title: Assessment of the Effect of Methotrexate Therapy on Bone Metabolism in Patients with Rheumatoid Arthritis.
abstract: Proinflammatory cytokines and growth factors, which regulate mutual interactions between immune system cells and bone tissue cells, play a major role in the formation of bone changes in rheumatoid arthritis (RA). The aim of the work was to assess serum concentration of osteoprotegerin (OPG), RANKL, Dkk-1 and sclerostin in RA patients compared to a control group and to analyze changes of these concentrations during methotrexate (MTX) therapy. Patients enrolled in the study were 30 women of Caucasian origin aged 30-74 years with RA. Patients with active form of the disease were administered recommended doses of MTX for at least 6 months. The study group was divided into subgroup I-patients with improvement; and subgroup II-patients with no improvement. The control group consisted of 12 healthy women in the age of 41-73. Before MTX therapy, RA patients had higher levels of RANKL (644.97 ± 477.13 vs. 255.19 ± 130.26 pmol/l), lower values of OPG/RANKL (0.01 ± 0.0101 vs. 0.02 ± 0.0078) and higher levels of Dkk-1 protein (1821.32 ± 1060.28 vs. 548.52 ± 36.35 pg/ml) compared to the control group. In the analyzed group of patients (all patients receiving MTX regardless of responder non responder status) after 6 months of therapy, a statistically significant increase in the ratio of OPG/RANKL was found (0.0118 ± 0.0102 vs. 0.0141 ± 0.0118; p = 0.02). The index value of OPG/RANKL differed significantly depending on the resultant effect of treatment (0.01702 ± 0.01274 in the subgroup of improvement vs. 0.00675 ± 0.00289 in the subgroup without improvement). The difference in the mean concentrations of Dkk-1 before and after treatment with MTX between subgroups I and II was statistically significant (p = 0.002). In subgroup I, mean concentration of Dkk-1 decreased after 6 months of treatment with MTX (2054.72 ± 1004.74 vs. 1831.70 ± 851.70 pg/ml); while in subgroup II, the mean concentration of Dkk-1 increased (1214.48 ± 738.32 vs. 2275.01 ± 1385.23 pg/ml). There were no statistically significant changes in the mean concentrations of sclerostin before and after treatment with MTX (in whole group treatment with MTX, in subgroup I, and in subgroup II). The results confirm the presence of disorders of bone metabolism in patients with RA. Treatment with MTX affects the value of the ratio of OPG/RANKL and concentration of Dkk-1.
authors.affiliation: Department of Rheumatology and Internal Medicine, Wroclaw Medical University, Wrocław, Poland. jurekswierkot0@poczta.onet.pl.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Świerkot
authors.affiliation: Department of Rheumatology and Internal Medicine, Wroclaw Medical University, Wrocław, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Gruszecka
authors.affiliation: Department of Pharmacology, Wroclaw Medical University, Wrocław, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Matuszewska
authors.affiliation: Department of Rheumatology and Internal Medicine, Wroclaw Medical University, Wrocław, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Wiland
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D054316:Biomarkers, Pharmacological / Q000097:blood; D019485:Bone Morphogenetic Proteins / Q000097:blood; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D005819:Genetic Markers; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood*; D008727:Methotrexate / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D053244:Osteoprotegerin / Q000097:blood; D053245:RANK Ligand / Q000097:blood*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018501:Antirheumatic Agents; D054316:Biomarkers, Pharmacological; D019485:Bone Morphogenetic Proteins; C501126:DKK1 protein, human; D005819:Genetic Markers; D036341:Intercellular Signaling Peptides and Proteins; D053244:Osteoprotegerin; D053245:RANK Ligand; C422903:SOST protein, human; D008727:Methotrexate
keywords: Dkk-1; Methotrexate; Osteoprotegerin; RANKL; Rheumatoid arthritis
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