Skip to main content

Advertisement

Log in

Influence of Rituximab on markers of bone remodeling in patients with rheumatoid arthritis: a prospective open-label pilot study

  • Short Communication
  • Published:
Rheumatology International Aims and scope Submit manuscript

Abstract

Immune system and bone are interacting in a complex way. Rheumatoid arthritis is characterized not only by joint destruction, but also by development of systemic osteopenia and osteoporosis. The CD20-depleting antibody Rituximab (Rtx) is a novel therapeutic option able significantly to slow the destructive joint process of rheumatoid arthritis. However, there are little data whether Rtx influences systemic bone remodeling. In the present prospective study, we evaluated the influence of Rtx on markers of bone metabolism with a follow-up of 3–15 months after Rtx therapy (2 dose of each 1,000 mg) in 13 patients with rheumatoid arthritis. There was no significant change of the bone formation markers bone alkaline phosphatase and c-terminal propeptide of collagen I. However, a non-significant tendency of decrease of RANKL (with no chance of osteoprotegerin) and a significant decrease of the bone degradation marker desoxypyridinolin crosslinked collagen I was observed 15 months after Rtx application. These initial results provide no evidence of a negative systemic influence of Rtx on bone remodeling. In contrast, it appears that Rtx lowered osteoclast activity often found increased in active rheumatoid arthritis contributing to osteoporosis in this disease.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

References

  1. Lee DM, Weinblatt ME (2001) Rheumatoid arthritis. Lancet 358:903–911

    Article  CAS  PubMed  Google Scholar 

  2. Gough MA, Lilley J, Eyre S, Holder RL, Emery P (1994) Generalized bone loss in patients with early rheumatoid arthritis. Ann Rheum Dis 53:14–17

    Article  CAS  PubMed  Google Scholar 

  3. Solomon DH, Finkelstein JS, Shadick N, Le Boff MS et al (2009) The relationship between focal erosions and generalized bone loss in patients with early rheumatoid arthritis. Arthritis Rheum 60:1624–1631

    Article  PubMed  Google Scholar 

  4. Haugeberg G, Orstavik RE, Uhlig T, Falch JA, Halse JI, Kvien TK (2002) Bone loss in patients with rheumatoid arthritis: results from a population-based cohort of 366 patients followed up for two years. Arthritis Rheum 46:1720–1728

    Article  PubMed  Google Scholar 

  5. Caetano-Lopes J, Canhao H, Fonseca JE (2009) Osteoimmunology—the hidden immune regulation of bone. Autoimmun Rev 8:250–255

    Article  CAS  PubMed  Google Scholar 

  6. Nakashima T, Takayanagi H (2008) The dynamic interplay between osteoclasts and the immune system. Arch Biochem Biophys 473:166–171

    Article  CAS  PubMed  Google Scholar 

  7. Horowitz MC, Lorenzo JA (2007) Immunologic regulation of bone development. Adv Exp Med Biol 602:47–56

    Article  PubMed  Google Scholar 

  8. Takaynagi H (2007) Osteoimmunology: shared mechanisms and crosstalk between the immune and bone systems. Nat Rev Immunol 7:292–304

    Article  Google Scholar 

  9. Sambrook P (2007) Tumour necrosis factor blockade and the risk of osteoporosis: back to the future. Arthritis Res Ther 9:107

    Article  PubMed  Google Scholar 

  10. Lange U, Teichmann J, Müller-Ladner U, Struck J (2005) Increase of bone mineral density of patients with rheumatoid arthritis treated with anti-TNF alpha antibody. A prospective open-label pilot study. Rheumatology (Oxford) 44:1546–1548

    Article  CAS  Google Scholar 

  11. Wijbrandts CA, Klaasen R, Dijkgraaf MG, Gerlag DM, van Eck-Smit BL, Tak PP (2009) Bone mineral density in rheumatoid arthritis patients 1 year after adalimumab therapy arrest of bone loss. Ann Rheum Dis 68:373–376

