Skip to main content

Advertisement

SpringerLink
Log in

Short-Term Effects of TNF Inhibitors on Bone Turnover Markers and Bone Mineral Density in Rheumatoid Arthritis

  • Original Research
  • Published:
Calcified Tissue International Aims and scope Submit manuscript

Abstract

TNFα inhibitors (TNFαI) exert positive effects on disease activity in rheumatoid arthritis (RA). Bone involvement is a major determinant of functional impairment in this disease. Here we investigated the short-term effects of TNFαI therapy on bone metabolism and density. We studied 54 patients with RA starting a TNFαI biologic drug, in whom any factor known to interfere with bone metabolism was excluded or rigorously accounted for. We measured at baseline and after 6-month therapy bone turnover markers: N-propeptide of type I collagen (P1NP), and bone alkaline phosphates for bone formation and serum C-terminal telopeptide of type I collagen (CTX) for bone resorption. We also evaluated bone mineral density (BMD) at hip and lumbar by dual-energy X-ray absorptiometry. All bone markers rose significantly and these changes were not dependent on steroid dosage. A significant decrease in femoral neck BMD was also observed. These results indicate that TNFαI therapy in RA over 6 months is associated with an early increase in bone turnover and a decline in hip BMD.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Nam JL, Ramiro S, Gaujoux-Viala C, Takase K, Leon-Garcia M, Emery P, Gossec L, Landewe R, Smolen JS, Buch MH (2014) Efficacy of biological disease-modifying antirheumatic drugs: a systematic literature review informing the 2013 update of the EULAR recommendations for the management of rheumatoid arthritis. Ann Rheum Dis 73:516–528. doi:10.1136/annrheumdis-2013-204577

    Article  CAS  PubMed  Google Scholar 

  2. Machado MA, Barbosa MM, Almeida AM, de Araújo VE, Kakehasi AM, Andrade EI, Cherchiglia ML, Acurcio Fde A (2013) Treatment of ankylosing spondylitis with TNF blockers: a meta-analysis. Rheumatol Int 33:2199–2213

    Article  CAS  PubMed  Google Scholar 

  3. Goulabchand R, Mouterde G, Barnetche T, Lukas C, Morel J, Combe B (2014) Effect of tumour necrosis factor blockers on radiographic progression of psoriatic arthritis: a systematic review and meta-analysis of randomized controlled trials. Ann Rheum Dis 73:414–419

    Article  PubMed  Google Scholar 

  4. Keystone EC, Kavanaugh AF, Sharp JT, Tannenbaum H, Hua Y, Teoh LS, Fischkoff SA, Chartash EK (2004) Radiographic, clinical, and functional outcomes of treatment with adalimumab (a human anti-tumor necrosis factor monoclonal antibody) in patients with active rheumatoid arthritis receiving concomitant methotrexate therapy: a randomized, placebo-controlled, 52-week trial. Arthritis Rheumatol 50:1400–1411

    Article  CAS  Google Scholar 

  5. Murphy E, Roux-Lombard P, Rooney T, Fitzgerald O, Dayer JM, Bresnihan B (2009) Serum levels of tissue inhibitor of metalloproteinase-1 and periarticular bone loss in early rheumatoid arthritis. Clin Rheumatol 28:285–291

    Article  PubMed  Google Scholar 

  6. Schett G (2009) Osteoimmunology in rheumatic diseases. Arthritis Res Ther 11:210

    Article  PubMed  PubMed Central  Google Scholar 

  7. Takayanagi H (2009) Osteoimmunology and the effects of the immune system on bone. Nat Rev Rheumatol 5:667–676

    Article  CAS  PubMed  Google Scholar 

  8. Vandooren B, Yeremenko N, Noordenbos T, Bras J, Tak PP, Baeten D (2009) Mediators of structural remodeling in peripheral spondylarthritis. Arthritis Rheumatol 60:3534–3545

    Article  CAS  Google Scholar 

  9. Frediani B, Allegri A, Falsetti P, Storri L, Bisogno S, Baldi F et al (2001) Bone mineral density in patients with psoriatic arthritis. J Rheumatol 28:138–143

    CAS  PubMed  Google Scholar 

  10. Schett G, Redlich K, Hayer S, Zwerina J, Bolon B, Dunstan C et al (2003) Osteoprotegerin protects against generalized bone loss in tumor necrosis factor-transgenic mice. Arthritis Rheumatol 48:2042–2051

