Skip to main content
Top
Published in: Arthritis Research & Therapy 1/2016

Open Access 01-12-2016 | Research article

Anti-citrullinated protein antibodies and high levels of rheumatoid factor are associated with systemic bone loss in patients with early untreated rheumatoid arthritis

Authors: Serena Bugatti, Laura Bogliolo, Barbara Vitolo, Antonio Manzo, Carlomaurizio Montecucco, Roberto Caporali

Published in: Arthritis Research & Therapy | Issue 1/2016

Login to get access

Abstract

Background

Autoantibodies such as anti-citrullinated protein antibodies (ACPA) are major risk factors for articular bone destruction from the earliest phases of rheumatoid arthritis (RA). The aim of the current study was to determine whether RA-associated autoantibodies also impact on systemic bone loss in patients with early disease.

Methods

Systemic bone mineral density (BMD) was measured in the lumbar spine and the hip in 155 consecutive treatment-naïve patients with early RA (median symptom duration 13 weeks). Demographic and disease-specific parameters, including clinical disease activity, ultrasonographic (US) examination of the hands and wrists, radiographic scoring of joint damage, ACPA and rheumatoid factor (RF) levels were recorded from all patients. Reduced BMD was defined as Z score ≤ -1 SD and analysed in relation to disease-related characteristics and autoantibody subgroups.

Results

Reduced BMD was found in 25.5 % of the patients in the spine and 19.4 % in the hip. Symptom duration, clinical and US disease activity, functional disability and radiographic damage did not significantly impact on spine and hip BMD loss in regression analyses adjusted for possible confounders (age, gender, menopausal status, current smoking, body mass index). In contrast, ACPA positivity (at any level) negatively affected the spine Z-score (adjusted OR (95 % CI) 2.76 (1.19 to 6.42)); the hip Z score was affected by high titres only (adjusted OR (95 % CI) 2.96 (1.15 to 7.66)). The association of ACPA with reduced BMD in the spine was confirmed even at low levels of RF (adjusted OR (95 % CI) 2.65 (1.01 to 7.24)), but was further increased by concomitant high RF (adjusted OR (95 % CI) 3.38 (1.11 to 10.34)). In contrast, Z scores in the hip were significantly reduced only in association with high ACPA and RF (adjusted OR (95 % CI) 4.96 (1.48 to 16.64)).

