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Erschienen in: Current Rheumatology Reports 4/2017

01.04.2017 | Spondyloarthritis (M Khan, Section Editor)

The Paradox of Bone Formation and Bone Loss in Ankylosing Spondylitis: Evolving New Concepts of Bone Formation and Future Trends in Management

verfasst von: Marina N. Magrey, Muhammad A. Khan

Erschienen in: Current Rheumatology Reports | Ausgabe 4/2017

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Abstract

Purpose of Review

The purpose of the study is to briefly review the molecular mechanisms that leads to structural damage in ankylosing spondylitis (AS), defined as new bone formation resulting in complete or incomplete ankylosis of the spine, and the impact of treatment with biologics to retard this process.

Recent Findings

The understanding of molecular mechanisms leading to new bone formation in AS has significantly improved but is still incomplete. Availability of biologics has greatly enhanced the treatment of patients with AS, but its impact on slowing the structural damage is still a matter of debate, although a few observational studies have shown that long term use of TNF-α blockers may slow radiographic progression. The availability of newer biologics targeting IL-17/1L23 has shown some promising results in slowing radiographic progression in AS.

Summary

Although the availability of TNF-inhibitors has greatly enhanced the treatment options for patients with AS, their impact on slowing the structural damage is still not clearly established. However, preliminary results using newer biologics targeting IL-17/1L23 axis are more encouraging but longer follow-up is needed.
Literatur
1.
Zurück zum Zitat •• Taurog JD, Chhabra A, Colbert RA. Ankylosing spondylitis and axial spondyloarthritis. N Engl J Med. 2016;374:2563–74. This review article highlights recent advances in our understanding of relationship between spondyloarthritis and ankylosing spondylitis and treatments available.CrossRefPubMed •• Taurog JD, Chhabra A, Colbert RA. Ankylosing spondylitis and axial spondyloarthritis. N Engl J Med. 2016;374:2563–74. This review article highlights recent advances in our understanding of relationship between spondyloarthritis and ankylosing spondylitis and treatments available.CrossRefPubMed
2.
Zurück zum Zitat Khan MA. Ankylosing spondylitis and related spondyloarthropathies: the dramatic advances in the past decade. Rheumatology (Oxford). 2011;50:637–9.CrossRef Khan MA. Ankylosing spondylitis and related spondyloarthropathies: the dramatic advances in the past decade. Rheumatology (Oxford). 2011;50:637–9.CrossRef
3.
Zurück zum Zitat Appel H, Maier R, Loddenkemper C, et al. Immunohistochemical analysis of osteoblasts in zygapophyseal joints of patients with ankylosing spondylitis reveal repair mechanisms similar to osteoarthritis. J Rheumatol. 2010;37:823–8.CrossRefPubMed Appel H, Maier R, Loddenkemper C, et al. Immunohistochemical analysis of osteoblasts in zygapophyseal joints of patients with ankylosing spondylitis reveal repair mechanisms similar to osteoarthritis. J Rheumatol. 2010;37:823–8.CrossRefPubMed
4.
Zurück zum Zitat Lories RJ, Schett G. Pathophysiology of new bone formation and ankylosis in spondyloarthritis. Rheum Dis Clin N Am. 2012;38:555–67.CrossRef Lories RJ, Schett G. Pathophysiology of new bone formation and ankylosis in spondyloarthritis. Rheum Dis Clin N Am. 2012;38:555–67.CrossRef
5.
Zurück zum Zitat Biver E, Hardouin P, Caverzasio J. The “bone morphogenic proteins” pathways in bone and joint diseases: translational perspectives from physiopathology to therapeutic targets. Cytokine Growth Factor Rev. 2013;24:69–81.CrossRefPubMed Biver E, Hardouin P, Caverzasio J. The “bone morphogenic proteins” pathways in bone and joint diseases: translational perspectives from physiopathology to therapeutic targets. Cytokine Growth Factor Rev. 2013;24:69–81.CrossRefPubMed
7.
Zurück zum Zitat Lories RJU, Derese I, Luyten FP. Modulation of bone morphogenetic protein signaling inhibits the onset and progression of ankylosing enthesitis. J Clin Invest. 2005;115:1571–9.CrossRefPubMedPubMedCentral Lories RJU, Derese I, Luyten FP. Modulation of bone morphogenetic protein signaling inhibits the onset and progression of ankylosing enthesitis. J Clin Invest. 2005;115:1571–9.CrossRefPubMedPubMedCentral
8.
Zurück zum Zitat Joo YB, Bang SY, Kim TH, Shim SC, Lee S, et al. Bone morphogenetic protein 6 polymorphisms are associated with radiographic progression in ankylosing spondylitis. PLoS One. 2014;9:e104966.CrossRefPubMedPubMedCentral Joo YB, Bang SY, Kim TH, Shim SC, Lee S, et al. Bone morphogenetic protein 6 polymorphisms are associated with radiographic progression in ankylosing spondylitis. PLoS One. 2014;9:e104966.CrossRefPubMedPubMedCentral
9.
