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Observational Study
. 2025 Feb;36(2):245-254.
doi: 10.1007/s00198-024-07309-9. Epub 2024 Dec 3.

Bisphosphonate drug holidays in osteoporosis according to fracture risk profile

Asunción Salmoral  1 , P Peris  2 , C López Medina  3 , H Flórez  2 , M Barceló  4 , M Pascual Pastor  4 , I Ros  5 , D Grados  6 , P Aguado  7 , S García  7 , L López  8 , L Gifre  9 , D Cerdá  10 , F J Aguilar  11 , B Panero  11 , E Costa  12 , E Casado  12 , B Hernández  13 , A Martínez Ferrer  14 , J Graña  15 , I Gómez  3 , N Guañabens  2 ; OsteoResSer Working Group of the Spanish Society of Rheumatology
Affiliations
Free article
Observational Study

Bisphosphonate drug holidays in osteoporosis according to fracture risk profile

Asunción Salmoral et al. Osteoporos Int. 2025 Feb.
Free article

Abstract

We analyzed the incidence of fractures and changes in bone mineral density and bone turnover markers in 264 patients who discontinued bisphosphonates. Fractures were recorded in 12.3%. Half were clinical vertebral fractures. We identified patients with a high-risk profile who should not discontinue treatment.

Objective: The optimal length of bisphosphonate discontinuation is unknown, as is the type of patient who could benefit from this approach. The objectives of the study were to analyze, in clinical practice, the incidence of fractures and associated risk factors, changes in bone mineral density (BMD) and bone turnover markers (BTMs) after discontinuation of bisphosphonates.

Methods: This observational retrospective study included 264 patients from 14 Spanish rheumatology departments. Postmenopausal women or men with osteoporosis received alendronate or risedronate for ≥ 5 years or zoledronate for ≥ 3 years and had discontinued treatment for ≥ 1 year or ≥ 2 years, respectively. Spinal X-rays were obtained before discontinuation and in suspected clinical vertebral fracture during follow-up. BMD and BTMs were determined before discontinuation and at different time points.

Results: The mean discontinuation time was 2.7 (± 6.7) years. Thirty-two patients (12.3%) had 36 fractures, mainly clinical vertebral fractures. The main risk factor for fracture was a high-risk profile (femoral neck T-score ≤ -2.5 and/or a history of fracture and/or multiple fractures [≥ 5 years]) before discontinuation. At 12 months, 10.41% of patients with high-risk profile experienced a fracture, being 0.8% and 1.08% in moderate- and low-risk patients, respectively. Significant BMD loss at the femoral neck and total hip was detected, with duration of discontinuation being the key factor. PINP was the marker with the greatest changes.

Conclusions: We identified a profile of patients with osteoporosis who should not discontinue bisphosphonates, owing to the possibility of fractures, especially vertebral, which are already evident the first year after discontinuation.

Keywords: Bisphosphonate; Drug holidays; Fragility fracture; High risk of fracture.

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Conflict of interest statement

Declarations. Conflicts of interest: A. Salmoral has received fees for lectures, courses or congress registration from Theramex, Gedeon-Ritcher and Amgen. P. Peris has received fees for lectures, consultant or congress registration from Amgen, UCB, FAES Pharma, Gedeon Richter Theramex y Rubió. C. López Medina has received honoraria as speaker fees/consulting from Abbvie, Janssen, Lilly, MSD, Novartis, Pfizer and UCB. I. Ros has received fees for lectures or courses from Amgen, UCB and Theramex. P. Aguado has received fees for lectures and/or advice from Abbie, Alexion, Amgen, Astra Zeneca, Eli Lilly, Faes, Gedeon-Richter, GP Pharm, Kyowa Kirin, MSD, Rubió and Theramex. S. Garcia has received fees for lectures or congress registration from Amgen, UCB, Gedeon Richter, Lilly, Abbvie, Grünenthal pharma, Italfarmaco and GP-pharm. L. Gifre declares receipt of lecture fees or congress registration from UCB, Amgen, Rubió, Stada, Theramex, Lilly, Abbie, Astellas, Kyowa Kyrin and Gebro. D. Cerdá has received fees for lectures, consultant or congress registration from Amgen, UCB, Lilly, Gebro, Italfármaco and Abbvie. F. J. Aguilar has received fees for lectures, consultant, editor and congress registration from Amgen, UCB, FAES Pharma, Gebro, Gedeon Richter, Theramex and Asacpharma. E. Costa has received congress funding from Rubió, Amgen and Kyowa-kirin. E. Casado has received fees for conferences and consultancies from Amgen, UCB, Theramex, STADA, Italfarmaco, FAES, Gedeon-Richter, GP-Pharm and Rubió; and has received congress funding from UCB, Amgen, Rubió and Theramex. A. Martínez-Ferrer has received fees for lectures or congress registration from Amgen, UCB, Gedeon Richter, Theramex and STADA. J. Graña has received fees for lectures, consultant or congress registration from Amgen, UCB, FAES Pharma, Gebro, Gedeon Richter and Theramex. N. Guañabens has received honoraria for advisory boards or lectures from Amgen, Eli Lilly, Theramex, Gedeon Richter and UCB.

References

    1. Black DM, Cummings SR, Karp DB, for the Fracture Intervention Trial Research Group et al (1996) Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Lancet 348:1535–1541 - DOI - PubMed
    1. Cummings SR, Black DM, Thompson DE, for the Fracture Intervention Trial Research Group et al (1998) Effect of Alendronate on Risk on Fracture in Women with low bone density but without vertebral Fractures. JAMA 280(24):2077–2082 - DOI - PubMed
    1. Black DM, Delmas PD, Eastell R et al for the HORIZON Pivotal Fracture Trial (2007) Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med 356:1809–1822 - DOI - PubMed
    1. McClung M, Harris ST, Miller PD et al (2013) Bisphosphonate therapy for osteoporosis: benefits, risks, and drug holiday. Am J Med 126:13–20 - DOI - PubMed
    1. Lin JH (1996) Bisphosphonates: a review of their pharmacokinetic properties. Bone 18(2):75–85 - DOI - PubMed

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