{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T01:13:55Z","timestamp":1779930835260,"version":"3.53.1"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2017,7,29]],"date-time":"2017-07-29T00:00:00Z","timestamp":1501286400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01 HL46959"],"award-info":[{"award-number":["R01 HL46959"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["R01 AR052817"],"award-info":[{"award-number":["R01 AR052817"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,12,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:sec>\n                  <jats:title>\u2003<\/jats:title>\n                  <jats:p>Epidemiologic studies have demonstrated an association of elevated plasma homocysteine levels with greater bone resorption and fracture risk. Vitamins B12, B6, and folic acid are cofactors in homocysteine metabolism, and supplementation with B vitamins is effective in lowering homocysteine levels in humans. However, randomized trials of supplemental B vitamins for reduction of fracture risk have been limited. Therefore, we performed an ancillary study to the Women's Antioxidant and Folic Acid Cardiovascular Study (WAFACS), a large randomized trial of women with preexisting cardiovascular disease or three or more coronary risk factors, to test whether a daily B vitamin intervention including folic acid (2.5\u2009mg\/day), vitamin B6 (50\u2009mg\/day), and vitamin B12 (1\u2009mg\/day) reduces nonspine fracture risk over 7.3 years of treatment and follow-up. Among 4810 women, we confirmed 349 nonspine fracture cases by centralized review of medical records. In a substudy of 300 women (150 in treatment group and 150 controls) with paired plasma samples at randomization and follow-up (7.3 years later), we measured two bone turnover markers, including C-terminal cross-linking telopeptide of type I collagen (CTX) and intact type I procollagen N-propeptide (P1NP). In Cox proportional hazards models based on intention-to-treat, we found no significant effects of B vitamin supplementation on nonspine fracture risk (relative hazard\u2009=\u20091.08; 95% confidence interval, 0.88 to 1.34). In a nested case-cohort analysis, there were no significant effects of B vitamins on fracture risk among women with elevated plasma homocysteine levels, or low levels of vitamins B12 or B6, or folate at baseline. Furthermore, treatment with B vitamins had no effect on change in markers of bone turnover. We found no evidence that daily supplementation with B vitamins reduces fracture risk or rates of bone metabolism in middle-aged and older women at high risk of cardiovascular disease. \u00a9 2017 American Society for Bone and Mineral Research.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1002\/jbmr.3229","type":"journal-article","created":{"date-parts":[[2017,7,29]],"date-time":"2017-07-29T12:36:37Z","timestamp":1501331797000},"page":"2331-2338","source":"Crossref","is-referenced-by-count":41,"title":["Effect of Combination Folic Acid, Vitamin B6, and Vitamin B12 Supplementation on Fracture Risk in Women: A Randomized, Controlled Trial"],"prefix":"10.1093","volume":"32","author":[{"given":"Katie L","family":"Stone","sequence":"first","affiliation":[{"name":"Department of Epidemiology and BiostatisticsUniversity of CaliforniaSan FranciscoSan Francisco, CAUSA"},{"name":"Research InstituteCalifornia Pacific Medical CenterSan FranciscoCAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Yung","family":"Lui","sequence":"additional","affiliation":[{"name":"Research InstituteCalifornia Pacific Medical CenterSan FranciscoCAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William G","family":"Christen","sequence":"additional","affiliation":[{"name":"Department of MedicineBrigham and Women's HospitalHarvard Medical SchoolBostonMAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aron M","family":"Troen","sequence":"additional","affiliation":[{"name":"Institute of BiochemistryFood and Nutrition ScienceThe Robert H. Smith Faculty of Agriculture Food and EnvironmentThe Hebrew University of JerusalemJerusalemIsrael"},{"name":"Vitamin Metabolism LaboratoryJean Mayer United States Department of Agriculture (USDA) Human Nutrition Research Center on Aging at Tufts UniversityBostonMAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas C","family":"Bauer","sequence":"additional","affiliation":[{"name":"Department of MedicineUniversity of CaliforniaSan FranciscoSan Francisco, CAUSA"},{"name":"Department of Epidemiology and BiostatisticsUniversity of CaliforniaSan FranciscoSan Francisco, CAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah","family":"Kado","sequence":"additional","affiliation":[{"name":"Department of Internal MedicineUniversity of CaliforniaSan DiegoSan Diego, CAUSA"},{"name":"Department of Family Medicine & Public HealthUniversity of CaliforniaSan DiegoSan Diego, CAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Schambach","sequence":"additional","affiliation":[{"name":"Research InstituteCalifornia Pacific Medical CenterSan FranciscoCAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven R","family":"Cummings","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and BiostatisticsUniversity of CaliforniaSan FranciscoSan Francisco, CAUSA"},{"name":"Research InstituteCalifornia Pacific Medical CenterSan FranciscoCAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JoAnn E","family":"Manson","sequence":"additional","affiliation":[{"name":"Department of MedicineBrigham and Women's HospitalHarvard Medical SchoolBostonMAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2017,7,29]]},"reference":[{"issue":"12","key":"2024021014194561700_jbmr3229-bib-0001","doi-asserted-by":"crossref","first-page":"1726","DOI":"10.1007\/s00198-006-0172-4","article-title":"An estimate of the worldwide prevalence and disability associated with osteoporotic fractures","volume":"17","author":"Johnell","year":"2006","journal-title":"Osteoporos Int"},{"issue":"5","key":"2024021014194561700_jbmr3229-bib-0002","doi-asserted-by":"crossref","first-page":"331","DOI":"10.7326\/0003-4819-131-5-199909070-00003","article-title":"Serum total homocysteine concentrations in the third National Health and Nutrition Examination Survey (1991-1994): population reference ranges and contribution of vitamin status to high serum concentrations","volume":"131","author":"Selhub","year":"1999","journal-title":"Ann Intern 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