Osteoporosis International

, Volume 25, Issue 12, pp 2755–2765 | Cite as

Comparison of the effect of 18-month daily teriparatide administration on patients with rheumatoid arthritis and postmenopausal osteoporosis patients

  • K. Ebina
  • J. Hashimoto
  • K. Shi
  • M. Kashii
  • M. Hirao
  • H. Yoshikawa
Original Article



Patients with rheumatoid arthritis showed greater response to 18-month administration of daily teriparatide especially in the increase of bone formation markers at 1 month and femoral neck bone mineral density at 18 months compared to postmenopausal osteoporosis patients.


The aim of this study was to evaluate the effects of 18-month administration of daily teriparatide (TPTD) in osteoporosis patients with rheumatoid arthritis (RA) by comparing that of postmenopausal osteoporosis patients (Porosis).


The effects of TPTD were examined between RA (n = 70; age 68.4 years; disease activity score assessing 28 joints with CRP [DAS28-CRP] 2.8; rheumatoid factor [RF] positivity 75.5 %) with 77.1 % of prior bisphosphonate (BP), 84.3 % of oral prednisolone (PSL) (4.4 mg/day at baseline), 25.7 % of biologics, and Porosis (n = 62; age 71.3 years) with 77.4 % of prior BP.


Femoral neck (FN) bone mineral density (BMD) increase at 18 months was significantly greater in RA compared to Porosis (4.7 vs. 0.7 %, P = 0.038), whereas it was 9.7 versus 7.9 % (P = 0.736) in the lumbar spine (LS). The increase of bone formation markers (bone alkaline phosphatase [bone ALP] and N-terminal type I procollagen propeptide [PINP]) at 1 month were all significantly greater in RA compared to Porosis. A multivariate logistic regression analysis revealed that the significant indicator of 18-month BMD increase in RA was a 3-month increase of under-carboxylated osteocalcin (ucOC) for LS (β = 0.446, P = 0.005) and baseline ucOC for FN (β = 0.554, P = 0.001), in which both showed significant negative correlation with baseline PSL dose.


RA showed greater response to daily TPTD administration, especially in the increase of bone formation markers at 1 month and FN BMD increase at 18 months compared to Porosis.


Postmenopausal osteoporosis Prednisolone Rheumatoid arthritis Teriparatide Under-carboxylated osteocalcin 



This work was supported by grants from the Japan Osteoporosis Foundation. The funding organization had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Conflicts of interest



