Bone Involvement in Patients with Spondyloarthropathies.
Journal
Calcified tissue international
ISSN: 1432-0827
Titre abrégé: Calcif Tissue Int
Pays: United States
ID NLM: 7905481
Informations de publication
Date de publication:
04 2022
04 2022
Historique:
received:
19
07
2021
accepted:
24
11
2021
pubmed:
24
1
2022
medline:
26
4
2022
entrez:
23
1
2022
Statut:
ppublish
Résumé
Spondyloarthropathies (SpA) are common systemic inflammatory rheumatic diseases, in which, as in other rheumatic diseases, levels of markers of bone resorption are elevated, leading to bone loss and elevated risk of vertebral fractures. However, the diseases are also associated with new bone formation in the spine, the so-called syndesmophytes. We tried to unravel the pathogenesis of formation and growth of syndesmophytes and evaluated new diagnostic and treatment options. After a successful meeting of the Working Group on Rheumatic Diseases at the ECTS 2020, we (WL and CR) were excited about the quality of the speakers (CM, JH, AG, and GL) and their complimentary lectures. Given the relative lack of reviews on spondyloarthropathies and bone, we decided to work together on a comprehensive review that might be interesting for basic scientists and clinically relevant for clinicians. Radiographic progression in axSpA is linked to several risk factors, like male sex, smoking, HLA-B-27, increased levels of CRP, presence of syndesmophytes, and marked inflammation on MRI. The potential role of mechanical stress in the context of physically demanding jobs has been also suggested to promote structural damages. Different treatment options from NSAIDs to biologic agents like TNF inhibitors (TNFi) or IL-17inhibitors (IL-17i) result in a reduction of inflammation and symptoms. However, all these different treatment options failed to show clear and reproducible results on inhibition on syndesmophyte formation. The majority of data are available on TNFi, and some studies suggested an effect in subgroups of patients with ankylosing spondylitis. Less information is available on NSAIDs and IL-17i. Since IL-17i have been introduced quite recently, more studies are expected. IL-17 inhibitors (Il-17i) potently reduce signs and symptoms, but serum level of IL-17 is not elevated, therefore, IL-17 probably has mainly a local effect. The failure of anti-IL-23 in axSpA suggests that IL-17A production could be independent from IL-23. It may be upregulated by TNFα, resulting in lower expression of DKK1 and RANKL and an increase in osteogenesis. In active AS markers of bone resorption are increased, while bone formation markers can be increased or decreased. Bone Turnover markers and additional markers related to Wnt such as DKK1, sclerostin, and RANKL are valuable for elucidating bone metabolism on a group level and they are not (yet) able to predict individual patient outcomes. The gold standard for detection of structural lesions in clinical practice is the use of conventional radiographics. However, the resolution is low compared to the change over time and the interval for detecting changes are 2 years or more. Modern techniques offer substantial advantages such as the early detection of bone marrow edema with MRI, the fivefold increased detection rate of new or growing syndesmophytes with low-dose CT, and the decrease in 18F-fluoride uptake during treatment with TNFα-inhibitors (TNFi) in a pilot study in 12 AS patients. Detection of bone involvement by new techniques, such as low-dose CT, MRI and 18-Fluoride PET-scans, and bone turnover markers, in combination with focusing on high-risk groups such as patients with early disease, elevated CRP, syndesmophytes at baseline, male patients and patients with HLA-B27 + are promising options for the near future. However, for optimal prevention of formation of syndesmophytes we need more detailed insight in the pathogenesis of bone formation in axSpA and probably more targeted therapies.
Identifiants
pubmed: 35066596
doi: 10.1007/s00223-021-00933-1
pii: 10.1007/s00223-021-00933-1
doi:
Substances chimiques
Anti-Inflammatory Agents, Non-Steroidal
0
Interleukin-17
0
Tumor Necrosis Factor-alpha
0
Fluorides
Q80VPU408O
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
393-420Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
Références
Lories RJ, Luyten FP, de Vlam K (2009) Progress in spondylarthritis. Mechanisms of new bone formation in spondyloarthritis. Arthritis Res Ther 11(2):221
pubmed: 19439035
pmcid: 2688182
van der Heijde D et al (2008) Radiographic findings following two years of infliximab therapy in patients with ankylosing spondylitis. Arthritis Rheumatol 58(10):3063–3070
van der Heijde D et al (2008) Radiographic progression of ankylosing spondylitis after up to two years of treatment with etanercept. Arthritis Rheumatol 58(5):1324–1331
van der Heijde D, Landewé R, van der Linden S (2005) How should treatment effect on spinal radiographic progression in patients with ankylosing spondylitis be measured? Arthritis Rheumatol 52(7):1979–1985
Haroon N et al (2013) The Impact of TNF-inhibitors on radiographic progression in Ankylosing Spondylitis. Arthritis Rheumtol 65(10):2645–2654
Ramiro S, Stolwijk C, van Tubergen A, van der Heijde D, Dougados M, van den Bosch F, Landewé R (2015 Jan) Evolution of radiographic damage in ankylosing spondylitis: a 12 year prospective follow-up of the OASIS study. Ann Rheum Dis 74(1):52–59
pubmed: 23956249
Gong Y, Zheng N, Chen SB et al (2012) Ten years’ experience with needle biopsy in the early diagnosis of sacroiliitis. Arthritis Rheumatol 64:1399–1406
Baraliakos X et al (2014) A long-term observational study using MRI and conventional radiography. Ann Rheum Dis 73:1819–1825. https://doi.org/10.1136/annrheumdis-2013-203425
doi: 10.1136/annrheumdis-2013-203425
pubmed: 23852807
Schett G, Rudwaleit M (2010) Can we stop progression of ankylosing spondylitis? Best Pract Res Clin Rheumatol 24(3):363–371. https://doi.org/10.1016/j.berh.2010.01.005
doi: 10.1016/j.berh.2010.01.005
pubmed: 20534370
Baraliakos X, Listing J, Rudwaleit M et al (2007) Progression of radiographic damage in patients with ankylosing spondylitis: defining the central role of syndesmophytes. Ann Rheum Dis 66:910–915
pubmed: 17329306
pmcid: 1955120
Poddubnyy D, Haibel H, Listing J et al (2012) Baseline radiographic damage, elevated acute phase reactant levels, and cigarette smoking status predict spinal radiographic progression in early axial spondylarthritis. Arthritis Rheumatol 64:1388–1398
