Circulating levels of osteopontin, osteoprotegerin, total soluble receptor activator of nuclear factor-kappa B ligand, and high-sensitivity C-reactive protein in patients with active rheumatoid arthritis randomized to etanercept alone or in combination with methotrexate.
OBJECTIVE
To determine whether circulating levels of osteopontin (OPN), osteoprotegerin (OPG), total soluble receptor activator of nuclear factor-kappa B ligand (total sRANKL), and high-sensitivity C-reactive protein (hsCRP) change in patients with rheumatoid arthritis (RA) during immunosuppressive therapy.


METHODS
Twenty-five active RA patients were randomized to treatment with either etanercept alone or in combination with methotrexate (MTX). The treatment response after 16 weeks was assessed using the European League Against Rheumatism (EULAR) response criteria. Blood samples were taken before the start of and every fourth week during the study. OPN, OPG, and total sRANKL were measured by enzyme-linked immunosorbent assays (ELISAs) and hsCRP by highly sensitive turbidometry.


RESULTS
At baseline, OPN and hsCRP were significantly (p<0.001) elevated compared to healthy persons. Compared to baseline only hsCRP levels decreased significantly (p<0.05 to p<0.001) in the EULAR responders through the study. OPN remained significantly (p<0.05) elevated at 16 weeks in patients with a low disease activity score (DAS< or =3.2). Total sRANKL increased significantly (p<0.05) from baseline to week 12. No statistically significant changes were observed in the non-responders.


CONCLUSIONS
Active RA patients showed increased circulating levels of hsCRP and OPN, but only hsCRP decreased during etanercept therapy. Our findings suggest that OPN, OPG, total sRANKL, and hsCRP reflect different aspects of the inflammatory process in RA.
Sennels
Hp
H
Department of Clinical Biochemistry, Hvidovre Hospital, Copenhagen University Hospital, Hvidovre, Denmark. HSennels@dadlnet.dk
Sørensen
S
S
Ostergaard
M
M
Knudsen
Ls
L
Hansen
Ms
M
Skjødt
H
H
Peters
Nd
N
Colic
A
A
Grau
K
K
Jacobsen
S
S
D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000188:drug therapy*; D015415:Biomarkers / Q000097:blood*; D002097:C-Reactive Protein / Q000378:metabolism; D004359:Drug Therapy, Combination; D000068800:Etanercept; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D008875:Middle Aged; D053495:Osteopontin / Q000097:blood; D053244:Osteoprotegerin / Q000097:blood; D053245:RANK Ligand / Q000097:blood; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use*; D012720:Severity of Illness Index
D015415:Biomarkers; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D053244:Osteoprotegerin; D053245:RANK Ligand; D018124:Receptors, Tumor Necrosis Factor; D053495:Osteopontin; D002097:C-Reactive Protein; D000068800:Etanercept; D008727:Methotrexate