Current Osteoporosis Reports

, Volume 16, Issue 1, pp 13–25 | Cite as

Genetics of Osteopetrosis

  • Eleonora Palagano
  • Ciro Menale
  • Cristina Sobacchi
  • Anna Villa
Genetics (M Johnson and S Ralston, Section Editors)
Part of the following topical collections:
  1. Topical Collection on Genetics


Purpose of Review

The term osteopetrosis refers to a group of rare skeletal diseases sharing the hallmark of a generalized increase in bone density owing to a defect in bone resorption. Osteopetrosis is clinically and genetically heterogeneous, and a precise molecular classification is relevant for prognosis and treatment. Here, we review recent data on the pathogenesis of this disorder.

Recent Findings

Novel mutations in known genes as well as defects in new genes have been recently reported, further expanding the spectrum of molecular defects leading to osteopetrosis.


Exploitation of next-generation sequencing tools is ever spreading, facilitating differential diagnosis. Some complex phenotypes in which osteopetrosis is accompanied by additional clinical features have received a molecular classification, also involving new genes. Moreover, novel types of mutations have been recognized, which for their nature or genomic location are at high risk being neglected. Yet, the causative mutation is unknown in some patients, indicating that the genetics of osteopetrosis still deserves intense research efforts.


Osteopetrosis Osteoclast Pathogenesis Next-generation sequencing 



We acknowledge the many authors whose original contribution in the field could not be cited in this minireview for the sake of brevity.

Authors’ contribution

All the authors contributed to organize, draft, and revise the manuscript.


This work was partially supported by the European Community’s Seventh Framework Program (FP7/2007–2013, SYBIL Project), by PRIN Projects (20102M7T8X_003 and 2015F3JHMB_004) to AV and by Programma Nazionale per la Ricerca-Consiglio Nazionale delle Ricerche Aging Project to AV, and by Ministero della Salute - Giovani Ricercatori (grant GR-2011-02348266) to CS.

Compliance with Ethical Standards

Conflict of Interest

Eleonora Palagano, Cristina Sobacchi, Anna Villa, and Ciro Menale declare no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Eleonora Palagano
    • 1
    • 2
  • Ciro Menale
    • 1
    • 3
  • Cristina Sobacchi
    • 1
    • 3
  • Anna Villa
    • 1
    • 3
  1. 1.Humanitas Clinical and Research InstituteRozzanoItaly
  2. 2.Department of Medical Biotechnologies and Translational MedicineUniversity of MilanMilanItaly
  3. 3.Milan UnitCNR-IRGBMilanItaly

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