Evolving concepts of new bone formation in axial spondyloarthritis: Insights from animal models and human studies

Taurog, 2016, Ankylosing spondylitis and axial spondyloarthritis, N Engl J Med, 374, 2563, 10.1056/NEJMra1406182 Sieper, 2017, Axial spondyloarthritis, Lancet, 390, 73, 10.1016/S0140-6736(16)31591-4 Baraliakos, 2009, The natural course of radiographic progression in ankylosing spondylitis-evidence for major individual variations in a large proportion of patients, J Rheumatol, 36, 997, 10.3899/jrheum.080871 Lefebvre, 2010, Vertebrate skeletogenesis, Curr Top Dev Biol, 90, 291, 10.1016/S0070-2153(10)90008-2 Zhou, 2014, Chondrocytes transdifferentiate into osteoblasts in endochondral bone during development, postnatal growth and fracture healing in mice, PLoS Genet, 10, e1004820, 10.1371/journal.pgen.1004820 Lories, 2009, Progress in spondylarthritis. Mechanisms of new bone formation in spondyloarthritis, Arthritis Res Ther, 11, 221, 10.1186/ar2642 Appel, 2010, Immunohistochemical analysis of osteoblasts in zygapophyseal joints of patients with ankylosing spondylitis reveal repair mechanisms similar to osteoarthritis, J Rheumatol, 37, 823, 10.3899/jrheum.090986 Appel, 2006, Immunohistologic analysis of zygapophyseal joints in patients with ankylosing spondylitis, Arthritis Rheum, 54, 2845, 10.1002/art.22060 Appel, 2006, Correlation of histopathological findings and magnetic resonance imaging in the spine of patients with ankylosing spondylitis, Arthritis Res Ther, 8, R143, 10.1186/ar2035 Francois, 2000, Histopathologic evidence that sacroiliitis in ankylosing spondylitis is not merely enthesitis, Arthritis Rheum, 43, 2011, 10.1002/1529-0131(200009)43:9<2011::AID-ANR12>3.0.CO;2-Y Francois, 1982, Some pathological features of ankylosing spondylitis as revealed by microradiography and tetracycline labelling, Clin Rheumatol, 1, 23, 10.1007/BF02032472 Lories, 2009, Bone morphogenetic protein signaling and arthritis, Cytokine Growth Factor Rev, 20, 467, 10.1016/j.cytogfr.2009.10.009 Lories, 2005, Modulation of bone morphogenetic protein signaling inhibits the onset and progression of ankylosing enthesitis, J Clin Invest, 115, 1571, 10.1172/JCI23738 van Beuningen, 1998, Differential effects of local application of BMP-2 or TGF-beta 1 on both articular cartilage composition and osteophyte formation, Osteoarthritis Cartilage, 6, 306, 10.1053/joca.1998.0129 Lories, 2004, Ankylosing enthesitis, dactylitis, and onychoperiostitis in male DBA/1 mice: a model of psoriatic arthritis, Ann Rheum Dis, 63, 595, 10.1136/ard.2003.013599 Matthys, 2003, Dependence on interferon-gamma for the spontaneous occurrence of arthritis in DBA/1 mice, Arthritis Rheum, 48, 2983, 10.1002/art.11273 Lories, 2007, Evidence for uncoupling of inflammation and joint remodeling in a mouse model of spondylarthritis, Arthritis Rheum, 56, 489, 10.1002/art.22372 Vieira-Sousa, 2015, Review: animal models as a tool to dissect pivotal pathways driving spondyloarthritis, Arthritis Rheum, 67, 2813, 10.1002/art.39282 Sherlock, 2012, IL-23 induces spondyloarthropathy by acting on ROR-gammat+ CD3+CD4-CD8- entheseal resident T cells, Nat Med, 18, 1069, 10.1038/nm.2817 Diarra, 2007, Dickkopf-1 is a master regulator of joint remodeling, Nat Med, 13, 156, 10.1038/nm1538 Jacques, 2014, Proof of concept: enthesitis and new bone formation in spondyloarthritis are driven by mechanical strain and stromal cells, Ann Rheum Dis, 73, 437, 10.1136/annrheumdis-2013-203643 Armaka, 2008, Mesenchymal cell targeting by TNF as a common pathogenic principle in chronic inflammatory joint and intestinal diseases, J Exp Med, 205, 331, 10.1084/jem.20070906 Uderhardt, 2010, Blockade of Dickkopf (DKK)-1 