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Mechanisms of pathologic new bone formation

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Abstract

Pathologic new bone formation occurs in response to a variety of stimuli. Heterotopic and orthotopic bone formation can interfere with the normal function of the joint and can contribute to disability in inflammatory joint diseases. Syndesmophyte formation and progressive ankylosis are characteristic features of spondyloarthropathies, including psoriatic arthritis and ankylosing spondylitis, and they can be regarded as abnormal bone remodeling. Successful blocking of inflammation in patients with spondyloarthropathy apparently fails to halt progression of ankylosis in cohort studies. This suggests that though they may be linked in some way, bone formation and inflammation are largely independent phenomena. Indeed, new bone formation also occurs in diseases such as osteoarthritis and diffuse idiopathic skeletal hyperostosis. Therefore, therapeutic strategies in spondyloarthropathy ideally should control both inflammation and bone formation.

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References and Recommended Reading

  1. D’Agostino MA, Said-Nahal R, Hacquard-Bouder C, et al.: Assessment of peripheral enthesitis in the spondylarthropathies by ultrasonography combined with power Doppler: a cross-sectional study. Arthritis Rheum 2003, 48:523–533.

    Article  PubMed  Google Scholar 

  2. McGonagle D: Imaging the joint and enthesis: insights into pathogenesis of psoriatic arthritis. Ann Rheum Dis 2005, 64(Suppl 2):ii58-ii60.

    Article  PubMed  Google Scholar 

  3. Braun J, Bollow M, Neure L, 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.

    Article  PubMed  CAS  Google Scholar 

  4. Laloux L, Voisin MC, Allain J, et al.: Immunohistological study of entheses in spondyloarthropathies: comparison in rheumatoid arthritis and osteoarthritis. Ann Rheum Dis 2001, 60:316–321.

    Article  PubMed  CAS  Google Scholar 

  5. McGonagle D, Marzo-Ortega H, O’Connor P, et al.: Histological assessment of the early enthesitis lesion in spondyloarthropathy. Ann Rheum Dis 2002, 61:534–537.

    Article  PubMed  CAS  Google Scholar 

  6. François RJ, Neure L, Sieper J, Braun J: Immunohistological examination of open sacroiliac biopsies of patients with ankylosing spondylitis: detection of tumour necrosis factor alpha in two patients with early disease and transforming growth factor beta in three more advanced cases. Ann Rheum Dis 2006, 65:713–720. A study of sacroiliac histology indicating that different molecules may be involved in early and late stages. However, the results should be considered as a starting point for further investigation as only a few biopsies have been studied.

    Article  PubMed  CAS  Google Scholar 

  7. Ritchlin CT, Haas-Smith SA, Li P, et al.: Mechanisms of TNF-alpha- and RANKL-mediated osteoclastogenesis and bone resorption in psoriatic arthritis. J Clin Invest 2003, 111:821–831. This paper highlights the role of osteoclasts in tissue destruction in psoriatic arthritis.

    Article  PubMed  CAS  Google Scholar 

  8. Boonen A, Chorus A, Miedema H, et al.: Withdrawal from labour force due to work disability in patients with ankylosing spondylitis. Ann Rheum Dis 2001, 60:1033–1039.

    Article  PubMed  CAS  Google Scholar 

  9. François RJ: Microradiographic study of the intervertebral bridges in ankylosing spondylitis and in the normal sacrum. Ann Rheum Dis 1965, 24:481–489.

    Article  PubMed  Google Scholar 

  10. de VlamK, Mielants H, Veys EM: Involvement of the zygapophyseal joint in ankylosing spondylitis: relation to the bridging syndesmophyte. J Rheumatol 1999, 26:1738–1745.

    PubMed  Google Scholar 

  11. Helliwell PS, Hickling P, Wright V: Do the radiological changes of classic ankylosing spondylitis differ from the changes found in the spondylitis associated with inflammatory bowel disease, psoriasis, and reactive arthritis? Ann Rheum Dis 1998, 57:135–140.

    Article  PubMed  CAS  Google Scholar 

  12. Gran JT, Skomsvoll JF: The outcome of ankylosing spondylitis: a study of 100 patients. Br J Rheumatol 1997, 36:766–771.

    Article  PubMed  CAS  Google Scholar 

  13. van der HeijdeD, Landewe R, van der LindenS: How should treatment effect on spinal radiographic progression in patients with ankylosing spondylitis be measured? Arthritis Rheum 2005, 52:1979–1985.

    Article  PubMed  CAS  Google Scholar 

  14. Hayami T, Pickarski M, Zhuo Y, et al.: Characterization of articular cartilage and subchondral bone changes in the rat anterior cruciate ligament transection and meniscectomized models of osteoarthritis. Bone 2006, 38:234–243.

    Article  PubMed  Google Scholar 

  15. Fornasier VL, Littlejohn G, Urowitz MB, et al.: Spinal entheseal new bone formation: the early changes of spinal diffuse idiopathic skeletal hyperostosis. J Rheumatol 1983, 10:939–947.

