Skip to main content
SpringerLink
Log in

Lokale und systemische Knocheneffekte bei rheumatoider Arthritis

Local and systemic bone effects of rheumatoid arthritis

  • Leitthema
  • Published:
Zeitschrift für Rheumatologie Aims and scope Submit manuscript

Zusammenfassung

Die rheumatoide Arthritis gefährdet Knochen nicht nur lokal, sondern stellt auch einen wesentlichen Risikofaktor zur Entwicklung einer Osteoporose dar, die durch eine verminderte Knochenqualität und ein erhöhtes Frakturrisiko definiert ist. Vor allem die proinflammatorischen Zytokine Tumornekrosefaktor α (TNF-α), Interleukin (IL)-6 und IL-17 tragen zur lokalen und systemischen Knochendestruktion bei. Obwohl die Entzündung mittels Glukokortikoiden gut in Schach gehalten werden kann, ist auch ihre Verabreichung mit einem erhöhten Frakturrisiko verbunden. Aus diesen Gründen ist auf eine ausreichende Kalzium- und Vitamin-D-Zufuhr zu achten. In vielen Fällen ist auch die Messung der Knochendichte zu empfehlen.

Abstract

Rheumatoid arthritis (RA) is a bone-destructive disease that is a serious risk factor for the development of osteoporosis, which is defined by a loss in bone quality and an increased fracture risk. The proinflammatory cytokines tumor necrosis factor-α (TNFα), interleukin-6 (IL-6) and IL-17, in particular, contribute to local and systemic bone loss in RA. While effectively reducing inflammation, glucocorticoids add to the fracture risk. Therefore, an adequate supply of calcium and vitamin D is essential. For many patients with RA, bone density measurements are recommended.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Abb. 1

Literatur

  1. Neve A, Corrado A, Cantatore FP (2011) Osteoblast physiology in normal and pathological conditions. Cell Tissue Res 343(2):289–302

    Article  PubMed  CAS  Google Scholar 

  2. Kong YY, Feige U, Sarosi I et al (1999) Activated T cells regulate bone loss and joint destruction in adjuvant arthritis through osteoprotegerin ligand. Nature 402(6759):304–309

    Article  PubMed  CAS  Google Scholar 

  3. Confavreux CB, Chapurlat RD (2011) Systemic bone effects of biologic therapies in rheumatoid arthritis and ankylosing spondylitis. Osteoporos Int 22(4):1023–1036

    Article  PubMed  CAS  Google Scholar 

  4. Smolen JS, Han C, Heijde DM van der et al (2009) Radiographic changes in rheumatoid arthritis patients attaining different disease activity states with methotrexate monotherapy and infliximab plus methotrexate: the impacts of remission and tumour necrosis factor blockade. Ann Rheum Dis 68(6):823–827

    Article  PubMed  CAS  Google Scholar 

  5. Keystone E, Emery P, Peterfy CG et al (2009) Rituximab inhibits structural joint damage in patients with rheumatoid arthritis with an inadequate response to tumour necrosis factor inhibitor therapies. Ann Rheum Dis 68(2):216–221

    Article  PubMed  CAS  Google Scholar 

  6. Bathon J, Robles M, Ximenes AC et al (2011) Sustained disease remission and inhibition of radiographic progression in methotrexate-naive patients with rheumatoid arthritis and poor prognostic factors treated with abatacept: 2-year outcomes. Ann Rheum Dis 70(11):1949–1956

    Article  PubMed  CAS  Google Scholar 

  7. Genovese MC, Bathon JM, Martin RW et al (2002) Etanercept versus methotrexate in patients with early rheumatoid arthritis: two-year radiographic and clinical outcomes. Arthritis Rheum 46(6):1443–1450

    Article  PubMed  CAS  Google Scholar 

  8. Lipsky PE, Heijde DM van der, St Clair EW et al (2000) Infliximab and methotrexate in the treatment of rheumatoid arthritis. N Engl J Med 343(22):1594–1602

    Article  PubMed  CAS  Google Scholar 

  9. Keystone EC, Kavanaugh AF, Sharp JT et al (2004) Radiographic, clinical, and functional outcomes of treatment with adalimumab (a human anti-tumor necrosis factor monoclonal antibody) in patients with active rheumatoid arthritis receiving concomitant methotrexate therapy: a randomized, placebo-controlled, 52-week trial. Arthritis Rheum 50(5):1400–1411

