{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T16:51:33Z","timestamp":1779123093503,"version":"3.51.4"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2024,3,14]],"date-time":"2024-03-14T00:00:00Z","timestamp":1710374400000},"content-version":"vor","delay-in-days":1585,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"},{"start":{"date-parts":[[2020,11,11]],"date-time":"2020-11-11T00:00:00Z","timestamp":1605052800000},"content-version":"am","delay-in-days":366,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#am"},{"start":{"date-parts":[[2019,12,12]],"date-time":"2019-12-12T00:00:00Z","timestamp":1576108800000},"content-version":"vor","delay-in-days":31,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000005","name":"Department of Defense","doi-asserted-by":"publisher","award":["NIA2P30AG028716-06"],"award-info":[{"award-number":["NIA2P30AG028716-06"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"Department of Defense","doi-asserted-by":"publisher","award":["NIAK24AG049077-0IAI"],"award-info":[{"award-number":["NIAK24AG049077-0IAI"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"Department of Defense","doi-asserted-by":"publisher","award":["W81XWH-12-2-0093"],"award-info":[{"award-number":["W81XWH-12-2-0093"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["NIA2P30AG028716\u201006"],"award-info":[{"award-number":["NIA2P30AG028716\u201006"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["NIAK24AG049077\u20100IAI"],"award-info":[{"award-number":["NIAK24AG049077\u20100IAI"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["W81XWH\u201012\u20102\u20100093"],"award-info":[{"award-number":["W81XWH\u201012\u20102\u20100093"]}],"id":[{"id":"10.13039\/100000005","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>Acetylcholinesterase inhibitors (AChEIs) have been noted to increase bone density and quality in mice. Human studies are limited but suggest an association with improved bone healing after hip fracture. We examined the relationship between AChEI use and fracture risk in a national cohort of 360,015 male veterans aged 65 to 99\u2009years with dementia but without prior fracture using Veterans Affairs (VA) hospital, Medicare, and pharmacy records from 2000 to 2010. Diagnosis of dementia, any clinical fracture (excluding facial and digital), comorbidities, and medications were identified using ICD-9 and drug class codes. Cox proportional hazard models considering AChEI use as a time-varying covariate and adjusting for fall and fracture risk factors compared the time-to-fracture in AChEI users versus non-AChEI users. Potential confounders included demographics (age, race, body mass index), comorbidities associated with fracture or falls (diabetes, lung disease, stroke, Parkinson's, seizures, etc.) and medications associated with fracture or falls (bisphosphonates, glucocorticoids, androgen deprivation therapy [ADT], proton pump inhibitors [PPIs], selective serotonin receptor inhibitors [SSRIs], etc.). Competing mortality risk was considered using the methods of Fine and Gray. To account for persistent effects on bone density or quality that might confer protection after stopping the medication, we completed a secondary analysis using the medication possession ratio (MPR) as a continuous variable in logistic regression models and also compared MPR increments of 10% to minimal\/no use (MPR 0 to &amp;lt;0.10). Among older veterans with diagnosis of dementia, 20.1% suffered a fracture over an average of 4.6\u2009years of follow-up. Overall, 42.3% of the cohort were prescribed AChEIs during the study period. The hazard of any fracture among AChEI users compared with those on other\/no dementia medications was significantly lower in fully adjusted models (hazard ratio [HR] =\u20090.81; 95% confidence interval [CI] 0.75\u20130.88). After considering competing mortality risk, fracture risk remained 18% lower in veterans using AChEIs (HR = 0.82; 95% CI 0.76\u20130.89). \u00a9 2019 American Society for Bone and Mineral Research. Published 2019. This article is a U.S. Government work and is in the public domain in the USA.