Machado PM, Baraliakos X, van der Heijde D, Braun J, Landewé R (2016) MRI vertebral corner inflammation followed by fat deposition is the strongest contributor to the development of new bone at the same vertebral corner: a multilevel longitudinal analysis in patients with ankylosing spondylitis. Ann Rheum Dis 75:1486–1493
pubmed: 26462728
Ramiro S, van Tubergen A, van der Heijde D et al (2014) Brief report : erosions and sclerosis on radiographs precede the subsequent development of syndesmophytes at the same site: a twelve-year prospective follow-up of patients with ankylosing spondylitis. Arthritis Rheumatol 66:2773–2779
pubmed: 25048876
Ward MM, Hendrey MR, Malley JD, Learch TJ, Davis JC Jr, Reveille JD, Weisman MH (2009) Clinical and immunogenetic prognostic factors for radiographic severity in ankylosing spondylitis. Arthritis Rheumatol 61(7):859–866
Ramiro S, Landewé R, van Tubergen A, Boonen A, Stolwijk C, Dougados M, van den Bosch F, van der Heijde D (2015) Lifestyle factors may modify the effect of disease activity on radiographic progression in patients with ankylosing spondylitis: a longitudinal analysis. RMD Open 1(1):e000153
pubmed: 26535153
pmcid: 4623363
Perrotta FM, Lories R, Lubrano E (2021) To move or not to move: the paradoxical effect of physical exercise in axial spondyloarthritis. RMD Open 7(1):e001480
pubmed: 33547227
pmcid: 7871344
Hamersma J, Cardon LR, Bradbury L, Brophy S, van der Horst-Bruinsma I, Calin A, Brown MA (2001) Is disease severity in ankylosing spondylitis genetically determined? Arthritis Rheumatol 44(6):1396–1400
Haroon N, Maksymowych WP, Rahman P, Tsui FW, O’Shea FD, Inman RD (2012) Radiographic severity of ankylosing spondylitis is associated with polymorphism of the large multifunctional peptidase 2 gene in the Spondyloarthritis Research Consortium of Canada cohort. Arthritis Rheumatol 64(4):1119–1126
Bartolomé N, Szczypiorska M, Sánchez A, Sanz J, Juanola-Roura X, Gratacós J, Zarco-Montejo P, Collantes E, Martínez A, Tejedor D, Artieda M, Mulero J (2012) Genetic polymorphisms inside and outside the MHC improve prediction of AS radiographic severity in addition to clinical variables. Rheumatology (Oxford) 51(8):1471–1478
Cortes A, Maksymowych WP, Wordsworth BP, Inman RD, Danoy P, Rahman P, Stone MA, Corr M, Gensler LS, Gladman D, Morgan A, Marzo-Ortega H, Ward MM, SPARCC (Spondyloarthritis Research Consortium of Canada), TASC (Australo-Anglo-American Spondyloarthritis Consortium), Learch TJ, Reveille JD, Brown MA, Weisman MH (2015) Association study of genes related to bone formation and resorption and the extent of radiographic change in ankylosing spondylitis. Ann Rheum Dis 74(7):1387–1393
pubmed: 24651623
Baeten D, Østergaard M, Wei JC-C, Sieper J, Järvinen P, Tam L-S et al (2018) Risankizumab, an IL-23 inhibitor, for ankylosing spondylitis: results of a randomised, double-blind, placebo-controlled, proof-of-concept, dose-finding phase 2 study. Ann Rheum Dis 2018:213328
Baeten D, Sieper J, Braun J, Baraliakos X, Dougados M, Emery P et al (2015) Secukinumab, an interleukin-17A inhibitor ankylosing spondylitis. N Engl J Med 373(26):2534–2548
pubmed: 26699169
Braun J, Baraliakos X, Deodhar A, Baeten D, Sieper J, Emery P et al (2017) Effect of secukinumab on clinical and radiographic outcomes in ankylosing spondylitis: 2-year results from the randomised phase III MEASURE 1 study. Ann Rheum Dis 76(6):1070–1077
pubmed: 27965257
Deodhar A, van der Heijde D, Gensler LS, Kim TH, Maksymowych WP, Østergaard M, Poddubnyy D, Marzo-Ortega H, Bessette L, Tomita T, Leung A, Hojnik M, Gallo G, Li X, Adams D, Carlier H, Sieper J (2020) Ixekizumab for patients with non-radiographic axial spondyloarthritis (COAST-X): a randomised, placebo-controlled trial. Lancet 395(10217):53–64
pubmed: 31813637
Dougados M, Wei JC, Landewé R, Sieper J, Baraliakos X, Van den Bosch F, Maksymowych WP, Ermann J, Walsh JA, Tomita T, Deodhar A, van der Heijde D, Li X, Zhao F, Bertram CC, Gallo G, Carlier H, Gensler LS (2020) Efficacy and safety of ixekizumab through 52 weeks in two phase 3, randomised, controlled clinical trials in patients with active radiographic axial spondyloarthritis (COAST-V and COAST-W). Ann Rheum Dis 79(2):176–185
pubmed: 31685553
Rosine N, Etcheto A, Hendel-Chavez H, Seror R, Briot K, Molto A, Chanson P, Taoufik Y, Wendling D, Lories R, Berenbaum F, van den Berg R, Claudepierre P, Feydy A, Dougados M, Roux C, Miceli-Richard C (2018 May 16) Increase In Il-31 serum levels is associated with reduced structural damage in early axial spondyloarthritis. Sci Rep 8(1):7731
pubmed: 29769586
pmcid: 5956108
Appel H, Maier R, Wu P, Scheer R, Hempfing A, Kayser R et al (2011) Analysis of IL-17(+) cells in facet joints of patients with spondyloarthritis suggests that the innate immune pathway might be of greater relevance than the Th17-mediated adaptive immune response. Arthritis Res Ther 13(3):R95
pubmed: 21689402
pmcid: 3218910
Watad A, Rowe H, Russell T, Zhou Q, Anderson LK, Khan A et al (2020) Normal human enthesis harbours conventional CD4+ and CD8+ T cells with regulatory features and inducible IL-17A and TNF expression. Ann Rheum Dis 79(8):1044–1054
pubmed: 32404344
Cuthbert RJ, Fragkakis EM, Dunsmuir R, Li Z, Coles M, Marzo-Ortega H et al (2017) Brief report: group 3 innate lymphoid cells in human enthesis. Arthritis Rheumatol 69(9):1816–1822
pubmed: 28511289
Cuthbert RJ, Watad A, Fragkakis EM, Dunsmuir R, Loughenbury P, Khan A et al (2019) Evidence that tissue resident human enthesis γδT-cells can produce IL-17A independently of IL-23R transcript expression. Ann Rheum Dis 78(11):1559–1565
pubmed: 31530557
Vieira-Sousa E, van Duivenvoorde LM, Fonseca JE, Lories RJ, Baeten DL (2015) Review: animal models as a tool to dissect pivotal pathways driving spondyloarthritis. Arthritis Rheumatol 67(11):2813–2827
pubmed: 26215401
Ruutu M, Thomas G, Steck R, Degli-Esposti MA, Zinkernagel MS, Alexander K et al (2012) β-glucan triggers spondylarthritis and Crohn’s disease-like ileitis in SKG mice. Arthritis Rheumatol 64(7):2211–2222
van Tok MN, Na S, Lao CR, Alvi M, Pots D, van de Sande MGH et al (2018) The initiation, but not the persistence, of experimental spondyloarthritis is dependent on interleukin-23 signaling. Front Immunol 9:1550
pubmed: 30038617
pmcid: 6046377
Sherlock JP, Joyce-Shaikh B, Turner SP, Chao C-C, Sathe M, Grein J et al (2012) IL-23 induces spondyloarthropathy by acting on ROR-γt+ CD3+CD4-CD8- entheseal resident T cells. Nat Med 18(7):1069–1076
pubmed: 22772566
Reinhardt A, Yevsa T, Worbs T, Lienenklaus S, Sandrock I, Oberdörfer L et al (2016) Interleukin-23-dependent γ/δ T cells produce interleukin-17 and accumulate in the enthesis, aortic valve, and ciliary body in mice. Arthritis Rheumatol 68(10):2476–2486
pubmed: 27111864
