Early effects of tumor necrosis factor inhibition on bone homeostasis after soluble tumor necrosis factor receptor use.
OBJECTIVE
Our aim was to assess whether short-term treatment with soluble tumor necrosis factor (TNF) receptor affects circulating markers of bone metabolism in rheumatoid arthritis (RA) patients.


METHODS
Thirty-three active RA patients, treated with oral disease-modifying antirheumatic drugs (DMARDs) and glucocorticoids for > 6 months, were administered etanercept for 12 weeks. Serum levels of bone metabolism markers were compared among patients treated with DMARDs at baseline and after etanercept treatment, normal controls and naive RA patients not previously treated with DMARDs (both age- and gender-matched).


RESULTS
Bone-specific alkaline phosphatase (BSALP) and serum c-telopeptide (CTX)-1 levels were lower in RA patients treated with DMARDs than in DMARD-naive RA patients. After 12 weeks of etanercept treatment, serum CTX-1 and sclerostin levels increased. In patients whose DAS28 improved, the sclerostin level increased from 1.67 ± 2.12 pg/mL at baseline to 2.51 ± 3.03 pg/mL, which was statistically significant (p = 0.021). Increases in sclerostin levels after etanercept treatment were positively correlated with those of serum CTX-1 (r = 0.775), as were those of BSALP (r = 0.755).


CONCLUSIONS
RA patients treated with DMARDs showed depressed bone metabolism compared to naive RA patients. Increases in serum CTX-1 and sclerostin levels after short-term etanercept treatment suggest reconstitution of bone metabolism homeostasis.
Division of Rheumatology, Department of Internal Medicine, Inha University Hospital, Incheon, Korea.
Mie Jin
MJ
Lim
Division of Rheumatology, Department of Internal Medicine, Inha University Hospital, Incheon, Korea.
Seong Ryul
SR
Kwon
Division of Rheumatology, Department of Internal Medicine, Inha University Hospital, Incheon, Korea.
Kowoon
K
Joo
Division of Rheumatology, Department of Internal Medicine, Inha University Hospital, Incheon, Korea.
Min Jung
MJ
Son
Department of Occupational and Environmental Medicine, Inha University Hospital, Incheon, Korea.
Shin-Goo
SG
Park
Division of Rheumatology, Department of Internal Medicine, Inha University Hospital, Incheon, Korea.
Won
W
Park
D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000469:Alkaline Phosphatase / Q000097:blood; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D015415:Biomarkers / Q000097:blood; D019485:Bone Morphogenetic Proteins / Q000097:blood; D016723:Bone Remodeling / Q000187:drug effects*; D024042:Collagen Type I / Q000097:blood; D000068800:Etanercept; D005260:Female; D005819:Genetic Markers; D006706:Homeostasis; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage*; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D018836:Inflammation Mediators / Q000097:blood; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000097:blood; D018124:Receptors, Tumor Necrosis Factor / Q000008:administration & dosage*; D013997:Time Factors; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
D048868:Adaptor Proteins, Signal Transducing; D015415:Biomarkers; D019485:Bone Morphogenetic Proteins; D024042:Collagen Type I; D005819:Genetic Markers; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D018836:Inflammation Mediators; D010455:Peptides; D018124:Receptors, Tumor Necrosis Factor; C422903:SOST protein, human; D014409:Tumor Necrosis Factor-alpha; C052929:collagen type I trimeric cross-linked peptide; D000469:Alkaline Phosphatase; D000068800:Etanercept
Arthritis, rheumatoid; Bone remodeling; TNFR-Fc fusion protein