Conclusions

Systemic BMD in patients with early RA is reduced in relation with ACPA positivity and high RF levels. This finding supports the notion that RA-associated autoimmunity may have a direct causative role in bone remodeling.
Literature
1.
go back to reference Walsh NC, Gravallese EM. Bone remodeling in rheumatic disease: a question of balance. Immunol Rev. 2010;233:301–12.CrossRefPubMed Walsh NC, Gravallese EM. Bone remodeling in rheumatic disease: a question of balance. Immunol Rev. 2010;233:301–12.CrossRefPubMed
3.
go back to reference Bugatti S, Manzo A, Caporali R, Montecucco C. Assessment of synovitis to predict bone erosions in rheumatoid arthritis. Ther Adv Musculoskelet Dis. 2012;4:235–44.CrossRefPubMedPubMedCentral Bugatti S, Manzo A, Caporali R, Montecucco C. Assessment of synovitis to predict bone erosions in rheumatoid arthritis. Ther Adv Musculoskelet Dis. 2012;4:235–44.CrossRefPubMedPubMedCentral
4.
go back to reference Harre U, Georgess D, Bang H, Bozec A, Axmann R, Ossipova E, et al. Induction of osteoclastogenesis and bone loss by human autoantibodies against citrullinated vimentin. J Clin Invest. 2012;122:1791–802.CrossRefPubMedPubMedCentral Harre U, Georgess D, Bang H, Bozec A, Axmann R, Ossipova E, et al. Induction of osteoclastogenesis and bone loss by human autoantibodies against citrullinated vimentin. J Clin Invest. 2012;122:1791–802.CrossRefPubMedPubMedCentral
5.
go back to reference Krishnamurthy A, Joshua V, Haj Hensvold A, Jin T, Sun M, Vivar N, et al. Identification of a novel chemokine-dependent molecular mechanism underlying rheumatoid arthritis-associated autoantibody-mediated bone loss. Ann Rheum Dis. 2016;75:721–9.CrossRefPubMed Krishnamurthy A, Joshua V, Haj Hensvold A, Jin T, Sun M, Vivar N, et al. Identification of a novel chemokine-dependent molecular mechanism underlying rheumatoid arthritis-associated autoantibody-mediated bone loss. Ann Rheum Dis. 2016;75:721–9.CrossRefPubMed
6.
go back to reference Rönnelid J, Wick MC, Lampa J, Lindblad S, Nordmark B, Klareskog L, et al. Longitudinal analysis of citrullinated protein/peptide antibodies (anti-CP) during 5 year follow up in early rheumatoid arthritis: anti-CP status predicts worse disease activity and greater radiological progression. Ann Rheum Dis. 2005;64:1744–9.CrossRefPubMedPubMedCentral Rönnelid J, Wick MC, Lampa J, Lindblad S, Nordmark B, Klareskog L, et al. Longitudinal analysis of citrullinated protein/peptide antibodies (anti-CP) during 5 year follow up in early rheumatoid arthritis: anti-CP status predicts worse disease activity and greater radiological progression. Ann Rheum Dis. 2005;64:1744–9.CrossRefPubMedPubMedCentral
7.
go back to reference van der Helm-van Mil AH, Verpoort KN, Breedveld FC, Toes RE, Huizinga TW. Antibodies to citrullinated proteins and differences in clinical progression of rheumatoid arthritis. Arthritis Res Ther. 2005;7:R949–58.CrossRef van der Helm-van Mil AH, Verpoort KN, Breedveld FC, Toes RE, Huizinga TW. Antibodies to citrullinated proteins and differences in clinical progression of rheumatoid arthritis. Arthritis Res Ther. 2005;7:R949–58.CrossRef
8.
go back to reference Syversen SW, Gaarder PI, Goll GL, Ødegård S, Haavardsholm EA, Mowinckel P, et al. High anti-cyclic citrullinated peptide levels and an algorithm of four variables predict radiographic progression in patients with rheumatoid arthritis: results from a 10-year longitudinal study. Ann Rheum Dis. 2008;67:212–7.CrossRefPubMed Syversen SW, Gaarder PI, Goll GL, Ødegård S, Haavardsholm EA, Mowinckel P, et al. High anti-cyclic citrullinated peptide levels and an algorithm of four variables predict radiographic progression in patients with rheumatoid arthritis: results from a 10-year longitudinal study. Ann Rheum Dis. 2008;67:212–7.CrossRefPubMed
9.
