Osteoclastic activation rather than suppression of bone formation has been
suggested to be the dominant process leading to bone loss in rheumatoid arthritis
(RA). Although many studies have already shown the correlation of urinary
pyridinoline (PYD) and deoxypyridinoline (DPD) levels with RA-related bone loss,
urinary cross-linked N-telopeptides of type I collagen (NTx), a more specific marker
of bone-derived type I collagen fragments in urine than urinary PYD and DPD in RA,
has not been adequately studied. The purpose of the present study was to determine
clinical factors that are associated with an increase in urinary NTx levels in
patients with RA. One hundred and eighty-four patients with RA and 185 sex- and
age-matched controls were enrolled in the study: 71 men, 37–68 years of age (RA: 31,
controls: 40); 129 premenopausal women, 30–48 years of age (RA: 67, controls: 62),
and 169 postmenopausal women, 48–69 years of age (RA: 86, controls: 83). The
correlations of urinary NTx levels, measured by enzyme-linked immunosorbent assay
with anatomic grade in the wrist, functional class, duration of disease, steroid
use, modified health assessment questionnaire (HAQ) score for the upper and lower
extremities, the levels of serum c-reactive protein and rheumatoid factor (RF),
erythrocyte sedimentation rate, and/or years since menopause were examined by
multiple regression analysis. Urinary NTx levels (nmol BCE/mmol Cr) did not differ
significantly between men with RA and controls (53.2 ± 29.6 vs 41.0 ± 19.6,
respectively), whereas urinary NTx levels were significantly higher in pre- and
postmenopausal women with RA than in respective controls (premenopausal women: 57.1
± 36.6 vs 42.3 ± 21.3, P <0.01; women: 76.2 ± 27.3 vs 57.1 ± 28.3, P <0.001).
In men with RA, no clinical factors were significantly correlated with urinary NTx
levels. In premenopausal women with RA, functional class, HAQ score for the upper
extremities, and RF were significantly correlated with urinary NTx levels (all P
<0.05); in postmenopausal women with RA, functional class and RF were
significantly correlated with urinary NTx levels (both P <0.05). These findings
suggest that urinary NTx levels were significantly higher only in women with RA than
in age-matched controls, and a RA-related increase in urinary NTx levels may be
associated with physical inactivity and disease activity.