van Tok MN, van Duivenvoorde LM, Kramer I, Ingold P, Pfister S, Roth L et al (2019) Interleukin-17A inhibition diminishes inflammation and new bone formation in experimental spondyloarthritis. Arthritis Rheumatol 71(4):612–625
pubmed: 30390386
Asari T, Furukawa K-I, Tanaka S, Kudo H, Mizukami H, Ono A et al (2012) Mesenchymal stem cell isolation and characterization from human spinal ligaments. Biochem Biophys Res Commun 417(4):1193–1199
pubmed: 22234304
Huang H, Kim HJ, Chang EJ, Lee ZH, Hwang SJ, Kim HM, Lee Y, Kim HH (2009 Oct) IL-17 stimulates the proliferation and differentiation of human mesenchymal stem cells: implications for bone remodeling. Cell Death Differ 16(10):1332–1343
pubmed: 19543237
Nam D, Mau E, Wang Y, Wright D, Silkstone D, Whetstone H et al (2012) T-lymphocytes enable osteoblast maturation via IL-17F during the early phase of fracture repair. PLoS ONE 7(6):e40044
pubmed: 22768215
pmcid: 3386936
Osta B, Lavocat F, Eljaafari A, Miossec P (2014) Effects of interleukin-17A on osteogenic differentiation of isolated human mesenchymal stem cells. Front Immunol 5:425
pubmed: 25228904
pmcid: 4151036
Croes M, Kruyt MC, Groen WM, van Dorenmalen KMA, Dhert WJA, Öner FC et al (2018) Interleukin 17 enhances bone morphogenetic protein-2-induced ectopic bone formation. Sci Rep 8(1):7269
pubmed: 29740080
pmcid: 5940874
Riegel A, Maurer T, Prior B, Stegmaier S, Heppert V, Wagner C et al (2012) Human polymorphonuclear neutrophils express RANK and are activated by its ligand. RANKL. Eur J Immunol. 42(4):975–981
pubmed: 22531921
Moutsopoulos NM, Zerbe CS, Wild T, Dutzan N, Brenchley L, DiPasquale G et al (2017) Interleukin-12 and interleukin-23 blockade in leukocyte adhesion deficiency type 1. N Engl J Med 376(12):1141–1146
pubmed: 28328326
pmcid: 5494261
Moutsopoulos NM, Konkel J, Sarmadi M, Eskan MA, Wild T, Dutzan N et al (2014) Defective neutrophil recruitment in leukocyte adhesion deficiency type I disease causes local IL-17-driven inflammatory bone loss. Sci Transl Med. 6(229):229ra40
pubmed: 24670684
pmcid: 4090608
Papagoras C, Chrysanthopoulou A, Mitsios A, Ntinopoulou M, Tsironidou V, Batsali AK et al (2021) IL 17A expressed on neutrophil extracellular traps promotes mesenchymal stem cell differentiation towards bone-forming cells in ankylosing spondylitis. Eur J Immunol 51:930
pubmed: 33340091
Fassio A, Gatti D, Rossini M, Idolazzi L, Giollo A, Adami G et al (2019) Secukinumab produces a quick increase in WNT signalling antagonists in patients with psoriatic arthritis. Clin Exp Rheumatol févr 37(1):133–136
McGeachy MJ, Chen Y, Tato CM, Laurence A, Joyce-Shaikh B, Blumenschein WM, McClanahan TK, O’Shea JJ, Cua DJ (2009) The interleukin 23 receptor is essential for the terminal differentiation of interleukin 17-producing effector T helper cells in vivo. Nat Immunol 10:314–324
pubmed: 19182808
pmcid: 2945605
Baeten D, Østergaard M, Wei JC, Sieper J, Järvinen P, Tam LS, Salvarani C, Kim TH, Solinger A, Datsenko Y, Pamulapati C, Visvanathan S, Hall DB, Aslanyan S, Scholl P, Padula SJ (2018 Sep) Risankizumab, an IL-23 inhibitor, for ankylosing spondylitis: results of a randomised, double-blind, placebo-controlled, proof-of-concept, dose-finding phase 2 study. Ann Rheum Dis 77(9):1295–1302
pubmed: 29945918
Deodhar A, Gensler LS, Sieper J, Clark M, Calderon C, Wang Y, Zhou Y, Leu JH, Campbell K, Sweet K, Harrison DD, Hsia EC, van der Heijde D (2019) Three multicenter, randomized, double-blind, placebo-controlled studies evaluating the efficacy and safety of ustekinumab in axial spondyloarthritis. Arthritis Rheumatol 71(2):258–270
pubmed: 30225992
Ritchlin C, Rahman P, Kavanaugh A, McInnes IB, Puig L, Li S, Wang Y, Shen YK, Doyle MK, Mendelsohn AM, Gottlieb AB, PSUMMIT 2 Study Group. Efficacy and safety of the anti-IL-12/23 p40 monoclonal antibody, ustekinumab, in patients with active psoriatic arthritis despite conventional non-biological and biological anti-tumour necrosis factor therapy: 6-month and 1-year results of the phase 3, multicentre, double-blind, placebo-controlled, randomised PSUMMIT 2 trial.
McInnes IB, Kavanaugh A, Gottlieb AB, Puig L, Rahman P, Ritchlin C, Brodmerkel C, Li S, Wang Y, Mendelsohn AM, Doyle MK (2013) Efficacy and safety of ustekinumab in patients with active psoriatic arthritis: 1 year results of the phase 3, multicentre, double-blind, placebo-controlled PSUMMIT 1 trial. Lancet 382(9894):780–789
pubmed: 23769296
Reinhardt A, Yevsa T, Worbs T, Lienenklaus S, Sandrock I, Oberdörfer L, Korn T, Weiss S, Förster R, Prinz I (2016 Oct) Interleukin-23-dependent γ/δ T cells produce interleukin-17 and accumulate in the enthesis, aortic valve, and ciliary body in mice. Arthritis Rheumatol 68(10):2476–2486
pubmed: 27111864
Cuthbert RJ, Watad A, Fragkakis EM, Dunsmuir R, Loughenbury P, Khan A, Millner PA, Davison A, Marzo-Ortega H, Newton D, Bridgewood C, McGonagle DG (2019 Nov) Evidence that tissue resident human enthesis γδT-cells can produce IL-17A independently of IL-23R transcript expression. Ann Rheum Dis 78(11):1559–1565
pubmed: 31530557
Gracey E, Qaiyum Z, Almaghlouth I, Lawson D, Karki S, Avvaru N, Zhang Z, Yao Y, Ranganathan V, Baglaenko Y, Inman RD (2016 Dec) IL-7 primes IL-17 in mucosal-associated invariant T (MAIT) cells, which contribute to the Th17-axis in ankylosing spondylitis. Ann Rheum Dis 75(12):2124–2132
pubmed: 27165176
Shah M, Maroof A, Gikas P, Mittal G, Keen R, Baeten D et al (2020) Dual neutralisation of IL-17F and IL-17A with bimekizumab blocks inflammation-driven osteogenic differentiation of human periosteal cells. RMD Open 6(2):e001306
pubmed: 32723833
pmcid: 7722278
Heiland GR, Appel H, Poddubnyy D et al (2012) High level of functional dickkopf-1 predicts protection from syndesmophyte formation in patients with ankylosing spondylitis. Ann Rheum Dis 71:572–574
pubmed: 22186710
Diarra D, Stolina M, Polzer K et al (2007) Dickkopf-1 is a master regulator of joint remodeling. Nat Med 13:156–163
pubmed: 17237793
Uderhardt S, Diarra D, Katzenbeisser J, David JP, Zwerina J, Richards W, Kronke G, Schett G (2010) Blockade of Dickkopf (DKK)-1 induces fusion of sacroiliac joints. Ann Rheum Dis 69:592–597
pubmed: 19304568
Gamez-Nava JI, de la Cerda-Trujillo LF, Vazquez-Villegas ML et al (2016) Association between bone turnover markers, clinical variables, spinal syndesmophytes and bone mineral density in Mexican patients with ankylosing spondylitis. Scand J Rheumatol 45:480–490
pubmed: 27218482
Arends S, Spoorenberg A, Bruyn GA, Houtman PM, Leijsma MK, Kallenberg CG, Brouwer E, van der Veer E (2011) The relation between bone mineral density, bone turnover markers, and vitamin D status in ankylosing spondylitis patients with active disease: a cross-sectional analysis. Osteoporos Int 22:1431–1439