Zurück zum Zitat Chen HA, Chen CH, Lin YJ, Chen PC, Chen WS, Lu CL, et al. Association of bone morphogenetic proteins with spinal fusion in ankylosing spondylitis. J Rheumatol. 2010;37:2126–32.CrossRefPubMed Chen HA, Chen CH, Lin YJ, Chen PC, Chen WS, Lu CL, et al. Association of bone morphogenetic proteins with spinal fusion in ankylosing spondylitis. J Rheumatol. 2010;37:2126–32.CrossRefPubMed
10.
Zurück zum Zitat Wendling D, Cedoz JP, Racadot E, Dumoulin G. Serum IL-17, BMP-7, and bone turnover markers in patients with ankylosing spondylitis. Joint Bone Spine. 2007;74:304–5.CrossRefPubMed Wendling D, Cedoz JP, Racadot E, Dumoulin G. Serum IL-17, BMP-7, and bone turnover markers in patients with ankylosing spondylitis. Joint Bone Spine. 2007;74:304–5.CrossRefPubMed
11.
Zurück zum Zitat El TM, Reis RL. Progenitor and stem cells for bone and cartilage regeneration. J Tissue Eng Regen Med. 2009;3:327–37.CrossRef El TM, Reis RL. Progenitor and stem cells for bone and cartilage regeneration. J Tissue Eng Regen Med. 2009;3:327–37.CrossRef
12.
Zurück zum Zitat Mohanty ST, Kottam L, Gambardella A, Nicklin MJ, Coulton L, Hughes D, et al. Alterations in the self-renewal and differentiation ability of bone marrow mesenchymal stem cells in a mouse model of rheumatoid arthritis. Arthritis Res Ther. 2010;12:R149.CrossRefPubMedPubMedCentral Mohanty ST, Kottam L, Gambardella A, Nicklin MJ, Coulton L, Hughes D, et al. Alterations in the self-renewal and differentiation ability of bone marrow mesenchymal stem cells in a mouse model of rheumatoid arthritis. Arthritis Res Ther. 2010;12:R149.CrossRefPubMedPubMedCentral
13.
Zurück zum Zitat Sun LY, Zhang HY, Feng XB, Hou YY, Lu LW, Fan LM. Abnormality of bone marrow-derived mesenchymal stem cells in patients with systemic lupus erythematosus. Lupus. 2007;16:121–8.CrossRefPubMed Sun LY, Zhang HY, Feng XB, Hou YY, Lu LW, Fan LM. Abnormality of bone marrow-derived mesenchymal stem cells in patients with systemic lupus erythematosus. Lupus. 2007;16:121–8.CrossRefPubMed
14.
Zurück zum Zitat •• Xie Z, Wang P, Li Y, Deng W, Zhang X, et al. Imbalance between bone morphogenetic protein 2 and noggin induces abnormal osteogenic differentiation of mesenchymal stem cells in ankylosing spondylitis. Arthritis Rheum. 2016;68:430–40. The study revealed a mechanism of pathologic osteogenesis in AS by demonstrating an imbalance between BMP-2 and Noggin secretion in AS patients that possibly leads to abnormal osteogenic differentiation of AS MSCs.CrossRef •• Xie Z, Wang P, Li Y, Deng W, Zhang X, et al. Imbalance between bone morphogenetic protein 2 and noggin induces abnormal osteogenic differentiation of mesenchymal stem cells in ankylosing spondylitis. Arthritis Rheum. 2016;68:430–40. The study revealed a mechanism of pathologic osteogenesis in AS by demonstrating an imbalance between BMP-2 and Noggin secretion in AS patients that possibly leads to abnormal osteogenic differentiation of AS MSCs.CrossRef
15.
Zurück zum Zitat •• Magrey MN, Haqqi T, Haseeb A. Identification of plasma microRNA expression profile in radiographic axial spondyloarthritis—a pilot study. Clin Rheumatol. 2016;35:1323–7. Brief report about microRNA expression in AS and microRNA 34a is differentially expressed in SpA and has been shown to inhibit bone loss.CrossRefPubMed •• Magrey MN, Haqqi T, Haseeb A. Identification of plasma microRNA expression profile in radiographic axial spondyloarthritis—a pilot study. Clin Rheumatol. 2016;35:1323–7. Brief report about microRNA expression in AS and microRNA 34a is differentially expressed in SpA and has been shown to inhibit bone loss.CrossRefPubMed
16.
Zurück zum Zitat Goldring SR, Goldring MB. Eating bone or adding it: the Wnt pathway decides. Nat Med. 2007;13:133–4.CrossRefPubMed Goldring SR, Goldring MB. Eating bone or adding it: the Wnt pathway decides. Nat Med. 2007;13:133–4.CrossRefPubMed
17.
