The RANKL/OPG system and bone mineral density in patients with chronic liver disease.
OBJECTIVE
Osteopenia and osteoporosis are common complications of chronic liver disease (CLD). Receptor activator of nuclear factor kappaB ligand (RANKL) and osteoprotegerin (OPG) regulate osteoclastogenesis and bone remodelling, and are involved in several inflammatory diseases. This study investigated the activation state of the RANKL/OPG system and its association with bone loss in CLD.


METHODS
Serum levels of OPG and sRANKL were determined in 193 patients with CLD and 56 age- and gender-matched healthy controls. Cellular sources of OPG and RANKL were determined immunohistochemically. Dual-energy x-ray absorptiometry was performed to determine bone mineral density (BMD) of lumbar spine and femoral neck.


RESULTS
sRANKL serum levels were significantly elevated in non-cirrhotic, but not cirrhotic patients compared to healthy controls. OPG serum levels were elevated 1.6-fold in non-cirrhotic and 2.8-fold in cirrhotic CLD patients. RANKL+ cells were mainly confined to portal fields, while OPG was broadly expressed. In the cirrhotic subgroup (87 patients) we observed a significantly higher OPG/sRANKL ratio in patients with osteopenia or osteoporosis of the lumbar spine and femoral neck region (T-score < -1) compared to those with normal BMD (T-score > or = -1).


CONCLUSIONS
CLD is associated with alterations in RANKL/OPG serum levels, which could modulate bone loss in CLD.
Moschen
Alexander R
AR
Division of Gastroenterology and Hepatology, Department of Medicine, Innsbruck Medical University, Innsbruck, Austria.
Kaser
Arthur
A
Stadlmann
Sylvia
S
Millonig
Gunda
G
Kaser
Susanne
S
Mühllechner
Petra
P
Habior
Andrzej
A
Graziadei
Ivo
I
Vogel
Wolfgang
W
Tilg
Herbert
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015519:Bone Density; D001851:Bone Diseases, Metabolic / Q000097:blood* / Q000209:etiology; D002352:Carrier Proteins / Q000097:blood*; D002908:Chronic Disease; D005260:Female; D006023:Glycoproteins / Q000097:blood*; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood* / Q000150:complications; D008107:Liver Diseases / Q000097:blood / Q000150:complications; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood*; D008875:Middle Aged; D010024:Osteoporosis / Q000097:blood / Q000209:etiology; 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 / Q000097:blood*
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