    Article  PubMed  CAS  Google Scholar 

  10. Kremer JM, Blanco R, Brzosko M et al (2008) Tocilizumab inhibits structural joint damage in rheumatoid arthritis patients with an inadequate response to methotrexate: results from the double-blind treatment phase of a randomized placebo-controlled trial of tocilizumab safety and prevention of structural joint damage at one year. Arhtritis Rheum 63(3):609–621

    Article  Google Scholar 

  11. Kensuke K, Amano K, Yamada S, Hatta K (2011) Tocilizumab monotherapy improves bone mineral density as well as TNF blockers plus methotrexate with methotrexate-resistant active rheumatoid arthritis. an open-label ramdomized clinical trial. T-bone trial. Arthritis Rheum 63(Suppl 10):147–148 (Ref Type: Abstract)

    Google Scholar 

  12. Smolen JS, Avila JC, Aletaha D (2012) Tocilizumab inhibits progression of joint damage in rheumatoid arthritis irrespective of its anti-inflammatory effects: disassociation of the link between inflammation and destruction. Ann Rheum Dis 71(5):687–693

    Article  PubMed  CAS  Google Scholar 

  13. Genovese MC, Van Den BF, Roberson SA et al (2010) LY2439821, a humanized anti-interleukin-17 monoclonal antibody, in the treatment of patients with rheumatoid arthritis: a phase I randomized, double-blind, placebo-controlled, proof-of-concept study. Arthritis Rheum 62(4):929–939

    Article  PubMed  CAS  Google Scholar 

  14. Genovese MC, Durez P, Richards HB et al (2011) One year efficacy and safety results of a phase II trial of secukinumab in patients with rheumatoid arthritis. Arthritis Rheum 63(Suppl 10):147–148 (Ref Type: Abstract)

    Google Scholar 

  15. Cohen SB, Dore RK, Lane NE et al (2008) Denosumab treatment effects on structural damage, bone mineral density, and bone turnover in rheumatoid arthritis: a twelve-month, multicenter, randomized, double-blind, placebo-controlled, phase II clinical trial. Arthritis Rheum 58(5):1299–1309

    Article  PubMed  CAS  Google Scholar 

  16. Dore RK, Cohen SB, Lane NE et al (2010) Effects of denosumab on bone mineral density and bone turnover in patients with rheumatoid arthritis receiving concurrent glucocorticoids or bisphosphonates. Ann Rheum Dis 69(5):872–875

    Article  PubMed  CAS  Google Scholar 

  17. Schett G, Redlich K, Hayer S et al (2003) Osteoprotegerin protects against generalized bone loss in tumor necrosis factor-transgenic mice. Arthritis Rheum 48(7):2042–2051

    Article  PubMed  CAS  Google Scholar 

  18. De BF, Rucci N, Del FA et al (2006) Impaired skeletal development in interleukin-6-transgenic mice: a model for the impact of chronic inflammation on the growing skeletal system. Arthritis Rheum 54(11):3551–3563

    Article  Google Scholar 

  19. Ammann P, Rizzoli R, Bonjour JP et al (1997) Transgenic mice expressing soluble tumor necrosis factor-receptor are protected against bone loss caused by estrogen deficiency. J Clin Invest 99(7):1699–1703

    Article  PubMed  CAS  Google Scholar 

  20. Axmann R, Bohm C, Kronke G et al (2009) Inhibition of interleukin-6 receptor directly blocks osteoclast formation in vitro and in vivo. Arthritis Rheum 60(9):2747–2756

    Article  PubMed  CAS  Google Scholar 

  21. Polzer K, Joosten L, Gasser J et al (2010) Interleukin-1 is essential for systemic inflammatory bone loss. Ann Rheum Dis 69(1):284–290

    Article  PubMed  CAS  Google Scholar 

  22. Jiang Y, Genant HK, Watt I et al (2000) A multicenter, double-blind, dose-ranging, randomized, placebo-controlled study of recombinant human interleukin-1 receptor antagonist in patients with rheumatoid arthritis: radiologic progression and correlation of Genant and Larsen scores. Arthritis Rheum 43(5):1001–1009

    Article  PubMed  CAS  Google Scholar 

  23. Koenders MI, Lubberts E, Oppers-Walgreen B et al (2005) Blocking of interleukin-17 during reactivation of experimental arthritis prevents joint inflammation and bone erosion by decreasing RANKL and interleukin-1. Am J Pathol 167(1):141–149

    Article  PubMed  CAS  Google Scholar 

  24. Goswami J, Hernandez-Santos N, Zuniga LA, Gaffen SL (2009) A bone-protective role for IL-17 receptor signaling in ovariectomy-induced bone loss. Eur J Immunol 39(10):2831–2839