    PubMed  CAS  Google Scholar 

  16. Jones G, Cooley HM, Bellamy N: A cross-sectional study of the association between Heberden’s nodes, radiographic osteoarthritis of the hands, grip strength, disability and pain. Osteoarthritis Cartilage 2001, 9:606–611.

    Article  PubMed  CAS  Google Scholar 

  17. 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, 52:1756–1765.

    Article  PubMed  CAS  Google Scholar 

  18. Davis JCJr, van der Eijde D, Braun J, et al.: Recombinant human tumor necrosis factor receptor (etanercept) for treating ankylosing spondylitis: a randomized, controlled trial. Arthritis Rheum 2003, 48:3230–3236.

    Article  PubMed  CAS  Google Scholar 

  19. van der HeijdeD, Dijkmans B, Guesens P, et al.: Efficacy and safety of in.iximab in patients with ankylosing spondylitis: results of a randomized, placebo-controlled trial (ASSERT). Arthritis Rheum 2005, 52:582–591.

    Article  PubMed  CAS  Google Scholar 

  20. Mease PJ, Kivitz AJ, Burch FX, et al.: Etanercept treatment of psoriatic arthritis: safety, efficacy, and effect on disease progression. Arthritis Rheum 2004, 50:2264–2272.

    Article  PubMed  CAS  Google Scholar 

  21. Antoni CE, Kavanaugh A, Kirkham B, et al.: Sustained bene.ts of in.iximab therapy for dermatologic and articular manifestations of psoriatic arthritis: results from the in.iximab multinational psoriatic arthritis controlled trial (IMPACT). Arthritis Rheum 2005, 52:1227–1236.

    Article  PubMed  CAS  Google Scholar 

  22. Sieper J, Baraliakos X, Listing J, et al.: Persistent reduction of spinal in.ammation as assessed by magnetic resonance imaging in patients with ankylosing spondylitis after 2 yrs of treatment with the anti-tumour necrosis factor agent in.iximab. Rheumatology (Oxford) 2005, 44:1525–1530. This paper demonstrates the effect of anti-TNF on in.ammation but not on remodeling.

    Article  CAS  Google Scholar 

  23. Baraliakos X, Davis J, Tsuji W, Braun J: 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 2005, 52:1216–1223. Another demonstration of the effect of anti-TNF on in.ammation but not on remodeling.

    Article  PubMed  CAS  Google Scholar 

  24. Kavanaugh A, Antoni CE, Gladman D, et al.: The In.iximab Multinational Psoriatic Arthritis Controlled Trial (IMPACT): Results of radiographic analyses after 1 year. Ann Rheum Dis 2006, 65:1038–1043.

    Article  PubMed  CAS  Google Scholar 

  25. Wassenberg S, Fischer-Kahle V, Herborn G, Rau R: A method to score radiographic change in psoriatic arthritis. Z Rheumatol 2001, 60:156–166.

    Article  PubMed  CAS  Google Scholar 

  26. Lukic IK, Grcevic D, Kovacic N, et al.: Alteration of newly induced endochondral bone formation in adult mice without tumour necrosis factor receptor 1. Clin Exp Immunol 2005, 139:236–244.

    Article  PubMed  CAS  Google Scholar 

  27. Goldring MB, Tsuchimochi K, Ijiri K: The control of chondrogenesis. J Cell Biochem 2006, 97:33–44. This state-of-the-art review presents an excellent summary of molecular signaling in endochondral bone formation.

    Article  PubMed  CAS  Google Scholar 

  28. Kronenberg HM: Developmental regulation of the growth plate. Nature 2003, 423:332–336.

    Article  PubMed  CAS  Google Scholar 

  29. Gerber HP, Vu TH, Ryan AM, et al.: VEGF couples hypertrophic cartilage remodeling, ossification and angiogenesis during endochondral bone formation. Nat Med 1999, 5:623–628.

    Article  PubMed  CAS  Google Scholar 

  30. Zelzer E, Glotzer DJ, Hartmann C, et al.: Tissue speci.c regulation of VEGF expression during bone development requires Cbfa1/Runx2. Mech Dev 2001, 106:97–106.

    Article  PubMed  CAS  Google Scholar 

  31. Ducy P, Zhang R, Geoffroy V, et al.: Osf2/Cbfa1: a transcriptional activator of osteoblast differentiation. Cell 1997, 89:747–754.

    Article  PubMed  CAS  Google Scholar 

  32. Francois RJ, Gardner DL, Degrave EJ, Bywaters EG: Histopathologic evidence that sacroiliitis in ankylosing spondylitis is not merely enthesitis. Arthritis Rheum 2000, 43:2011–2024.

    Article  PubMed  CAS  Google Scholar 

  33. Francois RJ, Braun J, Khan MA: Entheses and enthesitis: a histopathologic review and relevance to spondyloarthritides. Curr Opin Rheumatol 2001, 13:255–264.

    Article  PubMed  CAS  Google Scholar 

  34. Lories RJ, Luyten FP: Bone morphogenetic protein signaling in joint homeostasis and disease. Cytokine Growth Factor Rev 2005, 16:287–298.