Zurück zum Zitat Xie W, Zhou L, Li S, Hui T, Chen D. Wnt/β-catenin signaling plays a key role in the development of spondyloarthritis. Ann N Y Acad Sci. 2016;1364:25–31.CrossRefPubMed Xie W, Zhou L, Li S, Hui T, Chen D. Wnt/β-catenin signaling plays a key role in the development of spondyloarthritis. Ann N Y Acad Sci. 2016;1364:25–31.CrossRefPubMed
18.
Zurück zum Zitat Uderhardt S, Diarra D, Katzenbeisser J, David JP, Zwerina J, et al. Blockade of Dickkopf (DKK)-1 induces fusion of sacroiliac joints. Ann Rheum Dis. 2010;3:592–7.CrossRef Uderhardt S, Diarra D, Katzenbeisser J, David JP, Zwerina J, et al. Blockade of Dickkopf (DKK)-1 induces fusion of sacroiliac joints. Ann Rheum Dis. 2010;3:592–7.CrossRef
19.
Zurück zum Zitat Kwon SR, Lim MJ, Suh CH, Park SG, Hong YS, Yoon BY, et al. 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. 2012;32:2523–7.CrossRefPubMed Kwon SR, Lim MJ, Suh CH, Park SG, Hong YS, Yoon BY, et al. 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. 2012;32:2523–7.CrossRefPubMed
20.
Zurück zum Zitat Heiland GR, Appel H, Poddubnyy D, Zwerina J, Hueber A, et al. High level of functional dickkopf-1 predicts protection from syndesmophyte formation in patients with ankylosing spondylitis. Ann Rheum Dis. 2012;71:572–4.CrossRefPubMed Heiland GR, Appel H, Poddubnyy D, Zwerina J, Hueber A, et al. High level of functional dickkopf-1 predicts protection from syndesmophyte formation in patients with ankylosing spondylitis. Ann Rheum Dis. 2012;71:572–4.CrossRefPubMed
21.
Zurück zum Zitat Appel H, Ruiz-Heiland G, Listing J, Zwerina J, Herrmann M, et al. Altered skeletal expression of sclerostin and its link to radiographic progression in ankylosing spondylitis. Arthritis Rheum. 2009;60:3257–62.CrossRefPubMed Appel H, Ruiz-Heiland G, Listing J, Zwerina J, Herrmann M, et al. Altered skeletal expression of sclerostin and its link to radiographic progression in ankylosing spondylitis. Arthritis Rheum. 2009;60:3257–62.CrossRefPubMed
22.
Zurück zum Zitat González-Chávez SA, Quiñonez-Flores CM, Pacheco-Tena C. Molecular mechanisms of bone formation in spondyloarthritis. Joint Bone Spine. 2016;83:394–400.CrossRefPubMed González-Chávez SA, Quiñonez-Flores CM, Pacheco-Tena C. Molecular mechanisms of bone formation in spondyloarthritis. Joint Bone Spine. 2016;83:394–400.CrossRefPubMed
23.
Zurück zum Zitat Jacques P, Lambrecht S, Verheugen E, Pauwels E, Kollias G, Armaka M, et al. Proof of concept: enthesitis and new bone formation in spondyloarthritis are driven by mechanical strain and stromal cells. Ann Rheum Dis. 2014;73:437–45.CrossRefPubMed Jacques P, Lambrecht S, Verheugen E, Pauwels E, Kollias G, Armaka M, et al. Proof of concept: enthesitis and new bone formation in spondyloarthritis are driven by mechanical strain and stromal cells. Ann Rheum Dis. 2014;73:437–45.CrossRefPubMed
24.
Zurück zum Zitat •• Shaw AT, Gravallese EM. Mediators of inflammation and bone remodeling in rheumatic disease. Semin Cell Dev Biol. 2016;49:2–10. This review article discusses the effects of cytokines on bone in two settings, rheumatoid arthritis and spondyloarthritis.CrossRefPubMed •• Shaw AT, Gravallese EM. Mediators of inflammation and bone remodeling in rheumatic disease. Semin Cell Dev Biol. 2016;49:2–10. This review article discusses the effects of cytokines on bone in two settings, rheumatoid arthritis and spondyloarthritis.CrossRefPubMed
25.
Zurück zum Zitat Walsh NC, Reinwald S, Manning CA, et al. Osteoblast function is compromised at sites of focal bone erosion in inflammatory arthritis. J Bone Miner Res. 2009;24:1572–85.CrossRefPubMed Walsh NC, Reinwald S, Manning CA, et al. Osteoblast function is compromised at sites of focal bone erosion in inflammatory arthritis. J Bone Miner Res. 2009;24:1572–85.CrossRefPubMed
26.
