Thiazide-associated hyponatremia attenuates the fracture-protective effect of thiazide: A population-based study
Thiazide, a first-line therapy for hypertension, lowers blood pressure, increases bone mineral density, and reduces the risk of fractures. However, hyponatremia, an adverse effect of thiazide, is associated with increased risk of osteoporosis and fractures. It is currently unclear whether thiazide-a...
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| creator | Yang, Lii-Jia Wu, Ping-Hsun Huang, Teng-Hui Lin, Ming-Yen Tsai, Jer-Chia |
| description | Thiazide, a first-line therapy for hypertension, lowers blood pressure, increases bone mineral density, and reduces the risk of fractures. However, hyponatremia, an adverse effect of thiazide, is associated with increased risk of osteoporosis and fractures. It is currently unclear whether thiazide-associated hyponatremia (TAH) outweighs the protective effects of thiazide.
Using data from Taiwan's National Health Insurance Research Database, we identified patients who were prescribed thiazide between 1998 and 2010. Those diagnosed with hyponatremia within three years after initiation of thiazide were selected for the TAH group. Thiazide users without hyponatremia were selected for the control group. The association between TAH and fracture risk was further evaluated using multivariable Cox regression models adjusted for comorbidities and medications. Subjects were followed up from the index date until the appearance of a fracture, death, or the end of a 3-year period.
A total of 1212 patients were included in the TAH group, matched with 4848 patients in the control group. The incidence rate of fracture was higher in the TAH group than in the control group (31.4 versus 20.6 per 1000 person-years). TAH was associated with a higher risk of total fractures (adjusted hazard ratio [aHR]: 1.47, 95% confidence interval [CI] = 1.15-1.88), vertebra fractures (aHR: 1.84, 95% CI = 1.12-3.01), and hip fractures (aHR: 1.66, 95% CI = 1.12-2.46) after controlling for comorbidities and other medications.
Thiazide users with hyponatremia have a higher risk of fracture than thiazide users without hyponatremia. The fracture-protective effect of thiazide is attenuated by TAH. |
| doi_str_mv | 10.1371/journal.pone.0208712 |
| format | Article |
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Using data from Taiwan's National Health Insurance Research Database, we identified patients who were prescribed thiazide between 1998 and 2010. Those diagnosed with hyponatremia within three years after initiation of thiazide were selected for the TAH group. Thiazide users without hyponatremia were selected for the control group. The association between TAH and fracture risk was further evaluated using multivariable Cox regression models adjusted for comorbidities and medications. Subjects were followed up from the index date until the appearance of a fracture, death, or the end of a 3-year period.
A total of 1212 patients were included in the TAH group, matched with 4848 patients in the control group. The incidence rate of fracture was higher in the TAH group than in the control group (31.4 versus 20.6 per 1000 person-years). TAH was associated with a higher risk of total fractures (adjusted hazard ratio [aHR]: 1.47, 95% confidence interval [CI] = 1.15-1.88), vertebra fractures (aHR: 1.84, 95% CI = 1.12-3.01), and hip fractures (aHR: 1.66, 95% CI = 1.12-2.46) after controlling for comorbidities and other medications.
