Calcified Tissue International

, Volume 102, Issue 5, pp 547–558 | Cite as

Bone Disease in Axial Spondyloarthritis

  • Margot Van Mechelen
  • Giulia Rossana Gulino
  • Kurt de Vlam
  • Rik Lories


Axial spondyloarthritis is a chronic inflammatory skeletal disorder with an important burden of disease, affecting the spine and sacroiliac joints and typically presenting in young adults. Ankylosing spondylitis, diagnosed by the presence of structural changes to the skeleton, is the prototype of this disease group. Bone disease in axial spondyloarthritis is a complex phenomenon with the coexistence of bone loss and new bone formation, both contributing to the morbidity of the disease, in addition to pain caused by inflammation. The skeletal structural changes respectively lead to increased fracture risk and to permanent disability caused by ankylosis of the sacroiliac joints and the spine. The mechanism of this new bone formation leading to ankylosis is insufficiently known. The process appears to originate from entheses, specialized structures that provide a transition zone in which tendon and ligaments insert into the underlying bone. Growth factor signaling pathways such as bone morphogenetic proteins, Wnts, and Hedgehogs have been identified as molecular drivers of new bone formation, but the relationship between inflammation and activation of these pathways remains debated. Long-standing control of inflammation appears necessary to avoid ankylosis. Recent evidence and concepts suggest an important role for biomechanical factors in both the onset and progression of the disease. With regard to new bone formation, these processes can be understood as ectopic repair responses secondary to inflammation-induced bone loss and instability. In this review, we discuss the clinical implications of the skeletal changes as well as the underlying molecular mechanisms, the relation between inflammation and new bone formation, and the potential role of biomechanical stress.


Axial spondyloarthritis Ankylosing spondylitis Enthesitis Enthesophytes Syndesmophytes 



MVM is the recipient of an Aspirant fellowship and GRG is the recipient of a post-doctoral fellowship from the Flanders Research Foundation (FWO-Vlaanderen). Research on the topic of the review is supported by FWO Grants G094614 and G095916 N.

Conflict of interest

Leuven Research and Development, the technology transfer office of KU Leuven, has received speaker’s and consultancy fees on behalf of R.L. from Abbvie, Boehringer-Ingelheim, Celgene, Janssen, Novartis, Merck, Pfizer, and UCB, and research grants from Boehringer-Ingelheim, Celgene, and Pfizer. KDV reports speaker’s and consultancy fees from Abbvie, Celgene, Johnson & Johnson, Merck, Novartis, Pfizer, and UCB.


