{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T15:59:51Z","timestamp":1781625591083,"version":"3.54.5"},"reference-count":21,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2024,5,31]],"date-time":"2024-05-31T00:00:00Z","timestamp":1717113600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,5,31]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Previous studies have demonstrated that the administration of zoledronic acid (ZOL) once yearly for 3 years or once over 3 years, yields similar antifracture efficacy. Bone turnover markers can predict the antifracture efficacy of antiresorptive agents, with procollagen type 1\u00a0N-terminal propeptide (P1NP) being the most useful marker. In this retrospective cohort study, we explored the effects of intravenous dosing of ZOL guided by serum (S)-P1NP assessment on bone mineral density (BMD) and fractures. Consenting patients (N\u2009=\u2009202, mean age 68.2\u00a0years) with osteoporosis were treated with ZOL for an average of 4.4 (range 2-8) years. S-P1NP and BMD were measured at baseline and every 1-2\u00a0years. We assessed the number of subsequent vertebral and nonvertebral fractures in the 2-year time periods. The number of patients assessed was 202, 147, 69, and 29 at years 1-2, 3-4, 5-6, and 7-8, respectively. A new ZOL infusion was given if S-P1NP exhibited values above 35\u00a0\u03bcg\/L. BMD increased by 6.2% (SD 4.0) over the first 2 years and stabilized in years 2-8 (P\u2009&amp;lt;.05). Median S-P1NP exhibited an initial reduction from 58.0 to 31.3\u00a0\u03bcg\/L at year 2 and then increased to 39.0\u00a0\u03bcg\/L at years 7-8. Compared with fractures observed in the last 2 years before baseline, fracture rates exhibited consistent reductions, for vertebral fractures odds ratio (OR) [95% confidence interval]\u2009=\u20090.61 [0.47, 0.80], P\u2009&amp;lt;.001 and for nonvertebral fractures OR\u2009=\u20090.23 [0.18, 0.31], P\u2009&amp;lt;.001. In conclusion, intermittent dosing of intravenous ZOL based on the assessment of S-P1NP with cut-off at 35\u00a0\u03bcg\/L resulted in an initial increase followed by a stable BMD, suppression of S-P1NP, and stable reduction of fractures for 8\u00a0years. Only 39% of patients needed more than one infusion. This approach reduces healthcare costs and might also reduce the risk of rare side effects such as osteonecrosis of the jaw and atypical femoral fracture.<\/jats:p>","DOI":"10.1093\/jbmrpl\/ziae072","type":"journal-article","created":{"date-parts":[[2024,5,31]],"date-time":"2024-05-31T18:17:05Z","timestamp":1717179425000},"source":"Crossref","is-referenced-by-count":4,"title":["Intermittent dosing of zoledronic acid based on bone turnover marker assessment reduces vertebral and non-vertebral fractures"],"prefix":"10.1093","volume":"8","author":[{"given":"Tove Tveitan","family":"Borgen","sequence":"first","affiliation":[{"name":"Drammen Hospital Department of Rheumatology, , N-3004 Drammen, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sindre","family":"Lee-\u00d8deg\u00e5rd","sequence":"additional","affiliation":[{"name":"Morbid Obesity and Preventive Medicine, Oslo University Hospital Department of Endocrinology, , 0424 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara Fink","family":"Eriksen","sequence":"additional","affiliation":[{"name":"University of Aarhus Faculty of Medicine, , 8000 Aarhus, Denmark"},{"name":"Spesialistsenteret Pilestredet Park , 0176 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik Fink","family":"Eriksen","sequence":"additional","affiliation":[{"name":"Spesialistsenteret Pilestredet Park , 0176 Oslo, Norway"},{"name":"University of Oslo Faculty of Dentistry, , 1142 Blindern, Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,5,31]]},"reference":[{"issue":"4","key":"2024062706004485400_ref1","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1002\/jbmr.3355","article-title":"Treatment-related changes in bone turnover and fracture risk reduction in clinical trials of anti-resorptive drugs: a meta-regression","volume":"33","author":"Bauer","year":"2018","journal-title":"J Bone Miner Res"},{"issue":"2","key":"2024062706004485400_ref2","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1002\/jbmr.4178","article-title":"Treatment-related changes in bone turnover and fracture risk reduction in clinical trials of antiresorptive drugs: proportion of treatment effect explained","volume":"36","author":"Eastell","year":"2021","journal-title":"J Bone Miner Res"},{"issue":"5","key":"2024062706004485400_ref3","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1007\/s00223-014-9842-y","article-title":"A meta-analysis of reference markers of bone turnover for prediction of fracture","volume":"94","author":"Johansson","year":"2014","journal-title":"Calcif Tissue Int"},{"issue":"6","key":"2024062706004485400_ref4","doi-asserted-by":"crossref","first-page":"e10633","DOI":"10.1002\/jbm4.10633","article-title":"Target values and daytime variation of bone turnover markers in monitoring osteoporosis treatment after fractures","volume":"6","author":"Borgen","year":"2022","journal-title":"JBMR Plus"},{"issue":"sup2","key":"2024062706004485400_ref5","doi-asserted-by":"crossref","first-page":"32","DOI":"10.3109\/13697137.2015.1099092","article-title":"Bisphosphonate drug holidays \u2013 when, why and for how long?","volume":"18","author":"Anagnostis","year":"2015","journal-title":"Climacteric"},{"issue":"2","key":"2024062706004485400_ref6","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1210\/jc.2012-2868","article-title":"Reduction in the risk of clinical fractures after a single dose of zoledronic acid 5 milligrams","volume":"98","author":"Reid","year":"2013","journal-title":"J Clin Endocrinol Metab"},{"issue":"36","key":"2024062706004485400_ref7","doi-asserted-by":"crossref","first-page":"E1130","DOI":"10.1503\/cmaj.161207","article-title":"Duration