ArticleJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research2025
Circulating neurodegenerative brain injury markers and hip fracture and fall hospitalizations: the Cardiovascular Health Study.
Jane A Cauley, Petra Buzkova, Howard A Fink, Joshua I Barzilay, Rachel E Elam, Oscar L Lopez, Lauren Carlson, John A Robbins, Luc Djousse, Kenneth J Mukamal
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In one paragraphArticle in Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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5 · Who and what moneyAuthors and funding
10 authors.
Jane A CauleyDepartment of Epidemiology, School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, United States.ORCID 0000-0003-0752-4408 Petra BuzkovaDepartment of Biostatistics, University of Washington, Seattle, WA 98195, United States.
Howard A FinkGeriatric Research Education and Clinical Center, Minneapolis VA Healthcare System, Minneapolis, MN 55417, United States.ORCID 0000-0002-5985-5447 Joshua I BarzilayDivision of Endocrinology, Kaiser Permanente of Georgia, and Department of Endocrinology, Emory University School of Medicine, Atlanta, GA 30322, United States.ORCID 0000-0001-7044-4166 Rachel E ElamDivision of Rheumatology, Medical College of Georgia at Augusta University, Augusta, GA 30912, United States.ORCID 0000-0001-9927-6063 Oscar L LopezDepartment of Neurology, University of Pittsburgh, Pittsburgh, PA 15261, United States.
Lauren CarlsonDepartment of Epidemiology, School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, United States.
John A RobbinsDepartment of Medicine, University of California, Davis, CA 94143, United States.
Luc DjousseDivision of Aging, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, United States.
Kenneth J MukamalDepartment of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, United States.
Funding
Oregon Clinical and Translational Research Institute - The National COVID Cohort Collaborative (N3C)UL1TR002369 · NCATS · OREGON HEALTH & SCIENCE UNIVERSITY · PI Cynthia D Morris, Christopher G. Slatore · 2017 to 2026
$78.4MExceptional Survival: Trajectories to Functional Aging (CHS All Stars)R01AG023629 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI NEWMAN, ANNE B. · 2004 to 2016
$9.5MOsteoporotic Fractures in Men (MrOS) - San Francisco Coordinating CenterU01AR066160 · NIAMS · CALIFORNIA PACIFIC MED CTR RES INSTITUTE · PI CUMMINGS, STEVEN RON · 2013 to 2017
$9.3MCARDIOVASCULAR HEALTH STUDY (CHS) - TASK AREA C, STUDY CLOSEOUT75N92021D00006 · NHLBI · UNIVERSITY OF WASHINGTON · PI PSATY, BRUCE · 2021 to 2024
$8.4MCHS research resources for the cardiovascular health of older adultsU01HL130114 · NHLBI · UNIVERSITY OF WASHINGTON · PI BURKE, GREGORY L, KRONMAL, RICHARD A · 2016 to 2019
$6.6MTRAINING IN THE EPIDEMIOLOGY OF AGINGT32AG000181 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI STROTMEYER, ELSA S. · 1989 to 2025
$6.2MCardiovascular Epidemiology Training ProgramT32HL083825 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI AKIRA SEKIKAWA · 2008 to 2026
$6.1MOsteoporotic Fractures in Men (MrOS) - MinneapolisU01AG042145 · NIA · UNIVERSITY OF MINNESOTA · PI ENSRUD, KRISTINE · 2013 to 2019
$5.3MOsteporotic Fractures in Men (MrOS)- Admin CenterU01AG027810 · NIA · OREGON HEALTH & SCIENCE UNIVERSITY · PI ORWOLL, ERIC S. · 2006 to 2017
$5.1MCHS Events Follow-up StudyU01HL080295 · NHLBI · UNIVERSITY OF WASHINGTON · PI PSATY, BRUCE M · 2005 to 2008
$4.6MTRIAL OF A COGNITIVE INTERVENTION FOR OLDER ADULTSU01AG014260 · NIA · JOHNS HOPKINS UNIVERSITY · PI REBOK, GEORGE W. · 1996 to 2010
$3.4MOsteoporotic Fractures in Men (MrOS) - PortlandU01AG042124 · NIA · OREGON HEALTH & SCIENCE UNIVERSITY · PI ORWOLL, ERIC S. · 2013 to 2019
