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Recent studies have linked higher white matter hyperintensities (WMH) to reduced BMD, increasing the risk of fractures and falls in older adults. However, limited evidence exists regarding the dose\u2013response relationship between WMH and bone health in a larger and younger population. Our study aimed to examine the association of WMH volume with BMD, incident fractures and falls, focusing on dose\u2013response relationship with varying levels of WMH volume. We included 26\u2009410 participants from the UK Biobank. The association between WMH volume and BMD was analyzed using multiple linear regression. Cox regression models were used to estimate the hazard ratios of incident fractures and falls. Restricted cubic spline (RCS) fitted for linear and Cox regression models were employed to explore potential non-linearity. Over a mean follow-up time of 3.8\u00a0yr, we documented 59 hip fractures, 392 all fractures, and 375 fall incidents. When applying RCS, L-shaped relationships were identified between WMH volume and BMD across all 4 sites. Compared with those in the lowest fifth of WMH volume, individuals in the second to the highest fifths were associated with a reduction of 0.0102\u20130.0305\u00a0g\/cm2 in femur neck BMD, 0.0075\u20130.0273\u00a0g\/cm2 in femur troch BMD, 0.0173\u20130.0345\u00a0g\/cm2 in LS BMD, and 0.0141\u20130.0339\u00a0g\/cm2 in total body BMD. The association was more pronounced among women and younger participants under age 65 (Pinteraction\u2009&amp;lt;\u2009.05). Per 1 SD increment of WMH volume was associated with 36.9%, 20.1%, and 14.3% higher risks of incident hip fractures, all fractures, and falls. Genetically determined WMH or apolipoprotein E genotypes did not modify these associations. We demonstrated that a greater WMH was associated with BMD in an L-shaped dose\u2013response manner, especially in women and those under 65\u00a0yr.<\/jats:p>","DOI":"10.1093\/jbmr\/zjae031","type":"journal-article","created":{"date-parts":[[2024,2,21]],"date-time":"2024-02-21T17:38:30Z","timestamp":1708537110000},"page":"408-416","source":"Crossref","is-referenced-by-count":8,"title":["Association of white matter hyperintensities with BMD, incident fractures, and falls in the UK Biobank cohort"],"prefix":"10.1093","volume":"39","author":[{"given":"Lishan","family":"Cai","sequence":"first","affiliation":[{"name":"Department of Epidemiology , School of Public Health (Shenzhen), , Guangming District, Shenzhen 518107 , China"},{"name":"Sun Yat-sen University , School of Public Health (Shenzhen), , Guangming District, Shenzhen 518107 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingyu","family":"Lv","sequence":"additional","affiliation":[{"name":"Department of Epidemiology , School of Public Health (Shenzhen), , Guangming District, Shenzhen 518107 , China"},{"name":"Sun Yat-sen University , School of Public Health (Shenzhen), , Guangming District, Shenzhen 518107 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Epidemiology , School of Public Health and Tropical Medicine, , New Orleans, LA 70112 , United States"},{"name":"Tulane University , School of Public Health and Tropical Medicine, , New Orleans, LA 70112 , United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Epidemiology , School of Public Health and Tropical Medicine, , New Orleans, LA 70112 , United States"},{"name":"Tulane University , School of Public Health and Tropical Medicine, , New Orleans, LA 70112 , United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Epidemiology , School of Public Health and Tropical Medicine, , New Orleans, LA 70112 , United States"},{"name":"Tulane University , School of Public Health and Tropical Medicine, , New Orleans, LA 70112 , United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoriko","family":"Heianza","sequence":"additional","affiliation":[{"name":"Department of Epidemiology , School of Public Health and Tropical Medicine, , New Orleans, LA 70112 , United States"},{"name":"Tulane University , School of Public Health and Tropical Medicine, , New Orleans, LA 70112 , United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8041-7791","authenticated-orcid":false,"given":"Lu","family":"Qi","sequence":"additional","affiliation":[{"name":"Department of Epidemiology , School of Public Health and Tropical Medicine, , New Orleans, LA 70112 , United States"},{"name":"Tulane University , School of Public Health and Tropical Medicine, , New Orleans, LA 70112 , United States"},{"name":"Department of Nutrition, Harvard T.H. Chan School of Public Health , Boston, MA 02115 , United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Epidemiology , School of Public Health (Shenzhen), , Guangming District, Shenzhen 518107 , China"},{"name":"Sun Yat-sen University , School of Public Health (Shenzhen), , Guangming District, Shenzhen 518107 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,2,21]]},"reference":[{"issue":"929","key":"2024050213184999200_ref1","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1136\/pmj.79.929.133","article-title":"What is osteoporosis?","volume":"79","author":"Christodoulou","year":"2003","journal-title":"Postgrad Med J"},{"key":"2024050213184999200_ref2","doi-asserted-by":"crossref","first-page":"7707","DOI":"10.2147\/IJGM.S329992","article-title":"Associations of sex hormone-binding globulin with bone 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