pubmed: 20603707
Arends S, Spoorenberg A, Efde M, Bos R, Leijsma MK, Bootsma H, Veeger NJ, Brouwer E, van der Veer E (2014) Higher bone turnover is related to spinal radiographic damage and low bone mineral density in ankylosing spondylitis patients with active disease: a cross-sectional analysis. PLoS ONE 9:e99685
pubmed: 24918782
pmcid: 4053372
Toussirot E, Dumoulin G, Saas P, Nguyen NU, Le Huédé G, Wendling D (2008) Increased tartrate-resistant acid phosphatase serum levels in ankylosing spondylitis and relationship with the inflammatory process. Ann Rheum Dis 67:430–431
pubmed: 18292108
Wang L, Gao L, Jin D, Wang P, Yang B, Deng W, Xie Z, Tang Y, Wu Y, Shen H (2015) The relationship of bone mineral density to oxidant/antioxidant status and inflammatory and bone turnover markers in a multicenter cross-sectional study of young men with ankylosing spondylitis. Calcif Tissue Int 97:12–22
pubmed: 26025702
Borman P, Bodur H, Bingöl N, Bingöl S, Bostan EE (2001) Bone mineral density and bone turnover markers in a group of male ankylosing spondylitis patients: relationship to disease activity. J Clin Rheumatol 7:315–321
pubmed: 17039162
Park MC, Chung SJ, Park YB, Lee SK (2008) Bone and cartilage turnover markers, bone mineral density, and radiographic damage in men with ankylosing spondylitis. Yonsei Med J 49:288–294
pubmed: 18452267
pmcid: 2615310
Arends S, Spoorenberg A, Brouwer E, van der Veer E (2014) Clinical studies on bone-related outcome and the effect of TNF-α blocking therapy in ankylosing spondylitis. Curr Opin Rheumatol 26:259–268
pubmed: 24625371
Arends S, Spoorenberg A, Houtman PM, Leijsma MK, Bos R, Kallenberg CG, Groen H, Brouwer E, van der Veer E (2012) The effect of three years of TNFα blocking therapy on markers of bone turnover and their predictive value for treatment discontinuation in patients with ankylosing spondylitis: a prospective longitudinal observational cohort study. Arthritis Res Ther 14:R98
pubmed: 22546520
pmcid: 3446472
Li H, Li Q, Chen X, Ji C, Gu J (2015) Anti-tumor necrosis factor therapy increased spine and femoral neck bone mineral density of patients with active ankylosing spondylitis with low bone mineral density. J Rheumatol 42:1413–1417
pubmed: 26077412
Gengenbacher M, Sebald HJ, Villiger PM, Hofstetter W, Seitz M (2008) Infliximab inhibits bone resorption by circulating osteoclast precursor cells in patients with rheumatoid arthritis and ankylosing spondylitis. Ann Rheum Dis 67:620–624
pubmed: 17720725
Visvanathan S, van der Heijde D, Deodhar A, Wagner C, Baker DG, Han J, Braun J (2009) Effects of infliximab on markers of inflammation and bone turnover and associations with bone mineral density in patients with ankylosing spondylitis. Ann Rheum Dis 68:175–182
pubmed: 18495735
Choi ST, Kim JH, Kang EJ, Lee SW, Park MC, Park YB, Lee SK (2008) Osteopontin might be involved in bone remodelling rather than in inflammation in ankylosing spondylitis. Rheumatology (Oxford) 47:1775–1779
van der Weijden MA, van Denderen JC, Lems WF, Nurmohamed MT, Dijkmans BA, van der Horst-Bruinsma IE (2016) Etanercept increases bone mineral density in ankylosing spondylitis, but does not prevent vertebral fractures: results of a prospective observational cohort study. J Rheumatol 43:758–764
pubmed: 26879348
Sarikaya S, Basaran A, Tekin Y, Ozdolap S, Ortancil O (2007) Is osteoporosis generalized or localized to central skeleton in ankylosing spondylitis? J Clin Rheumatol 13:20–24
pubmed: 17278944
Mitra D, Elvins DM, Collins AJ (1999) Biochemical markers of bone metabolism in mild ankylosing spondylitis and their relationship with bone mineral density and vertebral fractures. J Rheumatol 26:2201–2204
pubmed: 10529140
Speden DJ, Calin AI, Ring FJ, Bhalla AK (2002) Bone mineral density, calcaneal ultrasound, and bone turnover markers in women with ankylosing spondylitis. J Rheumatol 29:516–521
pubmed: 11908565
Franck H, Keck E (1993) Serum osteocalcin and vitamin D metabolites in patients with ankylosing spondylitis. Ann Rheum Dis 52:343–346
pubmed: 8323382
pmcid: 1005047
Huang J, Song G, Yin Z, Fu Z, Ye Z (2016) Alteration of bone turnover markers in canonical wingless pathway in patients with ankylosing spondylitis. Arch Rheumatol 31:221–228
pubmed: 29900942
pmcid: 5827846
Bay-Jensen AC, Leeming DJ, Kleyer A, Veidal SS, Schett G, Karsdal MA (2012) Ankylosing spondylitis is characterized by an increased turnover of several different metalloproteinase-derived collagen species: a cross-sectional study. Rheumatol Int 32:3565–3572
pubmed: 22086471
Kwon SR, Lim MJ, Suh CH, Park SG, Hong YS, Yoon BY, Kim HA, Choi HJ, Park W (2012) Dickkopf-1 level is lower in patients with ankylosing spondylitis than in healthy people and is not influenced by anti-tumor necrosis factor therapy. Rheumatol Int 32:2523–2527
pubmed: 21833531
Franck H, Meurer T, Hofbauer LC (2004) Evaluation of bone mineral density, hormones, biochemical markers of bone metabolism, and osteoprotegerin serum levels in patients with ankylosing spondylitis. J Rheumatol 31:2236–2241
pubmed: 15517638
Klingberg E, Nurkkala M, Carlsten H, Forsblad-d’Elia H (2014) Biomarkers of bone metabolism in ankylosing spondylitis in relation to osteoproliferation and osteoporosis. J Rheumatol 41:1349–1356
pubmed: 24931960
Tuylu T, Sari I, Solmaz D, Kozaci DL, Akar S, Gunay N, Onen F, Akkoc N (2014) Fetuin-A is related to syndesmophytes in patients with ankylosing spondylitis: a case control study. Clinics (Sao Paulo, Brazil) 69:688–693
Nocturne G, Pavy S, Boudaoud S et al (2015) Increase in Dickkopf-1 serum level in recent spondyloarthritis. Data from the DESIR cohort. PLoS ONE 10:0134974
Korkosz M, Gąsowski J, Leszczyński P, Pawlak-Buś K, Jeka S, Kucharska E, Grodzicki T (2013) High disease activity in ankylosing spondylitis is associated with increased serum sclerostin level and decreased wingless protein-3a signaling but is not linked with greater structural damage. BMC Musculoskelet Disord 14:99
pubmed: 23509994
pmcid: 3639156
Taylan A, Sari I, Akinci B, Bilge S, Kozaci D, Akar S, Colak A, Yalcin H, Gunay N, Akkoc N (2012) Biomarkers and cytokines of bone turnover: extensive evaluation in a cohort of patients with ankylosing spondylitis. BMC Musculoskelet Disord 13:191
pubmed: 23025387
pmcid: 3492209
Rossini M, Viapiana O, Idolazzi L, Ghellere F, Fracassi E, Troplini S, Povino MR, Kunnathully V, Adami S, Gatti D (2016) Higher level of Dickkopf-1 is associated with low bone mineral density and higher prevalence of vertebral fractures in patients with ankylosing spondylitis. Calcif Tissue Int 98:438–445
