Skip to main content

Advertisement

SpringerLink
Log in

Effect of teriparatide on bone mineral density and biochemical markers in Japanese women with postmenopausal osteoporosis: a 6-month dose-response study

  • Original Article
  • Published:
Journal of Bone and Mineral Metabolism Aims and scope Submit manuscript

Abstract

The dose-response efficacy and safety with three doses of teriparatide and placebo was assessed, using oncedaily subcutaneous injections for 24 weeks, in Japanese postmenopausal women with osteoporosis at high risk of fracture for reasons of preexisting fracture(s), advanced age, and/or low bone mineral density (BMD). In this multicenter, randomized, placebo-controlled study, 159 subjects were randomized and 154 subjects were included for analysis. Teriparatide (10-μg, 20-μg, and 40-μg doses) showed a statistically significant increase with increasing treatment dose as assessed by the percent change of lumbar spine BMD from baseline to endpoint using Williams’ test when compared with placebo (P < 0.001). The mean (±SD) percent change in lumbar spine, femoral neck, and total hip BMD with the 20-μg dose from baseline to endpoint was 6.40% ± 4.76%, 1.83% ± 7.13%, and 1.91% ± 3.60%, respectively. Rapid and sustained increases in bone formation markers [type I procollagen N-terminal propeptide (PINP), type I procollagen C-terminal propeptide (PICP), and bone-specific alkaline phosphatase (BAP)], followed by late increases in a bone resorption marker [type I collagen cross-linked C-telopeptide (CTX)], were observed for the teriparatide treatment groups (20-μg, 40-μg), suggesting a persistent, positive, balanced anabolic effect of teriparatide. Optimal adherence was achieved by this daily self-injection treatment. Regarding safety, most of the adverse events were mild to moderate in severity. No study drug-or study procedure-related serious adverse events were reported during the treatment period. These results observed in Japanese patients may support the observation that teriparatide stimulates bone formation in patients with osteoporosis at a high risk of fracture.

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

Similar content being viewed by others

References

  1. Kanis JA, Brazier JE, Stevenson M, Calvert NW, Lloyd Jones M (2002) Treatment of established osteoporosis: a systematic review and cost-utility analysis. Health Technol Assess 6(29): 1–146

    PubMed  CAS  Google Scholar 

  2. 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(19): 1434–1441

    Article  PubMed  CAS  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(15):1762–1768

    Article  PubMed  CAS  Google Scholar 

  4. Keaveny TM, Donley DW, Hoffmann PF, Mitlak BH, Glass EV, San Martin JA (2007) Effects of teriparatide and alendronate on vertebral strength as assessed by finite element modeling of QCT scans in women with osteoporosis. J Bone Miner Res 22(1): 149–157

    Article  PubMed  CAS  Google Scholar 

  5. Jiang Y, Zhao JJ, Mitlak BH, Wang O, Genant HK, Eriksen EF (2003) Recombinant human parathyroid hormone (1–34) [teriparatide] improves both cortical and cancellous bone structure. J Bone Miner Res 18(11):1932–1941

    Article  PubMed  CAS  Google Scholar 

  6. Benhamou CL (2007) Effects of osteoporosis medications on bone quality. Joint Bone Spine 74(1):39–47

    Article  PubMed  CAS  Google Scholar 

  7. Miki T, Naka H (1996) Tests for calcium metabolism. In: Morii H (ed) Handbook for Bone/Calcium Test (in Japanese). Nakayama-Shoten, Tokyo, pp 10–14

    Google Scholar 

  8. Kanis JA, Borgstrom F, De Laet C, Johansson H, Johnell O, Jonsson B, Oden A, Zethraeus N, Pfleger B, Khaltaev N (2005) Assessment of fracture risk. Osteoporos Int 16(6):581–589

    Article  PubMed  Google Scholar 

  9. Kanis JA, Oden A, Johnell O, Johansson H, De Laet C, et al. (2007) The use of clinical risk factors enhances the performance of BMD in the prediction of hip and osteoporotic fractures in men and women. Osteoporos Int 18(8):1033–1046

    Article  PubMed  CAS  Google Scholar 

  10. Reginster JY, Sarlet N (2006) The treatment of severe postmenopausal osteoporosis: a review of current and emerging therapeutic options. Treat Endocrinol 5(1):15–23

    Article  PubMed  Google Scholar 

  11. Hagino H (2007) Features of limb fractures: a review of epidemiology from a Japanese perspective. J Bone Miner Metab 25(5): 261–265

    Article  PubMed  Google Scholar 

  12. Sakai A, Sakata T, Ikeda S, Uchida S, Okazaki R, Norimura T, Hori M, Nakamura T (1999) Intermittent administration of human parathyroid hormone (1–34) prevents immobilization-related bone loss by regulating bone marrow capacity for bone cells in ddY mice. J Bone Miner Res 14(10):1691–1699

    Article  PubMed  CAS  Google Scholar 

  13. Bellido T, Ali AA, Plotkin LI, Fu Q, Gubrij I, Roberson PK, Weinstein RS, O’Brien CA, Manolagas SC, Jilka RL (2003) Proteasomal degradation of Runx2 shortens parathyroid hormone-induced anti-apoptotic signaling in osteoblasts. A putative explanation for why intermittent administration is needed for bone anabolism. J Biol Chem 278(50):50259–50272

    Article  PubMed  CAS  Google Scholar 

  14. Hodsman AB, Steer BM (1993) Early histomorphometric changes in response to parathyroid hormone therapy in osteoporosis: evidence for de novo bone formation on quiescent cancellous surfaces. Bone (NY) 14(3):523–527