of antiresorptive activity of zoledronate in postmenopausal women with osteopenia: a randomized, controlled multidose trial","volume":"189","author":"Grey","year":"2017","journal-title":"CMAJ"},{"issue":"10","key":"2024062706004485400_ref8","doi-asserted-by":"crossref","first-page":"2251","DOI":"10.1002\/jbmr.103","article-title":"Prolonged antiresorptive activity of zoledronate: a randomized, controlled trial","volume":"25","author":"Grey","year":"2010","journal-title":"J Bone Miner Res"},{"issue":"6","key":"2024062706004485400_ref9","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1001\/jamainternmed.2015.0747","article-title":"Efficacy and safety of single-dose zoledronic acid for osteoporosis in frail elderly women: a randomized clinical trial","volume":"175","author":"Greenspan","year":"2015","journal-title":"JAMA Intern Med"},{"issue":"4","key":"2024062706004485400_ref10","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1007\/s00432-014-1853-6","article-title":"Risk factors influencing the duration of treatment with bisphosphonates until occurrence of an osteonecrosis of the jaw in 963 cancer patients","volume":"141","author":"Gabbert","year":"2015","journal-title":"J Cancer Res Clin Oncol"},{"issue":"10","key":"2024062706004485400_ref11","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1056\/NEJMc1403799","article-title":"Risk of atypical femoral fracture during and after bisphosphonate use","volume":"371","author":"Schilcher","year":"2014","journal-title":"N Engl J Med"},{"issue":"8","key":"2024062706004485400_ref12","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1002\/jbmr.1644","article-title":"Relationship of changes in total hip bone mineral density to vertebral and nonvertebral fracture risk in women with postmenopausal osteoporosis treated with once-yearly zoledronic acid 5 mg: the HORIZON-pivotal fracture trial (PFT)","volume":"27","author":"Jacques","year":"2012","journal-title":"J Bone Miner Res"},{"issue":"11","key":"2024062706004485400_ref13","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1016\/S2213-8587(17)30184-5","article-title":"Use of bone turnover markers in postmenopausal osteoporosis","volume":"5","author":"Eastell","year":"2017","journal-title":"Lancet Diabetes Endocrinol"},{"issue":"9","key":"2024062706004485400_ref14","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1002\/jbmr.5650080915","article-title":"Vertebral fracture assessment using a semiquantitative technique","volume":"8","author":"Genant","year":"1993","journal-title":"J Bone Miner Res"},{"issue":"1","key":"2024062706004485400_ref15","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/s00198-015-3145-7","article-title":"Response of bone turnover markers to three oral bisphosphonate therapies in postmenopausal osteoporosis: the TRIO study","volume":"27","author":"Naylor","year":"2016","journal-title":"Osteoporos Int"},{"issue":"5","key":"2024062706004485400_ref16","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1002\/jbmr.3654","article-title":"Comparison of BMD changes and bone formation marker levels 3 years after bisphosphonate discontinuation: FLEX and HORIZON-PFT extension I trials","volume":"34","author":"Kim","year":"2019","journal-title":"J Bone Miner Res"},{"issue":"18","key":"2024062706004485400_ref17","doi-asserted-by":"crossref","first-page":"1809","DOI":"10.1056\/NEJMoa067312","article-title":"Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis","volume":"356","author":"Black","year":"2007","journal-title":"N Engl J Med"},{"issue":"13","key":"2024062706004485400_ref18","first-page":"1288","article-title":"Fracture prevention with zoledronate in older women with osteopenia","volume":"380","author":"Reid","year":"2019","journal-title":"Reply N Engl J Med"},{"issue":"4","key":"2024062706004485400_ref19","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/S2213-8587(24)00003-2","article-title":"Duration of fracture prevention after zoledronate treatment in women with osteopenia: observational follow-up of a 6-year randomised controlled trial to 10 years","volume":"12","author":"Reid","year":"2024","journal-title":"Lancet Diabetes Endocrinol"},{"issue":"1","key":"2024062706004485400_ref20","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1007\/s11657-017-0375-7","article-title":"Exploring methods for comparing the real-world effectiveness of treatments for osteoporosis: adjusted direct comparisons versus using patients as their own control","volume":"12","author":"Karlsson","year":"2017","journal-title":"Arch Osteoporos"},{"issue":"1","key":"2024062706004485400_ref21","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1007\/s11657-018-0439-3","article-title":"Real-world effectiveness of osteoporosis therapies for fracture reduction in post-menopausal women","volume":"13","author":"Yusuf","year":"2018","journal-title":"Arch Osteoporos"}],"container-title":["JBMR Plus"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jbmrplus\/advance-article-pdf\/doi\/10.1093\/jbmrpl\/ziae072\/58029427\/ziae072.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jbmrplus\/article-pdf\/8\/7\/ziae072\/58342761\/ziae072.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jbmrplus\/article-pdf\/8\/7\/ziae072\/58342761\/ziae072.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,27]],"date-time":"2024-06-27T06:07:09Z","timestamp":1719468429000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jbmrplus\/article\/doi\/10.1093\/jbmrpl\/ziae072\/7685663"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,31]]},"references-count":21,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2024,5,31]]}},"URL":"https:\/\/doi.org\/10.1093\/jbmrpl\/ziae072","relation":{},"ISSN":["2473-4039"],"issn-type":[{"value":"2473-4039","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,7]]},"published":{"date-parts":[[2024,5,31]]},"article-number":"ziae072"}}