nach oben

Erschienen in:

28.02.2017 | Original Research

Titer-Dependent Effect of Anti-Citrullinated Protein Antibodies On Systemic Bone Mass in Rheumatoid Arthritis Patients

verfasst von: Giovanni Orsolini, Cristian Caimmi, Ombretta Viapiana, Luca Idolazzi, Elena Fracassi, Davide Gatti, Giovanni Adami, Maurizio Rossini

Erschienen in: Calcified Tissue International | Ausgabe 1/2017

Einloggen, um Zugang zu erhalten

Abstract

Bone loss in rheumatoid arthritis (RA) is a key feature both local and systemic. Anti-citrullinated protein antibodies (ACPA) have recently been found to directly induce differentiation and activation of osteoclasts and therefore contribute to periarticular bone loss. The aim of this study was to analyze the effect of ACPA on systemic bone mineral density (BMD) in patients with established RA. This is a cross-sectional study with a single-center RA population. BMD was measured with Dual X-ray absorptiometry at lumbar and femoral sites. ACPA were measured by EIA. Multivariate analysis was performed adjusting for the main confounding variables. One hundred twenty-seven RA patients were enrolled. In univariate analysis, ACPA-positive patients showed lower BMD Z-score (SD below the age- and gender-matched mean reference value) at femoral sites (p < 0.01). A negative correlation between ACPA titer and BMD Z-score at all sites was observed (p < 0.01). The multivariate analysis adjusted for the main confounding variables confirmed the negative effect of ACPA at femoral sites (p < 0.05), but not at lumbar spine BMD. No significant effect of rheumatoid factor has been observed. ACPA have a negative titer-dependent effect on BMD at femoral sites, mainly constituted by cortical bone. ACPA-positive patients, especially if at high titer, should undergo bone investigations and be treated with bone protecting agents. Disease-modifying anti-rheumatic drugs lowering ACPA titer might have positive effects on systemic bone mass.

Kleyer A, Schett G (2014) Arthritis and bone loss: a hen and egg story. Curr Opin Rheumatol 26:80–84CrossRefPubMed

Wang SY, Liu YY, Ye H, Guo JP, Li R, Liu X, Li ZG (2011) Circulating Dickkopf-1 is correlated with bone erosion and inflammation in rheumatoid arthritis. J Rheumatol 38:821–827CrossRefPubMed

Diarra D, Stolina M, Polzer K, Zwerina J, Ominsky MS, Dwyer D, Korb A, Smolen J, Hoffmann M, Scheinecker C, van der Heide D, Landewe R, Lacey D, Richards WG, Schett G (2007) Dickkopf-1 is a master regulator of joint remodeling. Nat Med 13:156–163CrossRefPubMed

Gravallese EM (2002) Bone destruction in arthritis. Ann Rheum Dis 61(Suppl 2):ii84–i86CrossRefPubMedPubMedCentral

Adamopoulos IE, Mellins ED (2015) Alternative pathways of osteoclastogenesis in inflammatory arthritis. Nat Rev Rheumatol 11:189–194CrossRefPubMed

Kotake S, Nanke Y (2014) Effect of TNFalpha on osteoblastogenesis from mesenchymal stem cells. Biochim Biophys Acta 1840:1209–1213CrossRefPubMed

Rossini M, Viapiana O, Adami S, Fracassi E, Idolazzi L, Dartizio C, Povino MR, Orsolini G, Gatti D (2015) In patients with rheumatoid arthritis, Dickkopf-1 serum levels are correlated with parathyroid hormone, bone erosions and bone mineral density. Clin Exp Rheumatol 33:77–83PubMed

van der Helm-van Mil AH, Verpoort KN, Breedveld FC, Toes RE, Huizinga TW (2005) Antibodies to citrullinated proteins and differences in clinical progression of rheumatoid arthritis. Arthritis Res Ther 7:R949–R958CrossRef

Harre U, Georgess D, Bang H, Bozec A, Axmann R, Ossipova E, Jakobsson PJ, Baum W, Nimmerjahn F, Szarka E, Sarmay G, Krumbholz G, Neumann E, Toes R, Scherer HU, Catrina AI, Klareskog L, Jurdic P, Schett G (2012) Induction of osteoclastogenesis and bone loss by human autoantibodies against citrullinated vimentin. J Clin Invest 122:1791–1802CrossRefPubMedPubMedCentral

10.

