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International Osteoporosis Foundation and European Calcified Tissue Society Working Group. Recommendations for the screening of adherence to oral bisphosphonates

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Abstract

Summary

Adherence to oral bisphosphonates is low. A screening strategy is proposed based on the response of biochemical markers of bone turnover after 3 months of therapy. If no change is observed, the clinician should reassess the adherence to the treatment and also other potential issues with the drug.

Introduction

Low adherence to oral bisphosphonates is a common problem that jeopardizes the efficacy of treatment of osteoporosis. No clear screening strategy for the assessment of compliance is widely accepted in these patients.

Methods

The International Osteoporosis Foundation and the European Calcified Tissue Society have convened a working group to propose a screening strategy to detect a lack of adherence to these drugs. The question to answer was whether the bone turnover markers (BTMs) PINP and CTX can be used to identify low adherence in patients with postmenopausal osteoporosis initiating oral bisphosphonates for osteoporosis. The findings of the TRIO study specifically address this question and were used as the basis for testing the hypothesis.

Results

Based on the findings of the TRIO study, specifically addressing this question, the working group recommends measuring PINP and CTX at baseline and 3 months after starting therapy to check for a decrease above the least significant change (decrease of more than 38% for PINP and 56% for CTX). Detection rate for the measurement of PINP is 84%, for CTX 87% and, if variation in at least one is considered when measuring both, the level of detection is 94.5%.

Conclusions

If a significant decrease is observed, the treatment can continue, but if no decrease occurs, the clinician should reassess to identify problems with the treatment, mainly low adherence.

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Author information

Authors and Affiliations

  1. Department of Internal Medicine, Hospital del Mar-IMIM-Universitat Autònoma and CIBERFES-ISCIII, P Maritim 25–29, 08003, Barcelona, Spain

    A. Diez-Perez

  2. Academic Unit of Bone Metabolism, Mellanby Centre for Bone Research, University of Sheffield, Sheffield, UK

    K. E. Naylor & R. Eastell

  3. Institute of Clinical Research, Odense Patient Data Explorative Network, University of Southern Denmark, Odense, Denmark

    B. Abrahamsen

  4. Department of Medicine, Holbæk Hospital, Holbæk, Denmark

    B. Abrahamsen

  5. Independent Scientific Consultant, Florence, Italy

    D. Agnusdei

  6. Mineral and Bone Metabolic Unit, Department of Surgery and Translational Medicine, University of Florence, Florence, Italy

    M. L. Brandi

  7. MRC Lifecourse Epidemiology Unit, Southampton General Hospital, University of Southampton, Southampton, UK

    C. Cooper & E. Dennison

  8. NIHR Musculoskeletal Biomedical Research Unit, Institute of Musculoskeletal Sciences, University of Oxford, and CIBERFES-ISCIII, Oxford, UK

    C. Cooper

  9. Department of Endocrinology, Morbid Obesity and Preventive Medicine, Oslo University Hospital and University of Oslo, Oslo, Norway

    E. F. Eriksen

  10. Duke University Center for the Study of Aging and Human Development, Duke University Medical Center, Durham, NC, USA

    D. T. Gold

  11. Rheumatology Department, Hospital Clínic, University of Barcelona, CIBERehd, Barcelona, Spain

    N. Guañabens

  12. Department of Bone Oncology, Endocrinology and Reproductive Medicine, Nordwest Hospital, Frankfurt, Germany

    P. Hadji

  13. Department of Health Services Research, School for Public Health & Primary Care (CAPHRI), Maastricht University, Maastricht, The Netherlands

    M. Hiligsmann

  14. Centre for Behavioural Medicine, UCL School of Pharmacy, University College London, London, UK

    R. Horne

  15. Department of Nutritional Sciences and Department of Medicine, St. Michael’s Hospital, University of Toronto, Toronto, Canada

    R. Josse

  16. Centre for Metabolic Bone Diseases, Centre for Integrated Research in Musculoskeletal Ageing, University of Sheffield, Sheffield, UK

