title: VITAL-Bone Health: rationale and design of two ancillary studies evaluating the effects of vitamin D and/or omega-3 fatty acid supplements on incident fractures and bone health outcomes in the VITamin D and OmegA-3 TriaL (VITAL).
abstract: BACKGROUND
  Although vitamin D is widely used to promote skeletal health, definitive data on benefits and risks of supplemental vitamin D alone on bone are lacking. Results from large, randomized controlled trials in the general population are sparse. Data on the effects of supplemental omega-3 fatty acids (FAs) on bone are also limited.
  
  
  METHODS
  The VITamin D and OmegA-3 TriaL (VITAL) is a double-blind, placebo-controlled trial assessing the role of vitamin D3 (2000 IU/d) and omega-3 FA (1g/d) supplements in reducing risks of cancer and cardiovascular disease among U.S. men aged ≥50 and women aged ≥55. To comprehensively test effects of supplemental vitamin D and/or omega-3 FAs on skeletal health, the VITAL: Effects on Fractures ancillary study is determining the effects of these supplements on incident fractures among 25,875 participants enrolled in the parent trial. Study investigators adjudicate fractures through a detailed review of medical records and radiological images (hip and femur). In a complementary ancillary, VITAL: Effects on Structure and Architecture is determining the effects of supplemental vitamin D and/or omega-3 FAs on bone with detailed phenotyping during in-person visits. Comprehensive assessments of bone density, turnover, structure/architecture, body composition, and physical performance are being performed at baseline and 2 years post-randomization.
  
  
  CONCLUSIONS
  Results from these studies will clarify the relationship between supplemental vitamin D and/or omega-3 FAs on bone health outcomes, and inform clinical care and public health guidelines on the use of supplemental vitamin D for the primary prevention of fractures in women and men.
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, United States; Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, United States. Electronic address: MLEBOFF@PARTNERS.ORG.
authors.forename: Meryl S
authors.initials: MS
authors.lastname: LeBoff
authors.affiliation: Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, United States. Electronic address: AYUE@PARTNERS.ORG.
authors.forename: Amy Y
authors.initials: AY
authors.lastname: Yue
authors.affiliation: Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, United States. Electronic address: PCOPELAND2@PARTNERS.ORG.
authors.forename: Trisha
authors.initials: T
authors.lastname: Copeland
authors.affiliation: Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, United States; Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, United States. Electronic address: NCOOK@PARTNERS.ORG.
authors.forename: Nancy R
authors.initials: NR
authors.lastname: Cook
authors.affiliation: Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, United States; Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, United States. Electronic address: JBURING@PARTNERS.ORG.
authors.forename: Julie E
authors.initials: JE
authors.lastname: Buring
authors.affiliation: Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, United States; Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, United States. Electronic address: JMANSON@PARTNERS.ORG.
authors.forename: JoAnn E
authors.initials: JE
authors.lastname: Manson
mesh_terms: D015502:Absorptiometry, Photon; D000368:Aged; D015519:Bone Density; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D002762:Cholecalciferol / Q000627:therapeutic use*; D019587:Dietary Supplements; D004311:Double-Blind Method; D015525:Fatty Acids, Omega-3 / Q000627:therapeutic use*; D005260:Female; D005269:Femur / Q000000981:diagnostic imaging; D050723:Fractures, Bone / Q000453:epidemiology*; D006621:Hip Joint / Q000000981:diagnostic imaging; D006801:Humans; D008297:Male; D008875:Middle Aged; D014057:Tomography, X-Ray Computed
chemical_list: D050071:Bone Density Conservation Agents; D015525:Fatty Acids, Omega-3; D002762:Cholecalciferol
keywords: Bone mineral density; Bone turnover; Fractures; Omega-3 fatty acids; Trabecular bone score; Vitamin D