{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T20:22:58Z","timestamp":1791318178095,"version":"4.3.1"},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2020,12,1]],"date-time":"2020-12-01T00:00:00Z","timestamp":1606780800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"},{"start":{"date-parts":[[2021,9,28]],"date-time":"2021-09-28T00:00:00Z","timestamp":1632787200000},"content-version":"vor","delay-in-days":301,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100010740","name":"Asahi Kasei Pharma Corporation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010740","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008792","name":"Funding for original HORIZON trial: Novartis: Pharma","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008792","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010740","name":"Asahi Kasei Pharma Corporation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010740","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008792","name":"Novartis Pharma","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008792","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["asbmr.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,12,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Zoledronic acid (ZOL) as a yearly infusion is effective in reducing fracture risk. An acute-phase reaction (APR), consisting of flu-like symptoms within 3\u2009days after infusion, is commonly seen. The objective of this analysis was to investigate whether APR occurrence influences drug efficacy. This analysis uses data from the 3-year randomized clinical trial, Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly-Pivotal Fracture Trial (HORIZON-PFT). APRs were identified as adverse events within 3\u2009days of first infusion with higher frequency in ZOL than placebo. To compare mean 3-year change in bone mineral density (BMD) in ZOL versus placebo, among women with and without APR, t tests were used. Logistic regression was used to examine the relationship between APR occurrence and odds of incident morphometric vertebral fracture. Cox regression was used to determine the risk of nonvertebral and hip fractures for women with versus without APR. Logistic and Cox models were used to determine the risk of incident fracture in ZOL versus placebo for women with and without an APR. The analysis included 3862 women in the ZOL group and 3852 in placebo, with 42.4% in ZOL versus 11.8% in placebo experiencing an APR. The difference in BMD mean change for ZOL versus placebo was similar for women with and without an APR (all p interaction &amp;gt;0.10). Among ZOL women, those with APR had 51% lower vertebral fracture risk than those without (odds ratio [OR]\u00a0=\u00a00.49, p\u00a0&amp;lt;\u20090.001). A similar but nonsignificant trend was observed for nonvertebral and hip fracture (relative hazard [RH]\u00a0=\u00a00.82, p\u2009=\u00a00.10; RH\u00a0=\u00a00.70, p\u2009=\u00a00.22, respectively). There was a greater treatment-related reduction in vertebral fracture risk among women with APR (OR\u00a0=\u00a00.19) than those without (OR\u00a0=\u00a00.38) (p interaction\u00a0=\u00a00.01). Our results suggest that women starting ZOL who experience an APR will have a larger reduction in vertebral fracture risk with ZOL. \u00a9 2021 American Society for Bone and Mineral Research (ASBMR).<\/jats:p>","DOI":"10.1002\/jbmr.4434","type":"journal-article","created":{"date-parts":[[2021,9,29]],"date-time":"2021-09-29T01:29:41Z","timestamp":1632878981000},"page":"21-28","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["The Interaction of Acute-Phase Reaction and Efficacy for Osteoporosis After Zoledronic Acid: HORIZON Pivotal Fracture Trial"],"prefix":"10.1093","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5318-7575","authenticated-orcid":false,"given":"Dennis M.","family":"Black","sequence":"first","affiliation":[{"name":"Department of Epidemiology and Biostatistics University of California, San Francisco San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6021-5458","authenticated-orcid":false,"given":"Ian R.","family":"Reid","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Auckland Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3091-8205","authenticated-orcid":false,"given":"Nicola","family":"Napoli","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Bone and Mineral Diseases, Musculoskeletal Research Center Washington University School of Medicine St. Louis MO USA"},{"name":"Division of Endocrinology and Diabetes University Campus Bio-Medico di Roma Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1153-828X","authenticated-orcid":false,"given":"Susan K.","family":"Ewing","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics University of California, San Francisco San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6599-6185","authenticated-orcid":false,"given":"Masataka","family":"Shiraki","sequence":"additional","affiliation":[{"name":"Research Institute and Practice for Involutional Diseases Nagano Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshitaka","family":"Nakamura","sequence":"additional","affiliation":[{"name":"National Center for Global Health and Medicine Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhiro","family":"Takeuchi","sequence":"additional","affiliation":[{"name":"Okinaka Memorial Institute for Medical Research Tokyo Japan"},{"name":"Toranomon Hospital Endocrine Center Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4750-9125","authenticated-orcid":false,"given":"Anne L.","family":"Schafer","sequence":"additional","affiliation":[{"name":"Endocrine Research Unit San Francisco Veterans Affairs Health Care System San Francisco CA USA"},{"name":"Department of Medicine University of California, San Francisco San Francisco CA USA"},{"name":"Department of Epidemiology and Biostatistics University of California, San Francisco San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6889-9636","authenticated-orcid":false,"given":"Tiffany Y.","family":"Kim","sequence":"additional","affiliation":[{"name":"Endocrine Research Unit San Francisco Veterans Affairs Health Care System San Francisco CA USA"},{"name":"Department of Medicine University of California, San Francisco San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0752-4408","authenticated-orcid":false,"given":"Jane A.","family":"Cauley","sequence":"additional","affiliation":[{"name":"Department of Epidemiology Graduate School of Public Health, University of Pittsburgh Pittsburgh PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,9,28]]},"reference":[{"issue":"18","key":"2024012714042861100_jbmr4434-bib-0001","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":"9","key":"2024012714042861100_jbmr4434-bib-0002","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1056\/NEJMoa011807","article-title":"Intravenous zoledronic acid in postmenopausal women with low bone mineral density","volume":"346","author":"Reid","year":"2002","journal-title":"N Engl J 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