  1. 1.
    Rudwaleit M, van der Heijde D, Landewe R, Listing J, Akkoc N, Brandt J, Braun J, Chou CT, Collantes-Estevez E, Dougados M, Huang F, Gu J, Khan MA, Kirazli Y, Maksymowych WP, Mielants H, Sorensen IJ, Ozgocmen S, Roussou E, Valle-Onate R, Weber U, Wei J, Sieper J (2009) The development of assessment of spondyloarthritis international society classification criteria for axial spondyloarthritis (part II): validation and final selection. Ann Rheum Dis 68(6):777–783. CrossRefPubMedGoogle Scholar
  2. 2.
    van der Linden S, Valkenburg HA, Cats A (1984) Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria. Arthritis Rheum 27(4):361–368CrossRefPubMedGoogle Scholar
  3. 3.
    McGonagle D, Lories RJ, Tan AL, Benjamin M (2007) The concept of a “synovio-entheseal complex” and its implications for understanding joint inflammation and damage in psoriatic arthritis and beyond. Arthritis Rheum 56(8):2482–2491. CrossRefPubMedGoogle Scholar
  4. 4.
    McGonagle D, Gibbon W, Emery P (1998) Classification of inflammatory arthritis by enthesitis. Lancet 352(9134):1137–1140. CrossRefPubMedGoogle Scholar
  5. 5.
    Sieper J, Poddubnyy D (2017) Axial spondyloarthritis. Lancet. PubMedGoogle Scholar
  6. 6.
    Rudwaleit M, van der Heijde D, Landewe R, Akkoc N, Brandt J, Chou CT, Dougados M, Huang F, Gu J, Kirazli Y, Van den Bosch F, Olivieri I, Roussou E, Scarpato S, Sorensen IJ, Valle-Onate R, Weber U, Wei J, Sieper J (2011) The assessment of spondyloarthritis international society classification criteria for peripheral spondyloarthritis and for spondyloarthritis in general. Ann Rheum Dis 70(1):25–31. CrossRefPubMedGoogle Scholar
  7. 7.
    Carter S, Lories RJ (2011) Osteoporosis: a paradox in ankylosing spondylitis. Curr Osteoporos Rep 9(3):112–115. CrossRefPubMedGoogle Scholar
  8. 8.
    Schett G, Gravallese E (2012) Bone erosion in rheumatoid arthritis: mechanisms, diagnosis and treatment. Nat Rev Rheumatol 8(11):656–664. CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Shaw AT, Gravallese EM (2016) Mediators of inflammation and bone remodeling in rheumatic disease. Semin Cell Dev Biol 49:2–10. CrossRefPubMedGoogle Scholar
  10. 10.
    Navallas M, Ares J, Beltran B, Lisbona MP, Maymo J, Solano A (2013) Sacroiliitis associated with axial spondyloarthropathy: new concepts and latest trends. Radiographics 33(4):933–956. CrossRefPubMedGoogle Scholar
  11. 11.
    Maksymowych WP (2016) Imaging in axial spondyloarthritis: evaluation of inflammatory and structural changes. Rheum Dis Clin North Am 42(4):645–662. CrossRefPubMedGoogle Scholar
  12. 12.
    Berthelot JM, Le Goff B, Maugars Y (2013) Pathogenesis of hyperostosis: a key role for mesenchymatous cells? Joint Bone Spine 80(6):592–596. CrossRefPubMedGoogle Scholar
  13. 13.
    Machado PM, Baraliakos X, van der Heijde D, Braun J, Landewe 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(8):1486–1493. CrossRefPubMedGoogle Scholar
  14. 14.
    Maksymowych WP, Wichuk S, Chiowchanwisawakit P, Lambert RG, Pedersen SJ (2017) Fat metaplasia on MRI of the sacroiliac joints increases the propensity for disease progression in the spine of patients with spondyloarthritis. RMD Open 3(1):e000399. CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Pray C, Feroz NI, Nigil Haroon N (2017) Bone mineral density and fracture risk in ankylosing spondylitis: a meta-analysis. Calcif Tissue Int. PubMedGoogle Scholar
  16. 16.
    Machado P, Landewe R, Braun J, Hermann KG, Baker D, van der Heijde D (2010) Both structural damage and inflammation of the spine contribute to impairment of spinal mobility in patients with ankylosing spondylitis. Ann Rheum Dis 69(8):1465–1470. CrossRefPubMedGoogle Scholar
  17. 17.
    Landewe R, Dougados M, Mielants H, van der Tempel H, van der Heijde D (2009) Physical function in ankylosing spondylitis is independently determined by both disease activity and radiographic damage of the spine. Ann Rheum Dis 68(6):863–867. CrossRefPubMedGoogle Scholar
  18. 18.
    Poddubnyy D, Fedorova A, Listing J, Haibel H, Baraliakos X, Braun J, Sieper J (2016) physical function and spinal mobility remain stable despite radiographic spinal progression in patients with ankylosing spondylitis treated with TNF-alpha inhibitors for Up to 10 years. J Rheumatol 43(12):2142–2148. CrossRefPubMedGoogle Scholar