induces fusion of sacroiliac joints, Ann Rheum Dis, 69, 592, 10.1136/ard.2008.102046 Lories, 2013, To Wnt or not to Wnt: the bone and joint health dilemma, Nat Rev Rheumatol, 9, 328, 10.1038/nrrheum.2013.25 Heiland, 2012, High level of functional dickkopf-1 predicts protection from syndesmophyte formation in patients with ankylosing spondylitis, Ann Rheum Dis, 71, 572, 10.1136/annrheumdis-2011-200216 Ruiz-Heiland, 2012, Blockade of the hedgehog pathway inhibits osteophyte formation in arthritis, Ann Rheum Dis, 71, 400, 10.1136/ard.2010.148262 Sieper, 2008, Critical appraisal of assessment of structural damage in ankylosing spondylitis: implications for treatment outcomes, Arthritis Rheum, 58, 649, 10.1002/art.23260 Lories, 2010, Are current available therapies disease-modifying in spondyloarthritis?, Best Pract Res Clin Rheumatol, 24, 625, 10.1016/j.berh.2010.05.005 Maksymowych, 2012, Motion for debate: the development of ankylosis in ankylosing spondylitis is largely dependent on inflammation, Arthritis Rheum, 64, 1713, 10.1002/art.34442 van der Heijde, 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, 10.1186/ar2794 van der Heijde, 2008, Radiographic findings following two years of infliximab therapy in patients with ankylosing spondylitis, Arthritis Rheum, 58, 3063, 10.1002/art.23901 van der Heijde, 2008, Radiographic progression of ankylosing spondylitis after up to two years of treatment with etanercept, Arthritis Rheum, 58, 1324, 10.1002/art.23471 Lories, 2012, Primed for inflammation: enthesis-resident T cells, Nat Med, 18, 1018, 10.1038/nm.2854 Shaw, 2016, IL-17A deficiency promotes periosteal bone formation in a model of inflammatory arthritis, Arthritis Res Ther, 18, 104, 10.1186/s13075-016-0998-x Ono, 2016, IL-17-producing gammadelta T cells enhance bone regeneration, Nat Commun, 7, 10928, 10.1038/ncomms10928 Van Mechelen, 2017, Bone disease in axial spondyloarthritis, Calcif Tissue Int, 102, 547, 10.1007/s00223-017-0356-2 Van Mechelen, 2016, Microtrauma: no longer to be ignored in spondyloarthritis?, Curr Opin Rheumatol, 28, 176, 10.1097/BOR.0000000000000254 Carter, 2011, Osteoporosis: a paradox in ankylosing spondylitis, Curr Osteoporos Rep, 9, 112, 10.1007/s11914-011-0058-z Ebihara, 2015, Interleukin-17 is a critical target for the treatment of ankylosing enthesitis and psoriasis-like dermatitis in mice, Autoimmunity, 48, 259, 10.3109/08916934.2014.976630 Glatigny, 2012, Proinflammatory Th17 cells are expanded and induced by dendritic cells in spondylarthritis-prone HLA-B27-transgenic rats, Arthritis Rheum, 64, 110, 10.1002/art.33321 Reinhardt, 2016, Interleukin-23-dependent gamma/delta T cells produce interleukin-17 and accumulate in the enthesis, aortic valve, and ciliary body in mice, Arthritis Rheum, 68, 2476, 10.1002/art.39732 Cuthbert, 2017, Brief report: group 3 innate lymphoid cells in human enthesis, Arthritis Rheum, 69, 1816, 10.1002/art.40150 Haroon, 2013, The impact of tumor necrosis factor alpha inhibitors on radiographic progression in ankylosing spondylitis, Arthritis Rheum, 65, 2645 Maas, 2017, Ankylosing spondylitis patients at risk of poor radiographic outcome show diminishing spinal radiographic progression during long-term treatment with TNF-alpha inhibitors, PLoS One, 12, e0177231, 10.1371/journal.pone.0177231 Maksymowych, 2015, The effect of TNF Inhibition on radiographic progression in ankylosing spondylitis: an observational cohort study of 374 patients, Arthritis & Rheumatology., 67 Usmani, 2017, The effect of cigarette smoke on bone formation in ankylosing spondylitis, J Rheumatol, 44, 909 Machado, 2015, MRI vertebral corner inflammation followed by fat deposition is the strongest