Relationship between urinary pyridinium cross-links, disease activity and disease subsets of ankylosing spondylitis.

Abstract

In this study, we aimed to determine the urinary levels of pyridinium cross-links and urinary beta-isomerized fragments derived from the C-telopeptide of the alpha1 chain of type I collagen (beta-CTX) as markers of bone resorption in patients with ankylosing spondylitis (AS), and to study their relationship to markers of disease activity [erythrocyte sedimentation rate (ESR)] and to disease subsets of this condition. The serum calcium, osteocalcin (OC), parathormone (PTH), 25 OHD3 levels, beta-CTX and the urinary combined free pyridinolines (f-Pyr + f-Dpyr), urinary free deoxypyridinoline (f-Dpyr) and urinary free pyridinoline (f-Pyr) were evaluated and compared in 32 AS patients and 25 controls. Bone mineral density (BMD) was evaluated at the lumbar spine and the femoral neck. The serum markers of bone metabolism (serum calcium, PTH, 25 OHD3 and OC) were in the normal range in the AS group. AS patients had a lowered lumbar spine BMD (P = 0.01) (corresponding T score: P = 0.03), but femoral neck BMD did not differ significantly between AS and controls (P = 0.08) (corresponding T score: P = 0.11). There was no difference in the urinary levels of pyridinium cross-links and beta-CTX between AS patients and controls. A positive correlation between ESR, (f-Pyr + f-Dpyr) (r = 0.42; P = 0.018) and f-Dpyr (r = 0.49; P = 0.005) was observed. In the different disease subsets of AS, we found that patients with peripheral involvement had higher (f-Pyr + f-Dpyr) (P = 0.04) and f-Dpyr levels (P = 0.04), patients with early disease had elevated (f-Pyr + f-Dpyr) (P = 0.01), f-Dpyr (P = 0.02) and f-Pyr (P = 0.01) levels, and that those with raised ESR had enhanced f-Dpyr (P = 0.009) excretion. Patients were then stratified according to disease duration, peripheral involvement and sex, and this allowed us to observe that only urinary f-Dpyr remained elevated in patients independently from these variables and that raised ESR is the more relevant parameter for explaining this high level of excretion. We conclude that there was no difference in the levels of urinary pyridinium cross-links and beta-CTX between AS and controls. However, urinary excretion of some of these collagen compounds was enhanced in subgroups of AS, mainly in patients with raised ESR. Thus, AS patients with laboratory evidence of active disease could have a higher risk of bone loss.