Skip to main content
SpringerLink
Log in

A retrospective analysis of nonresponse to daily teriparatide treatment

  • Original Article
  • Published:
Osteoporosis International Aims and scope Submit manuscript

An Erratum to this article was published on 17 May 2016

Abstract

Summary

Some patients with osteoporosis do not respond to teriparatide treatment. Prior bisphosphonate use, lower bone turnover marker (BTMs) concentrations, and lower early increases in BTMs were significantly associated with a blunted lumbar spine (LS) bone mineral density (BMD) response to daily treatment with teriparatide, although the impact was limited.

Introduction

Some osteoporosis patients do not respond to teriparatide treatment. To better understand the factors underlying treatment nonresponses, we compared nonresponders’ and responders’ characteristics.

Methods

We retrospectively analyzed 354 male and female patients with osteoporosis who were administered teriparatide (20 μg/day) for 24 months. The patients were categorized as responders (≥3 % lumber spine (LS) bone mineral density (BMD) increase) or nonresponders (<3 % LS BMD increase), and the groups were compared.

Results

The univariate analyses determined that prior bisphosphonate use, a lower baseline procollagen type I N-terminal propeptide (PINP) concentration and a lower urinary N-telopeptide of type I collagen (uNTX) concentration at baseline were significantly associated with teriparatide nonresponses, but these factors were not significant following multivariate analysis. Diminished early increases in the bone turnover markers (BTMs) were also related to nonresponses after teriparatide treatment began. In the nonresponders, the mean (standard deviation (SD)) absolute LS and femoral neck (FN) BMD changes were −0.002 g/cm2 (0.032) and −0.010 g/cm2 (0.045), respectively. In the responders, the mean (SD) absolute LS and FN BMD changes were 0.118 g/cm2 (0.056) and 0.021 g/cm2 (0.046), respectively. The serum PINP and uNTX levels increased rapidly in both groups, but the responders showed higher early absolute serum PINP and uNTX increases.

Conclusions

The factors associated with nonresponses were prior bisphosphonate use, lower baseline BTM levels, and lower early increases in the BTMs after starting teriparatide treatment, but the impact of these factors on achieving a ≥3 % LS BMD increase at 24 months was limited.

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
Fig. 2

Similar content being viewed by others

References

  1. Klotzbuecher CM, Ross PD, Landsman PB, Abbott TA 3rd, Berger M (2000) Patients with prior fractures have an increased risk of future fractures: a summary of the literature and statistical synthesis. J Bone Miner Res 15:721–739

    Article  CAS  PubMed  Google Scholar 

  2. Lindsay R, Scheele WH, Neer R, Pohl G, Adami S, Mautalen C, Reginster JY, Stepan JJ, Myers SL, Mitlak BH (2004) Sustained vertebral fracture risk reduction after withdrawal of teriparatide in postmenopausal women with osteoporosis. Arch Intern Med 164:2024–2030

    Article  PubMed  Google Scholar 

  3. McClung MR, San Martin J, Miller PD, Civitelli R, Bandeira F, Omizo M, Donley DW, Dalsky GP, Eriksen EF (2005) Opposite bone remodeling effects of teriparatide and alendronate in increasing bone mass. Arch Intern Med 165:1762–1768

    Article  CAS  PubMed  Google Scholar 

  4. Miyauchi A, Matsumoto T, Sugimoto T, Tsujimoto M, Warner MR, Nakamura T (2010) Effects of teriparatide on bone mineral density and bone turnover markers in Japanese subjects with osteoporosis at high risk of fracture in a 24-month clinical study: 12-month, randomized, placebo-controlled, double-blind and 12-month open-label phases. Bone 47:493–502

    Article  CAS  PubMed  Google Scholar 

  5. Niimi R, Kono T, Nishihara A, Hasegawa M, Matsumine A, Kono T, Sudo A (2015) Analysis of daily teriparatide treatment for osteoporosis in men. Osteoporos Int 26:1303–1309

