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Published in: Arthritis Research & Therapy 3/2007

Open Access 01-06-2007 | Research article

A 1-year case-control study in patients with rheumatoid arthritis indicates prevention of loss of bone mineral density in both responders and nonresponders to infliximab

Authors: Hubert Marotte, Beatrice Pallot-Prades, Laurent Grange, Philippe Gaudin, Christian Alexandre, Pierre Miossec

Published in: Arthritis Research & Therapy | Issue 3/2007

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Abstract

The goal of the present study was to record changes in bone mineral density (BMD) and markers of bone turnover in patients with rheumatoid arthritis (RA) who were treated with methotrexate combined (or not combined) with infliximab. Included were 90 patients with RA who required anti-TNF-α therapy with infliximab because of persistent active disease despite treatment with methotrexate. The historical control group included 99 patients with RA who were treated with methotrexate at a time when anti-TNF-α treatment was not yet available. Lumbar and femoral neck BMD was measured using dual energy X-ray absorptiometry at baseline and 1 year later. Osteocalcin, C-terminal cross-linked telopeptide of type I collagen, parathyroid hormone and 25-hydroxycholecalciferol were measured in plasma at baseline and 1 year later. At 1 year BMD had decreased in the control group at spine (P < 0.01) and femoral neck (P < 0.001). In contrast, BMD at spine and femoral neck did not change after 1 year of infliximab treatment. At the same time point, no change in bone remodelling markers was observed. No association was observed between clinical response and changes in BMD, indicating that even those who did not respond clinically did not lose bone over a 1-year period. These data confirm the BMD decrease observed in RA patients treated with methotrexate alone. This bone loss was prevented by infliximab therapy. Importantly, this beneficial effect was also observed in apparent nonresponders.
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Literature
1.
go back to reference Kroot EJ, Nieuwenhuizen MG, de Waal Malefijt MC, van Riel PL, Pasker-de Jong PC, Laan RF: Change in bone mineral density in patients with rheumatoid arthritis during the first decade of the disease. Arthritis Rheum. 2001, 44: 1254-1260. 10.1002/1529-0131(200106)44:6<1254::AID-ART216>3.0.CO;2-G.CrossRefPubMed Kroot EJ, Nieuwenhuizen MG, de Waal Malefijt MC, van Riel PL, Pasker-de Jong PC, Laan RF: Change in bone mineral density in patients with rheumatoid arthritis during the first decade of the disease. Arthritis Rheum. 2001, 44: 1254-1260. 10.1002/1529-0131(200106)44:6<1254::AID-ART216>3.0.CO;2-G.CrossRefPubMed
2.
go back to reference Gough AK, Lilley J, Eyre S, Holder RL, Emery P: Generalised bone loss in patients with early rheumatoid arthritis. Lancet. 1994, 344: 23-27. 10.1016/S0140-6736(94)91049-9.CrossRefPubMed Gough AK, Lilley J, Eyre S, Holder RL, Emery P: Generalised bone loss in patients with early rheumatoid arthritis. Lancet. 1994, 344: 23-27. 10.1016/S0140-6736(94)91049-9.CrossRefPubMed
3.
go back to reference Laan RF, Buijs WC, Verbeek AL, Draad MP, Corstens FH, van de Putte LB, van Riel PL: Bone mineral density in patients with recent onset rheumatoid arthritis: influence of disease activity and functional capacity. Ann Rheum Dis. 1993, 52: 21-26.PubMedCentralCrossRefPubMed Laan RF, Buijs WC, Verbeek AL, Draad MP, Corstens FH, van de Putte LB, van Riel PL: Bone mineral density in patients with recent onset rheumatoid arthritis: influence of disease activity and functional capacity. Ann Rheum Dis. 1993, 52: 21-26.PubMedCentralCrossRefPubMed