pubmed: 26645432
Sakellariou GT, Iliopoulos A, Konsta M, Kenanidis E, Potoupnis M, Tsiridis E, Gavana E, Sayegh FE (2017) Serum levels of Dkk-1, sclerostin and VEGF in patients with ankylosing spondylitis and their association with smoking, and clinical, inflammatory and radiographic parameters. Joint Bone Spine 84:309–315
pubmed: 27369645
Daoussis D, Liossis SN, Solomou EE, Tsanaktsi A, Bounia K, Karampetsou M, Yiannopoulos G, Andonopoulos AP (2010) Evidence that Dkk-1 is dysfunctional in ankylosing spondylitis. Arthritis Rheum 62:150–158
pubmed: 20039407
Gulyás K, Horváth Á, Végh E et al (2020) Effects of 1-year anti-TNF-α therapies on bone mineral density and bone biomarkers in rheumatoid arthritis and ankylosing spondylitis. Clin Rheumatol 39:167–175
pubmed: 31522318
Ustun N, Tok F, Kalyoncu U, Motor S, Yuksel R, Yagiz AE, Guler H, Turhanoglu AD (2014) Sclerostin and Dkk-1 in patients with ankylosing spondylitis. Acta rReumatol Portuguesa 39:146–151
Appel H, Ruiz-Heiland G, Listing J et al (2009) Altered skeletal expression of sclerostin and its link to radiographic progression in ankylosing spondylitis. Arthritis Rheum 60:3257–3262
pubmed: 19877044
Drake MT, Fenske JS, Blocki FA, Zierold C, Appelman-Dijkstra N, Papapoulos S, Khosla S (2018) Validation of a novel, rapid, high precision sclerostin assay not confounded by sclerostin fragments. Bone 111:36–43
pubmed: 29550267
pmcid: 5924723
Chen M, Hu X, Wu M et al (2019) Serum levels of OPG, RANKL, and RANKL/OPG ratio in patients with ankylosing spondylitis: a systematic review and meta-analysis. Immunol Invest 48:490–504
pubmed: 30689477
Bowness P (2015) HLA-B27. Annu Rev Immunol 33:29–48
pubmed: 25861975
Acebes C, de la Piedra C, Traba ML, Seibel MJ, García Martín C, Armas J, Herrero-Beaumont G (1999) Biochemical markers of bone remodeling and bone sialoprotein in ankylosing spondylitis. Clinica Chim Acta 289:99–110
Bronson WD, Walker SE, Hillman LS, Keisler D, Hoyt T, Allen SH (1998) Bone mineral density and biochemical markers of bone metabolism in ankylosing spondylitis. J Rheumatol 25:929–935
pubmed: 9598894
Chen CH, Chen HA, Liao HT, Liu CH, Tsai CY, Chou CT (2010) Soluble receptor activator of nuclear factor-kappaB ligand (RANKL) and osteoprotegerin in ankylosing spondylitis: OPG is associated with poor physical mobility and reflects systemic inflammation. Clin Rheumatol 29:1155–1161
pubmed: 20690034
Dhir V, Srivastava R, Aggarwal A (2013) Circulating levels of soluble receptor activator of N-κ B ligand and matrix metalloproteinase 3 (and their antagonists) in Asian Indian patients with ankylosing spondylitis. Int J Rheumatol 2013:814350
pubmed: 24078814
pmcid: 3773996
El Maghraoui A, Tellal S, Chaouir S, Lebbar K, Bezza A, Nouijai A, Achemlal L, Bouhssain S, el Derouiche M (2005) Bone turnover markers, anterior pituitary and gonadal hormones, and bone mass evaluation using quantitative computed tomography in ankylosing spondylitis. Clin Rheumatol 24:346–351
pubmed: 15592691
Grisar J, Bernecker PM, Aringer M et al (2002) Ankylosing spondylitis, psoriatic arthritis, and reactive arthritis show increased bone resorption, but differ with regard to bone formation. J Rheumatol 29:1430–1436
pubmed: 12136902
Hou C, Luan L, Ren C (2018) Oxidized low-density lipoprotein promotes osteoclast differentiation from CD68 positive mononuclear cells by regulating HMGB1 release. Biochem Biophys Res Commun 495:1356–1362
pubmed: 29146189
Jadon DR, Sengupta R, Nightingale A et al (2017) Serum bone-turnover biomarkers are associated with the occurrence of peripheral and axial arthritis in psoriatic disease: a prospective cross-sectional comparative study. Arthritis Res Ther 19:210
pubmed: 28934972
pmcid: 5609020
Kim HR, Lee SH, Kim HY (2006) Elevated serum levels of soluble receptor activator of nuclear factors-kappaB ligand (sRANKL) and reduced bone mineral density in patients with ankylosing spondylitis (AS). Rheumatology (Oxford) 45:1197–1200
Marhoffer W, Stracke H, Masoud I, Scheja M, Graef V, Bolten W, Federlin K (1995) Evidence of impaired cartilage/bone turnover in patients with active ankylosing spondylitis. Ann Rheum Dis 54:556–559
pubmed: 7668898
pmcid: 1009934
Muntean L, Rojas-Vargas M, Font P, Simon SP, Rednic S, Schiotis R, Stefan S, Tamas MM, Bolosiu HD, Collantes-Estévez E (2011) Relative value of the lumbar spine and hip bone mineral density and bone turnover markers in men with ankylosing spondylitis. Clin Rheumatol 30:691–695
pubmed: 21221691
Niu CC, Lin SS, Yuan LJ, Chen LH, Yang CY, Chung AN, Lu ML, Tsai TT, Lai PL, Chen WJ (2017) Correlation of blood bone turnover biomarkers and Wnt signaling antagonists with AS, DISH, OPLL, and OYL. BMC Musculoskelet Disord 18:61
pubmed: 28153008
pmcid: 5290649
Perpétuo IP, Raposeiro R, Caetano-Lopes J, Vieira-Sousa E, Campanilho-Marques R, Ponte C, Canhão H, Ainola M, Fonseca JE (2015) Effect of tumor necrosis factor inhibitor therapy on osteoclasts precursors in ankylosing spondylitis. PLoS ONE 10:e0144655
pubmed: 26674064
pmcid: 4682624
Serdaroğlu Beyazal M, Erdoğan T, Türkyılmaz AK, Devrimsel G, Cüre MC, Beyazal M, Sahin I (2016) Relationship of serum osteoprotegerin with arterial stiffness, preclinical atherosclerosis, and disease activity in patients with ankylosing spondylitis. Clin Rheumatol 35:2235–2241
pubmed: 26847856
Sun W, Tian L, Jiang L, Zhang S, Zhou M, Zhu J, Xue J (2019) Sclerostin rather than Dickkopf-1 is associated with mSASSS but not with disease activity score in patients with ankylosing spondylitis. Clin Rheumatol 38:989–995
pubmed: 30443790
Vosse D, Landewé R, Garnero P, van der Heijde D, van der Linden S, Geusens P (2008) Association of markers of bone- and cartilage-degradation with radiological changes at baseline and after 2 years follow-up in patients with ankylosing spondylitis. Rheumatology (Oxford) 47:1219–1222
Yilmaz N, Ozaslan J (2000) Biochemical bone turnover markers in patients with ankylosing spondylitis. Clin Rheumatol 19:92–98
pubmed: 10791618
Yuan TL, Chen J, Tong YL, Zhang Y, Liu YY, Wei JC, Liu Y, Zhao Y, Herrmann M (2016) Serum heme oxygenase-1 and BMP-7 are potential biomarkers for bone metabolism in patients with rheumatoid arthritis and ankylosing spondylitis. Biomed Res Int 2016:7870925
pubmed: 27314037
pmcid: 4899581
Wang R, Ward MM (2018) Epidemiology of axial spondyloarthritis: an update. Curr Opin Rheumatol 30(2):137–143
pubmed: 29227352
pmcid: 5811203
Lambert RG, Bakker PA, van der Heijde D, Weber U, Rudwaleit M, Hermann KG et al (2016) Defining active sacroiliitis on MRI for classification of axial spondyloarthritis: update by the ASAS MRI working group. Ann Rheum Dis 75(11):1958–1963
pubmed: 26768408