<\/jats:p>","DOI":"10.1002\/jbmr.3916","type":"journal-article","created":{"date-parts":[[2019,11,11]],"date-time":"2019-11-11T22:01:51Z","timestamp":1573509711000},"page":"440-445","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Acetylcholinesterase Inhibitors Are Associated with Reduced Fracture Risk among Older Veterans with Dementia"],"prefix":"10.1093","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4053-3608","authenticated-orcid":false,"given":"Abayomi N","family":"Ogunwale","sequence":"first","affiliation":[{"name":"Durham Veterans Affairs Medical Center Durham NC USA"},{"name":"Department of Medicine, Duke University Durham NC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cathleen S","family":"Colon-Emeric","sequence":"additional","affiliation":[{"name":"Durham Veterans Affairs Medical Center Durham NC USA"},{"name":"Department of Medicine, Duke University Durham NC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard","family":"Sloane","sequence":"additional","affiliation":[{"name":"Durham Veterans Affairs Medical Center Durham NC USA"},{"name":"Department of Medicine, Duke University Durham NC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert A","family":"Adler","sequence":"additional","affiliation":[{"name":"Virginia Commonwealth University School of Medicine Richmond VA USA"},{"name":"Hunter Holmes McGuire Veterans Affairs Medical Center Richmond VA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenneth W","family":"Lyles","sequence":"additional","affiliation":[{"name":"Durham Veterans Affairs Medical Center Durham NC USA"},{"name":"Department of Medicine, Duke University Durham NC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6909-4418","authenticated-orcid":false,"given":"Richard H","family":"Lee","sequence":"additional","affiliation":[{"name":"Durham Veterans Affairs Medical Center Durham NC USA"},{"name":"Department of Medicine, Duke University Durham NC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2019,11,11]]},"reference":[{"issue":"11 Suppl 18","key":"2024031503440988300_jbmr3916-bib-0001","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1017\/S1092852900014164","article-title":"The interplay of neurotransmitters in Alzheimer's disease","volume":"10","author":"Frances","year":"2005","journal-title":"CNS Spectr."},{"issue":"10","key":"2024031503440988300_jbmr3916-bib-0002","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1111\/j.1532-5415.1995.tb07005.x","article-title":"Bone density, vitamin D nutrition, and parathyroid hormone levels in women with dementia","volume":"43","author":"Kipen","year":"1995","journal-title":"J Am Geriatr Soc."},{"issue":"2","key":"2024031503440988300_jbmr3916-bib-0003","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1177\/2151458510389463","article-title":"Dementia and hip fractures: development of a pathogenic framework for understanding and studying risk","volume":"1","author":"Friedman","year":"2010","journal-title":"Geriatr Orthop Surg Rehabil."},{"issue":"5","key":"2024031503440988300_jbmr3916-bib-0004","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1212\/WNL.0b013e31829d8599","article-title":"Preclinical Alzheimer disease and risk of falls","volume":"81","author":"Stark","year":"2013","journal-title":"Neurology."},{"issue":"2","key":"2024031503440988300_jbmr3916-bib-0005","first-page":"124","article-title":"Cholinergic regulation of bone","volume":"13","author":"Eimar","year":"2013","journal-title":"J Musculoskelet Neuronal Interact."},{"issue":"4","key":"2024031503440988300_jbmr3916-bib-0006","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.3233\/JAD-160658","article-title":"Early evidence of low bone density and decreased serotonergic synthesis in the dorsal raphe of a tauopathy model of Alzheimer's disease","volume":"55","author":"Dengler-Crish","year":"2017","journal-title":"J Alzheimers Dis."},{"key":"2024031503440988300_jbmr3916-bib-0007","doi-asserted-by":"crossref","first-page":"S312","DOI":"10.4103\/0019-5545.224472","article-title":"Clinical practice guidelines for management of dementia","volume":"60","author":"Shaji","year":"2018","journal-title":"Indian J Psychiatry."},{"issue":"8","key":"2024031503440988300_jbmr3916-bib-0008","doi-asserted-by":"crossref","first-page":"1540","DOI":"10.1111\/jgs.14226","article-title":"Treatment patterns with antidementia drugs in the United States: Medicare cohort study","volume":"64","author":"Koller","year":"2016","journal-title":"J Am Geriatr Soc."},{"issue":"5","key":"2024031503440988300_jbmr3916-bib-0009","doi-asserted-by":"crossref","first-page":"370","DOI":"10.7326\/0003-4819-148-5-200803040-00008","article-title":"Current pharmacologic treatment of dementia: a clinical practice guideline from the American College of Physicians and the American Academy of Family Physicians","volume":"148","author":"Qaseem","year":"2008","journal-title":"Ann Intern Med."},{"key":"2024031503440988300_jbmr3916-bib-0010","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.bone.2015.12.009","article-title":"Donepezil regulates energy metabolism and favors bone mass accrual","volume":"84","author":"Eimar","year":"2016","journal-title":"Bone."},{"issue":"1","key":"2024031503440988300_jbmr3916-bib-0011","doi-asserted-by":"crossref","first-page":"e00013","DOI":"10.1016\/j.heliyon.2015.e00013","article-title":"Donepezil prevents RANK-induced bone loss via inhibition of osteoclast differentiation by downregulating acetylcholinesterase","volume":"1","author":"Sato","year":"2015","journal-title":"Heliyon."