    Article  CAS  PubMed  Google Scholar 

  12. Bagust A, Boland A, Hockenhull J, Fleeman N et al (2009) Rituximab for the treatment of rheumatoid arthritis. Health Technol Assess 13(Suppl 2):23–29

    Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  14. Li Y, Toraldo G, Li A, Yang X et al (2007) B cells and T cells are critical for the preservation of bone homeostasis and attainment of peak bone mass in vivo. Blood 109:3839–3848

    Article  CAS  PubMed  Google Scholar 

  15. Hayer S, Polzer K, Brandl A, Zwerina J, Kireva T, Smolen JS, Schett G (2008) B cell infiltrates induce endostal bone formation in inflammatory arthritis. J Bone Miner Res 23:1650–1660

    Article  CAS  PubMed  Google Scholar 

  16. Boyce BF, Xing L (2008) Bruton and Tec: new links in osteoimmunology. Cell Metab 7:283–285

    Article  CAS  PubMed  Google Scholar 

  17. Kanamaru F, Iwai H, Ikeda T, Nakajiama A, Shikawa I, Azuma M (2004) Expression of membrane -bound and soluble receptor activator of NF kappa B ligand (RANKL) in human T cells. Immunol Lett 94:239–246

    Article  CAS  PubMed  Google Scholar 

  18. Nakashima T, Takayanagi H (2009) Osteoclast and the immune system. J Bone Miner Metab 27:519–529

    Article  CAS  PubMed  Google Scholar 

  19. Ott SM (2005) Sclerostin and Wnt signaling—the pathway to bone strength. J Clin Endocrin Metabol 90:6741–6743

    Article  Google Scholar 

  20. Veverka V, Henry AJ, Slocombe BM, Ventom A et al (2009) Characterization of the structural features and interactions of sclerostin: molecular insight into a key regulator of Wnt-mediated bone formation. J Biol Chem 284:10890–11000

    Article  CAS  PubMed  Google Scholar 

  21. Garnero P, Thompson E, Woodwork T, Smolen JS (2010) Rapid and sustained improvement of bone and cartilage turnover markers with the anti-interleukin receptor inhibitor tocilizumab plus methotrexate in patients with 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 62:33–43

    Article  CAS  PubMed  Google Scholar 

  22. Zonnefeld IM, Bakker WK, Dijkstra PF, Bos JD, van Soesbergen RM, Dinant HJ (1996) Methotrexate osteopathy in long-term, low-dose methotrexate treatment for psoriasis and psoriatic arthritis. Arch Dermatol 132:184–187

    Article  Google Scholar 

  23. Tannirandorn P, Epstein S (2000) Drug induced bone loss. Osteoporosis Int 11:637–659

    Article  CAS  Google Scholar 

  24. Lorenzo J, Horowitz M, Choi Y (2008) Osteoimmunology: interactions of the bone and immune system. Endocr Rev 29:403–440

    Article  CAS  PubMed  Google Scholar 

  25. Urbanek P, Wang Z, Fetka I, Wagner E, Busslinger M (1994) Complete block of early B cell differentiation and altered pattering of the posterior midbrain in mice lacking Pax5/BSAP. Cell 79:901–912

    Article  CAS  PubMed  Google Scholar 

  26. Horowitz MC, Xi Y, Pflugh DL, Hesslein DGT, Schatz DG, Lorenzo JA, Bothwell AL (2004) Pax5 deficient mice exhibit early onset osteoporosis with increased osteaclast progenitors. J Immunol 173:6583–6591

    CAS  PubMed  Google Scholar 

  27. Shinohara M, Koga T, Okamoto K, Sagaguchi S, Arai K et al (2008) Tyrosine kinases Btk and Tec regulate osteoclast differentiation by linking RANK and ITAM signals. Cell 132:794–806

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Gert Hein.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hein, G., Eidner, T., Oelzner, P. et al. Influence of Rituximab on markers of bone remodeling in patients with rheumatoid arthritis: a prospective open-label pilot study. Rheumatol Int 31, 269–272 (2011). https://doi.org/10.1007/s00296-010-1560-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00296-010-1560-9

Keywords

Navigation