  19. 19.
    Hauser B, Zhao S, Visconti MR, Riches PL, Fraser WD, Piec I, Goodson NJ, Ralston SH (2017) Autoantibodies to osteoprotegerin are associated with low hip bone mineral density and history of fractures in axial spondyloarthritis: a cross-sectional observational study. Calcif Tissue Int. PubMedCentralGoogle Scholar
  20. 20.
    Leone A, Marino M, Dell’Atti C, Zecchi V, Magarelli N, Colosimo C (2016) Spinal fractures in patients with ankylosing spondylitis. Rheumatol Int 36(10):1335–1346. CrossRefPubMedGoogle Scholar
  21. 21.
    Mandl P, Navarro-Compan V, Terslev L, Aegerter P, van der Heijde D, D’Agostino MA, Baraliakos X, Pedersen SJ, Jurik AG, Naredo E, Schueller-Weidekamm C, Weber U, Wick MC, Bakker PA, Filippucci E, Conaghan PG, Rudwaleit M, Schett G, Sieper J, Tarp S, Marzo-Ortega H, Ostergaard M, European League Against R (2015) EULAR recommendations for the use of imaging in the diagnosis and management of spondyloarthritis in clinical practice. Ann Rheum Dis 74(7):1327–1339. CrossRefPubMedGoogle Scholar
  22. 22.
    Kanis JA, McCloskey E, Johansson H, Oden A, Leslie WD (2012) FRAX((R)) with and without bone mineral density. Calcif Tissue Int 90(1):1–13. CrossRefPubMedGoogle Scholar
  23. 23.
    Lefebvre V, Bhattaram P (2010) Vertebrate skeletogenesis. Curr Top Dev Biol 90:291–317. CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Zhou X, von der Mark K, Henry S, Norton W, Adams H, de Crombrugghe B (2014) Chondrocytes transdifferentiate into osteoblasts in endochondral bone during development, postnatal growth and fracture healing in mice. PLoS Genet 10(12):e1004820. CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Lories RJ, Schett G (2012) Pathophysiology of new bone formation and ankylosis in spondyloarthritis. Rheum Dis Clin North Am 38(3):555–567. CrossRefPubMedGoogle Scholar
  26. 26.
    Lories R (2011) The balance of tissue repair and remodeling in chronic arthritis. Nat Rev Rheumatol 7(12):700–707. CrossRefPubMedGoogle Scholar
  27. 27.
    Gonzalez-Chavez SA, Quinonez-Flores CM, Pacheco-Tena C (2016) Molecular mechanisms of bone formation in spondyloarthritis. Joint Bone Spine 83(4):394–400. CrossRefPubMedGoogle Scholar
  28. 28.
    Lories RJ, Derese I, Luyten FP (2005) Modulation of bone morphogenetic protein signaling inhibits the onset and progression of ankylosing enthesitis. J Clin Invest 115(6):1571–1579. CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Lories RJ, Matthys P, de Vlam K, Derese I, Luyten FP (2004) Ankylosing enthesitis, dactylitis, and onychoperiostitis in male DBA/1 mice: a model of psoriatic arthritis. Ann Rheum Dis 63(5):595–598. CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Braem K, Luyten FP, Lories RJ (2012) Blocking p38 signalling inhibits chondrogenesis in vitro but not ankylosis in a model of ankylosing spondylitis in vivo. Ann Rheum Dis 71(5):722–728. CrossRefPubMedGoogle Scholar
  31. 31.
    Joo YB, Bang SY, Kim TH, Shim SC, Lee S, Joo KB, Kim JH, Min HJ, Rahman P, Inman RD (2014) Bone morphogenetic protein 6 polymorphisms are associated with radiographic progression in ankylosing spondylitis. PLoS ONE 9(8):e104966. CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Xie Z, Wang P, Li Y, Deng W, Zhang X, Su H, Li D, Wu Y, Shen H (2016) Imbalance between bone morphogenetic protein 2 and noggin induces abnormal osteogenic differentiation of mesenchymal stem cells in ankylosing spondylitis. Arthritis Rheumatol 68(2):430–440. CrossRefPubMedGoogle Scholar
  33. 33.
    Tsui FW, Tsui HW, Las Heras F, Pritzker KP, Inman RD (2014) Serum levels of novel noggin and sclerostin-immune complexes are elevated in ankylosing spondylitis. Ann Rheum Dis 73(10):1873–1879. CrossRefPubMedGoogle Scholar
  34. 34.
    Nusse R, Clevers H (2017) Wnt/beta-catenin signaling, disease, and emerging therapeutic modalities. Cell 169(6):985–999. CrossRefPubMedGoogle Scholar
  35. 35.
    Diarra D, Stolina M, Polzer K, Zwerina J, Ominsky MS, Dwyer D, Korb A, Smolen J, Hoffmann M, Scheinecker C, van der Heide D, Landewe R, Lacey D, Richards WG, Schett G (2007) Dickkopf-1 is a master regulator of joint remodeling. Nat Med 13(2):156–163. CrossRefPubMedGoogle Scholar
  36. 36.
    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(3):592–597. CrossRefPubMedGoogle Scholar
