Osteoporosis International

, Volume 23, Issue 12, pp 2885–2891 | Cite as

Effects of morning vs. evening teriparatide injection on bone mineral density and bone turnover markers in postmenopausal osteoporosis

  • D. Michalska
  • M. Luchavova
  • V. Zikan
  • I. RaskaJr
  • A. A. Kubena
  • J. J. Stepan
Original Article

Abstract

Summary

A 12-month morning teriparatide (TPTD) administration resulted in a larger increase in the lumbar spine bone mineral density (BMD) than the evening application. The results indicate that the response of bone cells to teriparatide treatment depends on dosing time.

Introduction

The aim of this study was to assess the long-term effects of the morning vs. the evening teriparatide administration on BMD and bone turnover markers (BTMs) in postmenopausal osteoporosis.

Methods

Fifty women with established postmenopausal osteoporosis were randomized to 12-month treatment with 20 μg of TPTD, administered daily in the morning or in the evening. The BMD and serum concentrations of C-terminal telopeptide of type I collagen, N-terminal propeptide of type I procollagen (PINP), and tartrate-resistant acid phosphatase isoform 5b (TRAP 5b) were measured at baseline, after 6 and 12 months. General linear model-repeated measurements were used to analyze the data.

Results

After 12 months, the lumbar spine BMD grew markedly (p < 0.001) with a significantly greater increase in the morning arm compared to the evening arm (9.1% vs. 4.8%, respectively, p < 0.05). The BMD at the distal radius significantly decreased (p < 0.001), with no differences between the arms. The BMD at proximal femur did not change significantly. After 6 months, the BTMs were significantly increased compared with baseline (p < 0.001). The increases in the evening arm vs. the morning arm, however, were more pronounced in PINP (+358% vs. +215%, respectively) and in TRAP 5b (+70% vs. +37%, respectively) (both p < 0.05).

Conclusion

12-month morning administration of TPTD resulted in a larger increase in the lumbar spine BMD than the evening application. The timing of TPTD administration may be important for its efficacy.

Keywords

Bone mineral density Bone turnover Postmenopausal osteoporosis Timing Teriparatide 

Notes

Acknowledgments

We thank Oldriska Lukaskova and Jana Krenkova for their excellent technical assistance. This work was supported by the IGA Ministry of Health of Czech Republic NS 10564-3.

Conflicts of interest

None.