Krishnamurthy A, Joshua V, Haj Hensvold A, Jin T, Sun M, Vivar N, Ytterberg AJ, Engstrom M, Fernandes-Cerqueira C, Amara K, Magnusson M, Wigerblad G, Kato J, Jimenez-Andrade JM, Tyson K, Rapecki S, Lundberg K, Catrina SB, Jakobsson PJ, Svensson C, Malmstrom V, Klareskog L, Wahamaa H, Catrina AI (2016) Identification of a novel chemokine-dependent molecular mechanism underlying rheumatoid arthritis-associated autoantibody-mediated bone loss. Ann Rheum Dis 75:721–729CrossRefPubMed

11.

Kleyer A, Finzel S, Rech J, Manger B, Krieter M, Faustini F, Araujo E, Hueber AJ, Harre U, Engelke K, Schett G (2014) Bone loss before the clinical onset of rheumatoid arthritis in subjects with anticitrullinated protein antibodies. Ann Rheum Dis 73:854–860CrossRefPubMed

12.

Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO 3rd, Birnbaum NS, Burmester GR, Bykerk VP, Cohen MD, Combe B, Costenbader KH, Dougados M, Emery P, Ferraccioli G, Hazes JM, Hobbs K, Huizinga TW, Kavanaugh A, Kay J, Kvien TK, Laing T, Mease P, Menard HA, Moreland LW, Naden RL, Pincus T, Smolen JS, Stanislawska-Biernat E, Symmons D, Tak PP, Upchurch KS, Vencovsky J, Wolfe F, Hawker G (2010) 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Ann Rheum Dis 69:1580–1588CrossRefPubMed

13.

Prevoo ML, van ‘t Hof MA, Kuper HH, van Leeuwen MA, van de Putte LB, van Riel PL (1995) Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum 38:44–48CrossRefPubMed

14.

Kanis JA (1994) Assessment of fracture risk and its application to screening for postmenopausal osteoporosis: synopsis of a WHO report. WHO Study Group. Osteoporos Int 4:368–381CrossRefPubMed

15.

Chang X, Yamada R, Suzuki A, Sawada T, Yoshino S, Tokuhiro S, Yamamoto K (2005) Localization of peptidylarginine deiminase 4 (PADI4) and citrullinated protein in synovial tissue of rheumatoid arthritis. Rheumatology (Oxford) 44:40–50CrossRef

16.

Foulquier C, Sebbag M, Clavel C, Chapuy-Regaud S, Al Badine R, Mechin MC, Vincent C, Nachat R, Yamada M, Takahara H, Simon M, Guerrin M, Serre G (2007) Peptidyl arginine deiminase type 2 (PAD-2) and PAD-4 but not PAD-1, PAD-3, and PAD-6 are expressed in rheumatoid arthritis synovium in close association with tissue inflammation. Arthritis Rheum 56:3541–3553CrossRefPubMed

17.

Schett G, Gravallese E (2012) Bone erosion in rheumatoid arthritis: mechanisms, diagnosis and treatment. Nat Rev Rheumatol 8:656–664CrossRefPubMedPubMedCentral

18.

van Tuyl LH, Voskuyl AE, Boers M, Geusens P, Landewe RB, Dijkmans BA, Lems WF (2010) Baseline RANKL:OPG ratio and markers of bone and cartilage degradation predict annual radiological progression over 11 years in rheumatoid arthritis. Ann Rheum Dis 69:1623–1628CrossRefPubMed

19.

Boumans MJ, Thurlings RM, Yeo L, Scheel-Toellner D, Vos K, Gerlag DM, Tak PP (2012) Rituximab abrogates joint destruction in rheumatoid arthritis by inhibiting osteoclastogenesis. Ann Rheum Dis 71:108–113CrossRefPubMed

20.

Rooney T, Edwards CK 3rd, Gogarty M, Greenan L, Veale DJ, FitzGerald O, Dayer JM, Bresnihan B (2010) Synovial tissue rank ligand expression and radiographic progression in rheumatoid arthritis: observations from a proof-of-concept randomized clinical trial of cytokine blockade. Rheumatol Int 30:1571–1580CrossRefPubMed

21.

