{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T12:21:51Z","timestamp":1765887711193},"reference-count":14,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2015,7,30]],"date-time":"2015-07-30T00:00:00Z","timestamp":1438214400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Intern Med"],"published-print":{"date-parts":[[2016,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Data from observational studies have suggested that thiazide diuretics protect against fractures. Few studies have investigated time frames from initiation of treatment to fracture occurrence.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To evaluate the time to spinal, hip, femur, wrist and upper extremity fracture occurrence before and after thiazide exposure.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A matched retrospective cohort study of patient information from national Danish patient databases was conducted. Patients with reimbursed prescriptions for noncompounded thiazide diuretics with potassium supplementation (Anatomical Therapeutic Chemical classification system code C03<jats:styled-content style=\"fixed-case\">AB<\/jats:styled-content>) between 1996 and 2011 were matched with nonexposed control subjects by date of birth and gender. Weekly odds ratios (<jats:styled-content style=\"fixed-case\">OR<\/jats:styled-content>s) of fracture occurrence and total incidence rates (<jats:styled-content style=\"fixed-case\">IR<\/jats:styled-content>s) and incidence rate ratios (<jats:styled-content style=\"fixed-case\">IRR<\/jats:styled-content>s) of fracture risk were calculated for the periods before treatment initiation, weeks 1\u201342 and weeks 43\u2013780.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 1\u00a0602\u00a0141 \u2018thiazide exposure periods\u2019 (46\u00a08271 individuals) and 1\u00a0530\u00a0233 \u2018nonexposure periods\u2019 (655\u00a0399 individuals) were included in the analysis. Thiazide use was associated with factors of increased <jats:italic>de novo<\/jats:italic> fracture risk. Weekly adjusted fracture risk between exposure and nonexposure was increased prior to commencing thiazide therapy, further increasing from weeks 1\u201342\u00a0weeks and then decreasing gradually from weeks 43\u2013780. There was a decreasing trend in total age\u2010adjusted risk during these periods: <jats:styled-content style=\"fixed-case\">IRR<\/jats:styled-content> [95% confidence interval 1.44 [1.42; 1.47], 1.27 [1.24; 1.29] and 1.14 [1.11; 1.18], respectively. Prescription patterns showed several treatment breaks amongst thiazide users.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>It appears that thiazides reduce the background risk of fracture that is increased prior to commencing therapy. Long duration and continuity of thiazide exposure seems to be important to obtain this protective effect on fracture risk, but we have found in this study that this approach is not always used in clinical practice.<\/jats:p><\/jats:sec>","DOI":"10.1111\/joim.12397","type":"journal-article","created":{"date-parts":[[2015,7,30]],"date-time":"2015-07-30T06:33:07Z","timestamp":1438237987000},"page":"110-122","source":"Crossref","is-referenced-by-count":20,"title":["Continuous and long\u2010term treatment is more important than dosage for the protective effect of thiazide use on bone metabolism and fracture risk"],"prefix":"10.1111","volume":"279","author":[{"given":"C.","family":"Kruse","sequence":"first","affiliation":[{"name":"Department of Endocrinology Aalborg University Hospital Aalborg Denmark"},{"name":"Clinical Institute Aalborg University Hospital Aalborg Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P.","family":"Eiken","sequence":"additional","affiliation":[{"name":"Department of Cardiology Nephrology and Endocrinology Nordsj\u00e6llands Hospital Hilleroed Hilleroed Denmark"},{"name":"Faculty of Health Sciences University of Copenhagen Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P.","family":"Vestergaard","sequence":"additional","affiliation":[{"name":"Department of Endocrinology Aalborg University Hospital Aalborg Denmark"},{"name":"Clinical Institute Aalborg University Hospital Aalborg Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,7,30]]},"reference":[{"key":"e_1_2_8_2_1","first-page":"CD005195","article-title":"Thiazide diuretics and the risk of hip fracture","author":"Aung K","year":"2011","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2005.09.026"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00198-006-0259-y"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-133-7-200010030-00010"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2362.2003.01103.x"},{"key":"e_1_2_8_7_1","unstructured":"Statistics Denmark http:\/\/www.dst.dk\/da\/Statistik\/emner\/befolkning-og-befolkningsfremskrivning\/folketal.aspx"},{"key":"e_1_2_8_8_1","unstructured":"Own data.7.3 million C03AB prescriptions vs. 87 000 C03AA prescriptions between 1996 and 2011."},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0026-0495(82)90115-9"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00198-012-2053-3"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9343(00)00510-6"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1359\/JBMR.051003"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004670050398"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwf007"},{"key":"e_1_2_8_15_1","first-page":"3741","article-title":"[Landspatientregisteret. 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