Zurück zum Zitat Braun J, Bollow M, Neure L, Seipelt E, Seyrekbasan F, Herbst H, et al. Use of immunohistologic and in situ hybridization techniques in the examination of sacroiliac joint biopsy specimens from patients with ankylosing spondylitis. Arthritis Rheum. 1995;38:499–505.CrossRefPubMed Braun J, Bollow M, Neure L, Seipelt E, Seyrekbasan F, Herbst H, et al. Use of immunohistologic and in situ hybridization techniques in the examination of sacroiliac joint biopsy specimens from patients with ankylosing spondylitis. Arthritis Rheum. 1995;38:499–505.CrossRefPubMed
27.
Zurück zum Zitat Im CH, Kang EH, Ki JY, et al. Receptor activator of nuclear factor kappa B ligand-mediated osteoclastogenesis is elevated in ankylosing spondylitis. Clin Exp Rheumatol. 2009;27:620–5.PubMed Im CH, Kang EH, Ki JY, et al. Receptor activator of nuclear factor kappa B ligand-mediated osteoclastogenesis is elevated in ankylosing spondylitis. Clin Exp Rheumatol. 2009;27:620–5.PubMed
28.
Zurück zum Zitat Sieper J, Poddubnyy D. Inflammation, new bone formation and treatment options in axial spondyloarthritis. Ann Rheum Dis. 2014;73:1439–41.CrossRefPubMed Sieper J, Poddubnyy D. Inflammation, new bone formation and treatment options in axial spondyloarthritis. Ann Rheum Dis. 2014;73:1439–41.CrossRefPubMed
29.
Zurück zum Zitat Pedersen SJ, Sorensen IJ, Lambert RG, Hermann KG, Garnero P, Johansen JS, et al. Radiographic progression is associated with resolution of systemic inflammation in patients with axial spondylarthritis treated with tumor necrosis factor a inhibitors: a study of radiographic progression, inflammation on magnetic resonance imaging, and circulating biomarkers of inflammation, angiogenesis, and cartilage and bone turnover. Arthritis Rheum. 2011;63:3789–800.CrossRefPubMed Pedersen SJ, Sorensen IJ, Lambert RG, Hermann KG, Garnero P, Johansen JS, et al. Radiographic progression is associated with resolution of systemic inflammation in patients with axial spondylarthritis treated with tumor necrosis factor a inhibitors: a study of radiographic progression, inflammation on magnetic resonance imaging, and circulating biomarkers of inflammation, angiogenesis, and cartilage and bone turnover. Arthritis Rheum. 2011;63:3789–800.CrossRefPubMed
30.
Zurück zum Zitat Lories RJ, Derese I, de Bari C, Luyten FP. Evidence for uncoupling of inflammation and joint remodeling in a mouse model of spondylarthritis. Arthritis Rheum. 2007;56:489–97.CrossRefPubMed Lories RJ, Derese I, de Bari C, Luyten FP. Evidence for uncoupling of inflammation and joint remodeling in a mouse model of spondylarthritis. Arthritis Rheum. 2007;56:489–97.CrossRefPubMed
31.
Zurück zum Zitat van der Heijde D, Salonen D, Weissman BN, Landewé R, Maksymowych WP, Kupper H, et al. Assessment of radiographic progression in the spines of patients with ankylosing spondylitis treated with adalimumab for up to 2 years. Arthritis Res Ther. 2009;11:R127.CrossRefPubMedPubMedCentral van der Heijde D, Salonen D, Weissman BN, Landewé R, Maksymowych WP, Kupper H, et al. Assessment of radiographic progression in the spines of patients with ankylosing spondylitis treated with adalimumab for up to 2 years. Arthritis Res Ther. 2009;11:R127.CrossRefPubMedPubMedCentral
32.
Zurück zum Zitat van der Heijde D et al. Radiographic findings following two years of infliximab therapy in patients with ankylosing spondylitis. Arthritis Rheum. 2008;58:3063–70.CrossRefPubMed van der Heijde D et al. Radiographic findings following two years of infliximab therapy in patients with ankylosing spondylitis. Arthritis Rheum. 2008;58:3063–70.CrossRefPubMed
33.
Zurück zum Zitat van der Heijde D, Landewé R, Einstein S, Ory P, Vosse D, Ni L, et al. Radiographic progression of ankylosing spondylitis after up to two years of treatment with etanercept. Arthritis Rheum. 2008;58:1324–31.CrossRefPubMed van der Heijde D, Landewé R, Einstein S, Ory P, Vosse D, Ni L, et al. Radiographic progression of ankylosing spondylitis after up to two years of treatment with etanercept. Arthritis Rheum. 2008;58:1324–31.CrossRefPubMed
34.
Zurück zum Zitat Baraliakos X, Haibel H, Listing J, Sieper J, Braun J. 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. 2014;73:710–5.CrossRefPubMed Baraliakos X, Haibel H, Listing J, Sieper J, Braun J. 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. 2014;73:710–5.CrossRefPubMed
35.