    Article  CAS  PubMed  Google Scholar 

  6. Ebina K, Hashimoto J, Shi K, Kashii M, Hirao M, Yoshikawa H (2014) Comparison of the effect of 18-month daily teriparatide administration on patients with rheumatoid arthritis and postmenopausal osteoporosis patients. Osteoporos Int 25:2755–2765. doi:10.1007/s00198-014-2819-x

    Article  CAS  PubMed  Google Scholar 

  7. Niimi R, Kono T, Nishihara A, Hasegawa M, Matsumine A, Kono T, Sudo A (2016) Usefulness of daily teriparatide treatment in elderly patients over 80 years of age. Osteoporos Int

  8. Vestergaard P, Jorgensen NR, Mosekilde L, Schwarz P (2007) Effects of parathyroid hormone alone or in combination with antiresorptive therapy on bone mineral density and fracture risk—a meta-analysis. Osteoporos Int 18:45–57

    Article  CAS  PubMed  Google Scholar 

  9. Neer RM, Arnaud CD, Zanchetta JR, Prince R, Gaich GA, Reginster JY, Hodsman AB, Eriksen EF, Ish-Shalom S, Genant HK, Wang O, Mitlak BH (2001) Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med 344:1434–1441

    Article  CAS  PubMed  Google Scholar 

  10. Gallagher JC, Rosen CJ, Chen P, Misurski DA, Marcus R (2006) Response rate of bone mineral density to teriparatide in postmenopausal women with osteoporosis. Bone 39:1268–1275

    Article  CAS  PubMed  Google Scholar 

  11. Niimi R, Kono T, Nishihara A, Hasegawa M, Matsumine A, Nakamura T, Kono T, Sudo A (2014) An algorithm using the early changes in PINP to predict the future BMD response for patients treated with daily teriparatide. Osteoporos Int 25:377–384. doi:10.1007/s00198-013-2426-2

    Article  CAS  PubMed  Google Scholar 

  12. Orimo H, Hayashi Y, Fukunaga M, Sone T, Fujiwara S, Shiraki M, Kushida K, Miyamoto S, Soen S, Nishimura J, Oh-Hashi Y, Hosoi T, Gorai I, Tanaka H, Igai T, Kishimoto H; Osteoporosis Diagnostic Criteria Review Committee: Japanese Society for Bone and Mineral Research (2001) Diagnostic criteria for primary osteoporosis: year 2000 revision. J Bone Miner Metab 19:331–337

    Article  Google Scholar 

  13. Genant HK, Wu CY, van Kuijk C, Nevitt MC (1993) Vertebral fracture assessment using a semiquantitative technique. J Bone Miner Res 8:1137–1148

    Article  CAS  PubMed  Google Scholar 

  14. Pham T, Azulay-Parrado J, Champsaur P, Chagnaud C, Legré V, Lafforgue P (2005) “Occult” osteoporotic vertebral fractures: vertebral body fractures without radiologic collapse. Spine (Phila Pa 1976) 30:2430–2435

    Article  Google Scholar 

  15. Niimi R, Kono T, Nishihara A, Hasegawa M, Matsumine A, Kono T, Sudo A (2014) Efficacy of the dynamic radiographs for diagnosing acute osteoporotic vertebral fractures. Osteoporos Int 25:605–612. doi:10.1007/s00198-013-2456-9

    Article  CAS  PubMed  Google Scholar 

  16. Eastell R, Krege JH, Chen P, Glass EV, Reginster JY (2006) Development of an algorithm for using PINP to monitor treatment of patients with teriparatide. Curr Med Res Opin 22:61–66

    Article  CAS  PubMed  Google Scholar 

  17. Niimi R, Kono T, Nishihara A, Hasegawa M, Matsumine A, Kono T, Sudo A (2014) Determinants associated with bone mineral density increase in response to daily teriparatide treatment in patients with osteoporosis. Bone 66:26–30. doi:10.1016/j.bone.2014.05.017