4.
go back to reference Pacifici R, Avioli LV: The effect of natural and surgical menopause on the secretion of cytokines from human blood monocytes. Osteoporos Int. 1993, 3 (Suppl 1): 106-107. 10.1007/BF01621879.CrossRefPubMed Pacifici R, Avioli LV: The effect of natural and surgical menopause on the secretion of cytokines from human blood monocytes. Osteoporos Int. 1993, 3 (Suppl 1): 106-107. 10.1007/BF01621879.CrossRefPubMed
5.
go back to reference Ammann P, Rizzoli R, Bonjour JP, Bourrin S, Meyer JM, Vassalli P, Garcia I: Transgenic mice expressing soluble tumor necrosis factor-receptor are protected against bone loss caused by estrogen deficiency. J Clin Invest. 1997, 99: 1699-1703.PubMedCentralCrossRefPubMed Ammann P, Rizzoli R, Bonjour JP, Bourrin S, Meyer JM, Vassalli P, Garcia I: Transgenic mice expressing soluble tumor necrosis factor-receptor are protected against bone loss caused by estrogen deficiency. J Clin Invest. 1997, 99: 1699-1703.PubMedCentralCrossRefPubMed
6.
go back to reference Bertolini DR, Nedwin GE, Bringman TS, Smith DD, Mundy GR: Stimulation of bone resorption and inhibition of bone formation in vitro by human tumour necrosis factors. Nature. 1986, 319: 516-518. 10.1038/319516a0.CrossRefPubMed Bertolini DR, Nedwin GE, Bringman TS, Smith DD, Mundy GR: Stimulation of bone resorption and inhibition of bone formation in vitro by human tumour necrosis factors. Nature. 1986, 319: 516-518. 10.1038/319516a0.CrossRefPubMed
7.
go back to reference Maini R, St Clair EW, Breedveld F, Furst D, Kalden J, Weisman M, Smolen J, Emery P, Harriman G, Feldmann M, Lipsky P: Infliximab (chimeric anti-tumour necrosis factor alpha monoclonal antibody) versus placebo in rheumatoid arthritis patients receiving concomitant methotrexate: a randomised phase III trial. ATTRACT Study Group. Lancet. 1999, 354: 1932-1939. 10.1016/S0140-6736(99)05246-0.CrossRefPubMed Maini R, St Clair EW, Breedveld F, Furst D, Kalden J, Weisman M, Smolen J, Emery P, Harriman G, Feldmann M, Lipsky P: Infliximab (chimeric anti-tumour necrosis factor alpha monoclonal antibody) versus placebo in rheumatoid arthritis patients receiving concomitant methotrexate: a randomised phase III trial. ATTRACT Study Group. Lancet. 1999, 354: 1932-1939. 10.1016/S0140-6736(99)05246-0.CrossRefPubMed
8.
go back to reference Smolen JS, Han C, Bala M, Maini RN, Kalden JR, van der Heijde D, Breedveld FC, Furst DE, Lipsky PE, ATTRACT Study Group: Evidence of radiographic benefit of treatment with infliximab plus methotrexate in rheumatoid arthritis patients who had no clinical improvement: a detailed subanalysis of data from the anti-tumor necrosis factor trial in rheumatoid arthritis with concomitant therapy study. Arthritis Rheum. 2005, 52: 1020-1030. 10.1002/art.20982.CrossRefPubMed Smolen JS, Han C, Bala M, Maini RN, Kalden JR, van der Heijde D, Breedveld FC, Furst DE, Lipsky PE, ATTRACT Study Group: Evidence of radiographic benefit of treatment with infliximab plus methotrexate in rheumatoid arthritis patients who had no clinical improvement: a detailed subanalysis of data from the anti-tumor necrosis factor trial in rheumatoid arthritis with concomitant therapy study. Arthritis Rheum. 2005, 52: 1020-1030. 10.1002/art.20982.CrossRefPubMed
9.
go back to reference Lange U, Teichmann J, Muller-Ladner U, Strunk J: Increase in bone mineral density of patients with rheumatoid arthritis treated with anti-TNF-alpha antibody: a prospective open-label pilot study. Rheumatology (Oxford). 2005, 44: 1546-1548. 10.1093/rheumatology/kei082.CrossRef Lange U, Teichmann J, Muller-Ladner U, Strunk J: Increase in bone mineral density of patients with rheumatoid arthritis treated with anti-TNF-alpha antibody: a prospective open-label pilot study. Rheumatology (Oxford). 2005, 44: 1546-1548. 10.1093/rheumatology/kei082.CrossRef
