Katalin Gulyás1,2, Ágnes Horváth1, Edit Végh1, Anita Pusztai1, Ágnes Szentpétery1,3,4, Zsófia Pethö1, Andrea Váncsa1, Nóra Bodnár1, Péter Csomor1, Attila Hamar1, Levente Bodoki1, Harjit Pal Bhattoa5, Balázs Juhász6, Zoltán Nagy1, Katalin Hodosi1, Tamás Karosi7, Oliver FitzGerald4, Gabriella Szücs1, Zoltán Szekanecz8, Szilvia Szamosi1, Sándor Szántó1,2. 1. Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Nagyerdei str 98, Debrecen, 4032, Hungary. 2. Department of Sports Medicine, Debrecen, Hungary. 3. Department of Rheumatology, Uppsala University Hospital, Uppsala, Sweden. 4. Department of Rheumatology, St. Vincent's University Hospital and Conway Institute for Biomolecular Research, University College Dublin, Dublin, Ireland. 5. Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary. 6. Department of Oncology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary. 7. Department of Otolaryngology, Borsod County Teaching Hospital, Miskolc, Hungary. 8. Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Nagyerdei str 98, Debrecen, 4032, Hungary. szekanecz.zoltan@med.unideb.hu.
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.
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.
Entities:
Keywords:
Biologics; Bone loss; DKK-1; Erosion; JAK inhibitors; Osteoporosis; Osteoprotegerin; RANKL; Rheumatoid arthritis; Sclerostin; Spondyloarthritis; Syndesmophyte
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Authors: Boglárka Soós; Miklós Fagyas; Ágnes Horváth; Edit Végh; Anita Pusztai; Monika Czókolyová; Alexandra Csongrádi; Attila Hamar; Zsófia Pethő; Nóra Bodnár; György Kerekes; Katalin Hodosi; Éva Szekanecz; Szilvia Szamosi; Sándor Szántó; Gabriella Szűcs; Zoltán Papp; Zoltán Szekanecz Journal: Front Med (Lausanne) Date: 2022-01-27
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