Thiazide users with hyponatremia have a higher risk of fracture than thiazide users without hyponatremia. The fracture-protective effect of thiazide is attenuated by TAH.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0208712</identifier><identifier>PMID: 30532245</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Aged ; Antihypertensive Agents - adverse effects ; Antihypertensive Agents - therapeutic use ; Biocompatibility ; Biology and Life Sciences ; Biomedical materials ; Blood pressure ; Bone density ; Bone mineral density ; Comorbidity ; Complications and side effects ; Confidence intervals ; Diagnosis ; Diuretics ; Dosage and administration ; Drug therapy ; Female ; Fractures ; Fractures (Injuries) ; Fractures, Bone - epidemiology ; Fractures, Bone - prevention & control ; Health risk assessment ; Heart failure ; Hip ; Hip fractures ; Humans ; Hypertension ; Hypertension - drug therapy ; Hypertension - epidemiology ; Hyponatremia ; Hyponatremia - epidemiology ; Hyponatremia - etiology ; Incidence ; Insurance ; Longitudinal Studies ; Male ; Medical research ; Medicine and Health Sciences ; Middle Aged ; National health insurance ; Nonsteroidal anti-inflammatory drugs ; Online databases ; Osteoporosis ; Patients ; Population studies ; Population-based studies ; Regression analysis ; Regression models ; Risk ; Risk Factors ; Spine ; Statistical analysis ; Thiazides ; Thiazides - adverse effects ; Thiazides - therapeutic use ; Vertebrae</subject><ispartof>PloS one, 2018-12, Vol.13 (12), p.e0208712-e0208712</ispartof><rights>COPYRIGHT 2018 Public Library of Science</rights><rights>2018 Yang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2018 Yang et al 2018 Yang et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-31dfaf0a2326fafe898befbee6bb7f225b5f1597d3034ad741353307202479f53</citedby><cites>FETCH-LOGICAL-c692t-31dfaf0a2326fafe898befbee6bb7f225b5f1597d3034ad741353307202479f53</cites><orcidid>0000-0002-0543-4313 ; 0000-0002-8194-4833</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6285977/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6285977/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30532245$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Blank, Robert Daniel</contributor><creatorcontrib>Yang, Lii-Jia</creatorcontrib><creatorcontrib>Wu, Ping-Hsun</creatorcontrib><creatorcontrib>Huang, Teng-Hui</creatorcontrib><creatorcontrib>Lin, Ming-Yen</creatorcontrib><creatorcontrib>Tsai, Jer-Chia</creatorcontrib><title>Thiazide-associated hyponatremia attenuates the fracture-protective effect of thiazide: A population-based study</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Thiazide, a first-line therapy for hypertension, lowers blood pressure, increases bone mineral density, and reduces the risk of fractures. However, hyponatremia, an adverse effect of thiazide, is associated with increased risk of osteoporosis and fractures. It is currently unclear whether thiazide-associated hyponatremia (TAH) outweighs the protective effects of thiazide.
Using data from Taiwan's National Health Insurance Research Database, we identified patients who were prescribed thiazide between 1998 and 2010. Those diagnosed with hyponatremia within three years after initiation of thiazide were selected for the TAH group. Thiazide users without hyponatremia were selected for the control group. The association between TAH and fracture risk was further evaluated using multivariable Cox regression models adjusted for comorbidities and medications. Subjects were followed up from the index date until the appearance of a fracture, death, or the end of a 3-year period.
A total of 1212 patients were included in the TAH group, matched with 4848 patients in the control group. The incidence rate of fracture was higher in the TAH group than in the control group (31.4 versus 20.6 per 1000 person-years). TAH was associated with a higher risk of total fractures (adjusted hazard ratio [aHR]: 1.47, 95% confidence interval [CI] = 1.15-1.88), vertebra fractures (aHR: 1.84, 95% CI = 1.12-3.01), and hip fractures (aHR: 1.66, 95% CI = 1.12-2.46) after controlling for comorbidities and other medications.
