High serum osteoprotegerin and low RANKL in primary biliary cirrhosis.
OBJECTIVE
Osteoprotegerin is decoy receptor for osteoclast activating factor, RANKL, and impairs osteoclast funtion. Since osteoporosis is common in primary biliary cirrhosis (PBC), we investigated osteoprotegerin, RANKL and markers of bone turnover in PBC.


METHODS
Serum osteoprotegerin, RANKL, osteocalcin (OC) and C-terminal cross-linking telopeptide of type I collagen (CTX-I) were measured by ELISA in 41 patients with PBC, 16 women with chronic hepatitis C (CHC), and as controls in 44 age-matched healthy and 74 post-menopausal osteopenic otherwise healthy women.


RESULTS
Serum osteoprotegerin levels were higher in PBC patients (7.8+/-3.0 pmol/l) than in healthy controls (4.4+/-2.3 pmol/l) and osteopenic women (4.0+/-1.0 pmol/l, P<0.0001 for both). RANKL levels were lower in PBC (0.9+/-1.8 pmol/l, P<0.0001) than in healthy controls (1.3+/-0.5 pmol/l). In CHC both osteoprotegerin (9.7+/-4.2 pmol/l) and RANKL (3.2+/-4.7 pmol/l) were elevated compared to the control groups (P<0.0001, for both). There was a positive correlation between serum osteoprotegerin and OC, CTX-I and AST but not with bone mineral density in PBC.


CONCLUSIONS
The mechanisms and role of elevated osteoprotegerin and low RANKL in PBC are unclear, but it might partly represent a compensatory mechanism to negative balance of bone remodeling. High OPG and RANKL levels found in CHC might suggest that inflammatory process in the liver could also contribute to the elevation of osteoprotegerin.
Szalay
Ferenc
F
1st Department of Medicine, Semmelweis University, Korányi St. 2/A, H-1083 Budapest, Hungary. szalay@bel1.sote.hu
Hegedus
Dalma
D
Lakatos
Peter Laszlo
PL
Tornai
Istvan
I
Bajnok
Eva
E
Dunkel
Kinga
K
Lakatos
Peter
P
D000328:Adult; D000368:Aged; D015415:Biomarkers; D015519:Bone Density; D016723:Bone Remodeling; D002352:Carrier Proteins / Q000097:blood*; D005260:Female; D005272:Femur Neck / Q000378:metabolism; D006023:Glycoproteins / Q000097:blood*; D019698:Hepatitis C, Chronic / Q000097:blood; D006801:Humans; D008105:Liver Cirrhosis, Biliary / Q000097:blood*; D008159:Lumbar Vertebrae / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000097:blood*; D008875:Middle Aged; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000097:blood*; D018124:Receptors, Tumor Necrosis Factor
D015415:Biomarkers; D002352:Carrier Proteins; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D053245:RANK Ligand; 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