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Osteologie 2009; 18(04): 260-267
DOI: 10.1055/s-0037-1619909
Rare bone diseases
Schattauer GmbH

Human recessive osteopetrosis

New understanding of osteoclast function through molecular and functional analysis of a rare genetic bone diseaseHumane rezessive OsteopetroseNeue Erkenntnisse zur Osteoklastenfunktion durch die molekulare und funktionale Analyse einer seltenen genetischen Knochenkrankheit
M. Helfrich
1   Bone and Musculoskeletal Research Programme, Division of Applied Medicine, School of Medicine, Institute of Medical Sciences, University of Aberdeen, Aberdeen, United Kingdom
,
B. Perdu
2   Department of Human Genetics, University of Antwerp, Edegem, Belgium
,
F. Coxon
1   Bone and Musculoskeletal Research Programme, Division of Applied Medicine, School of Medicine, Institute of Medical Sciences, University of Aberdeen, Aberdeen, United Kingdom
› Author AffiliationsThe authors wish to acknowledge funding from the European Calcified Tissue Society (a PhD studentship and exchange grant to BP and a career development award to MH) and from the Chief Scientist Office of the Scottish Executive (grant CZB/4/495 to MH and FC) for their work in this area. We also thank expert technical assistance from John Greenhorn, Kevin Mackenzie and Tabitha Schouten with the microscopical imaging shown.
Further Information

Publication History

received: 22 September 2009

accepted: 30 September 2009

Publication Date:
30 December 2017 (online)

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Summary

Osteopetrosis is an inherited high bone mass condition resulting from reduced osteoclast activity. Over the past ten years, many of the genes mutated in the various forms of osteopetrosis have been identified. It has become clear that there are not only dominant and recessive forms, but also that within the recessive forms subsets exist, classified as osteoclast-rich and osteoclast-poor. Here, we review the different genetic mutations that are known to cause osteopetrosis and then focus specifically on recessive types of the disease. We will illustrate how not only genetic analysis is important, but also that functional osteoclast assays in the laboratory, combined with bone histology, can help to come to a precise diagnosis. We then discuss how this rare condition has led to new insights in the complex process of bone resorption by osteoclasts. Our story is one of bedside to bench and back again.

Zusammenfassung

Bei der Osteopetrose handelt es sich um eine erblich bedingte erhebliche Zunahme der Knochenmasse infolge einer verminderten Osteoklastenaktivität. In den vergangenen zehn Jahren wurde eine Reihe von Genmutationen bei den verschiedenen Osteopetrose-Formen identifiziert. Es wurde klar, dass es nicht nur dominant und rezessiv vererbte Formen gibt, sondern dass innerhalb der rezessiven Formen Untergruppen existieren, die als osteoklastenreich und osteoklastenarm klassifiziert werden. In diesem Übersichtsartikel werden die verschiedenen bei Osteopetrose bekannten Genmutationen, mit besonderer Berücksichtigung der rezessiven Erkrankungsformen, dargestellt. Es wird gezeigt, dass nicht nur die genetische Analyse von Bedeutung ist, sondern dass auch ein funktionales Osteoklasten-Assay im Labor, kombiniert mit einer histologischen Untersuchung der Knochen, eine exakte Diagnosestellung erleichtern kann. Anschließend wird diskutiert, wie diese seltene Erkrankung zu neuen Einblicken in den komplexen Prozess der Knochenresorption durch Osteoklasten geführt hat. Es ist die Geschichte einer Entwicklung von der Klinik zur Molekulargenetik und wieder zurück.

Keywords

Osteopetrosis - osteoclast - acidification - endosomal trafficking

Schlüsselwörter

Osteopetrose - Osteoklast - Azidose - endosomaler Transport
 

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