title: Reducing glucocorticoid dosage improves serum osteocalcin in patients with rheumatoid arthritis-results from the TOMORROW study.
abstract: Decreasing the daily dose of glucocorticoids improved bone metabolic marker levels in patients with rheumatoid arthritis. However, changes in disease activity did not influence bone metabolism. Bone metabolism might thus remain uncontrolled even if disease activity is under good control. Decreasing glucocorticoid dosage appears important for improving bone metabolism.
  
  
  BACKGROUND
  Patients with rheumatoid arthritis (RA) develop osteoporosis more frequently than healthy individuals. Bone resorption is increased and bone formation is inhibited in patients with RA, and glucocorticoid negatively affects bone metabolism. We aimed to investigate factors influencing bone metabolic markers in patients with RA.
  
  
  METHODS
  We started the 10-year prospective cohort Total Management of Risk Factors in Rheumatoid Arthritis Patients to Lower Morbidity and Mortality (TOMORROW) study in 2010. We compared changes in urinary cross-linked N-telopeptide of type I collagen (uNTx) and serum osteocalcin (OC), as markers of bone resorption and formation, respectively, in 202 RA patients and age- and sex-matched volunteers between 2010 and 2011. We also investigated factors influencing ΔuNTx and ΔOC in the RA group using multivariate analysis.
  
  
  RESULTS
  Values of ΔuNTx were significantly lower in patients with RA than in healthy controls (-0.51 vs. 7.41 nmol bone collagen equivalents (BCE)/mmol creatinine (Cr); p = 0.0013), whereas ΔOC values were significantly higher in RA patients (0.94 vs. 0.37 ng/ml; p = 0.0065). Changes in prednisolone dosage correlated negatively with ΔOC (β = -0.229, p = 0.001), whereas changes in disease activity score, bisphosphonate therapy, and period of biologics therapy did not correlate significantly with ΔOC. No significant correlation was seen between ΔuNTx and change in prednisolone dosage.
  
  
  CONCLUSIONS
  Decreased glucocorticoid dosage improved bone metabolic markers in RA, but disease activity, bisphosphonate therapy, and period of biologics therapy did not influence levels of bone metabolic markers. Decreasing glucocorticoid dosage appears important for improving bone metabolic marker profiles in patients with RA.
authors: Department of Orthopaedic Surgery, Osaka City University Medical School, 1-4-3 Asahimachi, Abeno-ku, Osaka, 545-8585, Japan.
authors: M
authors: M
authors: Tada
authors: Department of Rheumatosurgery, Osaka City University Medical School, 1-4-3 Asahimachi, Abeno-ku, Osaka, 545-8585, Japan.
authors: K
authors: K
authors: Inui
authors: Center for Senile Degenerative Disorders, Osaka City University Medical School, 1-4-3 Asahimachi, Abeno-ku, Osaka, 545-8585, Japan.
authors: Y
authors: Y
authors: Sugioka
authors: Department of Orthopaedic Surgery, Osaka City University Medical School, 1-4-3 Asahimachi, Abeno-ku, Osaka, 545-8585, Japan.
authors: K
authors: K
authors: Mamoto
authors: Department of Orthopaedic Surgery, Osaka City University Medical School, 1-4-3 Asahimachi, Abeno-ku, Osaka, 545-8585, Japan.
authors: T
authors: T
authors: Okano
authors: Center for Senile Degenerative Disorders, Osaka City University Medical School, 1-4-3 Asahimachi, Abeno-ku, Osaka, 545-8585, Japan. tatsuya@med.osaka-cu.ac.jp.|Search Institute for Bone and Arthritis Disease, Shirahama Foundation for Health and Welfare, Nishimurogun Shirahamacho 1447, Wakayama, 649-2211, Japan. tatsuya@med.osaka-cu.ac.jp.
authors: T
authors: T
authors: Koike
authors: Department of Orthopaedic Surgery, Osaka City University Medical School, 1-4-3 Asahimachi, Abeno-ku, Osaka, 545-8585, Japan.
authors: H
authors: H
authors: Nakamura
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D015415:Biomarkers / Q000378:metabolism; D001862:Bone Resorption / Q000139:chemically induced / Q000188:drug therapy; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism; D016022:Case-Control Studies; D024042:Collagen Type I / Q000652:urine; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D015675:Osteocalcin / Q000097:blood*; D010012:Osteogenesis / Q000187:drug effects; D010455:Peptides / Q000652:urine; D011239:Prednisolone / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D011446:Prospective Studies; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers; D024042:Collagen Type I; D005938:Glucocorticoids; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; D015675:Osteocalcin; D011239:Prednisolone
keywords: Bone metabolic marker; Cohort study; Glucocorticoid; Rheumatoid arthritis