de Winter J, de Hooge M, van de Sande M, de Jong H, van Hoeven L, de Koning A et al (2018) Magnetic resonance imaging of the sacroiliac joints indicating sacroiliitis according to the assessment of spondyloArthritis international society definition in healthy individuals, runners, and women with postpartum back pain. Arthritis Rheumatol 70(7):1042–1048
pubmed: 29513924
pmcid: 6032910
Weber U, Maksymowych WP (2011) Sensitivity and specificity of magnetic resonance imaging for axial spondyloarthritis. Am J Med Sci 341(4):272–277
pubmed: 21358308
Wanders AJ, Landewe RB, Spoorenberg A, Dougados M, van der Linden S, Mielants H et al (2004) What is the most appropriate radiologic scoring method for ankylosing spondylitis? A comparison of the available methods based on the outcome measures in rheumatology clinical trials filter. Arthritis Rheum 50(8):2622–2632
pubmed: 15334477
Braun J, van den Berg R, Baraliakos X, Boehm H, Burgos-Vargas R, Collantes-Estevez E et al (2011) 2010 update of the ASAS/EULAR recommendations for the management of ankylosing spondylitis. Ann Rheum Dis 70(6):896–904
pubmed: 21540199
Sari I, Haroon N (2018) Radiographic progression in ankylosing spondylitis: from prognostication to disease modification. Curr Rheumatol Rep 20(12):82
pubmed: 30406859
Ramiro S, Stolwijk C, van Tubergen A, van der Heijde D, Dougados M, van den Bosch F et al (2015) Evolution of radiographic damage in ankylosing spondylitis: a 12 year prospective follow-up of the OASIS study. Ann Rheum Dis 74(1):52–59
pubmed: 23956249
Molto A, Freire V, Feydy A, Paternotte S, Maksymowych WP, Benhamou M et al (2014) Assessing structural changes in axial spondyloarthritis using a low-dose biplanar imaging system. Rheumatology (Oxford) 53(9):1669–1675
de Bruin F, de Koning A, van den Berg R, Baraliakos X, Braun J, Ramiro S et al (2018) Development of the CT Syndesmophyte Score (CTSS) in patients with ankylosing spondylitis: data from the SIAS cohort. Ann Rheum Dis 77(3):371–377
pubmed: 29127093
de Koning A, de Bruin F, van den Berg R, Ramiro S, Baraliakos X, Braun J et al (2018) Low-dose CT detects more progression of bone formation in comparison to conventional radiography in patients with ankylosing spondylitis: results from the SIAS cohort. Ann Rheum Dis 77(2):293–299
pubmed: 29127092
Diekhoff T, Hermann KG, Greese J, Schwenke C, Poddubnyy D, Hamm B et al (2017) Comparison of MRI with radiography for detecting structural lesions of the sacroiliac joint using CT as standard of reference: results from the SIMACT study. Ann Rheum Dis 76(9):1502–1508
pubmed: 28283515
Diekhoff T, Greese J, Sieper J, Poddubnyy D, Hamm B, Hermann KA (2018) Improved detection of erosions in the sacroiliac joints on MRI with volumetric interpolated breath-hold examination (VIBE): results from the SIMACT study. Ann Rheum Dis 77(11):1585–1589
pubmed: 30097454
Beltran LS, Samim M, Gyftopoulos S, Bruno MT, Petchprapa CN (2018) Does the addition of DWI to fluid-sensitive conventional MRI of the sacroiliac joints improve the diagnosis of sacroiliitis? AJR Am J Roentgenol 210(6):1309–1316
pubmed: 29629794
Bruijnen STG, Verweij NJF, van Duivenvoorde LM, Bravenboer N, Baeten DLP, van Denderen CJ et al (2018) Bone formation in ankylosing spondylitis during anti-tumour necrosis factor therapy imaged by 18F-fluoride positron emission tomography. Rheumatology (Oxford) 57(4):631–638
Park EK, Pak K, Park JH, Kim K, Kim SJ, Kim IJ et al (2017) Baseline increased 18F-fluoride uptake lesions at vertebral corners on positron emission tomography predict new syndesmophyte development in ankylosing spondylitis: a 2-year longitudinal study. Rheumatol Int 37(5):765–773
pubmed: 28154899
Ramirez J, Nieto-Gonzalez JC, Curbelo Rodriguez R, Castaneda S, Carmona L (2018) Prevalence and risk factors for osteoporosis and fractures in axial spondyloarthritis: a systematic review and meta-analysis. Semin Arthritis Rheum 48(1):44–52
pubmed: 29290311
Briot K, Durnez A, Paternotte S, Miceli-Richard C, Dougados M, Roux C (2013) Bone oedema on MRI is highly associated with low bone mineral density in patients with early inflammatory back pain: results from the DESIR cohort. Ann Rheum Dis 72(12):1914–1919
pubmed: 23161904
Schett G, David JP (2010) The multiple faces of autoimmune-mediated bone loss. Nat Rev Endocrinol 6(12):698–706
pubmed: 21045788
Cooper C, Carbone L, Michet CJ, Atkinson EJ, O’Fallon WM, Melton LJ 3rd (1994) Fracture risk in patients with ankylosing spondylitis: a population based study. J Rheumatol 21(10):1877–1882
pubmed: 7837154
Vosse D, Landewe R, van der Heijde D, van der Linden S, van Staa TP, Geusens P (2009) Ankylosing spondylitis and the risk of fracture: results from a large primary care-based nested case-control study. Ann Rheum Dis 68(12):1839–1842
pubmed: 19066179
Munoz-Ortego J, Vestergaard P, Rubio JB, Wordsworth P, Judge A, Javaid MK et al (2014) Ankylosing spondylitis is associated with an increased risk of vertebral and nonvertebral clinical fractures: a population-based cohort study. J Bone Miner Res 29(8):1770–1776
pubmed: 24619796
Sahuguet J, Fechtenbaum J, Molto A, Etcheto A, Lopez-Medina C, Richette P et al (2019) Low incidence of vertebral fractures in early spondyloarthritis: 5-year prospective data of the DESIR cohort. Ann Rheum Dis 78(1):60–65
pubmed: 30389692
Lim MJ, Kang KY (2020) A contemporary view of the diagnosis of osteoporosis in patients with axial spondyloarthritis. Front Med (Lausanne). 7:569449
pubmed: 33363182
pmcid: 7759657
Capaci K, Hepguler S, Argin M, Tas I (2003) Bone mineral density in mild and advanced ankylosing spondylitis. Yonsei Med J 44(3):379–384
pubmed: 12833574
Briot K, Etcheto A, Miceli-Richard C, Dougados M, Roux C (2016) Bone loss in patients with early inflammatory back pain suggestive of spondyloarthritis: results from the prospective DESIR cohort. Rheumatology (Oxford) 55(2):335–342
Durnez A, Paternotte S, Fechtenbaum J, Landewe RB, Dougados M, Roux C et al (2013) Increase in bone density in patients with spondyloarthritis during anti-tumor necrosis factor therapy: 6-year followup study. J Rheumatol 40(10):1712–1718
pubmed: 23950191
Ulu MA, Cevik R, Dilek B (2013) Comparison of PA spine, lateral spine, and femoral BMD measurements to determine bone loss in ankylosing spondylitis. Rheumatol Int 33(7):1705–1711
pubmed: 23274443
Donnelly S, Doyle DV, Denton A, Rolfe I, McCloskey EV, Spector TD (1994) Bone mineral density and vertebral compression fracture rates in ankylosing spondylitis. Ann Rheum Dis 53(2):117–121
pubmed: 8129456
pmcid: 1005263
Meirelles ES, Borelli A, Camargo OP (1999) Influence of disease activity and chronicity on ankylosing spondylitis bone mass loss. Clin Rheumatol 18(5):364–368