10.
go back to reference Vis M, Havaardsholm EA, Haugeberg G, Uhlig T, Voskuyl AE, van de Stadt RJ, Dijkmans BA, Woolf AD, Kvien TK, Lems WF: Evaluation of bone mineral density, bone metabolism, osteoprotegerin and RANKL serum levels during treatment with infliximab in patients with rheumatoid arthritis. Ann Rheum Dis. 2006, 65: 1495-1499. 10.1136/ard.2005.044198.PubMedCentralCrossRefPubMed Vis M, Havaardsholm EA, Haugeberg G, Uhlig T, Voskuyl AE, van de Stadt RJ, Dijkmans BA, Woolf AD, Kvien TK, Lems WF: Evaluation of bone mineral density, bone metabolism, osteoprotegerin and RANKL serum levels during treatment with infliximab in patients with rheumatoid arthritis. Ann Rheum Dis. 2006, 65: 1495-1499. 10.1136/ard.2005.044198.PubMedCentralCrossRefPubMed
11.
go back to reference Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, Healey LA, Kaplan SR, Liang MH, Luthra HS, et al: The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988, 31: 315-324. 10.1002/art.1780310302.CrossRefPubMed Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, Healey LA, Kaplan SR, Liang MH, Luthra HS, et al: The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988, 31: 315-324. 10.1002/art.1780310302.CrossRefPubMed
12.
go back to reference van Gestel AM, Prevoo ML, van 't Hof MA, van Rijswijk MH, van de Putte LB, van Riel PL: Development and validation of the European League Against Rheumatism response criteria for rheumatoid arthritis. Comparison with the preliminary American College of Rheumatology and the World Health Organization/International League Against Rheumatism Criteria. Arthritis Rheum. 1996, 39: 34-40. 10.1002/art.1780390105.CrossRefPubMed van Gestel AM, Prevoo ML, van 't Hof MA, van Rijswijk MH, van de Putte LB, van Riel PL: Development and validation of the European League Against Rheumatism response criteria for rheumatoid arthritis. Comparison with the preliminary American College of Rheumatology and the World Health Organization/International League Against Rheumatism Criteria. Arthritis Rheum. 1996, 39: 34-40. 10.1002/art.1780390105.CrossRefPubMed
13.
go back to reference Arlot ME, Sornay-Rendu E, Garnero P, Vey-Marty B, Delmas PD: Apparent pre- and postmenopausal bone loss evaluated by DXA at different skeletal sites in women: the OFELY cohort. J Bone Miner Res. 1997, 12: 683-90. 10.1359/jbmr.1997.12.4.683.CrossRefPubMed Arlot ME, Sornay-Rendu E, Garnero P, Vey-Marty B, Delmas PD: Apparent pre- and postmenopausal bone loss evaluated by DXA at different skeletal sites in women: the OFELY cohort. J Bone Miner Res. 1997, 12: 683-90. 10.1359/jbmr.1997.12.4.683.CrossRefPubMed
14.
go back to reference Allali F, Breban M, Porcher R, Maillefert JF, Dougados M, Roux C: Increase in bone mineral density of patients with spondyloarthropathy treated with anti-tumour necrosis factor alpha. Ann Rheum Dis. 2003, 62: 347-349. 10.1136/ard.62.4.347.PubMedCentralCrossRefPubMed Allali F, Breban M, Porcher R, Maillefert JF, Dougados M, Roux C: Increase in bone mineral density of patients with spondyloarthropathy treated with anti-tumour necrosis factor alpha. Ann Rheum Dis. 2003, 62: 347-349. 10.1136/ard.62.4.347.PubMedCentralCrossRefPubMed
15.
go back to reference Bernstein M, Irwin S, Greenberg GR: Maintenance infliximab treatment is associated with improved bone mineral density in Crohn's disease. Am J Gastroenterol. 2005, 100: 2031-2035. 10.1111/j.1572-0241.2005.50219.x.CrossRefPubMed Bernstein M, Irwin S, Greenberg GR: Maintenance infliximab treatment is associated with improved bone mineral density in Crohn's disease. Am J Gastroenterol. 2005, 100: 2031-2035. 10.1111/j.1572-0241.2005.50219.x.CrossRefPubMed