Thiazide users with hyponatremia have a higher risk of fracture than thiazide users without hyponatremia. The fracture-protective effect of thiazide is attenuated by TAH.</description><subject>Aged</subject><subject>Antihypertensive Agents - adverse effects</subject><subject>Antihypertensive Agents - therapeutic use</subject><subject>Biocompatibility</subject><subject>Biology and Life Sciences</subject><subject>Biomedical materials</subject><subject>Blood pressure</subject><subject>Bone density</subject><subject>Bone mineral density</subject><subject>Comorbidity</subject><subject>Complications and side effects</subject><subject>Confidence intervals</subject><subject>Diagnosis</subject><subject>Diuretics</subject><subject>Dosage and administration</subject><subject>Drug therapy</subject><subject>Female</subject><subject>Fractures</subject><subject>Fractures (Injuries)</subject><subject>Fractures, Bone - epidemiology</subject><subject>Fractures, Bone - prevention & control</subject><subject>Health risk assessment</subject><subject>Heart failure</subject><subject>Hip</subject><subject>Hip fractures</subject><subject>Humans</subject><subject>Hypertension</subject><subject>Hypertension - drug therapy</subject><subject>Hypertension - epidemiology</subject><subject>Hyponatremia</subject><subject>Hyponatremia - epidemiology</subject><subject>Hyponatremia - etiology</subject><subject>Incidence</subject><subject>Insurance</subject><subject>Longitudinal Studies</subject><subject>Male</subject><subject>Medical research</subject><subject>Medicine and Health Sciences</subject><subject>Middle Aged</subject><subject>National health insurance</subject><subject>Nonsteroidal anti-inflammatory drugs</subject><subject>Online databases</subject><subject>Osteoporosis</subject><subject>Patients</subject><subject>Population studies</subject><subject>Population-based studies</subject><subject>Regression analysis</subject><subject>Regression models</subject><subject>Risk</subject><subject>Risk Factors</subject><subject>Spine</subject><subject>Statistical analysis</subject><subject>Thiazides</subject><subject>Thiazides - adverse effects</subject><subject>Thiazides - therapeutic use</subject><subject>Vertebrae</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk9-L1DAQx4so3nn6H4gWBNGHrvnR9IcPwnL4Y-HgQE9fw7SdbLN0m16SHq5_vdnb3rGVe5A8ZJh85juZSSaKXlKyoDynHzZmtD10i8H0uCCMFDllj6JTWnKWZIzwx0f2SfTMuQ0hghdZ9jQ64cFiLBWn0XDVavijG0zAOVNr8NjE7S6Igre41RCD99iPwe9i32KsLNR-tJgM1nisvb7BGJUKVmxUIA5qH-NlPJhh7MBr0ycVuCDr_NjsnkdPFHQOX0z7WfTzy-er82_JxeXX1fnyIqmzkvmE00aBIsA4y4KBRVlUqCrErKpyxZiohKKizBtOeApNnlIuOCc5IyzNSyX4WfT6oDt0xsmpWU4yKmiehlYVgVgdiMbARg5Wb8HupAEtbx3GriVYr-sOpSApQJ2SjAqVikIVNMUGU0LLpg73IUHr05RtrLbY1Nh7C91MdH7S61auzY3MWBGqyIPAu0nAmusRnZdb7WrsOujRjLf3FjQjlO7RN_-gD1c3UWsIBehemZC33ovKpcgCQ_KsDNTiASqsJrx9HX6W0sE_C3g_CwiMx99-DaNzcvXj-_-zl7_m7NsjtkXofOtMN-6_j5uD6QGsrXHOorpvMiVyPxh33ZD7wZDTYISwV8cPdB90Nwn8L-pnCeQ</recordid><startdate>20181207</startdate><enddate>20181207</enddate><creator>Yang, Lii-Jia</creator><creator>Wu, Ping-Hsun</creator><creator>Huang, Teng-Hui</creator><creator>Lin, Ming-Yen</creator><creator>Tsai, Jer-Chia</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-0543-4313</orcidid><orcidid>https://orcid.org/0000-0002-8194-4833</orcidid></search><sort><creationdate>20181207</creationdate><title>Thiazide-associated hyponatremia attenuates the fracture-protective effect of thiazide: A population-based study</title><author>Yang, Lii-Jia ; Wu, Ping-Hsun ; Huang, Teng-Hui ; Lin, Ming-Yen ; Tsai, Jer-Chia</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-31dfaf0a2326fafe898befbee6bb7f225b5f1597d3034ad741353307202479f53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Aged</topic><topic>Antihypertensive Agents - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ, Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yang, Lii-Jia</au><au>Wu, Ping-Hsun</au><au>Huang, Teng-Hui</au><au>Lin, Ming-Yen</au><au>Tsai, Jer-Chia</au><au>Blank, Robert Daniel</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Thiazide-associated hyponatremia attenuates the fracture-protective effect of thiazide: A population-based study</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2018-12-07</date><risdate>2018</risdate><volume>13</volume><issue>12</issue><spage>e0208712</spage><epage>e0208712</epage><pages>e0208712-e0208712</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Thiazide, a first-line therapy for hypertension, lowers blood pressure, increases bone mineral density, and reduces the risk of fractures. However, hyponatremia, an adverse effect of thiazide, is associated with increased risk of osteoporosis and fractures. It is currently unclear whether thiazide-associated hyponatremia (TAH) outweighs the protective effects of thiazide.