pubmed: 10524549
Kang KY, Chung MK, Kim HN, Hong YS, Ju JH, Park SH (2018) Severity of sacroiliitis and erythrocyte sedimentation rate are associated with a low trabecular bone score in young male patients with ankylosing spondylitis. J Rheumatol 45(3):349–356
pubmed: 29335346
Wildberger L, Boyadzhieva V, Hans D, Stoilov N, Rashkov R, Aubry-Rozier B (2017) Impact of lumbar syndesmophyte on bone health as assessed by bone density (BMD) and bone texture (TBS) in men with axial spondyloarthritis. Joint Bone Spine 84(4):463–466
pubmed: 27450198
Kocijan R, Finzel S, Englbrecht M, Engelke K, Rech J, Schett G (2014) Differences in bone structure between rheumatoid arthritis and psoriatic arthritis patients relative to autoantibody positivity. Ann Rheum Dis 73(11):2022–2028
pubmed: 23926056
Klingberg E, Lorentzon M, Gothlin J, Mellstrom D, Geijer M, Ohlsson C et al (2013) Bone microarchitecture in ankylosing spondylitis and the association with bone mineral density, fractures, and syndesmophytes. Arthritis Res Ther 15(6):R179
pubmed: 24517240
pmcid: 3978766
Neumann A, Haschka J, Kleyer A, Schuster L, Englbrecht M, Berlin A et al (2018) Cortical bone loss is an early feature of nonradiographic axial spondyloarthritis. Arthritis Res Ther 20(1):202
pubmed: 30165891
pmcid: 6117894
van der Heijde D, Ramiro S, Landewé R et al (2017) 2016 update of the ASAS-EULAR management recommendations for axial spondyloarthritis. Ann Rheum Dis 76:978–991
pubmed: 28087505
Sepriano A, Regel A, van der Heijde D et al (2017) Efficacy and safety of biological and targeted-synthetic DMARDs: a systematic literature review informing the 2016 update of the ASAS/EULAR recommendations for the management of axial spondyloarthritis. RMD Open 3:e000396
pubmed: 28176964
pmcid: 5278329
Kroon FP, van der Burg LR, Ramiro S et al (2015) Non-steroidal anti-inflammatory drugs (NSAIDs) for axial spondyloarthritis (ankylosing spondylitis and non-radiographic axial spondyloarthritis). Cochrane Database Syst Rev 7:CD010952
Maxwell LJ, Zochling J, Boonen A et al (2015) TNF-alpha inhibitors for ankylosing spondylitis. Cochrane Database Syst Rev 4:CD005468
Dubash S, Bridgewood C, McGonagle D, Marzo-Ortega H (2019) The advent of IL-17A blockade in ankylosing spondylitis: secukinumab, ixekizumab and beyond. Expert Rev Clin Immunol 15:123–134
pubmed: 30576610
Yin Y, Wang M, Liu M et al (2020) Efficacy and safety of IL-17 inhibitors for the treatment of ankylosing spondylitis: a systematic review and meta-analysis. Arthritis Res Ther 22:111
pubmed: 32398096
pmcid: 7216398
Poddubnyy D, Rudwaleit M, Haibel H et al (2012) Effect of non-steroidal anti-inflammatory drugs on radiographic spinal progression in patients with axial spondyloarthritis: results from the German Spondyloarthritis Inception Cohort. Ann Rheum Dis 71:1616–1622
pubmed: 22459541
Haroon N, Inman RD, Learch TJ et al (2013) The impact of tumor necrosis factor α inhibitors on radiographic progression in ankylosing spondylitis. Arthritis Rheum 65:2645–2654
pubmed: 23818109
pmcid: 3974160
Ramiro S, Stolwijk C, van Tubergen A et al (2015) Evolution of radiographic damage in ankylosing spondylitis: a 12 year prospective follow-up of the OASIS study. Ann Rheum Dis 74:52–59
pubmed: 23956249
Park JW, Kim MJ, Lee JS et al (2019) Impact of tumor necrosis factor inhibitor versus nonsteroidal antiinflammatory drug treatment on radiographic progression in early ankylosing spondylitis: its relationship to inflammation control during treatment. Arthritis Rheumatol 71:82–90
pubmed: 29984487
Kang KY, Ju JH, Park SH, Kim HY (2013) The paradoxical effects of TNF inhibitors on bone mineral density and radiographic progression in patients with ankylosing spondylitis. Rheumatology (Oxford) 52:718–726
Baraliakos X, Haibel H, Listing J, Sieper J, Braun J (2014) Continuous long-term anti-TNF therapy does not lead to an increase in the rate of new bone formation over 8 years in patients with ankylosing spondylitis. Ann Rheum Dis 73:710–715
pubmed: 23505240
Park JW, Kwon HM, Park JK et al (2016) Impact of dose tapering of tumor necrosis factor inhibitor on radiographic progression in ankylosing spondylitis. PLoS ONE 11:e0168958
pubmed: 28033420
pmcid: 5199008
Molnar C, Scherer A, Baraliakos X (2018) TNF blockers inhibit spinal radiographic progression in ankylosing spondylitis by reducing disease activity: results from the Swiss Clinical Quality Management cohort. Ann Rheum Dis 77:63–69
pubmed: 28939631
Sepriano A, Ramiro S, Wichuk S (2021) TNF inhibitors reduce spinal radiographic progression in patients with radiographic axial spondyloarthritis: a longitudinal analysis from the ALBERTA FORCAST cohort. Arthritis Rheumatol. https://doi.org/10.1002/art.41667
doi: 10.1002/art.41667
pubmed: 33538097
pmcid: 8361759
Baraliakos X, Listing J, Rudwaleit M, Brandt J, Sieper J, Braun J (2005) Radiographic progression in patients with ankylosing spondylitis after 2 years of treatment with the tumour necrosis factor alpha antibody infliximab. Ann Rheum Dis 64:1462–1466
pubmed: 15778240
pmcid: 1755223
Baraliakos X, Listing J, Brandt J (2007) Radiographic progression in patients with ankylosing spondylitis after 4 years of treatment with the anti-TNF-alpha antibody infliximab. Rheumatology (Oxford) 46:1450–1453
van der Heijde D, Landewé R, Baraliakos X (2008) Radiographic findings following two years of infliximab therapy in patients with ankylosing spondylitis. Arthritis Rheum 58:3063–3070
pubmed: 18821688
van der Heijde D, Landewé R, Einstein S (2008) Radiographic progression of ankylosing spondylitis after up to two years of treatment with etanercept. Arthritis Rheum 58:1324–1331
pubmed: 18438853
van der Heijde D, Salonen D, Weissman BN (2009) Assessment of radiographic progression in the spines of patients with ankylosing spondylitis treated with adalimumab for up to 2 years. Arthritis Res Ther 11:R127
pubmed: 19703304
pmcid: 2745811
Braun J, Haibel H, de Hooge M (2019) Spinal radiographic progression over 2 years in ankylosing spondylitis patients treated with secukinumab: a historical cohort comparison. Arthritis Res Ther 21:142
pubmed: 31174584
pmcid: 6555995
Wanders A, Dv H, Landewé R (2005) Nonsteroidal antiinflammatory drugs reduce radiographic progression in patients with ankylosing spondylitis: a randomized clinical trial. Arthritis Rheum 52:1756–1765
pubmed: 15934081
Sieper J, Listing J, Poddubnyy D (2016) Effect of continuous versus on-demand treatment of ankylosing spondylitis with diclofenac over 2 years on radiographic progression of the spine: results from a randomised multicentre trial (ENRADAS). Ann Rheum Dis 75:1438–1443