    J. A. Kanis

  17. Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Graz, Austria

    B. Obermayer-Pietsch

  18. Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK

    D. Prieto-Alhambra

  19. Department of Public Health, Epidemiology and Health Economics, University of Liège, Liège, Belgium

    J.-Y. Reginster

  20. Service of Bone Diseases, Faculty of Medicine, Geneva University Hospitals, Geneva, Switzerland

    R. Rizzoli

  21. Cedars-Sinai/University of California, Los Angeles, USA

    S. Silverman

  22. Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands

    M. C. Zillikens

Authors
  1. A. Diez-Perez
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  2. K. E. Naylor
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  3. B. Abrahamsen
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  4. D. Agnusdei
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  5. M. L. Brandi
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  6. C. Cooper
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  7. E. Dennison
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  8. E. F. Eriksen
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  9. D. T. Gold
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  10. N. Guañabens
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  11. P. Hadji
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  12. M. Hiligsmann
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  13. R. Horne
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  14. R. Josse
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  15. J. A. Kanis
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  16. B. Obermayer-Pietsch
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  17. D. Prieto-Alhambra
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  18. J.-Y. Reginster
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  19. R. Rizzoli
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  20. S. Silverman
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  21. M. C. Zillikens
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  22. R. Eastell
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Consortia

Adherence Working Group of the International Osteoporosis Foundation and the European Calcified Tissue Society

Corresponding author

Correspondence to A. Diez-Perez.

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Conflict of interest

A Diez-Perez is speaker or advisor for Amgen, Lilly, Merck, UCB, and Active Life Sci. Bo Abrahamsen reports current institutional research grants and contracts with Novartis and UCB, past institutional research contracts with Amgen, and NPS Pharmaceuticals. D. Agnusdei has a consultancy contract with Eli Lilly. Erik F Eriksen is a speaker and advisor for Amgen, Lilly, Merck, IDS, and Shire. Núria Guañabens is speaker or advisor for Amgen, Lilly, and Alexion Pharmaceuticals. Robert Josse is medical advisory board member and speaker honoraria and research grant: Merck, Amgen, Lilly. Daniel Prieto-Alhambra’s research group has received unrestricted grants from AMGEN S.A. Jean-Yves Reginster has consulting fees or paid advisory boards in Servier, Novartis, Negma, Lilly, Wyeth, Amgen, GlaxoSmithKline, Roche, Merckle, Nycomed-Takeda, NPS, IBSA-Genevrier, Theramex, UCB, Asahi Kasei, Endocyte, and Radius Health, and also has lecture fees when speaking at the invitation of the commercial sponsors: Merck Sharp and Dohme, Lilly, Rottapharm, IBSA, Genevrier, Novartis, Servier, Roche, GlaxoSmithKline, Merckle, Teijin, Teva, Analis, Theramex, Nycomed, NovoNordisk, Ebewee Pharma, Zodiac, Danone, Will Pharma, Amgen, and PharmEvo. He has grant support from the industry as follows: Bristol Myers Squibb, Merck Sharp & Dohme, Rottapharm, Teva, Roche, Amgen, Lilly, Novartis, GlaxoSmithKline, Servier, Pfizer, Theramex, Danone, Organon, Therabel, Boehringer, Chiltern, and Galapagos. M. Carola Zillikens has received fee for speaking and advice from Amgen, Eli Lilly, and MSD. R. Eastell has consulting fees from Amgen, AstraZeneca, Chronos, GSK, Immunodiagnostic Systems, Fonterra Brands, Ono Pharma, Lilly, Bayer, Janssen Research, Alere, CL Biosystems, Teijin Pharm, D-Star, Roche Diagnostics, and Inverness Medical; grant support from Amgen, Alexion, Immunodiagnostic Systems, Roche, and AstraZeneca. Kim E Naylor, Maria Luisa Brandi, Cyrus Cooper, Elaine Dennison, Deborah Gold, Peyman Hadji, Mickael Hiligsmann, Robert Horne, John A Kanis, Barbara Obermayer-Pietsch, René Rizzoli, and Stuart Silverman have no conflict of interest.

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Diez-Perez, A., Naylor, K.E., Abrahamsen, B. et al. International Osteoporosis Foundation and European Calcified Tissue Society Working Group. Recommendations for the screening of adherence to oral bisphosphonates. Osteoporos Int 28, 767–774 (2017). https://doi.org/10.1007/s00198-017-3906-6

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