go back to reference van den Broek M, Dirven L, Klarenbeek NB, Molenaar TH, Han KH, Kerstens PJ, et al. The association of treatment response and joint damage with ACPA-status in recent-onset RA: a subanalysis of the 8-year follow-up of the BeSt study. Ann Rheum Dis. 2012;71:245–8.CrossRefPubMed van den Broek M, Dirven L, Klarenbeek NB, Molenaar TH, Han KH, Kerstens PJ, et al. The association of treatment response and joint damage with ACPA-status in recent-onset RA: a subanalysis of the 8-year follow-up of the BeSt study. Ann Rheum Dis. 2012;71:245–8.CrossRefPubMed
10.
go back to reference Hensvold AH, Joshua V, Li W, Larkin M, Qureshi F, Israelsson L, et al. Serum RANKL levels associate with anti- citrullinated protein antibodies in early untreated rheumatoid arthritis and are modulated following methotrexate. Arthritis Res Ther. 2015;17:239.CrossRefPubMedPubMedCentral Hensvold AH, Joshua V, Li W, Larkin M, Qureshi F, Israelsson L, et al. Serum RANKL levels associate with anti- citrullinated protein antibodies in early untreated rheumatoid arthritis and are modulated following methotrexate. Arthritis Res Ther. 2015;17:239.CrossRefPubMedPubMedCentral
11.
go back to reference Kleyer A, Finzel S, Rech J, Manger B, Krieter M, Faustini F, et al. Bone loss before the clinical onset of rheumatoid arthritis in subjects with anticitrullinated protein antibodies. Ann Rheum Dis. 2014;73:854–60.CrossRefPubMed Kleyer A, Finzel S, Rech J, Manger B, Krieter M, Faustini F, et al. Bone loss before the clinical onset of rheumatoid arthritis in subjects with anticitrullinated protein antibodies. Ann Rheum Dis. 2014;73:854–60.CrossRefPubMed
12.
go back to reference Catrina AI, Joshua V, Klareskog L, Malmström V. Mechanisms involved in triggering rheumatoid arthritis. Immunol Rev. 2016;269:162–74.CrossRefPubMed Catrina AI, Joshua V, Klareskog L, Malmström V. Mechanisms involved in triggering rheumatoid arthritis. Immunol Rev. 2016;269:162–74.CrossRefPubMed
13.
go back to reference Haugeberg G, Uhlig T, Falch JA, Halse JI, Kvien TK. Bone mineral density and frequency of osteoporosis in female patients with rheumatoid arthritis: results from 394 patients in the Oslo County Rheumatoid Arthritis register. Arthritis Rheum. 2000;43:522–30.CrossRefPubMed Haugeberg G, Uhlig T, Falch JA, Halse JI, Kvien TK. Bone mineral density and frequency of osteoporosis in female patients with rheumatoid arthritis: results from 394 patients in the Oslo County Rheumatoid Arthritis register. Arthritis Rheum. 2000;43:522–30.CrossRefPubMed
14.
go back to reference Lodder MC, de Jong Z, Kostense PJ, Molenaar ET, Staal K, Voskuyl AE, et al. Bone mineral density in patients with rheumatoid arthritis: relation between disease severity and low bone mineral density. Ann Rheum Dis. 2004;63:1576–80.CrossRefPubMedPubMedCentral Lodder MC, de Jong Z, Kostense PJ, Molenaar ET, Staal K, Voskuyl AE, et al. Bone mineral density in patients with rheumatoid arthritis: relation between disease severity and low bone mineral density. Ann Rheum Dis. 2004;63:1576–80.CrossRefPubMedPubMedCentral
15.
go back to reference Laan RF, Buijs WC, Verbeek AL, Draad MP, Corstens FH, van de Putte LB, et al. Bone mineral density in patients with recent onset rheumatoid arthritis: influence of disease activity and functional capacity. Ann Rheum Dis. 1993;52:21–6.CrossRefPubMedPubMedCentral Laan RF, Buijs WC, Verbeek AL, Draad MP, Corstens FH, van de Putte LB, et al. Bone mineral density in patients with recent onset rheumatoid arthritis: influence of disease activity and functional capacity. Ann Rheum Dis. 1993;52:21–6.CrossRefPubMedPubMedCentral
16.
go back to reference Shenstone BD, Mahmoud A, Woodward R, Elvins D, Palmer R, Ring F, et al. Bone mineral density in nonsteroid treated early rheumatoid arthritis. Ann Rheum Dis. 1994;53:681–4.CrossRefPubMedPubMedCentral Shenstone BD, Mahmoud A, Woodward R, Elvins D, Palmer R, Ring F, et al. Bone mineral density in nonsteroid treated early rheumatoid arthritis. Ann Rheum Dis. 1994;53:681–4.CrossRefPubMedPubMedCentral
17.
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;344:23–7.CrossRefPubMed Gough AK, Lilley J, Eyre S, Holder RL, Emery P. Generalised bone loss in patients with early rheumatoid arthritis. Lancet. 1994;344:23–7.CrossRefPubMed
18.