    Article  PubMed  CAS  Google Scholar 

  25. Tamura T, Udagawa N, Takahashi N et al (1993) Soluble interleukin-6 receptor triggers osteoclast formation by interleukin 6. Proc Natl Acad Sci U S A 90(24):11924–11928

    Article  PubMed  CAS  Google Scholar 

  26. Redlich K, Hayer S, Ricci R et al (2002) Osteoclasts are essential for TNF-alpha-mediated joint destruction. J Clin Invest 110(10):1419–1427

    PubMed  CAS  Google Scholar 

  27. David JP, Schett G (2010) TNF and bone. Curr Dir Autoimmun 11:135–144

    Article  PubMed  CAS  Google Scholar 

  28. Edwards CJ, Williams E (2010) The role of interleukin-6 in rheumatoid arthritis-associated osteoporosis. Osteoporos Int 21(8):1287–1293

    Article  PubMed  CAS  Google Scholar 

  29. Adamopoulos IE, Chao CC, Geissler R et al (2010) Interleukin-17A upregulates receptor activator of NF-kappaB on osteoclast precursors. Arthritis Res Ther 12(1):R29

    Article  PubMed  Google Scholar 

  30. Peruzzi B, Cappariello A, Del FA et al (2012) c-Src and IL-6 inhibit osteoblast differentiation and integrate IGFBP5 signalling. Nat Commun 3:630

    Article  PubMed  Google Scholar 

  31. Le GB, Blanchard F, Berthelot JM et al (2010) Role for interleukin-6 in structural joint damage and systemic bone loss in rheumatoid arthritis. Joint Bone Spine 77(3):201–205

    Article  Google Scholar 

  32. Garnero P, Thompson E, Woodworth T, Smolen JS (2010) Rapid and sustained improvement in bone and cartilage turnover markers with the anti-interleukin-6 receptor inhibitor tocilizumab plus methotrexate in rheumatoid arthritis patients with an inadequate response to methotrexate: results from a substudy of the multicenter double-blind, placebo-controlled trial of tocilizumab in inadequate responders to methotrexate alone. Arthritis Rheum 62(1):33–43

    Article  PubMed  CAS  Google Scholar 

  33. Karsdal M, Woodworth TG, Kenwright A et al (2010) Biochemical markers of bone balance (CTX-I/Osteocalcin) improve with tocilzumab treatment in a population of RA patients with an inadequate response to anti-TNF therapy. Arthritis Rheum 62(Suppl 10):615

    Article  Google Scholar 

  34. Patel S, Farragher T, Berry J et al (2007) Association between serum vitamin D metabolite levels and disease activity in patients with early inflammatory polyarthritis. Arthritis Rheum 56(7):2143–2149

    Article  PubMed  CAS  Google Scholar 

  35. Rossini M, Maddali BS, La MG et al (2010) Vitamin D deficiency in rheumatoid arthritis: prevalence, determinants and associations with disease activity and disability. Arthritis Res Ther 12(6):R216

    Article  PubMed  CAS  Google Scholar 

  36. Zwerina K, Baum W, Axmann R et al (2011) Vitamin D receptor regulates TNF-mediated arthritis. Ann Rheum Dis 70(6):1122–1129

    Article  PubMed  CAS  Google Scholar 

  37. Haugeberg G, Orstavik RE, Uhlig T et al (2002) Bone loss in patients with rheumatoid arthritis: results from a population-based cohort of 366 patients followed up for two years. Arthritis Rheum 46(7):1720–1728

    Article  PubMed  Google Scholar 

  38. Boonen S, Lips P, Bouillon R et al (2007) Need for additional calcium to reduce the risk of hip fracture with vitamin d supplementation: evidence from a comparative metaanalysis of randomized controlled trials. J Clin Endocrinol Metab 92(4):1415–1423

    Article  PubMed  CAS  Google Scholar 

  39. Bischoff-Ferrari HA, Dawson-Hughes B, Staehelin HB et al (2009) Fall prevention with supplemental and active forms of vitamin D: a meta-analysis of randomised controlled trials. BMJ 339:b3692

    Article  PubMed  CAS  Google Scholar 

  40. Kroot EJ, Nieuwenhuizen MG, Waal Malefijt MC de et al (2001) Change in bone mineral density in patients with rheumatoid arthritis during the first decade of the disease. Arthritis Rheum 44(6):1254–1260

