Calcified Tissue International

, Volume 77, Issue 5, pp 263–274 | Cite as

A Clinical and Molecular Overview of the Human Osteopetroses

Review article


The osteopetroses are a heterogeneous group of bone remodeling disorders characterized by an increase in bone density due to a defect in osteoclastic bone resorption. In humans, several types can be distinguished and a classification has been made based on their mode of inheritance, age of onset, severity, and associated clinical symptoms. The best-known forms of osteopetrosis are the malignant and intermediate autosomal recessive forms and the milder autosomal dominant subtypes. In addition to these forms, a restricted number of cases have been reported in which additional clinical features unrelated to the increased bone mass occur. During the last years, molecular genetic studies have resulted in the identification of several disease-causing gene mutations. Thus far, all genes associated with a human osteopetrosis encode proteins that participate in the functioning of the differentiated osteoclast. This contributed substantially to the understanding of osteoclast functioning and the pathogenesis of the human osteopetroses and will provide deeper insights into the molecular pathways involved in other bone pathologies, including osteoporosis.


Osteoclast Bone resorption Osteopetrosis Human 



We would like to thank Geert Mortier, MD, PhD, clinical geneticist at the Department of Medical Genetics of the University of Gent (Ghent, Belgium), and Filip Vanhoenacker, MD, PhD, radiologist at the Department of Radiology of the University Hospital of Antwerp (Antwerp, Belgium) who provided us with radiographs of the patients. This study is supported by the fund for scientific research flanders (FWO) with a research project (G.0404.00). WB and LVW are postdoctoral researchers of the FWD.


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© Springer Science+Business Media, Inc. 2005

Authors and Affiliations

  1. 1.Department of Medical GeneticsUniversity and University Hospital of AntwerpBelgium

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