Using data from Taiwan's National Health Insurance Research Database, we identified patients who were prescribed thiazide between 1998 and 2010. Those diagnosed with hyponatremia within three years after initiation of thiazide were selected for the TAH group. Thiazide users without hyponatremia were selected for the control group. The association between TAH and fracture risk was further evaluated using multivariable Cox regression models adjusted for comorbidities and medications. Subjects were followed up from the index date until the appearance of a fracture, death, or the end of a 3-year period.
A total of 1212 patients were included in the TAH group, matched with 4848 patients in the control group. The incidence rate of fracture was higher in the TAH group than in the control group (31.4 versus 20.6 per 1000 person-years). TAH was associated with a higher risk of total fractures (adjusted hazard ratio [aHR]: 1.47, 95% confidence interval [CI] = 1.15-1.88), vertebra fractures (aHR: 1.84, 95% CI = 1.12-3.01), and hip fractures (aHR: 1.66, 95% CI = 1.12-2.46) after controlling for comorbidities and other medications.
Thiazide users with hyponatremia have a higher risk of fracture than thiazide users without hyponatremia. The fracture-protective effect of thiazide is attenuated by TAH.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>30532245</pmid><doi>10.1371/journal.pone.0208712</doi><tpages>e0208712</tpages><orcidid>https://orcid.org/0000-0002-0543-4313</orcidid><orcidid>https://orcid.org/0000-0002-8194-4833</orcidid><oa>free_for_read</oa></addata></record> |
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| recordid | cdi_plos_journals_2151747128 |
| source | DOAJ, Directory of Open Access Journals; MEDLINE; Public Library of Science (PLoS) Journals Open Access; PubMed (Medline); Free E-Journal (出版社公開部分のみ）; Free Full-Text Journals in Chemistry |
| subjects | Aged Antihypertensive Agents - adverse effects Antihypertensive Agents - therapeutic use Biocompatibility Biology and Life Sciences Biomedical materials Blood pressure Bone density Bone mineral density Comorbidity Complications and side effects Confidence intervals Diagnosis Diuretics Dosage and administration Drug therapy Female Fractures Fractures (Injuries) Fractures, Bone - epidemiology Fractures, Bone - prevention & control Health risk assessment Heart failure Hip Hip fractures Humans Hypertension Hypertension - drug therapy Hypertension - epidemiology Hyponatremia Hyponatremia - epidemiology Hyponatremia - etiology Incidence Insurance Longitudinal Studies Male Medical research Medicine and Health Sciences Middle Aged National health insurance Nonsteroidal anti-inflammatory drugs Online databases Osteoporosis Patients Population studies Population-based studies Regression analysis Regression models Risk Risk Factors Spine Statistical analysis Thiazides Thiazides - adverse effects Thiazides - therapeutic use Vertebrae |
| title | Thiazide-associated hyponatremia attenuates the fracture-protective effect of thiazide: A population-based study |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-01T06%3A39%3A43IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Thiazide-associated%20hyponatremia%20attenuates%20the%20fracture-protective%20effect%20of%20thiazide:%20A%20population-based%20study&rft.jtitle=PloS%20one&rft.au=Yang,%20Lii-Jia&rft.date=2018-12-07&rft.volume=13&rft.issue=12&rft.spage=e0208712&rft.epage=e0208712&rft.pages=e0208712-e0208712&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0208712&rft_dat=%3Cgale_plos_%3EA564710769%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2151747128&rft_id=info:pmid/30532245&rft_galeid=A564710769&rft_doaj_id=oai_doaj_org_article_504aac40615f458f814ede4019dcbb70&rfr_iscdi=true |