},{"issue":"2","key":"2024031503440988300_jbmr3916-bib-0012","first-page":"69","article-title":"Effect of acetylcholinesterase inhibitors on post-surgical complications and mortality following a hip fracture: a cohort study","volume":"17","author":"Tamimi","year":"2017","journal-title":"J Musculoskelet Neuronal Interact."},{"issue":"7","key":"2024031503440988300_jbmr3916-bib-0013","doi-asserted-by":"crossref","first-page":"1518","DOI":"10.1002\/jbmr.1616","article-title":"Acetylcholinesterase inhibitors and the risk of hip fracture in Alzheimer's disease patients: a case-control study","volume":"27","author":"Tamimi","year":"2012","journal-title":"J Bone Miner Res."},{"issue":"4","key":"2024031503440988300_jbmr3916-bib-0014","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1007\/s00198-017-4346-z","article-title":"Acetylcholinesterase inhibitors and the risk of osteoporotic fractures: nested case-control study","volume":"29","author":"Tamimi","year":"2018","journal-title":"Osteoporos Int."},{"issue":"12","key":"2024031503440988300_jbmr3916-bib-0015","doi-asserted-by":"crossref","first-page":"1749","DOI":"10.1016\/j.mayocp.2018.06.024","article-title":"Limited osteoporosis screening effectiveness due to low treatment rates in a national sample of older men","volume":"93","author":"Colon-Emeric","year":"2018","journal-title":"Mayo Clin Proc."},{"issue":"3","key":"2024031503440988300_jbmr3916-bib-0016","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1111\/jgs.15256","article-title":"Competing risks of fracture and death in older adults with chronic kidney disease","volume":"66","author":"Hall","year":"2018","journal-title":"J Am Geriatr Soc."},{"issue":"1","key":"2024031503440988300_jbmr3916-bib-0017","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1210\/jc.2017-01593","article-title":"Clinical fractures among older men with diabetes are mediated by diabetic complications","volume":"103","author":"Lee","year":"2018","journal-title":"J Clin Endocrinol Metab."},{"issue":"7\u20138","key":"2024031503440988300_jbmr3916-bib-0018","doi-asserted-by":"crossref","first-page":"1280","DOI":"10.1345\/aph.1H018","article-title":"Measurement of adherence in pharmacy administrative databases: a proposal for standard definitions and preferred measures","volume":"40","author":"Hess","year":"2006","journal-title":"Ann Pharmacother."},{"issue":"11","key":"2024031503440988300_jbmr3916-bib-0019","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.1097\/01.mlr.0000182534.19832.83","article-title":"Coding algorithms for defining comorbidities in ICD-9-CM and ICD-10 administrative data","volume":"43","author":"Quan","year":"2005","journal-title":"Med Care."},{"issue":"4","key":"2024031503440988300_jbmr3916-bib-0020","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1111\/1475-6773.00165","article-title":"Improved comorbidity adjustment for predicting mortality in Medicare populations","volume":"38","author":"Schneeweiss","year":"2003","journal-title":"Health Serv Res."},{"issue":"1","key":"2024031503440988300_jbmr3916-bib-0021","first-page":"CD005593","article-title":"Cholinesterase inhibitors for Alzheimer's disease","author":"Birks","year":"2006","journal-title":"Cochrane Database Syst Rev"},{"issue":"4","key":"2024031503440988300_jbmr3916-bib-0022","first-page":"454","article-title":"Acetylcholinesterase inhibitors and healing of hip fracture in Alzheimer's disease patients: a retrospective cohort study","volume":"13","author":"Eimar","year":"2013","journal-title":"J Musculoskelet Neuronal Interact."},{"issue":"6","key":"2024031503440988300_jbmr3916-bib-0023","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1111\/j.1365-2826.2008.01732.x","article-title":"Central control of bone remodelling","volume":"20","author":"Takeda","year":"2008","journal-title":"J Neuroendocrinol."},{"issue":"38","key":"2024031503440988300_jbmr3916-bib-0024","doi-asserted-by":"crossref","first-page":"15455","DOI":"10.1073\/pnas.1206061109","article-title":"Skeletal parasympathetic innervation communicates central IL-1 signals regulating bone mass accrual","volume":"109","author":"Bajayo","year":"2012","journal-title":"Proc Natl Acad Sci USA."},{"issue":"3","key":"2024031503440988300_jbmr3916-bib-0025","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.cmet.2010.01.005","article-title":"Signaling through the M(3) muscarinic receptor favors bone mass accrual by decreasing sympathetic activity","volume":"11","author":"Shi","year":"2010","journal-title":"Cell Metab."