go back to reference Keller C, Hafström I, Svensson B. Bone mineral density in women and men with early rheumatoid arthritis. Scand J Rheumatol. 2001;30:213–20.CrossRefPubMed Keller C, Hafström I, Svensson B. Bone mineral density in women and men with early rheumatoid arthritis. Scand J Rheumatol. 2001;30:213–20.CrossRefPubMed
19.
go back to reference Forslind K, Keller C, Svensson B, Hafström I, BARFOT Study Group. Reduced bone mineral density in early rheumatoid arthritis is associated with radiological joint damage at baseline and after 2 years in women. J Rheumatol. 2003;30:2590–6.PubMed Forslind K, Keller C, Svensson B, Hafström I, BARFOT Study Group. Reduced bone mineral density in early rheumatoid arthritis is associated with radiological joint damage at baseline and after 2 years in women. J Rheumatol. 2003;30:2590–6.PubMed
20.
go back to reference Güler-Yüksel M, Bijsterbosch J, Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Ronday HK, Peeters AJ, et al. Bone mineral density in patients with recently diagnosed, active rheumatoid arthritis. Ann Rheum Dis. 2007;66:1508–12.CrossRefPubMedPubMedCentral Güler-Yüksel M, Bijsterbosch J, Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Ronday HK, Peeters AJ, et al. Bone mineral density in patients with recently diagnosed, active rheumatoid arthritis. Ann Rheum Dis. 2007;66:1508–12.CrossRefPubMedPubMedCentral
21.
go back to reference Montecucco C, Todoerti M, Sakellariou G, Sciré CA, Caporali R. Low-dose oral prednisone improves clinical and ultrasonographic remission rates in early rheumatoid arthritis: results of a 12-month open-label randomised study. Arthritis Res Ther. 2012;14:R112.CrossRefPubMedPubMedCentral Montecucco C, Todoerti M, Sakellariou G, Sciré CA, Caporali R. Low-dose oral prednisone improves clinical and ultrasonographic remission rates in early rheumatoid arthritis: results of a 12-month open-label randomised study. Arthritis Res Ther. 2012;14:R112.CrossRefPubMedPubMedCentral
22.
go back to reference Bugatti S, Manzo A, Benaglio F, Klersy C, Vitolo B, Todoerti M, et al. Serum levels of CXCL13 are associated with ultrasonographic synovitis and predict power Doppler persistence in early rheumatoid arthritis treated with non-biological disease-modifying anti-rheumatic drugs. Arthritis Res Ther. 2012;14:R34.CrossRefPubMedPubMedCentral Bugatti S, Manzo A, Benaglio F, Klersy C, Vitolo B, Todoerti M, et al. Serum levels of CXCL13 are associated with ultrasonographic synovitis and predict power Doppler persistence in early rheumatoid arthritis treated with non-biological disease-modifying anti-rheumatic drugs. Arthritis Res Ther. 2012;14:R34.CrossRefPubMedPubMedCentral
23.
go back to reference Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham 3rd CO, et al. 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Ann Rheum Dis. 2010;69:1580–8.CrossRefPubMed Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham 3rd CO, et al. 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Ann Rheum Dis. 2010;69:1580–8.CrossRefPubMed
24.
go back to reference Hecht C, Englbrecht M, Rech J, Schmidt S, Araujo E, Engelke K, et al. Additive effect of anti-citrullinated protein antibodies and rheumatoid factor on bone erosions in patients with RA. Ann Rheum Dis. 2015;74:2151–6.CrossRefPubMed Hecht C, Englbrecht M, Rech J, Schmidt S, Araujo E, Engelke K, et al. Additive effect of anti-citrullinated protein antibodies and rheumatoid factor on bone erosions in patients with RA. Ann Rheum Dis. 2015;74:2151–6.CrossRefPubMed
25.
go back to reference Backhaus M, Burmester GR, Gerber T, Grassi W, Machold KP, Swen WA, et al. Guidelines for musculoskeletal ultrasound in rheumatology. Ann Rheum Dis. 2001;60:641–9.CrossRefPubMedPubMedCentral Backhaus M, Burmester GR, Gerber T, Grassi W, Machold KP, Swen WA, et al. Guidelines for musculoskeletal ultrasound in rheumatology. Ann Rheum Dis. 2001;60:641–9.CrossRefPubMedPubMedCentral
26.