  37. 37.
    Heiland GR, Appel H, Poddubnyy D, Zwerina J, Hueber A, Haibel H, Baraliakos X, Listing J, Rudwaleit M, Schett G, Sieper J (2012) High level of functional dickkopf-1 predicts protection from syndesmophyte formation in patients with ankylosing spondylitis. Ann Rheum Dis 71(4):572–574. CrossRefPubMedGoogle Scholar
  38. 38.
    Ruiz-Heiland G, Horn A, Zerr P, Hofstetter W, Baum W, Stock M, Distler JH, Nimmerjahn F, Schett G, Zwerina J (2012) Blockade of the hedgehog pathway inhibits osteophyte formation in arthritis. Ann Rheum Dis 71(3):400–407. CrossRefPubMedGoogle Scholar
  39. 39.
    Haroon NN, Sriganthan J, Al Ghanim N, Inman RD, Cheung AM (2014) Effect of TNF-alpha inhibitor treatment on bone mineral density in patients with ankylosing spondylitis: a systematic review and meta-analysis. Semin Arthritis Rheum 44(2):155–161. CrossRefPubMedGoogle Scholar
  40. 40.
    Yago T, Nanke Y, Ichikawa N, Kobashigawa T, Mogi M, Kamatani N, Kotake S (2009) IL-17 induces osteoclastogenesis from human monocytes alone in the absence of osteoblasts, which is potently inhibited by anti-TNF-alpha antibody: a novel mechanism of osteoclastogenesis by IL-17. J Cell Biochem 108(4):947–955. CrossRefPubMedGoogle Scholar
  41. 41.
    Osta B, Benedetti G, Miossec P (2014) Classical and paradoxical effects of TNF-alpha on bone homeostasis. Front Immunol 5:48. PubMedPubMedCentralGoogle Scholar
  42. 42.
    Jacques P, Lambrecht S, Verheugen E, Pauwels E, Kollias G, Armaka M, Verhoye M, Van der Linden A, Achten R, Lories RJ, Elewaut D (2014) Proof of concept: enthesitis and new bone formation in spondyloarthritis are driven by mechanical strain and stromal cells. Ann Rheum Dis 73(2):437–445. CrossRefPubMedGoogle Scholar
  43. 43.
    Lories RJ, Derese I, de Bari C, Luyten FP (2007) Evidence for uncoupling of inflammation and joint remodeling in a mouse model of spondylarthritis. Arthritis Rheum 56(2):489–497. CrossRefPubMedGoogle Scholar
  44. 44.
    Lories RJ, Luyten FP, de Vlam K (2009) Progress in spondylarthritis. Mechanisms of new bone formation in spondyloarthritis. Arthritis Res Ther 11(2):221. CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Maksymowych WP, Chiowchanwisawakit P, Clare T, Pedersen SJ, Ostergaard 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(1):93–102. CrossRefPubMedGoogle Scholar
  46. 46.
    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(4):710–715. CrossRefPubMedGoogle Scholar
  47. 47.
    van der Heijde D, Salonen D, Weissman BN, Landewe R, Maksymowych WP, Kupper H, Ballal S, Gibson E, Wong R, Canadian study g, group As (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(4):R127. CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    van der Heijde D, Landewe R, Baraliakos X, Houben H, van Tubergen A, Williamson P, Xu W, Baker D, Goldstein N, Braun J, Ankylosing Spondylitis Study for the Evaluation of Recombinant Infliximab Therapy Study G (2008) Radiographic findings following two years of infliximab therapy in patients with ankylosing spondylitis. Arthritis Rheum 58(10):3063–3070. CrossRefGoogle Scholar
  49. 49.
    van der Heijde D, Landewe R, Einstein S, Ory P, Vosse D, Ni L, Lin SL, Tsuji W, Davis JC Jr (2008) Radiographic progression of ankylosing spondylitis after up to two years of treatment with etanercept. Arthritis Rheum 58(5):1324–1331. CrossRefPubMedGoogle Scholar
  50. 50.
    Haroon N, Inman RD, Learch TJ, Weisman MH, Lee M, Rahbar MH, Ward MM, Reveille JD, Gensler LS (2013) The impact of tumor necrosis factor alpha inhibitors on radiographic progression in ankylosing spondylitis. Arthritis Rheum 65(10):2645–2654. PubMedPubMedCentralGoogle Scholar
  51. 51.
    Maas F, Arends S, Brouwer E, Essers I, van der Veer E, Efde M, van Ooijen PM, Wolf R, Veeger NJ, Bootsma H, Wink FR, Spoorenberg A (2016) Reduction in spinal radiographic progression in ankylosing spondylitis patients receiving prolonged treatment with TNF-alpha inhibitors. Arthritis Care Res (Hoboken). Google Scholar
  52. 52.
    Guillot X, Prati C, Sondag M, Wendling D (2017) Etanercept for treating axial spondyloarthritis. Expert Opin Biol Ther 17(9):1173–1181. CrossRefPubMedGoogle Scholar
  53. 53.
