Toggle Main Menu Toggle Search

Open Access padlockePrints

Osteoclast-poor osteopetrosis

Lookup NU author(s): Dr Mario Abinun


Full text for this publication is not currently held within this repository. Alternative links are provided below where available.


© 2022 Elsevier Inc. Osteopetrosis (OPT) is a rare inherited bone disease characterized by a bone resorption defect, due to osteoclast malfunction (in osteoclast-rich, oc-rich, OPT forms) or absence (in oc-poor OPT forms). This causes severe clinical abnormalities, including increased bone density, lack of bone marrow cavity, stunted growth, macrocephaly, progressive deafness, blindness, hepatosplenomegaly, and severe anemia. The oc-poor subtype of OPT is ultra-rare in humans. It is caused by mutations in either the tumor necrosis factor ligand superfamily member 11 (TNFSF11) gene, encoding RANKL (Receptor Activator of Nuclear factor-kappa B [NF-κB] Ligand) which is expressed on cells of mesenchymal origin and lymphocytes, or the TNFRSF member 11A (TNFRSF11A) gene, encoding the RANKL functional receptor RANK which is expressed on cells of myeloid lineage including osteoclasts. Clinical presentation is usually severe with onset in early infancy or in fetal life, although as more patients are reported, expressivity is variable. Phenotypic variability of RANK-deficient OPT sometimes includes hypogammaglobulinemia or radiological features of dysosteosclerosis. Disease progression is somewhat slower in RANKL-deficient OPT than in other ‘malignant’ subtypes of OPT. While both RANKL and RANK are essential for normal bone turnover, hematopoietic stem cell transplantation (HSCT) is the treatment of choice only for patients with the RANK-deficient form of oc-poor OPT. So far, there is no cure for RANKL-deficient OPT.

Publication metadata

Author(s): Sobacchi C, Abinun M

Publication type: Article

Publication status: Published

Journal: Bone

Year: 2022

Volume: 164

Print publication date: 01/11/2022

Online publication date: 27/08/2022

Acceptance date: 23/08/2022

ISSN (print): 8756-3282

ISSN (electronic): 1873-2763

Publisher: Elsevier Inc.


DOI: 10.1016/j.bone.2022.116541

PubMed id: 36031188


Altmetrics provided by Altmetric