title: Decreased bone density, elevated serum osteoprotegerin, and beta-cross-laps in Wilson disease.
abstract: Osteopathia has been reported in Wilson disease (WD), but bone density has not been measured; therefore, we performed bone mineral density (BMD), bone mineral content (BMC), and quantitative bone ultrasound (QUS) assessments, as well as measured the serum levels of osteocalcin (OCN), beta-cross-laps (beta-CTx's), and the recently discovered osteoprotegerin (OPG) and its ligand RANKL to investigate the underlying mechanism of osseous disorders. Serum OCN, beta-CTx, OPG, and RANKL levels were measured by ELISA in 21 WD patients and in 20 age- and gender-matched healthy subjects. BMD, BMC, and QUS parameters were also determined. Osteoporosis was present in 9/21 (43%) WD patients. Abnormal QUS parameters were found in 7 (33%) of the patients. Although serum OCN levels were similar in patients and controls (29.93 +/- 24.65 mg/ml vs. 29.84 +/- 6.89 mg/ml), beta-CTx and OPG levels were significantly increased in WD compared with the healthy controls (625.4 +/- 312.3 pg/ml vs. 423.6 +/- 144.3 pg/ml and p = 0.022 and 7.2 +/- 3.4 pM vs. 3.5 +/- 1.0 pM and p < 0.001, respectively). No difference was observed in the RANKL level. There was a positive correlation between OCN and beta-CTx (r = 0.55; p = 0.01). We proved high occurrence of osteoporosis in WD. Negative bone remodeling balance is a consequence of increased bone resorption, which is indicated by elevated beta-CTx. The novel finding of elevated serum OPG may reflect a compensatory reaction to enhanced osteoclast activity, despite the normal OCN level.
authors.affiliation: First Department of Medicine, Semmelweis University, Budapest, Hungary.
authors.forename: D
authors.initials: D
authors.lastname: Hegedus
authors.forename: V
authors.initials: V
authors.lastname: Ferencz
authors.forename: P L
authors.initials: PL
authors.lastname: Lakatos
authors.forename: S
authors.initials: S
authors.lastname: Meszaros
authors.forename: P
authors.initials: P
authors.lastname: Lakatos
authors.forename: C
authors.initials: C
authors.lastname: Horvath
authors.forename: F
authors.initials: F
authors.lastname: Szalay
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015519:Bone Density; D001862:Bone Resorption; D002352:Carrier Proteins / Q000097:blood; D016022:Case-Control Studies; D003094:Collagen / Q000097:blood*; D003720:Densitometry; D004798:Enzymes / Q000032:analysis; D005260:Female; D006023:Glycoproteins / Q000097:blood*; D006527:Hepatolenticular Degeneration / Q000150:complications / Q000000981:diagnostic imaging / Q000503:physiopathology*; D006801:Humans; D008099:Liver / Q000201:enzymology; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood; D008875:Middle Aged; D015675:Osteocalcin / Q000097:blood; D010024:Osteoporosis / Q000175:diagnosis* / Q000209:etiology; D053244:Osteoprotegerin; D010446:Peptide Fragments / Q000097:blood*; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000097:blood*; D018124:Receptors, Tumor Necrosis Factor; D014463:Ultrasonography
chemical_list: D002352:Carrier Proteins; D004798:Enzymes; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D010446:Peptide Fragments; 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; C110762:glutamyl-lysyl-alanyl-histidyl-aspartyl-glycyl-glycyl-arginine; D015675:Osteocalcin; D003094:Collagen