Bone Abstracts

Osteoclasts are giant multinucleated skeletal cells of hematopoietic origin primarily responsible for bone resorption. Their functional impairment disturbs bone homeostasis and, to a variable extent, a number of other processes, such as growth, hematopoiesis and immune function. The accumulation of bone tissue owing to failure in bone resorption results in increased bone density, which is the hallmark of osteopetrosis (OP), a heterogeneous group of monogenic disorders with aut...

Osteoclast-poor autosomal recessive osteopetrosis is characterised by susceptibility to fracture despite high bone mineral density as a consequence of an absence of osteoclasts. One of the 12 receptor activator of NF-κB (RANK) mutations associated with this condition is a frameshift mutation encoding a protein that is truncated within the extracellular, N-terminal domain (R110Pfs). We investigated the effect of this mutation on osteoclast formation, receptor localisation ...

Twelve different mutations in TNFRSF11A (encoding the RANK receptor) have been associated with osteoclast-poor autosomal recessive osteopetrosis in patients. Two truncated RANK proteins resulting from substitution mutations (W434X and G280X), identified in two infants, cause loss of the intracellular oligomerisation motif and in the case of the G280X mutation the TRAF6 binding domain. A third mutation was identified in a 10-year-old patient and is a frameshift mutatio...

Autosomal Recessive Osteopetrosis (ARO) presents early in life with extreme sclerosis of the skeleton, reduction of bone marrow spaces, hepatosplenomegaly, cranial nerves compression and severe growth failure. ARO is often lethal and at present the only therapy is HSCT, which should be performed as soon as possible in order to obtain a major benefit. ARO is genetically heterogeneous and delays in clinical diagnosis sometimes occur, due to its rareness and to the presence of co...

Osteoclast-poor RANKL-dependent autosomal recessive osteopetrosis (ARO) is a rare bone disease characterized by an increase in bone density due to the failure of bone resorption by impaired osteoclast formation. Haematopoietic stem cell transplantation is not an effective therapy for this ARO form, since in bone RANKL is produced mainly by cells of mesenchymal origin. Whether also these cells, besides the osteoclast, are in some way affected by RANKL deficiency is not known. T...

Acrofrontofacionasal Dysostosis type 1 (AFFND1) is a rare human syndrome (estimated prevalence lower than 1:1,000,000), characterized by bone abnormalities in addition to other multiple congenital anomalies and intellectual disability. Only four AFFND1 families, three of Brazilian and one of Indian origin, have been described so far and an autosomal recessive pattern of inheritance has been suggested. The patients are severely affected: the main clinical features are intellect...