pubmed: 26242443
Braun J, Baraliakos X, Hermann KG (2014) The effect of two golimumab doses on radiographic progression in ankylosing spondylitis: results through 4 years of the GO-RAISE trial. Ann Rheum Dis 73:1107–1113
pubmed: 23644549
Braun J, Baraliakos X, Deodhar A (2017) Effect of secukinumab on clinical and radiographic outcomes in ankylosing spondylitis: 2-year results from the randomised phase III MEASURE 1 study. Ann Rheum Dis 76:1070–1077
pubmed: 27965257
Braun J, Baraliakos X, Deodhar A (2019) Secukinumab shows sustained efficacy and low structural progression in ankylosing spondylitis: 4-year results from the MEASURE 1 study. Rheumatology (Oxford) 58:859–868
Wang R, Bathon JM, Ward MM (2020) Nonsteroidal antiinflammatory drugs as potential disease-modifying medications in axial spondyloarthritis. Arthritis Rheumatol 72:518–528
pubmed: 31705611
pmcid: 7113090
Smith WL, DeWitt DL, Garavito RM (2000) Cyclooxygenases: structural, cellular, and molecular biology. Annu Rev Biochem 69:145–182
pubmed: 10966456
Weinreb M, Suponitzky I, Keila S (1997) Systemic administration of an anabolic dose of PGE2 in young rats increases the osteogenic capacity of bone marrow. Bone 20:521–526
pubmed: 9177865
Proft F, Muche B, Listing J, Rios-Rodriguez V, Sieper J, Poddubnyy D (2017) Study protocol: COmparison of the effect of treatment with Nonsteroidal anti- inflammatory drugs added to anti-tumour necrosis factor a therapy versus anti-tumour necrosis factor a therapy alone on progression of StrUctural damage in the spine over two years in patients with ankyLosing spondylitis (CONSUL)–an open-label randomized controlled multicenter trial. BMJ Open 7:e014591
pubmed: 28601821
pmcid: 5623356
Tan S, Wang R, Ward MM et al (2015) Syndesmophyte growth in ankylosing spondylitis. Curr Opin Rheumatol 27:326–332
pubmed: 26002023
pmcid: 4478446
Maksymowych WP, Chiowchanwisawakit P, Clare T, Pedersen SJ, Østergaard M, Lambert RG (2009) Inflammatory lesions of the spine on magnetic resonance imaging predict the development of new syndesmophytes in ankylosing spondylitis: evidence of a relationship between inflammation and new bone formation. Arthritis Rheum 60:93–102
pubmed: 19116919
Braun J, Baraliakos X, Hermann KG et al (2012) Golimumab reduces spinal inflammation in ankylosing spondylitis: MRI results of the randomised, placebo- controlled GO-RAISE study. Ann Rheum Dis 71:878–884
pubmed: 22128083
Braun J, Baraliakos X, Golder W et al (2003) Magnetic resonance imaging examinations of the spine in patients with ankylosing spondylitis, before and after successful therapy with infliximab: evaluation of a new scoring system. Arthritis Rheum 48:1126–1136
pubmed: 12687557
Baraliakos X, Davis J, Tsuji W, Braun J et al (2005) Magnetic resonance imaging examinations of the spine in patients with ankylosing spondylitis before and after therapy with the tumor necrosis factor alpha receptor fusion protein etanercept. Arthritis Rheum 52:1216–1223
pubmed: 15818694
Lambert RG, Salonen D, Rahman P et al (2007) Adalimumab significantly reduces both spinal and sacroiliac joint inflammation in patients with ankylosing spondylitis: a multicenter, randomized, double-blind, placebo-controlled study. Arthritis Rheum 56:4005–4014
pubmed: 18050198
Zhang JR, Liu XJ, Xu WD, Dai SM (2016) Effects of tumor necrosis factor-α inhibitors on new bone formation in ankylosing spondylitis. Joint Bone Spine 83:257–264
pubmed: 26678001
Claudepierre P, Wendling D (2008) Are inflammation and ossification on separate tracks in ankylosing spondylitis? Joint Bone Spine 75:520–522
pubmed: 18675574
Wendling D, Claudepierre P (2013) New bone formation in axial spondyloarthritis. Joint Bone Spine 80:454–458
pubmed: 23566662
Baraliakos X, Gensler LS, D’Angelo S et al (2020) Biologic therapy and spinal radiographic progression in patients with axial spondyloarthritis: a structured literature review. Ther Adv Musculoskelet Dis 12:1759720
Jeong H, Eun YH, Kim IY et al (2018) Effect of tumor necrosis factor α inhibitors on spinal radiographic progression in patients with ankylosing spondylitis. Int J Rheum Dis 21:1098–1105
pubmed: 29611287
Schett G, Lories RJ, D’Agostino MA (2017) Enthesitis: from pathophysiology to treatment. Nat Rev Rheumatol 13:731–741
pubmed: 29158573
Gravallese EM, Schett G (2018) Effects of the IL-23-IL-17 pathway on bone in spondyloarthritis. Nat Rev Rheumatol 14:631–640
pubmed: 30266977
Baraliakos X, Østergaard M, Gensler LS (2020) Comparison of the effects of secukinumab and adalimumab biosimilar on radiographic progression in patients with ankylosing spondylitis: design of a randomized, phase IIIb study (SURPASS). Clin Drug Investig 40:269–278
pubmed: 31983056
Russell RG (2011) Bisphosphonates: the first 40 years. Bone 49:2–19
pubmed: 21555003
Papapoulos SE (2020) Pamidronate; a model compound of the pharmacology of nitrogen-containing bisphosphonates; a Leiden historical perspective. Bone 134:115244
pubmed: 31958532
Rogers MJ, Mönkkönen J, Munoz MA (2020) Molecular mechanisms of action of bisphosphonates and new insights into their effects outside the skeleton. Bone 139:115493
pubmed: 32569873
Peris P, Monegal A, Guañabens N (2021) Bisphosphonates in inflammatory rheumatic diseases. Bone 146:115887
pubmed: 33592328
Giusti A, Camellino D, Saverino D et al (2020) Zoledronate decreases CTLA-4 in vivo and in vitro independently of its action on bone resorption. Bone 138:115512
pubmed: 32603908
Frediani B, Giusti A, Bianchi G et al (2018) Clodronate in the management of different musculoskeletal conditions. Minerva Med 109:300–325
pubmed: 29947493
Giusti A, Bianchi G (2015) Treatment of complex regional pain syndrome type I with bisphosphonates. RMD Open 1:e000056
pubmed: 26557377
pmcid: 4632140
Coates L, Packham JC, Creamer P et al (2017) Clinical efficacy of oral alendronate in ankylosing spondylitis: a randomised placebo-controlled trial. Clin Exp Rheumatol 35:445–451
pubmed: 28079501
Mok CC, Li OC, Chan KL, Ho LY, Hui PK (2015) Effect of golimumab and pamidronate on clinical efficacy and MRI inflammation in axial spondyloarthritis: a 48-week open randomized trial. Scand J Rheumatol 44:480–486
pubmed: 26271141
Viapiana O, Gatti D, Idolazzi L et al (2014) Bisphosphonates vs infliximab in ankylosing spondylitis treatment. Rheumatology (Oxford) 53:90–94
Maksymowych WP, Jhangri GS, Fitzgerald AA et al (2002) A six-month randomized, controlled, double-blind, dose-response comparison of intravenous pamidronate (60 mg versus 10 mg) in the treatment of nonsteroidal antiinflammatory drug-refractory ankylosing spondylitis. Arthritis Rheum 46:766–773
pubmed: 11920413