How useful are bone turnover markers in rheumatoid arthritis? Influence of disease activity and corticosteroid therapy.
Rheumatoid arthritis is associated with osteopenia possibly related to increased bone resorption. Until recently, the markers used to evaluate bone turnover lacked specificity, and as a result studies were difficult to interpret.


OBJECTIVE
To study bone remodeling in patients with rheumatoid arthritis, with special attention to the effects of corticosteroid therapy.


METHODS
Forty-eight patients (36 women and 12 men) with a mean age of 54.6 +/- 11.6 years and a mean disease duration of 11 +/- 9 years were studied. Thirty-nine patients (81%) had positive tests for rheumatoid factors, and 21 (43.7%) were under corticosteroid therapy, with a mean treatment duration of 4.5 +/- 2.9 years and a mean daily dosage of 9.4 +/- 2.5 mg prednisone. A group of age- and sex-matched controls was also studied. Serum levels of procollagen Type I C-terminal propeptide (PINP), procollagen Type I N-terminal propeptide (PINP), and procollagen type I C-terminal telopeptide (ICTP) were determined in all patients and controls. The first two markers reflect bone formation and the last bone resorption. Other tests performed in each patient were the erythrocyte sedimentation rate, serum C-reactive protein, serum total alkaline phosphatase, serum osteocalcin, 24-hour urinary hydroxyproline excretion, and calcium/creatinine ratio in a morning urine sample. Several clinical parameters were used to evaluate disease activity and severity in the rheumatoid arthritis patients.


RESULTS
ICTP levels were significantly elevated in the patients as compared with the controls (6.6 +/- 3.9 ng/ml versus 3.1 +/- 1.2 ng/ml, P = 0.0001), whereas no significant differences were found for PICP or PINP. Similar results were found when the analysis was confined to nonsteroid-medicated patients. Conversely, PICP levels were higher in steroid-medicated patients than in controls (P = 0.0132) and were correlated with steroid therapy duration (r = 0.436). ICTP levels were correlated with age (r = 0.3), Lee's index (r = 0.585), the Health Assessment Questionnaire score (r = 0.391), and the erythrocyte sedimentation rate (r = 0.442). Urinary hydroxyproline excretion was elevated in 41.6% of the patients.


CONCLUSIONS
Our data suggest that rheumatoid arthritis is associated with increased bone resorption, and that steroid therapy further accelerates bone remodeling in this disease.
Cortet
B
B
Rheumatology Department, Lille Teaching Hospital, France.
Flipo
R M
RM
Pigny
P
P
Duquesnoy
B
B
Racadot
A
A
Boersma
A
A
Delcambre
B
B
D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D000328:Adult; D000367:Age Factors; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000188:drug therapy; D015415:Biomarkers / Q000097:blood* / Q000652:urine; D016723:Bone Remodeling / Q000187:drug effects; D001862:Bone Resorption; D003094:Collagen / Q000032:analysis*; D024042:Collagen Type I; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood*; D010455:Peptides / Q000032:analysis*; D011347:Procollagen / Q000097:blood*
D000305:Adrenal Cortex Hormones; D015415:Biomarkers; D024042:Collagen Type I; D010446:Peptide Fragments; D010455:Peptides; D011347:Procollagen; C052929:collagen type I trimeric cross-linked peptide; C047202:procollagen Type I N-terminal peptide; C042813:procollagen type I carboxy terminal peptide; D003094:Collagen