Zurück zum Zitat •• Haroon N, Inman RD, Learch TJ, et al. The impact of tumor necrosis factor alpha inhibitors on radiographic progression in ankylosing spondylitis. Arthritis Rheum. 2013;65:2645–54. This observational study shows that long term use of TNF inhibitors decreases the odds of radiographic progression in AS.PubMedPubMedCentral •• Haroon N, Inman RD, Learch TJ, et al. The impact of tumor necrosis factor alpha inhibitors on radiographic progression in ankylosing spondylitis. Arthritis Rheum. 2013;65:2645–54. This observational study shows that long term use of TNF inhibitors decreases the odds of radiographic progression in AS.PubMedPubMedCentral
36.
Zurück zum Zitat •• Osta B, Benedetti G, Miossec P. Classical and paradoxical effects of TNF-α on bone homeostasis. Front Immunol. 2014;5:48. A thorough review about the effect on TNF-α on bone homeostasis.PubMedPubMedCentral •• Osta B, Benedetti G, Miossec P. Classical and paradoxical effects of TNF-α on bone homeostasis. Front Immunol. 2014;5:48. A thorough review about the effect on TNF-α on bone homeostasis.PubMedPubMedCentral
37.
Zurück zum Zitat Hess K, Ushmorov A, Fiedler J, Brenner RE, Wirth T. TNF alpha promotes osteogenic differentiation of human mesenchymal stem cells by triggering the NF-kappa B signaling pathway. Bone. 2009;45:367–76.CrossRefPubMed Hess K, Ushmorov A, Fiedler J, Brenner RE, Wirth T. TNF alpha promotes osteogenic differentiation of human mesenchymal stem cells by triggering the NF-kappa B signaling pathway. Bone. 2009;45:367–76.CrossRefPubMed
38.
Zurück zum Zitat Huang H, Zhao N, Xu X, Xu Y, Li S, Zhang J. Dose-specific effects of tumor necrosis factor alpha on osteogenic differentiation of mesenchymal stem cells. Cell Prolif. 2011;44:420–7.CrossRefPubMed Huang H, Zhao N, Xu X, Xu Y, Li S, Zhang J. Dose-specific effects of tumor necrosis factor alpha on osteogenic differentiation of mesenchymal stem cells. Cell Prolif. 2011;44:420–7.CrossRefPubMed
39.
Zurück zum Zitat Daoussis D, Liossis SN, Solomou EE, Tsanaktsi A, Bounia K, Karampetsou M, et al. Evidence that Dkk-1 is dysfunctional in ankylosing spondylitis. Arthritis Rheum. 2010;62:150–8.CrossRefPubMed Daoussis D, Liossis SN, Solomou EE, Tsanaktsi A, Bounia K, Karampetsou M, et al. Evidence that Dkk-1 is dysfunctional in ankylosing spondylitis. Arthritis Rheum. 2010;62:150–8.CrossRefPubMed
40.
Zurück zum Zitat van Duivenvoorde LM, Dorris ML, Satumtira N, van Tok MN, Redlich K, Tak PP, et al. Relationship between inflammation, bone destruction, and osteoproliferation in the HLA-B27/human β2-microglobulin-transgenic rat model of spondylarthritis. Arthritis Rheum. 2012;64:3210–9.CrossRefPubMedPubMedCentral van Duivenvoorde LM, Dorris ML, Satumtira N, van Tok MN, Redlich K, Tak PP, et al. Relationship between inflammation, bone destruction, and osteoproliferation in the HLA-B27/human β2-microglobulin-transgenic rat model of spondylarthritis. Arthritis Rheum. 2012;64:3210–9.CrossRefPubMedPubMedCentral
41.
Zurück zum Zitat Poddubnyy D, Haibel H, Listing J, Märker-Hermann E, Zeidler H, Braun J, et al. Baseline radiographic damage, elevated acute-phase reactant levels, and cigarette smoking status predict spinal radiographic progression in early axial spondylarthritis. Arthritis Rheum. 2012;64:1388–98.CrossRefPubMed Poddubnyy D, Haibel H, Listing J, Märker-Hermann E, Zeidler H, Braun J, et al. Baseline radiographic damage, elevated acute-phase reactant levels, and cigarette smoking status predict spinal radiographic progression in early axial spondylarthritis. Arthritis Rheum. 2012;64:1388–98.CrossRefPubMed
42.
Zurück zum Zitat •• Baraliakos X, Heldmann F, Callhoff J, Listing J, Appelboom T, Brandt J, et al. 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. 2014;73:1819–25. The study revealed that combination of acute inflammation on STIR sequence (fat-suppressed sequence) and fatty lesions are most predictive of syndesmophyte formation in AS.CrossRefPubMed •• Baraliakos X, Heldmann F, Callhoff J, Listing J, Appelboom T, Brandt J, et al. 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. 2014;73:1819–25. The study revealed that combination of acute inflammation on STIR sequence (fat-suppressed sequence) and fatty lesions are most predictive of syndesmophyte formation in AS.CrossRefPubMed
43.
