Changes in bone formation regulator biomarkers in early axial spondyloarthritis

Abstract

Abstract Objective The hallmark of advanced axial SpA (axSpA) is spine ankylosis due to excessive ectopic bone formation. This prospective study aimed to describe the changes in serum levels of different regulators [sclerostin, dickkopf-1 (DKK-1)] and markers of bone formation [bone morphogenetic protein 7 (BMP-7)] over 5 years in early axSpA patients and to assess determinants of such changes. Methods The DEvenir des Spondyloarthropathies Indifférenciées Récentes cohort is a prospective, multicentre French study of 708 patients with early (>3 months–<3 years) inflammatory back pain suggestive of axSpA. Serum levels of BMP-7, sclerostin and DKK-1 were assessed at baseline and after 2 and 5 years. Changes in bone formation regulators over time were analysed using mixed linear models. Results Serum BMP-7 significantly increased over time, with a median relative change of 223.7% [interquartile range (IQR) 0–10 700 (0.17 pg/ml/month), P < 0.001]. Serum sclerostin significantly increased over time, with a median relative change of 14.8% [IQR −7.9–41.4% (0.001 ng/ml/month), P < 0.001]. Serum DKK-1 did not significantly change over time. Serum BMP-7 increased over time in active disease (Ankylosing Spondylitis Disease Activity Score with CRP ≥1.3, P = 0.01), but the increase was less pronounced with TNF inhibitor (TNFi) use (P < 0.001). No determinant was associated with serum sclerostin change. Conclusion Serum BMP-7 change over 5 years was related with inflammation; it was increased in active disease, but the increase was low with TNFi use. Serum sclerostin levels significantly increased over time, but to a lesser degree than for serum BMP-7. Clinical trial registration https://clinicaltrials.gov/, NCT01648907.