    Van Mechelen M, Lories RJ (2016) Microtrauma: no longer to be ignored in spondyloarthritis? Curr Opin Rheumatol 28(2):176–180. CrossRefPubMedGoogle Scholar
  54. 54.
    Cheung PP (2017) Anti-IL17A in axial spondyloarthritis-where are we at? Front Med (Lausanne) 4:1. Google Scholar
  55. 55.
    Baeten D, Sieper J, Braun J, Baraliakos X, Dougados M, Emery P, Deodhar A, Porter B, Martin R, Andersson M, Mpofu S, Richards HB, Group MS, Group MS (2015) Secukinumab, an Interleukin-17A Inhibitor, in Ankylosing Spondylitis. N Engl J Med 373(26):2534–2548. CrossRefGoogle Scholar
  56. 56.
    Croes M, Oner FC, van Neerven D, Sabir E, Kruyt MC, Blokhuis TJ, Dhert WJ, Alblas J (2016) Proinflammatory T cells and IL-17 stimulate osteoblast differentiation. Bone 84:262–270. CrossRefPubMedGoogle Scholar
  57. 57.
    Uluckan O, Jimenez M, Karbach S, Jeschke A, Grana O, Keller J, Busse B, Croxford AL, Finzel S, Koenders M, van den Berg W, Schinke T, Amling M, Waisman A, Schett G, Wagner EF (2016) Chronic skin inflammation leads to bone loss by IL-17-mediated inhibition of Wnt signaling in osteoblasts. Sci Transl Med 8(330):330ra337. CrossRefGoogle Scholar
  58. 58.
    Uluckan O, Wagner EF (2016) Role of IL-17A signalling in psoriasis and associated bone loss. Clin Exp Rheumatol 34(4 Suppl 98):17–20PubMedGoogle Scholar
  59. 59.
    Miossec P (2017) Update on interleukin-17: a role in the pathogenesis of inflammatory arthritis and implication for clinical practice. RMD Open 3(1):e000284. CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    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. PubMedPubMedCentralGoogle Scholar
  61. 61.
    Lavocat F, Osta B, Miossec P (2016) Increased sensitivity of rheumatoid synoviocytes to Schnurri-3 expression in TNF-alpha and IL-17A induced osteoblastic differentiation. Bone 87:89–96. CrossRefPubMedGoogle Scholar
  62. 62.
    Wein MN, Jones DC, Shim JH, Aliprantis AO, Sulyanto R, Lazarevic V, Poliachik SL, Gross TS, Glimcher LH (2012) Control of bone resorption in mice by Schnurri-3. Proc Natl Acad Sci U S A 109(21):8173–8178. CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Braun J, Baraliakos X, Deodhar A, Baeten D, Sieper J, Emery P, Readie A, Martin R, Mpofu S, Richards HB, group Ms (2016) 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. Google Scholar
  64. 64.
    Ebihara S, Date F, Dong Y, Ono M (2015) Interleukin-17 is a critical target for the treatment of ankylosing enthesitis and psoriasis-like dermatitis in mice. Autoimmunity 48(4):259–266. CrossRefPubMedGoogle Scholar
  65. 65.
    Ono T, Okamoto K, Nakashima T, Nitta T, Hori S, Iwakura Y, Takayanagi H (2016) IL-17-producing gammadelta T cells enhance bone regeneration. Nat Commun 7:10928. CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Sieper J, Listing J, Poddubnyy D, Song IH, Hermann KG, Callhoff J, Syrbe U, Braun J, Rudwaleit M (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(8):1438–1443. CrossRefPubMedGoogle Scholar
  67. 67.
    Boersma JW (1976) Retardation of ossification of the lumbar vertebral column in ankylosing spondylitis by means of phenylbutazone. Scand J Rheumatol 5(1):60–64PubMedGoogle Scholar
  68. 68.
    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(6):e014591. CrossRefPubMedPubMedCentralGoogle Scholar
  69. 69.
    Sherlock JP, Joyce-Shaikh B, Turner SP, Chao CC, Sathe M, Grein J, Gorman DM, Bowman EP, McClanahan TK, Yearley JH, Eberl G, Buckley CD, Kastelein RA, Pierce RH, Laface DM, Cua DJ (2012) IL-23 induces spondyloarthropathy by acting on ROR-gammat + CD3 + CD4-CD8- entheseal resident T cells. Nat Med 18(7):1069–1076. CrossRefPubMedGoogle Scholar
  70. 70.
    Cuthbert RJ, Fragkakis EM, Dunsmuir R, Li Z, Coles M, Marzo-Ortega H, Giannoudis P, Jones E, El-Sherbiny YM, McGonagle D (2017) Human enthesis group 3 innate lymphoid cells. Arthritis Rheumatol. PubMedGoogle Scholar
  71. 71.
    Neerinckx B, Lories R (2017) Mechanisms, impact and prevention of pathological bone regeneration in spondyloarthritis. Curr Opin Rheumatol. PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  1. 1.Laboratory of Tissue Homeostasis and Disease, Skeletal Biology and Engineering Research Center, Department of Development and RegenerationKU LeuvenLeuvenBelgium
  2. 2.Division of RheumatologyUZ LeuvenLeuvenBelgium

Personalised recommendations