  1. 1.
    Peel NF, Moore DJ, Barrington NA, Bax DE, Eastell R (1995) Risk of vertebral fracture and relationship to bone mineral density in steroid treated rheumatoid arthritis. Ann Rheum Dis 54:801–806PubMedCentralPubMedCrossRefGoogle Scholar
  2. 2.
    van Staa TP, Geusens P, Bijlsma JW, Leufkens HG, Cooper C (2006) Clinical assessment of the long-term risk of fracture in patients with rheumatoid arthritis. Arthritis Rheum 54:3104–3112PubMedCrossRefGoogle Scholar
  3. 3.
    Wright NC, Lisse JR, Walitt BT, Eaton CB, Chen Z (2011) Arthritis increases the risk for fractures—results from the Women's Health Initiative. J Rheumatol 38:1680–1688PubMedCentralPubMedCrossRefGoogle Scholar
  4. 4.
    Kanis JA, Johansson H, Oden A et al (2004) A meta-analysis of prior corticosteroid use and fracture risk. J Bone Miner Res 19:893–899PubMedCrossRefGoogle Scholar
  5. 5.
    van Staa TP, Leufkens HG, Abenhaim L, Zhang B, Cooper C (2000) Oral corticosteroids and fracture risk: relationship to daily and cumulative doses. Rheumatology (Oxford) 39:1383–1389CrossRefGoogle Scholar
  6. 6.
    Braun T, Schett G (2012) Pathways for bone loss in inflammatory disease. Curr Osteoporos Rep 10:101–108PubMedCrossRefGoogle Scholar
  7. 7.
    Cortet B, Guyot MH, Solau E, Pigny P, Dumoulin F, Flipo RM, Marchandise X, Delcambre B (2000) Factors influencing bone loss in rheumatoid arthritis: a longitudinal study. Clin Exp Rheumatol 18:683–690PubMedGoogle Scholar
  8. 8.
    Guler-Yuksel M, Bijsterbosch J, Goekoop-Ruiterman YP et al (2007) Bone mineral density in patients with recently diagnosed, active rheumatoid arthritis. Ann Rheum Dis 66:1508–1512PubMedCentralPubMedCrossRefGoogle Scholar
  9. 9.
    Harre U, Georgess D, Bang H et al (2012) Induction of osteoclastogenesis and bone loss by human autoantibodies against citrullinated vimentin. J Clin Invest 122:1791–1802PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    Guler-Yuksel M, Allaart CF, Goekoop-Ruiterman YP, de Vries-Bouwstra JK, van Groenendael JH, Mallee C, de Bois MH, Breedveld FC, Dijkmans BA, Lems WF (2009) Changes in hand and generalised bone mineral density in patients with recent-onset rheumatoid arthritis. Ann Rheum Dis 68:330–336PubMedCrossRefGoogle Scholar
  11. 11.
    Canalis E, Giustina A, Bilezikian JP (2007) Mechanisms of anabolic therapies for osteoporosis. N Engl J Med 357:905–916PubMedCrossRefGoogle Scholar
  12. 12.
    Dobnig H, Turner RT (1995) Evidence that intermittent treatment with parathyroid hormone increases bone formation in adult rats by activation of bone lining cells. Endocrinology 136:3632–3638PubMedGoogle Scholar
  13. 13.
    Jilka RL, Weinstein RS, Bellido T, Roberson P, Parfitt AM, Manolagas SC (1999) Increased bone formation by prevention of osteoblast apoptosis with parathyroid hormone. J Clin Invest 104:439–446PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Almeida M, Han L, Ambrogini E, Weinstein RS, Manolagas SC (2011) Glucocorticoids and tumor necrosis factor alpha increase oxidative stress and suppress Wnt protein signaling in osteoblasts. J Biol Chem 286:44326–44335PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    Baron R, Hesse E (2012) Update on bone anabolics in osteoporosis treatment: rationale, current status, and perspectives. J Clin Endocrinol Metab 97:311–325PubMedCentralPubMedCrossRefGoogle Scholar
  16. 16.
    Drake MT, Srinivasan B, Modder UI, Peterson JM, McCready LK, Riggs BL, Dwyer D, Stolina M, Kostenuik P, Khosla S (2010) Effects of parathyroid hormone treatment on circulating sclerostin levels in postmenopausal women. J Clin Endocrinol Metab 95:5056–5062PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Saag KG, Zanchetta JR, Devogelaer JP, Adler RA, Eastell R, See K, Krege JH, Krohn K, Warner MR (2009) Effects of teriparatide versus alendronate for treating glucocorticoid-induced osteoporosis: thirty-six-month results of a randomized, double-blind, controlled trial. Arthritis Rheum 60:3346–3355PubMedCrossRefGoogle Scholar
  18. 18.
    Arnett FC, Edworthy SM, Bloch DA et al (1988) The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31:315–324PubMedCrossRefGoogle Scholar
  19. 19.
