title: Circulating sclerostin and Dickkopf-1 levels in patients with nonalcoholic fatty liver disease.
abstract: There is increasing evidence for bone-liver interplay. The main aim of this study was to determine serum sclerostin and Dickkopf (DKK)-1 levels in patients with nonalcoholic fatty liver disease (NAFLD) and their association with the disease severity. Patients with biopsy-proven NAFLD, 13 with nonalcoholic simple steatosis (SS) and 14 with steatohepatitis (NASH), and 20 gender-, age-, body mass index- and waist circumference-matched controls were enrolled. Serum sclerostin, DKK-1, bone turnover markers, vitamin D, insulin and standard biochemical and hematologic parameters were measured; lumbar spinal dual-energy X-ray absorptiometry was performed. We observed that there was a progressive decline in serum sclerostin levels from the controls (76.1 ± 6.8) to SS (53.5 ± 6.4) and NASH (46.0 ± 8.1 pmol/l) patients (p = 0.009); in adjusted pairwise comparisons, sclerostin was significantly higher in the controls than in NASH patients (p = 0.012). Although serum DKK-1 did not differ between groups (p = 0.135), there was a trend toward U-shaped distribution (controls 35.8 ± 2.8; SS 27.3 ± 2.9; NASH 36.8 ± 4.4 pmol/l). Higher DKK-1 levels were independently associated with NASH. Regarding specific histological lesions, DKK-1 levels were marginally lower in NAFLD patients with lower (≤33 %) than higher (>33 %) steatosis grade (27.7 ± 3.1 and 38.8 ± 4.7 pmol/l, respectively; p = 0.049). No other significant difference was observed within histological lesions. In conclusion, serum sclerostin levels were lower in NASH patients than in controls. DKK-1 levels were independently associated with NASH in NAFLD patients. The potential importance of these findings indicates a possible bone-liver interaction and warrants further investigation.
authors.affiliation: Second Medical Clinic, Aristotle University of Thessaloniki, Ippokration Hospital, 13 Simou Lianidi, 551 34, Thessaloniki, Macedonia, Greece. stergios@endo.gr.|Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. stergios@endo.gr.
authors.forename: Stergios A
authors.identifier: http://orcid.org/0000-0001-9232-4042
authors.initials: SA
authors.lastname: Polyzos
authors.affiliation: Department of Endocrinology, 424 General Military Hospital, Thessaloniki, Macedonia, Greece.
authors.forename: Athanasios D
authors.initials: AD
authors.lastname: Anastasilakis
authors.affiliation: Second Medical Clinic, Aristotle University of Thessaloniki, Ippokration Hospital, 13 Simou Lianidi, 551 34, Thessaloniki, Macedonia, Greece.
authors.forename: Jannis
authors.initials: J
authors.lastname: Kountouras
authors.affiliation: Department of Endocrinology and Diabetes, 251 Hellenic Air Force and VA General Hospital, Athens, Greece.
authors.forename: Polyzois
authors.initials: P
authors.lastname: Makras
authors.affiliation: Department of Medical Research, 251 Hellenic Air Force and VA General Hospital, Athens, Greece.
authors.forename: Athanasios
authors.initials: A
authors.lastname: Papatheodorou
authors.affiliation: Department of Medical Research, 251 Hellenic Air Force and VA General Hospital, Athens, Greece.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Kokkoris
authors.affiliation: Department of Rheumatology, 424 General Military Hospital, Thessaloniki, Macedonia, Greece.
authors.forename: Grigorios T
authors.initials: GT
authors.lastname: Sakellariou
authors.affiliation: Department of Clinical Therapeutics, University of Athens School of Medicine, Athens, Greece.
authors.forename: Evangelos
authors.initials: E
authors.lastname: Terpos
mesh_terms: D015502:Absorptiometry, Photon; D048868:Adaptor Proteins, Signal Transducing; D019485:Bone Morphogenetic Proteins / Q000097:blood*; D003430:Cross-Sectional Studies; D005260:Female; D005819:Genetic Markers; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood*; D008161:Lumbosacral Region / Q000000981:diagnostic imaging; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood* / Q000000981:diagnostic imaging; D012720:Severity of Illness Index; D013131:Spine / Q000000981:diagnostic imaging / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D019485:Bone Morphogenetic Proteins; C501126:DKK1 protein, human; D005819:Genetic Markers; D036341:Intercellular Signaling Peptides and Proteins; C422903:SOST protein, human
keywords: Bone turnover markers; Dickkopf-1; Nonalcoholic fatty liver disease; Nonalcoholic steatohepatitis; Sclerostin