Zurück zum Zitat Maksymowych WP, Chiowchanwisawakit P, Clare T, et al. 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. 2009;60:93–102.CrossRefPubMed Maksymowych WP, Chiowchanwisawakit P, Clare T, et al. 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. 2009;60:93–102.CrossRefPubMed
44.
Zurück zum Zitat Rudwaleit M, Jurik AG, Hermann KG, Landewe R, van der Heijde D, Baraliakos X, et al. Defining active sacroiliitis on magnetic resonance imaging (MRI) for classification of axial spondyloarthritis:a consensual approach by the ASAS/OMERACT MRI group. Ann Rheum Dis. 2009;68:1520–7.CrossRefPubMed Rudwaleit M, Jurik AG, Hermann KG, Landewe R, van der Heijde D, Baraliakos X, et al. Defining active sacroiliitis on magnetic resonance imaging (MRI) for classification of axial spondyloarthritis:a consensual approach by the ASAS/OMERACT MRI group. Ann Rheum Dis. 2009;68:1520–7.CrossRefPubMed
45.
Zurück zum Zitat •• Bleil J, Maier R, Hempfing A, Sieper J, Appel H, Syrbe U. Granulation tissue eroding the subchondral bone also promotes new bone formation in ankylosing spondylitis. Arthritis Rheum. 2016;68:2456–65. Granulation tissue and not fatty metaplasia may be promoting new bone formation in AS.CrossRef •• Bleil J, Maier R, Hempfing A, Sieper J, Appel H, Syrbe U. Granulation tissue eroding the subchondral bone also promotes new bone formation in ankylosing spondylitis. Arthritis Rheum. 2016;68:2456–65. Granulation tissue and not fatty metaplasia may be promoting new bone formation in AS.CrossRef
46.
Zurück zum Zitat Maksymowych WP, Morency N, Conner-Spady B, Lambert RG. Suppression of inflammation and effects on new bone formation in ankylosing spondylitis: evidence for a window of opportunity in disease modification. Ann Rheum Dis. 2013;72:23–8.CrossRefPubMed Maksymowych WP, Morency N, Conner-Spady B, Lambert RG. Suppression of inflammation and effects on new bone formation in ankylosing spondylitis: evidence for a window of opportunity in disease modification. Ann Rheum Dis. 2013;72:23–8.CrossRefPubMed
47.
Zurück zum Zitat •• Ward MM, Deodhar A, Akl EA, Lui A, Ermann J, Gensler LS, et al. American college of rheumatology/spondylitis association of america/spondyloarthritis research and treatment network 2015 recommendations for the treatment of ankylosing spondylitis and nonradiographic axial spondyloarthritis. Arthritis Care Res (Hoboken). 2016;68:151–66. ACR/SPARTAN recommendation for treatment of AS.CrossRef •• Ward MM, Deodhar A, Akl EA, Lui A, Ermann J, Gensler LS, et al. American college of rheumatology/spondylitis association of america/spondyloarthritis research and treatment network 2015 recommendations for the treatment of ankylosing spondylitis and nonradiographic axial spondyloarthritis. Arthritis Care Res (Hoboken). 2016;68:151–66. ACR/SPARTAN recommendation for treatment of AS.CrossRef
48.
Zurück zum Zitat Rohekar S, Chan J, Tse SM, Haroon N, Chandran V, Bessette L, et al. 2014 update of the Canadian rheumatology association/spondyloarthritis research consortium of Canada treatment recommendations for the management of spondyloarthritis. Part II: specific management recommendations. J Rheumatol. 2015;42:665–81.CrossRefPubMed Rohekar S, Chan J, Tse SM, Haroon N, Chandran V, Bessette L, et al. 2014 update of the Canadian rheumatology association/spondyloarthritis research consortium of Canada treatment recommendations for the management of spondyloarthritis. Part II: specific management recommendations. J Rheumatol. 2015;42:665–81.CrossRefPubMed
49.
Zurück zum Zitat Baraliakos X, van den Berg R, Braun J, van der Heijde D. Update of the literature review on treatment with biologics as a basis for the first update of the ASAS/EULAR management recommendations of ankylosing spondylitis. Rheumatology (Oxford). 2012;51:1378–87.CrossRef Baraliakos X, van den Berg R, Braun J, van der Heijde D. Update of the literature review on treatment with biologics as a basis for the first update of the ASAS/EULAR management recommendations of ankylosing spondylitis. Rheumatology (Oxford). 2012;51:1378–87.CrossRef
50.
Zurück zum Zitat Sieper J, Poddubnyy D. New evidence on the management of spondyloarthritis. Nat Rev Rheumatol. 2016;12:282–95.CrossRefPubMed Sieper J, Poddubnyy D. New evidence on the management of spondyloarthritis. Nat Rev Rheumatol. 2016;12:282–95.CrossRefPubMed
51.