contributor to the development of new bone at the same vertebral corner: a multi-level longitudinal analysis in patients with ankylosing spondylitis, Arthritis & Rheumatology., 67 Baraliakos, 2014, Which spinal lesions are associated with new bone formation in patients with ankylosing spondylitis treated with anti-TNF agents? A long-term observational study using MRI and conventional radiography, Ann Rheum Dis, 73, 1819, 10.1136/annrheumdis-2013-203425 van der Heijde, 2012, MRI inflammation at the vertebral unit only marginally predicts new syndesmophyte formation: a multilevel analysis in patients with ankylosing spondylitis, Ann Rheum Dis, 71, 369, 10.1136/annrheumdis-2011-200208 Ramiro, 2014, Higher disease activity leads to more structural damage in the spine in ankylosing spondylitis: 12-year longitudinal data from the OASIS cohort, Ann Rheum Dis, 73, 1455, 10.1136/annrheumdis-2014-205178 Molnar, 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, 10.1136/annrheumdis-2017-211544 Baraliakos, 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, 10.1136/annrheumdis-2012-202698 Braun, 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, 10.1136/annrheumdis-2016-209730 Ramiro, 2015, Lifestyle factors may modify the effect of disease activity on radiographic progression in patients with ankylosing spondylitis: a longitudinal analysis, RMD Open, 1, 10.1136/rmdopen-2015-000153 Lories, 2014, Bone formation in axial spondyloarthritis, Best Pract Res Clin Rheumatol, 28, 765, 10.1016/j.berh.2014.10.008 Cortes, 2015, Association study of genes related to bone formation and resorption and the extent of radiographic change in ankylosing spondylitis, Ann Rheum Dis, 74, 1387, 10.1136/annrheumdis-2013-204835 Evans, 2011, Interaction between ERAP1 and HLA-B27 in ankylosing spondylitis implicates peptide handling in the mechanism for HLA-B27 in disease susceptibility, Nat Genet, 43, 10.1038/ng.873 Spiro, 2010, BMP-7-Induced ectopic bone formation and fracture healing is impaired by systemic NSAID application in C57BL/6-Mice, J Orthop Res, 28, 785, 10.1002/jor.21044 Wanders, 2005, Nonsteroidal antiinflammatory drugs reduce radiographic progression in patients with ankylosing spondylitis: a randomized clinical trial, Arthritis Rheum, 52, 1756, 10.1002/art.21054 Kroon, 2012, Continuous NSAID use reverts the effects of inflammation on radiographic progression in patients with ankylosing spondylitis, Ann Rheum Dis, 71, 1623, 10.1136/annrheumdis-2012-201370 Sieper, 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, 10.1136/annrheumdis-2015-207897 Tsui, 2014, Serum levels of novel noggin and sclerostin-immune complexes are elevated in ankylosing spondylitis, Ann Rheum Dis, 73, 1873, 10.1136/annrheumdis-2013-203630 Luchetti, 2018, Sclerostin and antisclerostin antibody serum levels predict the presence of axial spondyloarthritis in patients with inflammatory bowel disease, J Rheumatol, 45, 630, 10.3899/jrheum.170833 Baraliakos, 2015, Effect of Interleukin-17A inhibition on spinal radiographic changes through 2 Years in patients with active ankylosing spondylitis: results of a phase 3 study with secukinumab, Arthritis & Rheumatology., 67, 3 Ranganathan, 2017, Macrophage migration inhibitory factor induces inflammation and predicts spinal progression in ankylosing spondylitis, Arthritis Rheum, 69, 1796, 10.1002/art.40175 Capkova, 1992, H-2 influence on ankylosing enthesopathy of the ankle (ANKENT), Folia Biol (Praha), 38, 258 van Duivenvoorde, 2012, Relationship between inflammation, bone destruction, and osteoproliferation in the HLA-B27/human beta2 -microglobulin-transgenic rat model of spondylarthritis, Arthritis Rheum, 64, 3210, 10.1002/art.34600