    Article  CAS  PubMed  Google Scholar 

  18. Du Bois D, Du Bois EF (1916) Clinical calorimetry: tenth paper a formula to estimate the approximate surface area if height and weight be known. Arch Intern Med (Chic) 17:863–871. doi:10.1001/archinte.1916.00080130010002

    Article  Google Scholar 

  19. Cohen A, Stein EM, Recker RR, Lappe JM, Dempster DW, Zhou H, Cremers S, McMahon DJ, Nickolas TL, Müller R, Zwahlen A, Young P, Stubby J, Shane E (2013) Teriparatide for idiopathic osteoporosis in premenopausal women: a pilot study. J Clin Endocrinol Metab 98:1971–1981. doi:10.1210/jc.2013-1172

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Heaney RP, Watson P (2011) Variability in the measured response of bone to teriparatide. Osteoporos Int 22:1703–1708. doi:10.1007/s00198-010-1376-1

    Article  CAS  PubMed  Google Scholar 

  21. Krege JH, Lane NE, Harris JM, Miller PD (2014) PINP as a biological response marker during teriparatide treatment for osteoporosis. Osteoporos Int 25(9):2159–2171. doi:10.1007/s00198-014-2646-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Boonen S, Marin F, Obermayer-Pietsch B, Simões ME, Barker C, Glass EV, Hadji P, Lyritis G, Oertel H, Nickelsen T, McCloskey EV, Investigators EUROFORS (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 93:852–860

    Article  CAS  PubMed  Google Scholar 

  23. Blumsohn A, Marin F, Nickelsen T, Brixen K, Sigurdsson G, González de la Vera J, Boonen S, Liu-Léage S, Barker C, Eastell R; EUROFORS Study Group (2011) Early changes in biochemical markers of bone turnover and their relationship with bone mineral density changes after 24 months of treatment with teriparatide. Osteoporos Int 22:1935–1946. doi:10.1007/s00198-010-1379-y

    Article  Google Scholar 

  24. Ettinger B, San Martin J, Crans G, Pavo I (2004) Differential effects of teriparatide on BMD after treatment with raloxifene or alendronate. J Bone Miner Res 19:745–751

    Article  CAS  PubMed  Google Scholar 

  25. Minne H, Audran M, Simões ME, Obermayer-Pietsch B, Sigurðsson G, Marín F, Dalsky GP, Nickelsen T; EUROFORS Study Group (2008) Bone density after teriparatide in patients with or without prior antiresorptive treatment: one-year results from the EUROFORS study. Curr Med Res Opin 24:3117–3128. doi:10.1185/03007990802466595

    Article  Google Scholar 

  26. Cosman F, Nieves J, Zion M, Woelfert L, Luckey M, Lindsay R (2005) Daily and cyclic parathyroid hormone in women receiving alendronate. New Engl J Med 353:566–575

    Article  CAS  PubMed  Google Scholar 

  27. 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 94:3772–3780. doi:10.1210/jc.2008-2719

    Article  CAS  PubMed  Google Scholar 

  28. Obermayer-Pietsch BM, Marin F, McCloskey EV, Hadji P, Farrerons J, Boonen S, Audran M, Barker C, Anastasilakis AD, Fraser WD, Nickelsen T, Investigators EUROFORS (2008) Effects of two years of daily teriparatide treatment on BMD in postmenopausal women with severe osteoporosis with and without prior antiresorptive treatment. J Bone Miner Res 23:1591–1600. doi:10.1359/jbmr.080506

    Article  CAS  PubMed  Google Scholar 

  29. Marcus R, Wang O, Satterwhite J, Mitlak B (2003) The skeletal response to teriparatide is largely independent of age, initial bone mineral density, and prevalent vertebral fractures in postmenopausal women with osteoporosis. J Bone Miner Res 18:18–23

    Article  CAS  PubMed  Google Scholar 

  30. Schwarz P, Jorgensen NR, Mosekilde L, Vestergaard P (2012) Effects of increasing age, dosage, and duration of PTH treatment on BMD increase--a meta-analysis. Calcif Tissue Int 90:165–173. doi:10.1007/s00223-011-9564-3

