Effects of 1-year anti-TNF-α therapies on bone mineral density and bone biomarkers in rheumatoid arthritis and ankylosing spondylitis

• DOI: 10.1007/s10067-019-04771-3
• Publication Date: 2019-09-14T13:02:43Z
• Authors: Katalin Gulyás; Ágnes Horváth; Edit Végh; Anita Pusztai; Ágnes Szentpétery; Zsófia Pethö; Andrea Váncsa; Nóra Bodnár; Péter Csomor; Attila Hamar; Levente Bodoki; Harjit Pal Bhattoa; Balázs Juhász; Zoltán Nagy; Katalin Hodosi; Tamás Karosi; Oliver FitzGerald; Gabriella Szücs; Zoltán Szekanecz; Szilvia Szamosi; Sándor Szántó
• Keywords: Adult; Male; Bone loss; Sclerostin; Biologics; Etanercept; DKK-1; Arthritis, Rheumatoid; Young Adult; 03 medical and health sciences; Absorptiometry, Photon; 0302 clinical medicine; Bone Density; Spondyloarthritis; Humans; Spondylitis, Ankylosing; Rheumatoid arthritis; Rheumatology and Autoimmunity; Adaptor Proteins, Signal Transducing; Aged; Aged, 80 and over; Reumatologi och inflammation; JAK inhibitors; Syndesmophyte; Klinisk medicin; Osteoprotegerin; RANKL; Middle Aged; 3. Good health; C-Reactive Protein; Erosion; Certolizumab Pegol; Osteoporosis; Intercellular Signaling Peptides and Proteins; Regression Analysis; Female; Tumor Necrosis Factor Inhibitors; Clinical Medicine; Biomarkers

Abstract

Objectives Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) have been associated with generalized and localized bone loss. We conducted a comprehensive study using imaging (dual-energy X-ray absorptiometry, DXA) and laboratory biomarkers in order to determine bone health and to study the effects of anti-tumor necrosis factor (TNF) biologics in RA and AS.

Patients and methods Thirty-six RA and 17 AS patients undergoing 1-year etanercept (ETN) or certolizumab-pegol (CZP) therapy were studied. Bone density was assessed by DXA at baseline and after 12 months. Serum C-reactive protein (CRP), calcium, phosphate, parathyroid hormone (PTH), vitamin D3, osteocalcin, procollagen type I N-propeptide (P1NP), C-terminal telopeptide (βCTX), osteoprotegerin, sclerostin (SOST), Dickkopf-1 (DKK-1), soluble receptor activator nuclear kappa B ligand (sRANKL), and cathepsin K (cathK) levels were determined at baseline and after 6 and 12 months.

Results TNF-α inhibition was clinically effective. Anti-TNF-α halted further bone loss over 1 year. In general, anti-TNF therapy significantly increased P1NP, SOST levels, and the P1NP/βCTX ratios, while decreased DKK-1 and CathK production at different time points in most patient subsets. In the full cohort and in RA, baseline and/or 12-month bone mineral density (BMD) at multiple sites exerted inverse relationships with CRP and βCTX, and positive correlation with SOST. In AS, L2-4 BMD after 1-year biologic therapy inversely correlated with baseline βCTX, while femoral neck BMD rather showed inverse correlations with CRP.

Conclusions Anti-TNF therapy slowed down generalized bone loss, in association with clinical improvements, in both diseases. TNF blockade may enhance bone formation and suppress joint destruction. Anti-TNF therapy may act inversely on DKK-1 and SOST. Independent predictors of BMD were SOST and βCTX in RA, whilst CRP in AS.Key Points• One-year anti-TNF therapy halted generalized bone loss in association with clinical improvement in arthritides.• Anti-TNF therapy may inversely act on DKK-1 and SOST.• Independent predictors of BMD were SOST and βCTX in RA, while CRP in AS.