    Boonen S, Marin F, Obermayer-Pietsch B et al (2008) Effects of previous antiresorptive therapy on the bone mineral density response to two years of teriparatide treatment in postmenopausal women with osteoporosis. J Clin Endocrinol Metab 93:852–860PubMedCrossRefGoogle Scholar
  20. 20.
    Gallacher SJ, Dixon T (2010) Impact of treatments for postmenopausal osteoporosis (bisphosphonates, parathyroid hormone, strontium ranelate, and denosumab) on bone quality: a systematic review. Calcif Tissue Int 87:469–484PubMedCrossRefGoogle Scholar
  21. 21.
    Burshell AL, Moricke R, Correa-Rotter R, Chen P, Warner MR, Dalsky GP, Taylor KA, Krege JH (2010) Correlations between biochemical markers of bone turnover and bone density responses in patients with glucocorticoid-induced osteoporosis treated with teriparatide or alendronate. Bone 46:935–939PubMedCrossRefGoogle Scholar
  22. 22.
    Cosman F, Wermers RA, Recknor C, Mauck KF, Xie L, Glass EV, Krege JH (2009) Effects of teriparatide in postmenopausal women with osteoporosis on prior alendronate or raloxifene: differences between stopping and continuing the antiresorptive agent. J Clin Endocrinol Metab 94:3772–3780PubMedCrossRefGoogle Scholar
  23. 23.
    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 (Oxford) 44:1546–1548CrossRefGoogle Scholar
  24. 24.
    Garnero P, Thompson E, Woodworth T, Smolen JS (2010) Rapid and sustained improvement in bone and cartilage turnover markers with the anti-interleukin-6 receptor inhibitor tocilizumab plus methotrexate in rheumatoid arthritis patients with an inadequate response to methotrexate: results from a substudy of the multicenter double-blind, placebo-controlled trial of tocilizumab in inadequate responders to methotrexate alone. Arthritis Rheum 62:33–43PubMedCrossRefGoogle Scholar
  25. 25.
    Booth SL, Centi A, Smith SR, Gundberg C (2013) The role of osteocalcin in human glucose metabolism: marker or mediator? Nat Rev Endocrinol 9:43–55PubMedCrossRefGoogle Scholar
  26. 26.
    Binkley N, Harke J, Krueger D, Engelke J, Vallarta-Ast N, Gemar D, Checovich M, Chappell R, Suttie J (2009) Vitamin K treatment reduces undercarboxylated osteocalcin but does not alter bone turnover, density, or geometry in healthy postmenopausal North American women. J Bone Miner Res 24:983–991PubMedCentralPubMedCrossRefGoogle Scholar
  27. 27.
    Mokuda S, Okuda Y, Onishi M, Sawada N, Matoba K, Yamada A, Jouyama K, Takasugi K (2011) Postmenopausal women with rheumatoid arthritis who are treated with raloxifene or alendronate or glucocorticoids have lower serum undercarboxylated osteocalcin (ucOC) levels. J Endocrinol Invest 35:661–664Google Scholar
  28. 28.
    Chen P, Satterwhite JH, Licata AA, Lewiecki EM, Sipos AA, Misurski DM, Wagman RB (2005) Early changes in biochemical markers of bone formation predict BMD response to teriparatide in postmenopausal women with osteoporosis. J Bone Miner Res 20:962–970PubMedCrossRefGoogle Scholar
  29. 29.
    Tsujimoto M, Chen P, Miyauchi A, Sowa H, Krege JH (2011) PINP as an aid for monitoring patients treated with teriparatide. Bone 48:798–803PubMedCrossRefGoogle Scholar
  30. 30.
    Rhee Y, Lee EY, Lezcano V, Ronda AC, Condon KW, Allen MR, Plotkin LI, Bellido T (2013) Resorption controls bone anabolism driven by parathyroid hormone (PTH) receptor signaling in osteocytes. J Biol Chem 288:29809–29820PubMedCentralPubMedCrossRefGoogle Scholar
  31. 31.
    Terpos E, Fragiadaki K, Konsta M, Bratengeier C, Papatheodorou A, Sfikakis PP (2011) Early effects of IL-6 receptor inhibition on bone homeostasis: a pilot study in women with rheumatoid arthritis. Clin Exp Rheumatol 29:921–925PubMedGoogle Scholar
  32. 32.
    Gifre L, Ruiz-Gaspa S, Monegal A, Nomdedeu B, Filella X, Guanabens N, Peris P (2013) Effect of glucocorticoid treatment on Wnt signalling antagonists (sclerostin and Dkk-1) and their relationship with bone turnover. Bone 57:272–276PubMedCrossRefGoogle Scholar

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2014

Authors and Affiliations

  • K. Ebina
    • 1
  • J. Hashimoto
    • 2
  • K. Shi
    • 1
  • M. Kashii
    • 1
  • M. Hirao
    • 1
  • H. Yoshikawa
    • 1
  1. 1.Department of Orthopaedic SurgeryOsaka University, Graduate School of MedicineSuitaJapan
  2. 2.Department of Rheumatology, National Hospital OrganizationOsaka Minami Medical CenterKawachinaganoJapan

Personalised recommendations