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Archives of Osteoporosis

, 13:50 | Cite as

Long-term benefits and risks of parathyroid hormone treatment in compliant osteoporotic patients. A Danish national register based cohort study

  • Anne-Luise ThorsteinssonEmail author
  • Louise Hansen
  • Peter Vestergaard
  • Pia Eiken
Original Article

Abstract

Purpose

Medical treatment of osteoporosis should preferably be both effective and have minimal side effects. The aim of the present study was to examine long-term benefits and risks of parathyroid hormone (PTH) treatment in compliant patients.

Methods

This is a nationwide retrospective cohort study based on national registers in which we identified 1739 patients treated with PTH (2003–2010) (index cases) for at least 18 months and with a medication possession rate of > 0.8. For comparison, patients treated with bisphosphonate (BP) (n = 13,131) and anti-osteoporotic treatment-naïve controls (n = 12,721) were selected. Incidence of fractures, drug consumption, and comorbidity were compared between the three cohorts. Mean follow-up of the PTH-treated patients was 4.3 years (range 1.8–8.7 years).

Results

Before initiation of treatment, PTH patients had a significantly higher Charlson comorbidity index score and more osteoporotic fractures than both BP patients and controls. No difference was detected in the incidence of fractures during PTH treatment or years after between PTH patients and BP patients. No significant difference in the use of drugs was seen between PTH and BP patients, except for PPI intake which was higher in PTH patients. No significant increases were found in the incidence of cancers or other ICD-10 diagnoses among PTH-treated patients in comparison with both BP and controls.

Conclusion

Overall, PTH treatment is effective and safe. Following PTH treatment in compliant patients, neither fracture incidence nor drug consumption differed between PTH-treated and BP-treated patients, despite the fact that PTH-treated patients had more severe osteoporosis. No increased incidence of malignant diseases or other diseases was detected.

Keywords

Parathyroid hormone Danish National Patient Register Teriparatide Osteoporosis Risk Benefit 

Notes

Funding information

This study was funded by a research grant from Nordsjællands Hospital and grants from Eli Lilly, the Danish Osteoporosis Society, the Foundation of Harald Jensen and wife, the Foundation of Olga Bryde Nielsen, and the Foundation of Tvergaard. The funders had no role in the study design, data collection, data analysis, preparation of the manuscript, or decision to publish.

Compliance with ethical standards

The study was approved by Statistics Denmark and controlled by the Danish Data Protection Agency. Approval from the Regional Committee on Biomedical Research Ethics is not required for registered studies in Denmark.

Conflicts of interest

AT has received a grant from Eli Lilly. PV has received unrestricted research grants from Servier and MSD Denmark and travel grants from Amgen, MSD, Eli Lilly, Novartis, and Servier. PE is an advisory board member of Eli Lilly, MSD, and Amgen and has received lecture fees from Eli Lilly and Amgen. LH has received grants from MSD Denmark and has received speaker fees from both MSD Denmark and Eli Lilly.