Zurück zum Zitat Maas F, Spoorenberg A, Brouwer E, Bos R, Efde M, Chaudhry RN, et al. Spinal radiographic progression in patients with ankylosing spondylitis treated with TNF-α blocking therapy: a prospective longitudinal observational cohort study. PLoS One. 2015;10(4):e0122693.CrossRefPubMedPubMedCentral Maas F, Spoorenberg A, Brouwer E, Bos R, Efde M, Chaudhry RN, et al. Spinal radiographic progression in patients with ankylosing spondylitis treated with TNF-α blocking therapy: a prospective longitudinal observational cohort study. PLoS One. 2015;10(4):e0122693.CrossRefPubMedPubMedCentral
52.
Zurück zum Zitat •• Maas F, Arends S, Brouwer E, Essers I, van der Veer E, Efde M, et al. Reduction in spinal radiographic progression in ankylosing spondylitis patients receiving prolonged treatment with TNF-α inhibitors. Arthritis Care Res (Hoboken). 2016. doi:10.1002/acr.23097. A longitudinal observational cohort study in daily clinical practice showed an overall slow and linear spinal radiographic progression in AS patients with long-term TNF-α blocking therapy. •• Maas F, Arends S, Brouwer E, Essers I, van der Veer E, Efde M, et al. Reduction in spinal radiographic progression in ankylosing spondylitis patients receiving prolonged treatment with TNF-α inhibitors. Arthritis Care Res (Hoboken). 2016. doi:10.​1002/​acr.​23097. A longitudinal observational cohort study in daily clinical practice showed an overall slow and linear spinal radiographic progression in AS patients with long-term TNF-α blocking therapy.
53.
Zurück zum Zitat van der Heijde D, Baraliakos X, Hermann KG, Landewé R, Machado P, Maksymowych W, Davies O, de Peyrecave N, Hoepken B, Bauer L, Nurminen T, Braun J. Four year imaging outcomes in patients with axial spondyloarthritis treated with certolizumab pegol, including patients with ankylosing spondylitis and non-radiographic axial spondyloarthritis [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). van der Heijde D, Baraliakos X, Hermann KG, Landewé R, Machado P, Maksymowych W, Davies O, de Peyrecave N, Hoepken B, Bauer L, Nurminen T, Braun J. Four year imaging outcomes in patients with axial spondyloarthritis treated with certolizumab pegol, including patients with ankylosing spondylitis and non-radiographic axial spondyloarthritis [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10).
54.
Zurück zum Zitat Sherlock JP, Joyce-Shaikh B, Turner SP, Chao CC, Sathe M, Grein J, et al. IL-23 induces spondyloarthropathy by acting on ROR-gammat+ CD3+CD4-CD8- entheseal resident T cells. Nat Med. 2012;18:1069–76.CrossRefPubMed Sherlock JP, Joyce-Shaikh B, Turner SP, Chao CC, Sathe M, Grein J, et al. IL-23 induces spondyloarthropathy by acting on ROR-gammat+ CD3+CD4-CD8- entheseal resident T cells. Nat Med. 2012;18:1069–76.CrossRefPubMed
55.
Zurück zum Zitat Smith JA, Colbert RA. The IL-23/IL-17 axis in spondyloarthritis pathogenesis: Th17 and beyond. Arthritis Rheum. 2014;66:231–41.CrossRef Smith JA, Colbert RA. The IL-23/IL-17 axis in spondyloarthritis pathogenesis: Th17 and beyond. Arthritis Rheum. 2014;66:231–41.CrossRef
56.
Zurück zum Zitat Appel H, Maier R, Wu P, Scheer R, Hempfing A, Kayser R, et al. 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. 2011;13:R95.CrossRefPubMedPubMedCentral Appel H, Maier R, Wu P, Scheer R, Hempfing A, Kayser R, et al. 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. 2011;13:R95.CrossRefPubMedPubMedCentral
57.
Zurück zum Zitat Shen H, Goodall JC, Hill Gaston JS. Frequency and phenotype of peripheral blood Th17 cells in ankylosing spondylitis and rheumatoid arthritis. Arthritis Rheum. 2009;60:1647–56.CrossRefPubMed Shen H, Goodall JC, Hill Gaston JS. Frequency and phenotype of peripheral blood Th17 cells in ankylosing spondylitis and rheumatoid arthritis. Arthritis Rheum. 2009;60:1647–56.CrossRefPubMed
58.
Zurück zum Zitat McGeachy MJ, Chen Y, Tato CM, Laurence A, Joyce-Shaikh B, Blumenschein WM, et al. The interleukin 23 receptor is essential for the terminal differentiation of interleukin 17-producing effector T helper cells in vivo. Nat Immunol. 2009;10:314–24.CrossRefPubMedPubMedCentral McGeachy MJ, Chen Y, Tato CM, Laurence A, Joyce-Shaikh B, Blumenschein WM, et al. The interleukin 23 receptor is essential for the terminal differentiation of interleukin 17-producing effector T helper cells in vivo. Nat Immunol. 2009;10:314–24.CrossRefPubMedPubMedCentral
59.