16.
go back to reference Garnero P, Jouvenne P, Buchs N, Delmas PD, Miossec P: Uncoupling of bone metabolism in rheumatoid arthritis patients with or without joint destruction: assessment with serum type I collagen breakdown products. Bone. 1999, 24: 381-385. 10.1016/S8756-3282(98)00193-8.CrossRefPubMed Garnero P, Jouvenne P, Buchs N, Delmas PD, Miossec P: Uncoupling of bone metabolism in rheumatoid arthritis patients with or without joint destruction: assessment with serum type I collagen breakdown products. Bone. 1999, 24: 381-385. 10.1016/S8756-3282(98)00193-8.CrossRefPubMed
17.
go back to reference Vis M, Wolbink GJ, Lodder MC, Kostense PJ, van de Stadt RJ, de Koning MH, Dijkmans BA, Lems WF: Early changes in bone metabolism in rheumatoid arthritis patients treated with infliximab. Arthritis Rheum. 2003, 48: 2996-2997. 10.1002/art.11292.CrossRefPubMed Vis M, Wolbink GJ, Lodder MC, Kostense PJ, van de Stadt RJ, de Koning MH, Dijkmans BA, Lems WF: Early changes in bone metabolism in rheumatoid arthritis patients treated with infliximab. Arthritis Rheum. 2003, 48: 2996-2997. 10.1002/art.11292.CrossRefPubMed
18.
go back to reference Torikai E, Kageyama Y, Takahashi M, Suzuki M, Ichikawa T, Nagafusa T, Nagano A: The effect of infliximab on bone metabolism markers in patients with rheumatoid arthritis. Rheumatology (Oxford). 2006, 45: 761-764. 10.1093/rheumatology/kei280.CrossRef Torikai E, Kageyama Y, Takahashi M, Suzuki M, Ichikawa T, Nagafusa T, Nagano A: The effect of infliximab on bone metabolism markers in patients with rheumatoid arthritis. Rheumatology (Oxford). 2006, 45: 761-764. 10.1093/rheumatology/kei280.CrossRef
19.
go back to reference Briot K, Garnero P, Le Henanff A, Dougados M, Roux C: Body weight, body composition and bone turnover changes in patients with spondyloarthropathy receiving anti-TNFalpha treatment. Ann Rheum Dis. 2005, 64: 1137-1140. 10.1136/ard.2004.028670.PubMedCentralCrossRefPubMed Briot K, Garnero P, Le Henanff A, Dougados M, Roux C: Body weight, body composition and bone turnover changes in patients with spondyloarthropathy receiving anti-TNFalpha treatment. Ann Rheum Dis. 2005, 64: 1137-1140. 10.1136/ard.2004.028670.PubMedCentralCrossRefPubMed
20.
go back to reference Ziolkowska M, Kurowska M, Radzikowska A, Luszczykiewicz G, Wiland P, Dziewczopolski W, Filipowicz-Sosnowska A, Pazdur J, Szechinski J, Kowalczewski J, et al: High levels of osteoprotegerin and soluble receptor activator of nuclear factor kappa B ligand in serum of rheumatoid arthritis patients and their normalization after anti-tumor necrosis factor alpha treatment. Arthritis Rheum. 2002, 46: 1744-1753. 10.1002/art.10388.CrossRefPubMed Ziolkowska M, Kurowska M, Radzikowska A, Luszczykiewicz G, Wiland P, Dziewczopolski W, Filipowicz-Sosnowska A, Pazdur J, Szechinski J, Kowalczewski J, et al: High levels of osteoprotegerin and soluble receptor activator of nuclear factor kappa B ligand in serum of rheumatoid arthritis patients and their normalization after anti-tumor necrosis factor alpha treatment. Arthritis Rheum. 2002, 46: 1744-1753. 10.1002/art.10388.CrossRefPubMed
Metadata
Title
A 1-year case-control study in patients with rheumatoid arthritis indicates prevention of loss of bone mineral density in both responders and nonresponders to infliximab
Authors
Hubert Marotte
Beatrice Pallot-Prades
Laurent Grange
Philippe Gaudin
Christian Alexandre
Pierre Miossec
Publication date
01-06-2007
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 3/2007
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/ar2219

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