F23.PubMedCrossRefGoogle Scholar
  43. Stark, Z., & Savarirayan, R. (2009). Osteopetrosis. Orphanet Journal of Rare Diseases, 45, 1–5.Google Scholar
  44. Steward, C. G. (2003). Neurological aspects of osteopetrosis. Neuropathology and Applied Neurobiology, 29, 87–97.PubMedCrossRefGoogle Scholar
  45. Steward, C. G. (2010). Hematopoietic stem cell transplantation for Osteopetrosis. Pediatric Clinics of North America, 57, 171–180.PubMedCrossRefGoogle Scholar
  46. Steward, C. G., Blair, A., Moppett, J., et al. (2005). High peripheral blood progenitor cell counts enable autologous backup before stem cell transplantation for malignant infantile osteopetrosis. Biology of Blood and Marrow Transplantation, 11, 115–121.PubMedCrossRefGoogle Scholar
  47. Van Hul, E., Gram, J., Bollerslev, J., et al. (2002). Localization of the gene causing autosomal dominant osteopetrosis type I to chromosome 11q12-13. Journal of Bone and Mineral Research, 17, 1111–1117.PubMedCrossRefGoogle Scholar
  48. Van Wesenbeeck, L., Odgren, P. R., Coxon, F. P., et al. (2007). Involvement of PLEKHM1 in osteoclastic vesicular transport and osteopetrosis in incisors absent rats and humans. The Journal of Clinical Investigation, 117, 919–930.PubMedCrossRefGoogle Scholar
  49. Villa, A., Guerrini, M. M., Cassani, B., et al. (2009). Infantile malignant, autosomal recessive osteopetrosis: The rich and the poor. Calcified Tissue International, 84, 1–12.PubMedCrossRefGoogle Scholar
  50. Waguespack, S. G., Koller, D. L., White, K. E., et al. (2003). Chloride channel 7 (ClCN7) gene mutations and autosomal dominant osteopetrosis, type II. Journal of Bone and Mineral Research, 18, 1513–1518.PubMedCrossRefGoogle Scholar
  51. Whyte, M. P. (1993). Carbonic anhydrase II deficiency. Clinical Orthopaedics and Related Research, 294, 52–63.PubMedGoogle Scholar
  52. Whyte, M. P., Chines, A., Silva, D. P., et al. (1996). Creatine kinase brain isoenzyme (BB-CK) presence in serum distinguishes osteopetrosis among the sclerosing bone disorders. Journal of Bone and Mineral Research, 11, 1438–1443.PubMedCrossRefGoogle Scholar
  53. Wilson, C. J., & Vellodi, A. (2000). Autosomal recessive osteopetrosis: Diagnosis, management, and outcome. Archives of Disease in Childhood, 83, 449–452.PubMedCrossRefGoogle Scholar
  54. Wong, M. L., Balkany, T. J., Reeves, J., et al. (1978). Head and neck manifestations of malignant osteopetrosis. Otolaryngology, 86, ORL585–594.Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Personalised recommendations