title: No increase in risk of hip fracture at high serum retinol concentrations in community-dwelling older Norwegians: the Norwegian Epidemiologic Osteoporosis Studies.
abstract: BACKGROUND
  Norway has the highest hip fracture rates worldwide and a relatively high vitamin A intake. Increased fracture risk at high intakes and serum concentrations of retinol (s-retinol) have been observed in epidemiologic studies.
  
  
  OBJECTIVE
  We aimed to study the association between s-retinol and hip fracture and whether high s-retinol may counteract a preventive effect of vitamin D.
  
  
  METHODS
  We conducted the largest prospective analysis of serum retinol and hip fracture to date in 21,774 men and women aged 65-79 y (mean age: 72 y) who attended 4 community-based health studies during 1994-2001. Incident hip fractures occurring up to 10.7 y after baseline were retrieved from electronic hospital discharge registers. Retinol determined by high-pressure liquid chromatography with ultraviolet detection in stored serum was available in 1154 incident hip fracture cases with valid body mass index (BMI) data and in a subcohort defined as a sex-stratified random sample (n = 1418). Cox proportional hazards regression weighted according to the stratified case-cohort design was performed.
  
  
  RESULTS
  There was a modest increased risk of hip fracture in the lowest compared with the middle quintile of s-retinol (HR: 1.41; 95% CI: 1.09, 1.82) adjusted for sex and study center. The association was attenuated after adjustment for BMI and serum concentrations of α-tocopherol (HR: 1.16; 95% CI: 0.88, 1.51). We found no increased risk in the upper compared with the middle quintile. No significant interaction between serum concentrations of 25-hydroxyvitamin D and s-retinol on hip fracture was observed (P = 0.68).
  
  
  CONCLUSIONS
  We found no evidence of an adverse effect of high serum retinol on hip fracture or any interaction between retinol and 25-hydroxyvitamin D. If anything, there tended to be an increased risk at low retinol concentrations, which was attenuated after control for confounders. We propose that cod liver oil, a commonly used food supplement in Norway, should not be discouraged as a natural source of vitamin D for fracture prevention.
authors.affiliation: Division of Epidemiology, Norwegian Institute of Public Health, Oslo, Norway; Department of Global Public Health and Primary Care and kristin.holvik@fhi.no.
authors.forename: Kristin
authors.identifier: http://orcid.org/0000-0003-3132-2822
authors.initials: K
authors.lastname: Holvik
authors.affiliation: Department of Health and Care Sciences, Faculty of Health Sciences, and Institute of Public Health, College of Medicine & Health Sciences, United Arab Emirates University, Al-Ain, United Arab Emirates;
authors.forename: Luai A
authors.initials: LA
authors.lastname: Ahmed
authors.affiliation: Department of Public Health and General Practice, Norwegian University of Science and Technology, Trondheim, Norway;
authors.forename: Siri
authors.initials: S
authors.lastname: Forsmo
authors.affiliation: Department of Clinical Science, University of Bergen, Bergen, Norway; Department of Rheumatology, Haukeland University Hospital, Bergen, Norway;
authors.forename: Clara G
authors.initials: CG
authors.lastname: Gjesdal
authors.affiliation: Tromsø Endocrine Research Group, Department of Clinical Medicine, UiT the Arctic University of Norway, Tromsø, Norway;
authors.forename: Guri
authors.initials: G
authors.lastname: Grimnes
authors.affiliation: Division of Epidemiology, Norwegian Institute of Public Health, Oslo, Norway; Department of Mathematics.
authors.forename: Sven Ove
authors.initials: SO
authors.lastname: Samuelsen
authors.affiliation: Department of Public Health and General Practice, Norwegian University of Science and Technology, Trondheim, Norway; Department of Obstetrics and Gynecology, St. Olav's Hospital, Trondheim, Norway.
authors.forename: Berit
authors.initials: B
authors.lastname: Schei
authors.affiliation: Department of Nutrition, Institute of Basic Medical Sciences, and.
authors.forename: Rune
authors.initials: R
authors.lastname: Blomhoff
authors.affiliation: Division of Epidemiology, Norwegian Institute of Public Health, Oslo, Norway; Department of Global Public Health and Primary Care and.
authors.forename: Grethe S
authors.initials: GS
authors.lastname: Tell
authors.affiliation: Division of Epidemiology, Norwegian Institute of Public Health, Oslo, Norway; Institute of Health and Society, University of Oslo, Oslo, Norway; and.
authors.forename: Haakon E
authors.initials: HE
authors.lastname: Meyer
mesh_terms: D015652:25-Hydroxyvitamin D 2 / Q000097:blood; D000368:Aged; D002112:Calcifediol / Q000097:blood; D016022:Case-Control Studies; D003060:Cod Liver Oil / Q000009:adverse effects; D015331:Cohort Studies; D019587:Dietary Supplements / Q000009:adverse effects; D058620:Elder Nutritional Physiological Phenomena; D005260:Female; D005500:Follow-Up Studies; D006620:Hip Fractures / Q000097:blood / Q000453:epidemiology* / Q000209:etiology / Q000628:therapy; D006801:Humans; D015994:Incidence; D008297:Male; D009664:Norway / Q000453:epidemiology; D009749:Nutrition Surveys; D009752:Nutritional Status; D058866:Osteoporotic Fractures / Q000097:blood / Q000453:epidemiology* / Q000209:etiology / Q000628:therapy; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012042:Registries; D012307:Risk Factors; D014801:Vitamin A / Q000008:administration & dosage / Q000097:blood*
chemical_list: D014801:Vitamin A; D015652:25-Hydroxyvitamin D 2; D003060:Cod Liver Oil; D002112:Calcifediol
keywords: Norway; case-cohort; elderly; hip fracture; retinol; vitamin A