    Article  CAS  PubMed  Google Scholar 

  31. Orwoll ES, Scheele WH, Paul S, Adami S, Syversen U, Diez-Perez A, Kaufman JM, Clancy AD, Gaich GA (2003) The effect of teriparatide [human parathyroid hormone (1-34)] therapy on bone density in men with osteoporosis. J Bone Miner Res 18:9–17

    Article  CAS  PubMed  Google Scholar 

  32. Farahmand P, Marin F, Hawkins F, Möricke R, Ringe JD, Glüer CC, Papaioannou N, Minisola S, Martínez G, Nolla JM, Niedhart C, Guañabens N, Nuti R, Martín-Mola E, Thomasius F, Peña J, Graeff C, Kapetanos G, Petto H, Gentzel A, Reisinger A, Zysset PK (2013) Early changes in biochemical markers of bone formation during teriparatide therapy correlate with improvements in vertebral strength in men with glucocorticoid-induced osteoporosis. Osteoporos Int 24:2971–2981. doi:10.1007/s00198-013-2379-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Tsujimoto M, Chen P, Miyauchi A, Sowa H, Krege JH (2011) PINP as an aid for monitoring patients treated with teriparatide. Bone 48:798–803. doi:10.1016/j.bone.2010.12.006

    Article  CAS  PubMed  Google Scholar 

  34. Lindsay R, Zhou H, Cosman F, Nieves J, Dempster DW, Hodsman AB (2007) Effects of a one-month treatment with PTH(1-34) on bone formation on cancellous, endocortical, and periosteal surfaces of the human ilium. J Bone Miner Res 22:495–502

    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(3):472–481. doi:10.1359/jbmr.090820

    Article  CAS  PubMed  Google Scholar 

  36. Chen P, Miller PD, Delmas PD, Misurski DA, Krege JH (2006) Change in lumbar spine BMD and vertebral fracture risk reduction in teriparatide-treated postmenopausal women with osteoporosis. J Bone Miner Res 21:1785–1790

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors thank Mr. Koji Fukuda, Mr. Hideki Ito, Mr. Takeshi Kato, Ms. Kana Nakanishi, Mr. Kenji Kuroda, Mr. Haruyoshi Mizuno, Mr. Yohei Takigawa, Mr. Yoshifumi Takahashi, Mr. Hiroaki Takeuchi, Homare Nakoshi, Momoko Mizutani, Koji Shibata, Nobuyuki Tanaka, and Akiko Mizutani for their diligence in preparing the clinical recordings. The authors thank Dr. Hideki Yamamoto and Dr. Takahito Saito for their cooperation with the osteoporosis treatment.

Author information

Authors and Affiliations

  1. Department of Orthopaedic Surgery, Tomidahama Hospital, 26-14, Tomidahamacho, Yokkaichi, Mie, 510-8008, Japan

    R. Niimi, T. Kono, A. Nishihara & T. Kono

  2. Department of Orthopaedic Surgery, Graduate School of Medicine, Mie University, Tsu, Japan

    M. Hasegawa & A. Sudo

Authors
  1. R. Niimi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. T. Kono
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. Nishihara
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M. Hasegawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. T. Kono
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. A. Sudo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to R. Niimi.

Ethics declarations

Conflicts of interest

None.

Ethical statement

The study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments, and it was approved by the Ethics Committee of Tomidahama Hospital. Written informed consent was obtained from each patient.

Additional information

An erratum to this article is available at http://dx.doi.org/10.1007/s00198-016-3625-4.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Niimi, R., Kono, T., Nishihara, A. et al. A retrospective analysis of nonresponse to daily teriparatide treatment. Osteoporos Int 27, 2845–2853 (2016). https://doi.org/10.1007/s00198-016-3581-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00198-016-3581-z

Keywords

Search

Navigation