go back to reference van der Heijde DM, van Riel PL, Nuver-Zwart IH, Gribnau FW. vad de Putte LB. Effects of hydroxychloroquine and sulphasalazine on progression of joint damage in rheumatoid arthritis. Lancet. 1989;1:1036–8.CrossRefPubMed van der Heijde DM, van Riel PL, Nuver-Zwart IH, Gribnau FW. vad de Putte LB. Effects of hydroxychloroquine and sulphasalazine on progression of joint damage in rheumatoid arthritis. Lancet. 1989;1:1036–8.CrossRefPubMed
27.
go back to reference Leslie WD, Adler RA, El-Hajj Fuleihan G, Hodsman AB, Kendler DL, McClung M, et al. Application of the 1994 WHO classification to populations other than postmenopausal Caucasian women: the 2005 ISCD Official Positions. J Clin Densitom. 2006;9:22–30.CrossRefPubMed Leslie WD, Adler RA, El-Hajj Fuleihan G, Hodsman AB, Kendler DL, McClung M, et al. Application of the 1994 WHO classification to populations other than postmenopausal Caucasian women: the 2005 ISCD Official Positions. J Clin Densitom. 2006;9:22–30.CrossRefPubMed
28.
go back to reference Rossini M, Viapiana O, Idolazzi L, Ghellere F, Fracassi E, Troplini S, et al. Higher level of Dickkopf-1 is associated with low bone mineral density and higher prevalence of vertebral fractures in patients with ankylosing spondylitis. Calcif Tissue Int. 2016;98:438–45.CrossRefPubMed Rossini M, Viapiana O, Idolazzi L, Ghellere F, Fracassi E, Troplini S, et al. Higher level of Dickkopf-1 is associated with low bone mineral density and higher prevalence of vertebral fractures in patients with ankylosing spondylitis. Calcif Tissue Int. 2016;98:438–45.CrossRefPubMed
29.
go back to reference Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988;31:315–24.CrossRefPubMed Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988;31:315–24.CrossRefPubMed
30.
go back to reference Güler-Yüksel M, Allaart CF, Goekoop-Ruiterman YP, de Vries-Bouwstra JK, van Groenendael JH, Mallée C, et al. Changes in hand and generalised bone mineral density in patients with recent-onset rheumatoid arthritis. Ann Rheum Dis. 2009;68:330–6.CrossRefPubMed Güler-Yüksel M, Allaart CF, Goekoop-Ruiterman YP, de Vries-Bouwstra JK, van Groenendael JH, Mallée C, et al. Changes in hand and generalised bone mineral density in patients with recent-onset rheumatoid arthritis. Ann Rheum Dis. 2009;68:330–6.CrossRefPubMed
31.
go back to reference Sokolove J, Johnson DS, Lahey LJ, Wagner CA, Cheng D, Thiele GM, et al. Rheumatoid factor as a potentiator of anti-citrullinated protein antibody-mediated inflammation in rheumatoid arthritis. Arthritis Rheumatol. 2014;66:813–21.CrossRefPubMedPubMedCentral Sokolove J, Johnson DS, Lahey LJ, Wagner CA, Cheng D, Thiele GM, et al. Rheumatoid factor as a potentiator of anti-citrullinated protein antibody-mediated inflammation in rheumatoid arthritis. Arthritis Rheumatol. 2014;66:813–21.CrossRefPubMedPubMedCentral
32.
go back to reference Laurent L, Anquetil F, Clavel C, Ndongo-Thiam N, Offer G, Miossec P, et al. IgM rheumatoid factor amplifies the inflammatory response of macrophages induced by the rheumatoid arthritis-specific immune complexes containing anticitrullinated protein antibodies. Ann Rheum Dis. 2015;74:1425–31.CrossRefPubMed Laurent L, Anquetil F, Clavel C, Ndongo-Thiam N, Offer G, Miossec P, et al. IgM rheumatoid factor amplifies the inflammatory response of macrophages induced by the rheumatoid arthritis-specific immune complexes containing anticitrullinated protein antibodies. Ann Rheum Dis. 2015;74:1425–31.CrossRefPubMed
33.
go back to reference Onal M, Xiong J, Chen X, Thostenson JD, Almeida M, Manolagas SC, et al. Receptor activator of nuclear factor kB ligand (RANKL) protein expression by B lymphocytes contributes to ovariectomy-induced bone loss. J Biol Chem. 2012;287:29851–60.CrossRefPubMedPubMedCentral Onal M, Xiong J, Chen X, Thostenson JD, Almeida M, Manolagas SC, et al. Receptor activator of nuclear factor kB ligand (RANKL) protein expression by B lymphocytes contributes to ovariectomy-induced bone loss. J Biol Chem. 2012;287:29851–60.CrossRefPubMedPubMedCentral
34.