Haynes D, Crotti T, Weedon H, Slavotinek J, Au V, Coleman M, Roberts-Thomson PJ, Ahern M, Smith MD (2008) Modulation of RANKL and osteoprotegerin expression in synovial tissue from patients with rheumatoid arthritis in response to disease-modifying antirheumatic drug treatment and correlation with radiologic outcome. Arthritis Rheum 59:911–920CrossRefPubMed

22.

Hensvold AH, Joshua V, Li W, Larkin M, Qureshi F, Israelsson L, Padyukov L, Lundberg K, Defranoux N, Saevarsdottir S, Catrina AI (2015) Serum RANKL levels associate with anti- citrullinated protein antibodies in early untreated rheumatoid arthritis and are modulated following methotrexate. Arthritis Res Ther 17:239CrossRefPubMedPubMedCentral

23.

Lu MC, Yu CL, Yu HC, Huang HB, Koo M, Lai NS (2016) Anti-citrullinated protein antibodies promote apoptosis of mature human Saos-2 osteoblasts via cell-surface binding to citrullinated heat shock protein 60. Immunobiology 221:76–83CrossRefPubMed

24.

Boyesen P, Hoff M, Odegard S, Haugeberg G, Syversen SW, Gaarder PI, Okkenhaug C, Kvien TK (2009) Antibodies to cyclic citrullinated protein and erythrocyte sedimentation rate predict hand bone loss in patients with rheumatoid arthritis of short duration: a longitudinal study. Arthritis Res Ther 11:R103CrossRefPubMedPubMedCentral

25.

Zhu TY, Griffith JF, Qin L, Hung VW, Fong TN, Au SK, Tang XL, Kwok AW, Leung PC, Li EK, Tam LS (2013) Structure and strength of the distal radius in female patients with rheumatoid arthritis: a case-control study. J Bone Miner Res 28:794–806CrossRefPubMed

26.

Bugatti S, Bogliolo L, Vitolo B, Manzo A, Montecucco C, Caporali R (2016) Anti-citrullinated protein antibodies and high levels of rheumatoid factor are associated with systemic bone loss in patients with early untreated rheumatoid arthritis. Arthritis Res Ther 18:226CrossRefPubMedPubMedCentral

27.

Rossini M, Bagnato G, Frediani B, Iagnocco A, G LAM, Minisola G, Caminiti M, Varenna M, Adami S (2011) Relationship of focal erosions, bone mineral density, and parathyroid hormone in rheumatoid arthritis. J Rheumatol 38:997–1002CrossRefPubMed

28.

Jensen T, Hansen M, Jensen KE, Podenphant J, Hansen TM, Hyldstrup L (2005) Comparison of dual X-ray absorptiometry (DXA), digital X-ray radiogrammetry (DXR), and conventional radiographs in the evaluation of osteoporosis and bone erosions in patients with rheumatoid arthritis. Scand J Rheumatol 34:27–33CrossRefPubMed

29.

Haugeberg G, Lodder MC, Lems WF, Uhlig T, Orstavik RE, Dijkmans BA, Kvien TK, Woolf AD (2004) Hand cortical bone mass and its associations with radiographic joint damage and fractures in 50–70 year old female patients with rheumatoid arthritis: cross sectional Oslo-Truro-Amsterdam (OSTRA) collaborative study. Ann Rheum Dis 63:1331–1334CrossRefPubMedPubMedCentral

30.

Hoff M, Haugeberg G, Odegard S, Syversen S, Landewe R, van der Heijde D, Kvien TK (2009) Cortical hand bone loss after 1 year in early rheumatoid arthritis predicts radiographic hand joint damage at 5-year and 10-year follow-up. Ann Rheum Dis 68:324–329CrossRefPubMed

31.

Sharp JT, Tsuji W, Ory P, Harper-Barek C, Wang H, Newmark R (2010) Denosumab prevents metacarpal shaft cortical bone loss in patients with erosive rheumatoid arthritis. Arthritis Care Res (Hoboken) 62:537–544CrossRef

32.

Kostenuik PJ, Smith SY, Jolette J, Schroeder J, Pyrah I, Ominsky MS (2011) Decreased bone remodeling and porosity are associated with improved bone strength in ovariectomized cynomolgus monkeys treated with denosumab, a fully human RANKL antibody. Bone 49:151–161CrossRefPubMed

33.

