Abstract
Hepatitis C-associated osteosclerosis (HCAO) is an impressive example of acquired diffuse osteosclerosis in adults, recently described in ten patients infected with hepatitis C virus (HCV). Its hallmark is a painful and generalized increase of bone mass. Bone biopsies show enhanced accretion rate, usually without histological abnormalities. The HCAO pathogenesis is hitherto unknown. HCV might induce a slow bone cell infection and the production of bone growth factors, such as insulin-like growth factors. Recently, receptor activator of nuclear factor-kappaB (RANK), its ligand (RANKL), and soluble decoy receptor osteoprotegerin (OPG) have been identified as a pivotal cytokine system in the bone remodeling control. We describe the 11th case of HCAO. Notably, the patient's bone biopsy showed the presence of a high number of OPG-positive osteoblasts, a slight increase of RANKL-positive stromal cells, and a dramatic reduction of the osteoclasts. Moreover, OPG serum levels were increased. These findings reported here for the first time are consistent with a pathogenetic role of the OPG/RANKL system imbalance in HCAO.
MeSH terms
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Absorptiometry, Photon
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Aged
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Biomarkers / metabolism
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Biopsy
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Bone Density
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Bone Remodeling / physiology*
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Bone and Bones / diagnostic imaging
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Bone and Bones / pathology
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Carrier Proteins / metabolism*
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Diagnosis, Differential
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Enzyme-Linked Immunosorbent Assay
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Glycoproteins / metabolism*
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Hepacivirus* / genetics
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Hepacivirus* / immunology
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Hepatitis C Antibodies / analysis
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Humans
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Immunoblotting
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Ligands
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Male
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Membrane Glycoproteins / metabolism*
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Osteoblasts / metabolism
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Osteoprotegerin
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Osteosclerosis / diagnosis
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Osteosclerosis / metabolism*
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Osteosclerosis / virology*
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RANK Ligand
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RNA, Viral / analysis
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Radionuclide Imaging
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Receptor Activator of Nuclear Factor-kappa B
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Receptors, Cytoplasmic and Nuclear / metabolism*
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Receptors, Tumor Necrosis Factor / metabolism*
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Reverse Transcriptase Polymerase Chain Reaction
Substances
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Biomarkers
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Carrier Proteins
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Glycoproteins
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Hepatitis C Antibodies
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Ligands
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Membrane Glycoproteins
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Osteoprotegerin
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RANK Ligand
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RNA, Viral
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Receptor Activator of Nuclear Factor-kappa B
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Receptors, Cytoplasmic and Nuclear
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Receptors, Tumor Necrosis Factor
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TNFRSF11A protein, human
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TNFRSF11B protein, human
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TNFSF11 protein, human