    Article  CAS  Google Scholar 

  11. Lee HL, Yi T, Woo KM, Ryoo HM, Kim GS, Baek JH (2010) Msx2 mediates the inhibitory action of TNF-alpha on osteoblast differentiation. Exp Mol Med 42:437–445

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Diarra D, Stolina M, Polzer K et al (2007) Dickkopf-1 is a master regulator of joint remodeling. Nat Med 13:156–163

    Article  CAS  PubMed  Google Scholar 

  13. Wei S, Kitaura H, Zhou P, Ross FP, Teitelbaum SL (2005) IL-1 mediates TNF-induced osteoclastogenesis. J Clin Invest 115:282–290

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Vis M, Wolbink GJ, Lodder MC, Kostense PJ, van de Stadt RJ, de Koning MHMT et al (2003) Early changes in bone metabolism in rheumatoid arthritis patients treated with infliximab. Arthritis Rheumatol 48:2996–3000

    Article  CAS  Google Scholar 

  15. Hermann J, Mueller T, Fahrleitner A, Dimai HP (2003) Early onset and effective inhibition of bone resorption in patients with rheumatoid arthritis treated with the tumour necrosis factor alpha anti-body infliximab. Clin Exp Rheumatol 21:473–476

    CAS  PubMed  Google Scholar 

  16. Korczowska I, Hrycaj P, Lacki JK (2004) Change in biomarkers of osteoporosis in rheumatoid arthritis patients treated with infliximab. Pol Arch Med Wewn 111:673–678

    PubMed  Google Scholar 

  17. Lange U, Teichmann J, Muller-Ladner U, Strunk J (2005) Increase in bone mineral density of patients with rheumatoid arthritis treated with anti-TNF-alpha antibody: a prospective open-label pilot study. Rheumatology 44:1546–1548

    Article  CAS  PubMed  Google Scholar 

  18. Torikai E, Kageyama Y, Takahashi M, Suzuki M, Ichikawa T, Nagafusa T et al (2006) The effect of infliximab on bone metabolism markers in patients with rheumatoid arthritis. Rheumatology 45:761–764

    Article  CAS  PubMed  Google Scholar 

  19. Vis M, Havaardsholm EA, Haugeberg G, Uhlig T, Voskuyl AE, van de Stadt RJ et al (2006) Evaluation of bone mineral density, bone metabolism, osteoprotegerin and receptor activator of the NF kB ligand serum levels during treatment with infliximab in patients with rheumatoid arthritis. Ann Rheum Dis 65:1495–1499

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Seriolo B, Paolino S, Sulli A, Ferretti V, Cutolo M (2006) Bone metabolism changes during anti-TNF-alpha therapy in patients with active rheumatoid arthritis. Ann NY Acad Sci 1069:420–427

    Article  CAS  PubMed  Google Scholar 

  21. Marotte H, Pallot-Prades B, Grange L, Gaudin P, Alexandre C, Miossec P (2007) 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. Arthritis Res Ther 9:R61

    Article  PubMed  PubMed Central  Google Scholar 

  22. Visvanathan S, Marini JC, Smolen JS, St. Clair WE, Pritchard C, Shergy W et al (2007) Changes in biomarkers of inflammation and bone turnover and associations with clinical efficacy following infliximab plus methotrexate therapy in patients with early rheumatoid arthritis. J Rheumatol 34:1465–1474

    CAS  PubMed  Google Scholar 

  23. Chopin F, Garnero P, le Henanff A, Debiais F, Daragon A, Roux C et al (2008) Long term effects of infliximab on bone and cartilage turnover markers in patients with rheumatoid arthritis. Ann Rheum Dis 67:353–357

    Article  CAS  PubMed  Google Scholar 

  24. Gengenbacher M, Sebald H-J, Villiger PM, Hofstetter W, Seitz M (2008) Infliximab inhibits bone resorption by circulating osteoclast precursor cells in patients with rheumatoid arthritis and ankylosing spondylitis. Ann Rheum Dis 67:620–624

    Article  CAS  PubMed  Google Scholar 

  25. Szentpetery A, McKenna MJ, Murray BF, Ng CT, Brady JJ, Morrin M, Radovits B, Veale DJ, Fitzgerald O (2013) Periarticular bone gain at proximal interphalangeal joints and changes in bone turnover markers in response to tumor necrosis factor inhibitors in rheumatoid and psoriatic arthritis. J Rheumatol 40:653–662

