Osteoprotegerin and osteocalcin are associated with atherosclerosis in patients with rheumatoid arthritis: a prospective cohort study.

Abstract

Patients with rheumatoid arthritis (RA) have an accelerated progression of atherosclerosis. The aim of this study was to examine the associations between subclinical atherosclerosis, assessed by intima-media thickness (IMT), and regulators of bone formation, markers of bone turnover and bone mineral density (BMD) in patients with RA. Patients with new-onset RA (n=79), aged ≤60 years at diagnosis, were consecutively included in a study of development of atherosclerosis. Ultrasound measurement of IMT of the common carotid artery was undertaken at inclusion (T0) and after 11 years (T11) (n=54). Bone turnover biomarkers were examined in samples collected at T0 and T11. BMD was assessed at T11. In patients with RA, osteocalcin (OCN) and osteoprotegerin (OPG) measured at T11 were significantly associated with IMT at T11, adjusted for systolic blood pressure (SBP) and age. BMD at T11 and the bone turnover markers procollagen type 1 N-terminal propeptide (P1NP) and carboxy-terminal crosslinked C-terminal telopeptide (CTX) were not associated with IMT. OPG, OCN and sclerostin at T0 were significantly associated with IMT at T11, and OPG and OCN at T0 were associated with change in IMT from T0 to T11. The associations between IMT and bone biomarkers were stronger in patients with joint erosions at onset of RA, than in patients with non-erosive disease. Atherosclerosis in patients with RA is associated with OPG and OCN, but not with BMD or markers reflecting ongoing bone turnover, indicating that atherosclerosis is not associated with bone turnover per se.