$3.0MNCATS NIH HHS UL1 TR002369NHLBI NIH HHS 75N92021D00006NHLBI NIH HHS HHSN268200800007CNHLBI NIH HHS HHSN268201200036CNHLBI NIH HHS HHSN268201800001CNHLBI NIH HHS N01 HC055222NHLBI NIH HHS N01 HC085079NHLBI NIH HHS N01 HC085080NHLBI NIH HHS N01 HC085081NHLBI NIH HHS N01 HC085082NHLBI NIH HHS N01 HC085083NHLBI NIH HHS N01 HC085086NHLBI NIH HHS N01HC55222NHLBI NIH HHS N01HC85079NHLBI NIH HHS N01HC85080NHLBI NIH HHS N01HC85081NHLBI NIH HHS N01HC85082NHLBI NIH HHS N01HC85083NHLBI NIH HHS N01HC85086NHLBI NIH HHS R01 HL120854NHLBI NIH HHS R01HL120854NHLBI NIH HHS R01 HL135625NHLBI NIH HHS R01HL135625NHLBI NIH HHS R01 HL172803NHLBI NIH HHS T32 HL083825NHLBI NIH HHS U01 HL080295NHLBI NIH HHS U01HL080295NHLBI NIH HHS U01 HL130114NHLBI NIH HHS U01HL130114NIAMS NIH HHS U01 AR066160NIA NIH HHS R01 AG023629NIA NIH HHS R01AG023629NIA NIH HHS T32 AG000181NIA NIH HHS U01 AG014260NIA NIH HHS U01 AG027810NIA NIH HHS U01 AG042124NIA NIH HHS U01 AG042139NIA NIH HHS U01 AG042140NIA NIH HHS U01 AG042143NIA NIH HHS U01 AG042145NIA NIH HHS U01 AG042168
6 · The paper itselfAbstract
Individuals with dementia have a heightened hip fracture and fall risk but whether markers of brain injury are associated with hip fracture and falls is unknown. We tested the hypothesis that higher circulating brain injury markers were associated with increased risk of hip fracture and fall hospitalizations. Brain injury markers were measured in 2141 participants (mean age 77.9 yr; 60% women). Brain injury markers included neurofilament light chain (NfL), a marker of axonal injury; glial fibrillary acidic protein (GFAP), a marker of astrocytic injury; total Tau, whose many functions include neuron microtubule stabilization; and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), a major protein of neurons. Incident hip fractures and hospitalizations for falls were identified through participant report and confirmed with medical records or medicare claims. Hazard ratios were computed for a doubling exposure (log2 transformed brain injury marker) using multivariable-adjusted Cox models. After a median follow-up of 11 yr, 304 incident hip fractures and 284 incident fall hospitalizations occurred. Doubling of GFAP and NfL were associated with a 22% (p = .048) and 42% (p < .001) higher risk of hip fracture, respectively. Additional adjustment for cognitive function, gait speed, grip strength, inflammatory markers, and depressive symptoms had no effect on results. Models that adjusted for all 4 brain markers showed that only NfL was independent of the other markers. Neurofilament light chain was also associated with a 47% increase risk of hospitalization for falls. There was no association of total Tau or UCH-L1 with hip fracture or falls. GFAP was also unrelated to fall hospitalizations. Neurofilament light chain was independently associated with an incident risk of hip fracture and fall hospitalizations. These results suggest that subclinical degrees of brain injury may contribute to falls and hip fracture. Future research is needed to test whether the association between NfL and hip fracture is independent of falls.
Indexed as
Accidental FallsBrain InjuriesHip FracturesHospitalizationAgedAged, 80 and overBiomarkersFemaleGlial Fibrillary Acidic ProteinHumansMaleNeurofilament ProteinsRisk Factorstau ProteinsUbiquitin ThiolesteraseBiomarkersGlial Fibrillary Acidic Proteinneurofilament protein LNeurofilament Proteinstau ProteinsUbiquitin Thiolesteraseagingbone–brain–nervous system interactionepidemiologyfracture risk assessmentosteoporosis
Identifiers
PMID41134198
PMCPMC12765681
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