Takeuchi T, Tanaka Y, Ishiguro N, Yamanaka H, Yoneda T, Ohira T, Okubo N, Genant HK, van der Heijde D (2016) Effect of denosumab on Japanese patients with rheumatoid arthritis: a dose-response study of AMG 162 (Denosumab) in patients with RheumatoId arthritis on methotrexate to Validate inhibitory effect on bone Erosion (DRIVE)-a 12-month, multicentre, randomised, double-blind, placebo-controlled, phase II clinical trial. Ann Rheum Dis 75:983–990CrossRefPubMed

34.

Cohen SB, Dore RK, Lane NE, Ory PA, Peterfy CG, Sharp JT, van der Heijde D, Zhou L, Tsuji W, Newmark R, Denosumab Rheumatoid Arthritis Study G (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 58:1299–1309CrossRefPubMed

35.

Rossini M, Adami G, Viapiana O, Idolazzi L, Gatti D (2016) Denosumab, cortical bone and bone erosions in rheumatoid arthritis. Ann Rheum Dis

36.

Kerr GS, Sabahi I, Richards JS, Caplan L, Cannon GW, Reimold A, Thiele GM, Johnson D, Mikuls TR (2011) Prevalence of vitamin D insufficiency/deficiency in rheumatoid arthritis and associations with disease severity and activity. J Rheumatol 38:53–59CrossRefPubMed

37.

Nielen MM, van Schaardenburg D, Reesink HW, Twisk JW, van de Stadt RJ, van der Horst-Bruinsma IE, de Koning MH, Habibuw MR, Dijkmans BA (2006) Simultaneous development of acute phase response and autoantibodies in preclinical rheumatoid arthritis. Ann Rheum Dis 65:535–537CrossRefPubMed

38.

Hughes-Austin JM, Deane KD, Derber LA, Kolfenbach JR, Zerbe GO, Sokolove J, Lahey LJ, Weisman MH, Buckner JH, Mikuls TR, O’Dell JR, Keating RM, Gregersen PK, Robinson WH, Holers VM, Norris JM (2013) Multiple cytokines and chemokines are associated with rheumatoid arthritis-related autoimmunity in first-degree relatives without rheumatoid arthritis: studies of the aetiology of Rheumatoid Arthritis (SERA). Ann Rheum Dis 72:901–907CrossRefPubMed

Titel: Titer-Dependent Effect of Anti-Citrullinated Protein Antibodies On Systemic Bone Mass in Rheumatoid Arthritis Patients
verfasst von: Giovanni Orsolini
Cristian Caimmi
Ombretta Viapiana
Luca Idolazzi
Elena Fracassi
Davide Gatti
Giovanni Adami
Maurizio Rossini
Publikationsdatum: 28.02.2017
Verlag: Springer US
Erschienen in: Calcified Tissue International / Ausgabe 1/2017
Print ISSN: 0171-967X
Elektronische ISSN: 1432-0827
DOI: https://doi.org/10.1007/s00223-017-0253-8

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

Notfall-TEP der Hüfte ist auch bei 90-Jährigen machbar

26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Bei schweren Reaktionen auf Insektenstiche empfiehlt sich eine spezifische Immuntherapie

25.04.2024 Allergien und Intoleranzreaktionen Nachrichten

Insektenstiche sind bei Erwachsenen die häufigsten Auslöser einer Anaphylaxie. Einen wirksamen Schutz vor schweren anaphylaktischen Reaktionen bietet die allergenspezifische Immuntherapie. Jedoch kommt sie noch viel zu selten zum Einsatz.

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

25.04.2024 Hypertonie Nachrichten

Beginnen ältere Männer im Pflegeheim eine Antihypertensiva-Therapie, dann ist die Frakturrate in den folgenden 30 Tagen mehr als verdoppelt. Besonders häufig stürzen Demenzkranke und Männer, die erstmals Blutdrucksenker nehmen. Dafür spricht eine Analyse unter US-Veteranen.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 1/2017

Long-Term Bone Scintigraphy Results After Intravenous Zoledronate in Paget’s Disease of Bone

Intermittent Ibandronate Maintains Bone Mass, Bone Structure, and Biomechanical Strength of Trabecular and Cortical Bone After Discontinuation of Parathyroid Hormone Treatment in Ovariectomized Rats

Bone Alkaline Phosphatase and Tartrate-Resistant Acid Phosphatase: Potential Co-regulators of Bone Mineralization

Histological and Ultrastructural Characterization of Alkaptonuric Tissues

Hyperkalemia is Associated with Increased 30-Day Mortality in Hip Fracture Patients