References

  1. 1.
    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 344:1434–1441PubMedCrossRefGoogle Scholar
  2. 2.
    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 18:9–17PubMedCrossRefGoogle Scholar
  3. 3.
    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 22:1173–1180PubMedCrossRefGoogle Scholar
  4. 4.
    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 18:1932–1941PubMedCrossRefGoogle Scholar
  5. 5.
    Paschalis EP, Glass EV, Donley DW, Eriksen EF (2005) Bone mineral and collagen quality in iliac crest biopsies of patients given teriparatide: new results from the fracture prevention trial. J Clin Endocrinol Metab 90:4644–4649PubMedCrossRefGoogle Scholar
  6. 6.
    Jilka RL (2007) Molecular and cellular mechanisms of the anabolic effect of intermittent PTH. Bone 40:1434–1446PubMedCrossRefGoogle Scholar
  7. 7.
    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 21:366–373PubMedCrossRefGoogle Scholar
  8. 8.
    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 22:495–502PubMedCrossRefGoogle Scholar
  9. 9.
    Demiralp B, Chen HL, Koh AJ, Keller ET, McCauley LK (2002) Anabolic actions of parathyroid hormone during bone growth are dependent on c-fos. Endocrinology 43:4038–4047CrossRefGoogle Scholar
  10. 10.
    Gooi JH, Pompolo S, Karsdal MA, Kulkarni NH, Kalajzic I, McAhren SH, Han B, Onyia JE, Ho PW, Gillespie MT et al (2010) Calcitonin impairs the anabolic effect of PTH in young rats and stimulates expression of sclerostin by osteocytes. Bone 46:1486–1497PubMedCrossRefGoogle Scholar
  11. 11.
    Pierroz DD, Bonnet N, Baldock PA, Ominsky MS, Stolina M, Kostenuik PJ, Ferrari SL (2010) Are osteoclasts needed for the bone anabolic response to parathyroid hormone? A study of intermittent parathyroid hormone with denosumab or alendronate in knock-in mice expressing humanized RANKL. J Biol Chem 285:28164–28173PubMedCrossRefGoogle Scholar
  12. 12.
    Black DM, Greenspan SL, Ensrud KE, Palermo L, McGowan JA, Lang TF, Garnero P, Bouxsein ML, Bilezikian JP, Rosen CJ, PaTH Study Investigators (2003) The effects of parathyroid hormone and alendronate alone or in combination in postmenopausal osteoporosis. N Engl J Med 349:1207–1215PubMedCrossRefGoogle Scholar
  13. 13.
    Finkelstein JS, Wyland JJ, Lee H, Neer RM (2010) Effects of teriparatide, alendronate, or both in women with postmenopausal osteoporosis. J Clin Endocrinol Metab 95:1838–1845PubMedCrossRefGoogle Scholar
  14. 14.
    Obermayer-Pietsch BM, Marin F, McCloskey EV, Hadji P, Farrerons J, Boonen S, Audran M, Barker C, Anastasilakis AD, Fraser WD, Nickelsen T, EUROFORS Investigators (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 23:1591–1600PubMedCrossRefGoogle Scholar
  15. 15.
    Qvist P, Christgau S, Pedersen BJ, Schlemmer A, Christiansen C (2002) Circadian variation in the serum concentration of C-terminal telopeptide of type I collagen (serum CTx): effects of gender, age, menopausal status, posture, daylight, serum cortisol, and fasting. Bone 31:57–61PubMedCrossRefGoogle Scholar
  16. 16.
    Nielsen HK (1994) Circadian and circatrigintan changes in osteoblastic activity assessed by serum osteocalcin. Physiological and methodological aspects. Dan Med Bull 41:216–227PubMedGoogle Scholar
  17. 17.
    Luchavova M, Zikan V, Michalska D, Raska I Jr, Kubena AA, Stepan JJ (2011) The effect of timing of teriparatide treatment on the circadian rhythm of bone turnover in postmenopausal osteoporosis. Eur J Endocrinol 164:643–648PubMedCrossRefGoogle Scholar
  18. 18.
    Henriksen K, Tanko LB, Qvist P, Delmas PD, Christiansen C, Karsdal MA (2007) Assessment of osteoclast number and function: application in the development of new and improved treatment modalities for bone diseases. Osteoporos Int 18:681–685PubMedCrossRefGoogle Scholar
  19. 19.
    Fraser WD, Logue FC, Christie JP, Gallacher SJ, Cameron D, O'Reilly DS, Beastall GH, Boyle IT (1998) Alteration of the circadian rhythm of intact parathyroid hormone and serum phosphate in women with established postmenopausal osteoporosis. Osteoporos Int 8:121–126PubMedCrossRefGoogle Scholar
  20. 20.
    Blumsohn A, Herrington K, Hannon RA, Shao P, Eyre DR, Eastell R (1994) The effect of calcium supplementation on the circadian rhythm of bone resorption. J Clin Endocrinol Metab 79:730–735PubMedCrossRefGoogle Scholar
  21. 21.
    Zikan V, Roubal P, Haas T, Stepan JJ (2001) Acute effects of calcium carbonate and milk on the calcium parathyroid axis and bone resorption in healthy women. In: Burckhardt P (ed) Nutritional aspects of osteoporosis. Academic, New York, pp 131–140Google Scholar
  22. 22.
    Deal C, Omizo M, Schwartz EN, Eriksen EF, Cantor P, Wang J, Glass EV, Myers SL, Krege JH (2005) Combination teriparatide and raloxifene therapy for postmenopausal osteoporosis: results from a 6-month double-blind placebo-controlled trial. J Bone Miner Res 20:1905–1911PubMedCrossRefGoogle Scholar
  23. 23.
    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 90:3970–3977PubMedCrossRefGoogle Scholar
  24. 24.
    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
  25. 25.
    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 22:1935–1946PubMedCrossRefGoogle Scholar
  26. 26.
    Girotra M, Rubin MR, Bilezikian JP (2006) The use of parathyroid hormone in the treatment of osteoporosis. Rev Endocr Metab Disord 7:113–121PubMedCrossRefGoogle Scholar
  27. 27.
    Parfitt AM (1982) The coupling of bone formation to bone resorption: a critical analysis of the concept and of its relevance to the pathogenesis of osteoporosis. Metab Bone Dis Relat Res 4:1–6PubMedCrossRefGoogle Scholar
  28. 28.
    Foldes J, Parfitt AM, Shih MS, Rao DS, Kleerekoper M (1991) Structural and geometric changes in iliac bone: relationship to normal aging and osteoporosis. J Bone Miner Res 6:759–766PubMedCrossRefGoogle Scholar

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2012

Authors and Affiliations

  • D. Michalska
    • 1
  • M. Luchavova
    • 1
  • V. Zikan
    • 1
  • I. RaskaJr
    • 1
  • A. A. Kubena
    • 2
  • J. J. Stepan
    • 3
  1. 1.Department of Internal Medicine III–Department of Endocrinology and MetabolismGeneral University Hospital and First Faculty of Medicine, Charles University, PraguePrague 2Czech Republic
  2. 2.Department of Social and Clinical PharmacyFaculty of Pharmacy, Charles University, Hradec KrálovéHradec KrálovéCzech Republic
  3. 3.Institute of Rheumatology and First Faculty of Medicine, Charles University, PraguePrague 2Czech Republic

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