go back to reference van der Linden MP, Knevel R, Huizinga TW, van der Helm-van Mil AH. Classification of rheumatoid arthritis: comparison of the 1987 American College of Rheumatology criteria and the 2010 American College of Rheumatology/European League Against Rheumatism criteria. Arthritis Rheum. 2011;63:37–42.CrossRefPubMed van der Linden MP, Knevel R, Huizinga TW, van der Helm-van Mil AH. Classification of rheumatoid arthritis: comparison of the 1987 American College of Rheumatology criteria and the 2010 American College of Rheumatology/European League Against Rheumatism criteria. Arthritis Rheum. 2011;63:37–42.CrossRefPubMed
35.
go back to reference Norli ES, Brinkmann GH, Kvien TK, Bjørneboe O, Haugen AJ, Nygaard H, et al. Self-limiting arthritis among patients fulfilling the 2010 ACR/EULAR classification criteria for rheumatoid arthritis in a very early arthritis cohort. Semin Arthritis Rheum. 2016;16:30119–6. doi:10.1016/j.semarthrit.2016.07.004. Norli ES, Brinkmann GH, Kvien TK, Bjørneboe O, Haugen AJ, Nygaard H, et al. Self-limiting arthritis among patients fulfilling the 2010 ACR/EULAR classification criteria for rheumatoid arthritis in a very early arthritis cohort. Semin Arthritis Rheum. 2016;16:30119–6. doi:10.​1016/​j.​semarthrit.​2016.​07.​004.
36.
go back to reference Nieuwenhuis WP, de Wit MP, Boonen A, van der Helm-van Mil AH. Changes in the clinical presentation of patients with rheumatoid arthritis from the early 1990s to the years 2010: earlier identification but more severe patient reported outcomes. Ann Rheum Dis. 2016. doi:10.1136/annrheumdis-2016-209949.PubMed Nieuwenhuis WP, de Wit MP, Boonen A, van der Helm-van Mil AH. Changes in the clinical presentation of patients with rheumatoid arthritis from the early 1990s to the years 2010: earlier identification but more severe patient reported outcomes. Ann Rheum Dis. 2016. doi:10.​1136/​annrheumdis-2016-209949.PubMed
37.
go back to reference Cader MZ, Filer A, Hazlehurst J, de Pablo P, Buckley CD, Raza K. Performance of the 2010 ACR/EULAR criteria for rheumatoid arthritis: comparison with 1987 ACR criteria in a very early synovitis cohort. Ann Rheum Dis. 2011;70:949–55.CrossRefPubMed Cader MZ, Filer A, Hazlehurst J, de Pablo P, Buckley CD, Raza K. Performance of the 2010 ACR/EULAR criteria for rheumatoid arthritis: comparison with 1987 ACR criteria in a very early synovitis cohort. Ann Rheum Dis. 2011;70:949–55.CrossRefPubMed
38.
go back to reference Gremese E, Salaffi F, Bosello SL, Ciapetti A, Bobbio-Pallavicini F, Caporali R, et al. Very early rheumatoid arthritis as a predictor of remission: a multicentre real life prospective study. Ann Rheum Dis. 2013;72:858–62.CrossRefPubMed Gremese E, Salaffi F, Bosello SL, Ciapetti A, Bobbio-Pallavicini F, Caporali R, et al. Very early rheumatoid arthritis as a predictor of remission: a multicentre real life prospective study. Ann Rheum Dis. 2013;72:858–62.CrossRefPubMed
39.
go back to reference Durán J, Combe B, Niu J, Rincheval N, Gaujoux-Viala C, Felson DT. The effect on treatment response of fibromyalgic symptoms in early rheumatoid arthritis patients: results from the ESPOIR cohort. Rheumatology. 2015;54:2166–70.PubMed Durán J, Combe B, Niu J, Rincheval N, Gaujoux-Viala C, Felson DT. The effect on treatment response of fibromyalgic symptoms in early rheumatoid arthritis patients: results from the ESPOIR cohort. Rheumatology. 2015;54:2166–70.PubMed
40.
go back to reference Ruyssen-Witrand A, van Steenbergen HW, van Heemst J, Gourraud PA, Nigon D, Lukas C, et al. A new classification of HLA-DRB1 alleles based on acid-base properties of the amino acids located at positions 13, 70 and 71: impact on ACPA status or structural progression, and meta-analysis on 1235 patients with rheumatoid from two cohorts (ESPOIR and EAC cohort). RMD Open. 2015;1, e000099.CrossRefPubMedPubMedCentral Ruyssen-Witrand A, van Steenbergen HW, van Heemst J, Gourraud PA, Nigon D, Lukas C, et al. A new classification of HLA-DRB1 alleles based on acid-base properties of the amino acids located at positions 13, 70 and 71: impact on ACPA status or structural progression, and meta-analysis on 1235 patients with rheumatoid from two cohorts (ESPOIR and EAC cohort). RMD Open. 2015;1, e000099.CrossRefPubMedPubMedCentral
