OPG/RANKL system imbalance in a case of hepatitis C-associated osteosclerosis: the pathogenetic key?
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.
Manganelli
Paolo
P
Dipartimento Osteo-Articolare, Unità Operativa di Reumatologia e Medicina Interna, Azienda Ospedaliera di Parma, Via Gramsci, 14, 43100, Parma, Italy. pmanganelli@ao.pr.it
Giuliani
Nicola
N
Fietta
Pieranna
P
Mancini
Cristina
C
Lazzaretti
Mirca
M
Pollini
Angela
A
Quaini
Federico
F
Pedrazzoni
Mario
M
D015502:Absorptiometry, Photon; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D015519:Bone Density; D016723:Bone Remodeling / Q000502:physiology*; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000473:pathology; D002352:Carrier Proteins / Q000378:metabolism*; D003937:Diagnosis, Differential; D004797:Enzyme-Linked Immunosorbent Assay; D006023:Glycoproteins / Q000378:metabolism*; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology; D018937:Hepatitis C Antibodies / Q000032:analysis; D006801:Humans; D015151:Immunoblotting; D008024:Ligands; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D010006:Osteoblasts / Q000378:metabolism; D053244:Osteoprotegerin; D010026:Osteosclerosis / Q000175:diagnosis / Q000378:metabolism* / Q000821:virology*; D053245:RANK Ligand; D012367:RNA, Viral / Q000032:analysis; D011877:Radionuclide Imaging; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D015415:Biomarkers; D002352:Carrier Proteins; D006023:Glycoproteins; D018937:Hepatitis C Antibodies; D008024:Ligands; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D053245:RANK Ligand; D012367:RNA, Viral; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C505686:TNFRSF11A protein, human; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human