Zurück zum Zitat van Tok M, van Duivenvoorde L, et al. Anti-IL17A treatment blocks new bone formation in experimental spondyloarthritis in HLA-B27 transgenic rats. Arthritis Rheumatol. 2015; 67 (suppl 10) [abstract]. van Tok M, van Duivenvoorde L, et al. Anti-IL17A treatment blocks new bone formation in experimental spondyloarthritis in HLA-B27 transgenic rats. Arthritis Rheumatol. 2015; 67 (suppl 10) [abstract].
60.
Zurück zum Zitat •• Braun J, Baraliakos X, Deodhar A, Baeten D, Sieper J, Emery P, Readie A, Martin R, Mpofu S, Richards HB. 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. 2016 Dec 13. The paper describes the results from the international phase III MEASURE 1 study which showed low mean progression rates in spinal radiographic change with the anti-interleukin 17A antibody, secukinumab in patients with AS. •• Braun J, Baraliakos X, Deodhar A, Baeten D, Sieper J, Emery P, Readie A, Martin R, Mpofu S, Richards HB. 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. 2016 Dec 13. The paper describes the results from the international phase III MEASURE 1 study which showed low mean progression rates in spinal radiographic change with the anti-interleukin 17A antibody, secukinumab in patients with AS.
61.
Zurück zum Zitat Boersma JW. Retardation of ossification of the lumbar vertebral column in ankylosing spondylitis by means of phenylbutazone. Scand J Rheumatol. 1976;5:60–4.PubMed Boersma JW. Retardation of ossification of the lumbar vertebral column in ankylosing spondylitis by means of phenylbutazone. Scand J Rheumatol. 1976;5:60–4.PubMed
62.
Zurück zum Zitat Wanders A, Heijde D, Landewe R, et al. Nonsteroidal antiinflammatory drugs reduce radiographic progression in patients with ankylosing spondylitis: a randomized clinical trial. Arthritis Rheum. 2005;52:1756–65.CrossRefPubMed Wanders A, Heijde D, Landewe R, et al. Nonsteroidal antiinflammatory drugs reduce radiographic progression in patients with ankylosing spondylitis: a randomized clinical trial. Arthritis Rheum. 2005;52:1756–65.CrossRefPubMed
63.
Zurück zum Zitat Poddubnyy D, Rudwaleit M, Haibel H, et al. Effect of nonsteroidal anti-inflammatory drugs on radiographic spinal progression in patients with axial spondyloarthritis: results from the German Spondyloarthritis Inception Cohort. Ann Rheum Dis. 2012;71:1616–22.CrossRefPubMed Poddubnyy D, Rudwaleit M, Haibel H, et al. Effect of nonsteroidal anti-inflammatory drugs on radiographic spinal progression in patients with axial spondyloarthritis: results from the German Spondyloarthritis Inception Cohort. Ann Rheum Dis. 2012;71:1616–22.CrossRefPubMed
64.
Zurück zum Zitat Lories RJ, Haroon N. Bone formation in axial spondyloarthritis. Best Pract Res Clin Rheumatol. 2014;28:765–77.CrossRefPubMed Lories RJ, Haroon N. Bone formation in axial spondyloarthritis. Best Pract Res Clin Rheumatol. 2014;28:765–77.CrossRefPubMed
65.
Zurück zum Zitat •• Sieper J, Listing J, Poddubnyy D, et al. Effect of continuous versus on-demand treatment of ankylosing spondylitis with diclofenac over 2 years on radiographic progression of the spine: results from a randomized multicenter trial (ENRADAS). Ann Rheum Dis. 2016;75:1438–43. The study could not confirm the disease modifying effect of NSAIDs in AS.CrossRefPubMed •• Sieper J, Listing J, Poddubnyy D, et al. Effect of continuous versus on-demand treatment of ankylosing spondylitis with diclofenac over 2 years on radiographic progression of the spine: results from a randomized multicenter trial (ENRADAS). Ann Rheum Dis. 2016;75:1438–43. The study could not confirm the disease modifying effect of NSAIDs in AS.CrossRefPubMed
Metadaten
Titel
The Paradox of Bone Formation and Bone Loss in Ankylosing Spondylitis: Evolving New Concepts of Bone Formation and Future Trends in Management
verfasst von
Marina N. Magrey
Muhammad A. Khan
Publikationsdatum
01.04.2017
Verlag
Springer US
Erschienen in
Current Rheumatology Reports / Ausgabe 4/2017
Print ISSN: 1523-3774
Elektronische ISSN: 1534-6307
DOI
https://doi.org/10.1007/s11926-017-0644-x

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