41.
go back to reference Fautrel B, Combe B, Rincheval N, Dougados M. ESPOIR Scientific Committee. Level of agreement of the 1987 ACR and 2010 ACR/EULAR rheumatoid arthritis classification criteria: an analysis based on ESPOIR cohort data. Ann Rheum Dis. 2012;71:386–9.CrossRefPubMed Fautrel B, Combe B, Rincheval N, Dougados M. ESPOIR Scientific Committee. Level of agreement of the 1987 ACR and 2010 ACR/EULAR rheumatoid arthritis classification criteria: an analysis based on ESPOIR cohort data. Ann Rheum Dis. 2012;71:386–9.CrossRefPubMed
42.
go back to reference Mawatari T, Miura H, Hamai S, Shuto T, Nakashima Y, Okazaki K, et al. Vertebral strength changes in rheumatoid arthritis patients treated with alendronate, as assessed by finite element analysis of clinical computed tomography scans: a prospective randomized clinical trial. Arthritis Rheum. 2008;58:3340–9.CrossRefPubMed Mawatari T, Miura H, Hamai S, Shuto T, Nakashima Y, Okazaki K, et al. Vertebral strength changes in rheumatoid arthritis patients treated with alendronate, as assessed by finite element analysis of clinical computed tomography scans: a prospective randomized clinical trial. Arthritis Rheum. 2008;58:3340–9.CrossRefPubMed
43.
go back to reference Koumakis E, Avouac J, Winzenrieth R, Toth E, Payet J, Kahan A, et al. Trabecular bone score in female patients with systemic sclerosis: comparison with rheumatoid arthritis and influence of glucocorticoid exposure. J Rheumatol. 2015;42:228–35.CrossRefPubMed Koumakis E, Avouac J, Winzenrieth R, Toth E, Payet J, Kahan A, et al. Trabecular bone score in female patients with systemic sclerosis: comparison with rheumatoid arthritis and influence of glucocorticoid exposure. J Rheumatol. 2015;42:228–35.CrossRefPubMed
44.
go back to reference Coiffier G, Bouvard B, Chopin F, Biver E, Funck-Brentano T, Garnero P, et al. Common bone turnover markers in rheumatoid arthritis and ankylosing spondylitis: a literature review. Joint Bone Spine. 2013;80:250–7.CrossRefPubMed Coiffier G, Bouvard B, Chopin F, Biver E, Funck-Brentano T, Garnero P, et al. Common bone turnover markers in rheumatoid arthritis and ankylosing spondylitis: a literature review. Joint Bone Spine. 2013;80:250–7.CrossRefPubMed
45.
go back to reference Carmeliet G, Dermauw V, Bouillon R. Vitamin D signaling in calcium and bone homeostasis: a delicate balance. Best Pract Res Clin Endocrinol Metab. 2015;29:621–31.CrossRefPubMed Carmeliet G, Dermauw V, Bouillon R. Vitamin D signaling in calcium and bone homeostasis: a delicate balance. Best Pract Res Clin Endocrinol Metab. 2015;29:621–31.CrossRefPubMed
46.
go back to reference Lin J, Liu J, Davies ML, Chen W. Serum vitamin D level and rheumatoid arthritis disease activity: review and meta-analysis. PLoS One. 2016;11, e0146351.CrossRefPubMedPubMedCentral Lin J, Liu J, Davies ML, Chen W. Serum vitamin D level and rheumatoid arthritis disease activity: review and meta-analysis. PLoS One. 2016;11, e0146351.CrossRefPubMedPubMedCentral
47.
go back to reference Kerr GS, Sabahi I, Richards JS, Caplan L, Cannon GW, Reimold A, et al. Prevalence of vitamin D insufficiency/deficiency in rheumatoid arthritis and associations with disease severity and activity. J Rheumatol. 2011;38:53–9.CrossRefPubMed Kerr GS, Sabahi I, Richards JS, Caplan L, Cannon GW, Reimold A, et al. Prevalence of vitamin D insufficiency/deficiency in rheumatoid arthritis and associations with disease severity and activity. J Rheumatol. 2011;38:53–9.CrossRefPubMed
Metadata
Title
Anti-citrullinated protein antibodies and high levels of rheumatoid factor are associated with systemic bone loss in patients with early untreated rheumatoid arthritis
Authors
Serena Bugatti
Laura Bogliolo
Barbara Vitolo
Antonio Manzo
Carlomaurizio Montecucco
Roberto Caporali
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 1/2016
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/s13075-016-1116-9

Other articles of this Issue 1/2016

Arthritis Research & Therapy 1/2016 Go to the issue