References

  1. 1.
    McClung M, Harris ST, Miller PD, Bauer DC, Davison KS, Dian L, Hanley DA, Kendler DL, Yuen CK, Lewiecki EM (2013) Bisphosphonate therapy for osteoporosis: benefits, risks, and drug holiday. Am J Med 126:13–20CrossRefGoogle Scholar
  2. 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 344:1434–1441CrossRefGoogle Scholar
  3. 3.
    Greenspan SL, Bone HG, Ettinger MP, Hanley DA, Lindsay R, Zanchetta JR, Blosch CM, Mathisen AL, Morris SA, Marriott TB, Treatment of Osteoporosis with Parathyroid Hormone Study Group (2007) Effect of recombinant human parathyroid hormone (1-84) on vertebral fracture and bone mineral density in postmenopausal women with osteoporosis: a randomized trial. Ann Intern Med 146:326–339CrossRefGoogle Scholar
  4. 4.
    Kaufman JM, Orwoll E, Goemaere S, San Martin J, Hossain A, Dalsky GP, Lindsay R, Mitlak BH (2005) Teriparatide effects on vertebral fractures and bone mineral density in men with osteoporosis: treatment and discontinuation of therapy. Osteoporos Int 16:510–516CrossRefGoogle Scholar
  5. 5.
    Saag KG, Shane E, Boonen S, Marin F, Donley DW, Taylor KA, Dalsky GP, Marcus R (2007) Teriparatide or alendronate in glucocorticoid-induced osteoporosis. N Engl J Med 357:2028–2039CrossRefGoogle Scholar
  6. 6.
    Silverman S, Miller P, Sebba A, Weitz M, Wan X, Alam J, Masica D, Taylor KA, Ruff VA, Krohn K (2013) The Direct Assessment of Nonvertebral Fractures in Community Experience (DANCE) study: 2-year nonvertebral fragility fracture results. Osteoporos Int 24:2309–2317CrossRefGoogle Scholar
  7. 7.
    Vahle JL, Long GG, Sandusky G, Westmore M, Ma YL, Sato M (2004) Bone neoplasms in F344 rats given teriparatide [rhPTH(1-34)] are dependent on duration of treatment and dose. Toxicol Pathol 32:426–438CrossRefGoogle Scholar
  8. 8.
    Bang UC, Hyldstrup L, Jensen JE (2014) The impact of recombinant parathyroid hormone on malignancies and mortality: 7 years of experience based on nationwide Danish registers. Osteoporos Int 25:639–644CrossRefGoogle Scholar
  9. 9.
    Andrews EB, Gilsenan AW, Midkiff K, Sherrill B, Wu Y, Mann BH, Masica D (2012) The US postmarketing surveillance study of adult osteosarcoma and teriparatide: study design and findings from the first 7 years. J Bone Miner Res 27:2429–2437CrossRefGoogle Scholar
  10. 10.
    Caggiari G, Leali PT, Mosele GR, Puddu L, Badessi F, Doria C (2016) Safety and effectiveness of teriparatide vs alendronate in postmenopausal osteoporosis: a prospective non randomized clinical study. Clin Cases Miner Bone Metab 13:200–203PubMedGoogle Scholar
  11. 11.
    Nishikawa A, Ishida T, Taketsuna M, Yoshiki F, Enomoto H (2016) Safety and effectiveness of daily teriparatide in a prospective observational study in patients with osteoporosis at high risk of fracture in Japan: final report. Clin Interv Aging 11:913–925CrossRefGoogle Scholar
  12. 12.
    Sikon A, Batur P (2010) Profile of teriparatide in the management of postmenopausal osteoporosis. Int J Womens Health 2:37–44CrossRefGoogle Scholar
  13. 13.
    Bodenner D, Redman C, Riggs A (2007) Teriparatide in the management of osteoporosis. Clin Interv Aging 2:499–507PubMedPubMedCentralGoogle Scholar
  14. 14.
    Yamamoto T, Taketsuna M, Guo X, Sato M, Sowa H (2014) The safety and effectiveness profile of daily teriparatide in a prospective observational study in Japanese patients with osteoporosis at high risk for fracture: interim report. J Bone Miner Metab 32:699–708CrossRefGoogle Scholar
  15. 15.
  16. 16.
    Charlson ME, Pompei P, Ales KL, MacKenzie CR (1987) A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 40:373–383CrossRefGoogle Scholar
  17. 17.
