Email updates

Keep up to date with the latest news and content from BMC Musculoskeletal Disorders and BioMed Central.

This article is part of the supplement: Abstracts from the Combined Northern and Yorkshire Deaneries Rheumatology Annual Conference 2012

Open Access Meeting abstract

Changes in bone density and bone turnover in patients with rheumatoid arthritis treated with rituximab, a B cell depleting monoclonal antibody (HORUS TRIAL)

Mohsen Elshahaly13*, Gillian Wheater2, Kamran Naraghi3, Stephen P Tuck13, Harish K Datta1, Wan-Fai Ng1 and Jacob M van Laar13

  • * Corresponding author: Mohsen Elshahaly

  • † Equal contributors

Author Affiliations

1 Musculoskeletal Research Group, Institute of Cellular Medicine, Newcastle University, Newcastle-upon-Tyne, UK

2 Department of Biochemistry, The James Cook University Hospital, Middlesbrough, UK

3 Department of Rheumatology, The James Cook University Hospital, Middlesbrough, UK

For all author emails, please log on.

BMC Musculoskeletal Disorders 2013, 14(Suppl 1):A10  doi:10.1186/1471-2474-14-S1-A10

The electronic version of this article is the complete one and can be found online at: http://www.biomedcentral.com/1471-2474/14/S1/A10


Published:14 February 2013

© 2013 Elshahaly et al; licensee BioMed Central Ltd.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Background

The mechanism of osteoporosis in rheumatoid arthritis (RA) is multifactorial. However, inflammation and autoimmunity are key players in its pathogenesis. Treatment with tumour necrosis factor alpha (TNFα) blockers has been shown to be beneficial for bone metabolism and they were able to prevent bone deformities in RA. Moreover, they improved the bone mineral density (BMD) [1]. However, the role of B lymphocytes in bone turnover is still controversial. Mice models showed that B cell deficiency resulted in marked osteopenia [2]. This was explained by the marked decrease in bone marrow levels of osteoprotegerin (OPG) produced by B cells. However, treatment of 46 RA patients with rituximab revealed a marked reduction of the bone resorption marker beta-crosslaps (βCTX) after 6 months [3].

Materials and methods

The HORUS trial aims to determine the effect of B cell depletion on bone turnover using bone markers and bone mineral density (BMD) measurements and to correlate these changes with circulating B cells in RA patients treated with rituximab. Forty-five RA patients are assessed every 3 months for one year following the administration of their first infusion of rituximab using clinical examination, BMD measured by DXA (primary endpoint), bone formation markers (BAP, OPG, P1NP, DKK1 and sclerostin), resorption markers (TRAP5b and CTX) in addition to flow cytometry (FACS) of peripheral blood CD19+ cells including subsets, and immunoglobulins.

Results

Forty-five RA patients have been recruited in this on-going trial in ten UK sites. Two patients have successfully completed the study so far. Six patients have been withdrawn from the trial. Three patients have been found to be osteoporotic so they had to be started on bisphosphonates. Two patients did not have an appropriate response to rituximab. One patient developed lymphoma. A 1% increase in BMD between baseline and 12 months is considered a significant improvement based on a meta-analysis on anti-resorptive agents in osteoporosis which concluded that a 1% gain in bone density of the spine was associated with a statistically significant reduction of 8% in non-vertebral fractures and a study in a large population cohort showing decline of bone density over time in RA patients not treated with anti-resorptive agents [4].

Conclusion

The HORUS trial examines the effects of rituximab on markers of bone turnover and bone mass in RA. This will help determine whether B cells play a role in RA associated bone loss.

Acknowledgements

We thank the principal investigators and the research nurses from the participating centres for their contribution and acknowledge Roche UK and the South Tees NHS Hospitals Foundation trust for sponsoring the study.

References

  1. Seriolo B, Paolino S, Sulli A, Ferretti V, Cutolo M: Bone metabolism changes during anti-TNF-alpha therapy in patients with active rheumatoid arthritis.

    Ann N Y Acad Sci 2006, 1069:420-7. PubMed Abstract | Publisher Full Text OpenURL

  2. Li Y, Toraldo G, Li A, et al.: B cells and T cells are critical for the preservation of bone homeostasis and attainment of peak bone mass in vivo.

    Blood 2007, 109(9):3839-48. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL

  3. Wheater G, Hogan V, Teng Y, et al.: Suppression of bone turnover by B-cell depletion in patients with rheumatoid arthritis.

    Osteoporosis International 22(12):3067-3072. OpenURL

  4. Haugeberg G, Ørstavik RE, Uhlig T, Falch JA, Halse JI, Kvien TK: Bone loss in patients with rheumatoid arthritis. Results from a population-based cohort of 366 patients followed up for two years.

    Arthritis Rheum 2002, 42:1720-8. OpenURL