    Article  CAS  PubMed  Google Scholar 

  26. Lim MJ, Kwon SR, Joo K, Son MJ, Park SG, Park W (2014) Early effects of tumor necrosis factor inhibition on bone homeostasis after soluble tumor necrosis factor receptor use. Korean J Intern Med 29:807–813

    Article  PubMed  PubMed Central  Google Scholar 

  27. Okano T, Koike T, Tada M, Sugioka Y, Mamoto K, Wakitani S, Nakamura H (2014) The limited effects of anti-tumor necrosis factor blockade on bone health in patients with rheumatoid arthritis under the use of glucocorticoid. J Bone Miner Metab 32:593–600

    Article  CAS  PubMed  Google Scholar 

  28. Aletaha D, Neogi T, Silman AJ et al (2010) 2010 EULAR and ACR rheumatoid arthritis classification criteria. Arthritis Rheumatol 62:2569–2581

    Article  Google Scholar 

  29. Singh JA, Furst DE, Bharat A, Curtis JR, Kavanaugh AF, Kremer JM, Moreland LW, O’Dell J, Winthrop KL, Beukelman T, Bridges SL Jr, Chatham WW, Paulus HE, Suarez-Almazor M, Bombardier C, Dougados M, Khanna D, King CM, Leong AL, Matteson EL, Schousboe JT, Moynihan E, Kolba KS, Jain A, Volkmann ER, Agrawal H, Bae S, Mudano AS, Patkar NM, Saag KG (2012) 2012 update of the 2008 American College of Rheumatology recommendations for the use of disease-modifying antirheumatic drugs and biologic agents in the treatment of rheumatoid arthritis. Arthritis Care Res (Hoboken) 64:625–639

    Article  CAS  Google Scholar 

  30. 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 Rheumatol 38:44–48

    Article  CAS  Google Scholar 

  31. Fransen J, van Riel PL (2009) The Disease Activity Score and the EULAR response criteria. Rheum Dis Clin North Am 35(4):745–757

    Article  PubMed  Google Scholar 

  32. Adami S, Gatti D, Viapiana O, Fiore CE, Nuti R, Luisetto G, Ponte M, Rossini M (2008) Physical activity and bone turnover markers: a cross-sectional and a longitudinal study. Calcif Tissue Int 83:388–392

    Article  CAS  PubMed  Google Scholar 

  33. Westendorf JJ, Kahler RA, Schroeder TM (2004) Wnt signaling in osteoblasts and bone diseases. Gene 27(341):19–39

    Article  Google Scholar 

  34. Rossini M, Gatti D, Adami S (2013) Involvement of WNT/β-catenin signaling in the treatment of osteoporosis. Calcif Tissue Int 93:121–132

    Article  CAS  PubMed  Google Scholar 

  35. Borggrefe J, Graeff C, Nickelsen TN, Marin F, Glüer CC (2010) Quantitative computed tomographic assessment of the effects of 24 months of teriparatide treatment on 3D femoral neck bone distribution, geometry, and bone strength: results from the EUROFORS study. J Bone Miner Res 25:472–481

    Article  CAS  PubMed  Google Scholar 

  36. Baum R, Gravallese EM (2014) Impact of inflammation on the osteoblast in rheumatic diseases. Curr Osteoporos Rep 12:9–16

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Rheumatology Section, Department of Medicine, University of Verona, Piazzale Ludovico Scuro, Policlinico G.B Rossi, 37134, Verona, Italy

    Giovanni Orsolini, Giovanni Adami, Silvano Adami, Ombretta Viapiana, Luca Idolazzi, Davide Gatti & Maurizio Rossini

Authors
  1. Giovanni Orsolini
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Giovanni Adami
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Silvano Adami
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ombretta Viapiana
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Luca Idolazzi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Davide Gatti
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Maurizio Rossini
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Giovanni Orsolini.

Ethics declarations

Conflict of Interest

Giovanni Orsolini, Giovanni Adami, Silvano Adami, Ombretta Viapiana, Luca Idolazzi, Davide Gatti and Maurizio Rossini have no conflict of interest to declare.

Human and Animal Rights and Informed Consent

The study was approved by the institutional review board of the Medical School of Verona and performed according to the Helsinki declaration. All patients provided written informed consent for their participation in the study.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Orsolini, G., Adami, G., Adami, S. et al. Short-Term Effects of TNF Inhibitors on Bone Turnover Markers and Bone Mineral Density in Rheumatoid Arthritis. Calcif Tissue Int 98, 580–585 (2016). https://doi.org/10.1007/s00223-016-0114-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00223-016-0114-x

Keywords

Search

Navigation