    Lægemiddelstyrelsen Vejledende kriterier for enkelttilskud—teriparatide (2017) https://laegemiddelstyrelsen.dk/da/tilskud/individuelle-tilskud/enkelttilskud/vejledende-kriterier/osteoporose-forsteo/
  18. 18.
  19. 19.
    Delmas PD, van de Langerijt L, Watts NB, Eastell R, Genant H, Grauer A, Cahall DL, IMPACT Study Group (2005) Underdiagnosis of vertebral fractures is a worldwide problem: the IMPACT study. J Bone Miner Res 20:557–563CrossRefGoogle Scholar
  20. 20.
    Andrews EB, Gilsenan AW, Midkiff KD, Harris DH (2015) Comments on bang et al.: the impact of recombinant parathyroid hormone on malignancies and mortality: 7 years of experience based on nationwide Danish registers. Osteoporos Int 26:1663–1664CrossRefGoogle Scholar
  21. 21.
    Langdahl BL, Ljunggren O, Benhamou CL, Marin F, Kapetanos G, Kocjan T, Lespessailles E, Napoli N, Nikolic T, Petto H, Moll T, Lindh E (2016) Fracture rate, quality of life and back pain in patients with osteoporosis treated with teriparatide: 24-month results from the Extended Forsteo Observational Study (ExFOS). Calcif Tissue Int 99:259–271CrossRefGoogle Scholar
  22. 22.
    Langdahl BL, Rajzbaum G, Jakob F, Karras D, Ljunggren O, Lems WF, Fahrleitner-Pammer A, Walsh JB, Barker C, Kutahov A, Marin F (2009) Reduction in fracture rate and back pain and increased quality of life in postmenopausal women treated with teriparatide: 18-month data from the European Forsteo Observational Study (EFOS). Calcif Tissue Int 85:484–493CrossRefGoogle Scholar
  23. 23.
    Blick SK, Dhillon S, Keam SJ (2008) Teriparatide: a review of its use in osteoporosis. Drugs 68:2709–2737CrossRefGoogle Scholar
  24. 24.
    European Medicines Agency Summary of product characteristics. (2017)Google Scholar
  25. 25.
    Jodkowska A, Tupikowski K, Szymczak J, Bohdanowicz-Pawlak A, Bolanowski M, Bednarek-Tupikowska G (2016) Interdisciplinary aspects of primary hyperparathyroidism: symptomatology in a series of 100 cases. Adv Clin Exp Med 25:285–293CrossRefGoogle Scholar
  26. 26.
    Broulik P, Adamek S, Libansky P, Kubinyi J (2015) Changes in the pattern of primary hyperparathyroidism in Czech Republic. Prague Med Rep 116:112–121CrossRefGoogle Scholar
  27. 27.
    Taylor WH, Khaleeli AA (2001) Coincident diabetes mellitus and primary hyperparathyroidism. Diabetes Metab Res Rev 17:175–180CrossRefGoogle Scholar
  28. 28.
    Fahrleitner-Pammer A, Langdahl BL, Marin F, Jakob F, Karras D, Barrett A, Ljunggren O, Walsh JB, Rajzbaum G, Barker C, Lems WF (2011) Fracture rate and back pain during and after discontinuation of teriparatide: 36-month data from the European Forsteo Observational Study (EFOS). Osteoporos Int 22:2709–2719CrossRefGoogle Scholar
  29. 29.
    Vellucci R, Mediati RD, Ballerini G (2014) Use of opioids for treatment of osteoporotic pain. Clin Cases Miner Bone Metab 11:173–176PubMedPubMedCentralGoogle Scholar
  30. 30.
    Khosla S, Bilezikian JP, Dempster DW, Lewiecki EM, Miller PD, Neer RM, Recker RR, Shane E, Shoback D, Potts JT (2012) Benefits and risks of bisphosphonate therapy for osteoporosis. J Clin Endocrinol Metab 97:2272–2282CrossRefGoogle Scholar

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2018

Authors and Affiliations

  • Anne-Luise Thorsteinsson
    • 1
    • 2
    Email author
  • Louise Hansen
    • 3
  • Peter Vestergaard
    • 4
  • Pia Eiken
    • 1
    • 2
  1. 1.Department of Cardiology, Nephrology and EndocrinologyNordsjællands HospitalHillerødDenmark
  2. 2.Faculty of Health and Medical SciencesUniversity of CopenhagenCopenhagenDenmark
  3. 3.Danish Center for Healthcare Improvements, Department of Business and ManagementAalborg UniversityAalborgDenmark
  4. 4.Departments of Clinical Medicine and EndocrinologyAalborg University HospitalAalborgDenmark

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