{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T13:30:42Z","timestamp":1793712642511,"version":"4.6.1"},"reference-count":88,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,3,9]],"date-time":"2021-03-09T00:00:00Z","timestamp":1615248000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Bisphosphonates are first-line therapy for osteoporosis, with alendronate, risedronate, and zoledronate as the main treatments used globally. After one year of therapy, bisphosphonates are retained in bone for extended periods with extended anti-fracture effects after discontinuation. Due to this continued fracture protection and the potential for rare adverse events associated with long-term use (atypical femoral fractures and osteonecrosis of the jaw), a drug holiday of two to three years is recommended for most patients after long-term bisphosphonate therapy. The recommendation for a drug holiday up to three years is derived primarily from extensions of pivotal trials with alendronate and zoledronate and select surrogate marker studies. However, certain factors may modify the duration of bisphosphonate effects on a drug holiday and warrant consideration when determining an appropriate time off-therapy. In this narrative review, we recall what is currently known about drug holidays and discuss what we believe to be the primary considerations and areas for future research regarding drug holiday duration: total bisphosphonate exposure, type of bisphosphonate used, bone mineral density and falls risk, and patient sex and body weight.<\/jats:p>","DOI":"10.3390\/jcm10051140","type":"journal-article","created":{"date-parts":[[2021,3,9]],"date-time":"2021-03-09T04:33:51Z","timestamp":1615264431000},"page":"1140","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Duration of Bisphosphonate Drug Holidays in Osteoporosis Patients: A Narrative Review of the Evidence and Considerations for Decision-Making"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1122-0071","authenticated-orcid":false,"given":"Kaleen N.","family":"Hayes","sequence":"first","affiliation":[{"name":"Dalla Lana School of Public Health, University of Toronto, Toronto, ON M5T 1P8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0119-1588","authenticated-orcid":false,"given":"Elizabeth M.","family":"Winter","sequence":"additional","affiliation":[{"name":"Center for Bone Quality, Division of Endocrinology, Department of Internal Medicine, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8584-9649","authenticated-orcid":false,"given":"Suzanne M.","family":"Cadarette","sequence":"additional","affiliation":[{"name":"Dalla Lana School of Public Health, University of Toronto, Toronto, ON M5T 1P8, Canada"},{"name":"Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON M5S 3M2, Canada"},{"name":"Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7082-8530","authenticated-orcid":false,"given":"Andrea M.","family":"Burden","sequence":"additional","affiliation":[{"name":"Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON M5S 3M2, Canada"},{"name":"Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zurich, 8093 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/1742-4933-2-14","article-title":"Osteoporosis, Inflammation and Ageing","volume":"2","author":"Ginaldi","year":"2005","journal-title":"Immun. 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