    CAS  Google Scholar 

  15. Ma YL, Zeng Q, Donley DW, Ste-Marie LG, Gallagher JC, Dalsky GP, Marcus R, Eriksen EF (2006) Teriparatide increases bone formation in modeling and remodeling osteons and enhances IGFII immunoreactivity in postmenopausal women with osteoporosis. J Bone Miner Res 21(6):855–864

    Article  PubMed  CAS  Google Scholar 

  16. Lindsay R, Cosman F, Zhou H, Bostrom MP, Shen VW, Cruz JD, Nieves JW, Dempster DW (2006) A novel tetracycline labeling schedule for longitudinal evaluation of the short-term effects of anabolic therapy with a single iliac crest bone biopsy: early actions of teriparatide. J Bone Miner Res 21(3):366–373

    Article  PubMed  CAS  Google Scholar 

  17. Compston JE (2007) Skeletal actions of intermittent parathyroid hormone: effects on bone remodelling and structure. Bone (NY) 40(6):1447–1452

    CAS  Google Scholar 

  18. Fujita T, Inoue T, Morii H, Morita R, Norimatsu H, Orimo H, Takahashi HE, Yamamoto K, Fukunaga M (1999) Effect of an intermittent weekly dose of human parathyroid hormone (1–34) on osteoporosis: a randomized double-masked prospective study using three dose levels. Osteoporos Int 9(4):296–306

    Article  PubMed  CAS  Google Scholar 

  19. Matsumoto T, Shiraki M, Hagino H, Iinuma H, Nakamura T (2006) Daily nasal spray of hPTH (1–34) for 3 months increases bone mass in osteoporotic subjects: a pilot study. Osteoporos Int 17(10):1532–1538

    Article  PubMed  CAS  Google Scholar 

  20. 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(11):1785–1790

    Article  PubMed  CAS  Google Scholar 

  21. Chen P, Miller PD, Recker R, Resch H, Rana A, Pavo I, Sipos AA (2007) Increases in BMD correlate with improvements in bone microarchitecture with teriparatide treatment in postmenopausal women with osteoporosis. J Bone Miner Res 22(8):1173–1180

    Article  PubMed  CAS  Google Scholar 

  22. 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(1):18–23

    Article  PubMed  CAS  Google Scholar 

  23. Kung AW, Pasion EG, Sofiyan M, Lau EM, Tay BK, Lam KS, Wilawan K, Ongphiphadhanakul B, Thiebaud D (2006) A comparison of teriparatide and calcitonin therapy in postmenopausal Asian women with osteoporosis: a 6-month study. Curr Med Res Opin 22(5):929–937

    Article  PubMed  CAS  Google Scholar 

  24. Hwang JS, Tu ST, Yang TS, Chen JF, Wang CJ, Tsai KS (2006) Teriparatide vs. calcitonin in the treatment of Asian postmenopausal women with established osteoporosis. Osteoporos Int 17(3):373–378

    Article  PubMed  CAS  Google Scholar 

  25. 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(6):962–970

    Article  PubMed  CAS  Google Scholar 

  26. Dobnig H, Sipos A, Jiang Y, Fahrleitner-Pammer A, Ste-Marie LG, Gallagher JC, Pavo I, Wang J, Eriksen EF (2005) Early changes in biochemical markers of bone formation correlate with improvements in bone structure during teriparatide therapy. J Clin Endocrinol Metab 90(7):3970–3977

    Article  PubMed  CAS  Google Scholar 

  27. 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(1):61–66

    Article  PubMed  CAS  Google Scholar 

  28. Rubin MR, Bilezikian JP (2003) The anabolic effects of parathyroid hormone therapy. Clin Geriatr Med 19(2):415–432

    Article  PubMed  Google Scholar 

  29. Canalis E, Giustina A, Bilezikian JP (2007) Mechanisms of anabolic therapies for osteoporosis. N Engl J Med 357(9): 905–916

    Article  PubMed  CAS  Google Scholar 

  30. Zanchetta JR, Bogado CE, Ferretti JL, Wang O, Wilson MG, Sato M, Gaich GA, Dalsky GP, Myers SL (2003) Effects of teriparatide [recombinant human parathyroid hormone (1–34)] on cortical bone in postmenopausal women with osteoporosis. J Bone Miner Res 18(3):539–543

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Lilly Research Laboratories Japan, Eli Lilly Japan K.K., Sannomiya Plaza Bldg., 7-1-5 Isogamidori, Chuo-ku, Kobe, 651-0086, Japan

    Akimitsu Miyauchi, Hirofumi Shigeta & Mika Tsujimoto

  2. Department of Medicine and Bioregulatory Sciences, University of Tokushima Graduate School of Health Biosciences, Tokushima, Japan

    Toshio Matsumoto

  3. Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA

    Daniel Thiebaud

  4. Department of Orthopedics, University of Occupational and Environmental Health, Kitakyushu, Japan

    Toshitaka Nakamura

Authors
  1. Akimitsu Miyauchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Toshio Matsumoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hirofumi Shigeta
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mika Tsujimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Daniel Thiebaud
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Toshitaka Nakamura
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Akimitsu Miyauchi.

About this article

Cite this article

Miyauchi, A., Matsumoto, T., Shigeta, H. et al. Effect of teriparatide on bone mineral density and biochemical markers in Japanese women with postmenopausal osteoporosis: a 6-month dose-response study. J Bone Miner Metab 26, 624–634 (2008). https://doi.org/10.1007/s00774-008-0871-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00774-008-0871-3

Key words

Search

Navigation