    Article  PubMed  CAS  Google Scholar 

  41. Meunier PJ, Dempster DW, Edouard C et al (1984) Bone histomorphometry in corticosteroid-induced osteoporosis and Cushing’s syndrome. Adv Exp Med Biol 171:191–200

    PubMed  CAS  Google Scholar 

  42. Dempster DW, Arlot MA, Meunier PJ (1983) Mean wall thickness and formation periods of trabecular bone packets in corticosteroid-induced osteoporosis. Calcif Tissue Int 35(4–5):410–417

    Google Scholar 

  43. Dalle CL, Arlot ME, Chavassieux PM et al (2001) Comparison of trabecular bone microarchitecture and remodeling in glucocorticoid-induced and postmenopausal osteoporosis. J Bone Miner Res 16(1):97–103

    Article  Google Scholar 

  44. Sambrook PN, Hughes DR, Nelson AE et al (2003) Osteocyte viability with glucocorticoid treatment: relation to histomorphometry. Ann Rheum Dis 62(12):1215–1217

    Article  PubMed  CAS  Google Scholar 

  45. Mokuda S, Okuda Y, Onishi M et al (2011) Postmenopausal women with rheumatoid arthritis who are treated with raloxifene or alendronate or glucocorticoids have lower serum undercarboxylated osteocalcin (ucOC) levels. J Endocrinol Invest (Sept30 Epub)

  46. Hofbauer LC, Rauner M (2009) Minireview: live and let die: molecular effects of glucocorticoids on bone cells. Mol Endocrinol 23(10):1525–1531

    Article  PubMed  CAS  Google Scholar 

  47. Hofbauer LC, Gori F, Riggs BL et al (1999) Stimulation of osteoprotegerin ligand and inhibition of osteoprotegerin production by glucocorticoids in human osteoblastic lineage cells: potential paracrine mechanisms of glucocorticoid-induced osteoporosis. Endocrinology 140(10):4382–4389

    Article  PubMed  CAS  Google Scholar 

  48. Rauner M, Goettsch C, Stein N et al (2011) Dissociation of osteogenic and immunological effects by the selective glucocorticoid receptor agonist, compound A, in human bone marrow stromal cells. Endocrinology 152(1):103–112

    Article  PubMed  CAS  Google Scholar 

  49. Hofbauer LC, Zeitz U, Schoppet M et al (2009) Prevention of glucocorticoid-induced bone loss in mice by inhibition of RANKL. Arthritis Rheum 60(5):1427–1437

    Article  PubMed  Google Scholar 

  50. Kim HJ, Zhao H, Kitaura H et al (2006) Glucocorticoids suppress bone formation via the osteoclast. J Clin Invest 116(8):2152–2160

    Article  PubMed  CAS  Google Scholar 

  51. Smolen JS, Landewe R, Breedveld FC et al (2010) EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs. Ann Rheum Dis 69(6):964–975

    Article  PubMed  CAS  Google Scholar 

  52. Hoes JN, Jacobs JW, Boers M et al (2007) EULAR evidence-based recommendations on the management of systemic glucocorticoid therapy in rheumatic diseases. Ann Rheum Dis 66(12):1560–1567

    Article  PubMed  CAS  Google Scholar 

  53. Goes MC van der, Jacobs JW, Boers M et al (2010) Monitoring adverse events of low-dose glucocorticoid therapy: EULAR recommendations for clinical trials and daily practice. Ann Rheum Dis 69(11):1913–1919

    Article  PubMed  Google Scholar 

Download references

Interessenkonflikt

Der korrespondierende Autor weist für sich und seine Koautoren auf folgende Beziehungen hin: Advisory Boards Abbott, Pfizer, Roche.

Author information

Authors and Affiliations

  1. Bereich Endokrinologie, Medizinische Klinik und Poliklinik III, Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden, Dresden, Deutschland

    M. Rauner & L.C. Hofbauer

  2. Bereich Rheumatologie, Medizinische Klinik und Poliklinik III, Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden, Fetscherstr. 74, 01307, Dresden, Deutschland

    M. Aringer

Authors
  1. M. Rauner
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. L.C. Hofbauer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. Aringer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M. Aringer.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rauner, M., Hofbauer, L. & Aringer, M. Lokale und systemische Knocheneffekte bei rheumatoider Arthritis. Z. Rheumatol. 71, 869–874 (2012). https://doi.org/10.1007/s00393-011-0927-y

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00393-011-0927-y

Schlüsselwörter

Keywords

Search

Navigation