},{"key":"2024031503440988300_jbmr3916-bib-0026","doi-asserted-by":"crossref","first-page":"45597","DOI":"10.1038\/srep45597","article-title":"The nicotinic acetylcholine receptor alpha7 subunit is an essential negative regulator of bone mass","volume":"7","author":"Mito","year":"2017","journal-title":"Sci Rep."},{"issue":"1","key":"2024031503440988300_jbmr3916-bib-0027","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.intimp.2015.06.029","article-title":"Bone status of adult female butyrylcholinesterase gene-deficient mice","volume":"29","author":"Haupt","year":"2015","journal-title":"Int Immunopharmacol."},{"issue":"21\u201322","key":"2024031503440988300_jbmr3916-bib-0028","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1016\/j.lfs.2012.07.024","article-title":"Quantitative analyses of bone composition in acetylcholine receptor M3R and alpha7 knockout mice","volume":"91","author":"Kliemann","year":"2012","journal-title":"Life Sci."},{"issue":"2","key":"2024031503440988300_jbmr3916-bib-0029","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1002\/jemt.10121","article-title":"Adrenergic regulation of bone metabolism: possible involvement of sympathetic innervation of osteoblastic and osteoclastic cells","volume":"58","author":"Togari","year":"2002","journal-title":"Microsc Res Tech."},{"issue":"2\u20133","key":"2024031503440988300_jbmr3916-bib-0030","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/S0167-4889(03)00042-9","article-title":"Effects of beta-adrenergic agonists on bone-resorbing activity in human osteoclast-like cells","volume":"1640","author":"Arai","year":"2003","journal-title":"Biochim Biophys Acta."},{"issue":"4","key":"2024031503440988300_jbmr3916-bib-0031","first-page":"A126","article-title":"Accuracy of Veterans Affairs databases for diagnoses of chronic diseases","volume":"6","author":"Singh","year":"2009","journal-title":"Prev Chronic Dis."},{"key":"2024031503440988300_jbmr3916-bib-0032","doi-asserted-by":"crossref","first-page":"S10","DOI":"10.1016\/j.injury.2017.08.031","article-title":"Dementia and fragility fractures: issues and solutions","volume":"48","author":"Vun","year":"2017","journal-title":"Injury."},{"issue":"6","key":"2024031503440988300_jbmr3916-bib-0033","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1111\/j.1532-5415.1994.tb06859.x","article-title":"Fracture risk in patients with Alzheimer's disease","volume":"42","author":"Melton","year":"1994","journal-title":"J Am Geriatr Soc."},{"key":"2024031503440988300_jbmr3916-bib-0034","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1186\/s12883-014-0175-2","article-title":"Increased risk of hip fractures in patients with dementia: a nationwide population-based study","volume":"14","author":"Wang","year":"2014","journal-title":"BMC Neurol."},{"issue":"9","key":"2024031503440988300_jbmr3916-bib-0035","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1016\/S1474-4422(07)70195-3","article-title":"Efficacy and adverse effects of cholinesterase inhibitors and memantine in vascular dementia: a meta-analysis of randomized controlled trials","volume":"6","author":"Kavirajan","year":"2007","journal-title":"Lancet Neurol."},{"issue":"5","key":"2024031503440988300_jbmr3916-bib-0036","doi-asserted-by":"crossref","first-page":"379","DOI":"10.7326\/0003-4819-148-5-200803040-00009","article-title":"Effectiveness of cholinesterase inhibitors and memantine for treating dementia: evidence review for a clinical practice guideline","volume":"148","author":"Raina","year":"2008","journal-title":"Ann Intern Med."}],"container-title":["Journal of Bone and Mineral Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jbmr.3916","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jbmr.3916","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/asbmr.onlinelibrary.wiley.com\/doi\/am-pdf\/10.1002\/jbmr.3916","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/35\/3\/440\/56443264\/jbmr3916.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/35\/3\/440\/56443264\/jbmr3916.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,15]],"date-time":"2024-03-15T03:47:14Z","timestamp":1710474434000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jbmr\/article\/35\/3\/440\/7591037"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11,11]]},"references-count":36,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2019,11,11]]},"published-print":{"date-parts":[[2020,12,1]]}},"URL":"https:\/\/doi.org\/10.1002\/jbmr.3916","relation":{},"ISSN":["0884-0431","1523-4681"],"issn-type":[{"value":"0884-0431","type":"print"},{"value":"1523-4681","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,12,1]]},"published":{"date-parts":[[2019,11,11]]},"assertion":[{"value":"2019-06-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-11-02","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-12-12","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}