    Article  PubMed  CAS  Google Scholar 

  35. Luyten FP, Lories RJ, Verschueren PC, et al.: Contemporary concepts of in.ammation, damage and repair in rheumatic diseases. Best Pract Res Clin Rheumatol 2006, In press.

  36. Conaghan PG, Vanharanta H, Dieppe PA: Is progressive osteoarthritis an atheromatous vascular disease? Ann Rheum Dis 2005, 64:1539–1541.

    Article  PubMed  CAS  Google Scholar 

  37. Hiraki Y, Shukunami C: Angiogenesis inhibitors localized in hypovascular mesenchymal tissues: chondromodulin-I and tenomodulin. Connect Tissue Res 2005, 46:3–11.

    Article  PubMed  CAS  Google Scholar 

  38. Baeten D, Demetter P, Cuvelier C, et al.: Comparative study of the synovial histology in rheumatoid arthritis, spondyloarthropathy, and osteoarthritis: in.uence of disease duration and activity. Ann Rheum Dis 2000, 59:945–953.

    Article  PubMed  CAS  Google Scholar 

  39. Canete JD, Pablos JL, Sanmarti R, et al.: Antiangiogenic effects of anti-tumor necrosis factor alpha therapy with in.iximab in psoriatic arthritis. Arthritis Rheum 2004, 50:1636–1641.

    Article  PubMed  CAS  Google Scholar 

  40. Zaka R, Williams CJ: Role of the progressive ankylosis gene in cartilage mineralization. Curr Opin Rheumatol 2006, 18:181–186.

    Article  PubMed  CAS  Google Scholar 

  41. Grisar J, Bernecker PM, Aringer M, et al.: Ankylosing spondylitis, psoriatic arthritis, and reactive arthritis show increased bone resorption, but differ with regard to bone formation. J Rheumatol 2002, 29:1430–1436.

    PubMed  Google Scholar 

  42. Kim TH, Stone M, Payne U, et al.: Cartilage biomarkers in ankylosing spondylitis: relationship to clinical variables and treatment response. Arthritis Rheum 2005, 52:885–891.

    Article  PubMed  CAS  Google Scholar 

  43. Franck H, Ittel T. Serum osteocalcin levels in patients with psoriatic arthritis: an extended report. Rheumatol Int 2000, 19:161–164.

    Article  PubMed  CAS  Google Scholar 

  44. Franck H, Meurer T, Hofbauer LC: Evaluation of bone mineral density, hormones, biochemical markers of bone metabolism, and osteoprotegerin serum levels in patients with ankylosing spondylitis. J Rheumatol 2004, 31:2236–2241.

    PubMed  CAS  Google Scholar 

  45. Lories RJ, Matthys P, Derese I, et al.: Ankylosing enthesitis, dactylitis and onychoperiostitis in a mouse model of psoriatic arthritis. Ann Rheum Dis 2004, 63:595–598.

    Article  PubMed  CAS  Google Scholar 

  46. Lories RJ, Derese I, Luyten FP: Modulation of bone morphogenetic protein signaling inhibits the onset and progression of ankylosing enthesitis. J Clin Invest 2005, 115:1571–1579. This paper identi.es BMP signaling as a new target to prevent joint ankylosis.

    Article  PubMed  CAS  Google Scholar 

  47. Lories RJ, Daans M, Matthys P, et al.: Noggin haploinsuf.ciency differentially affects tissue responses in destructive and remodeling arthritis. Arthritis Rheum 2006, 54:1736–1746.

    Article  PubMed  CAS  Google Scholar 

  48. Lories RJU, Derese I, Ceuppens JL, Luyten FP: Bone morphogenetic proteins 2 and 6, expressed in arthritic synovium, are regulated by proin.ammatory cytokines and differentially modulate.broblast-like synoviocyte apoptosis. Arthritis Rheum 2003, 48:2807–2818.

    Article  PubMed  CAS  Google Scholar 

  49. Bramlage CP, Haupl T, Kaps C, et al.: Decrease in expression of bone morphogenetic proteins 4 and 5 in synovial tissue of patients with osteoarthritis and rheumatoid arthritis. Arthritis Res Ther 2006, 8:R58.

    Article  PubMed  CAS  Google Scholar 

  50. Fearon U, Griosios K, Fraser A, et al.: Angiopoietins, growth factors, and vascular morphology in early arthritis. J Rheumatol 2003, 30:260–268.

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Division of Rheumatology, University Hospitals Leuven, B-3000, Herestraat 49, Leuven, Belgium

    Kurt de Vlam MD, PhD

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  1. Kurt de Vlam MD, PhD
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  2. Rik JU Lories MD, PhD
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  3. Frank P. Luyten MD, PhD
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Correspondence to Kurt de Vlam MD, PhD.

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de Vlam, K., Lories, R.J. & Luyten, F.P. Mechanisms of pathologic new bone formation. Curr Rheumatol Rep 8, 332–337 (2006). https://doi.org/10.1007/s11926-006-0061-z

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  • DOI: https://doi.org/10.1007/s11926-006-0061-z

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