title: Bone mineral density and incidence of stroke: European prospective investigation into cancer-norfolk population-based study, systematic review, and meta-analysis.
abstract: OBJECTIVE
  The prospective link between osteoporosis and future risk of stroke requires evidence from large-scale population-based long-term studies.
  
  
  METHODS
  Calcaneum broadband ultrasound attenuation was measured in the Norfolk cohort of the European Prospective Investigation into Cancer-Norfolk between 1997 and 2000. Incident strokes were ascertained by hospital record linkage and death certificates in March 2009 and December 2011, respectively. A search of MEDLINE and EMBASE was performed to evaluate the relationship between bone mineral density and incident stroke. After data extraction of relevant studies, pooled risk of stroke was estimated using meta-analysis.
  
  
  RESULTS
  In 14 290 participants (mean follow-up of 9.3 years; total person-years 132 574), there were 599 incident strokes. Participants in the lowest 10% of the calcaneum broadband ultrasound attenuation distribution had an increased stroke risk (hazard ratio 1.41; 95% confidence intervals, 1.02-1.94) compared with those in the top 30% of the distribution after adjustments. A decrease of ~1 standard deviation in broadband ultrasound attenuation (20 db/MHz) was associated with a 17% increase in relative risk of stroke (95% confidence intervals, 5%-30%). Meta-analysis of 4 studies (25 760 participants, 1237 cases of stroke) found that for every decrease in 1 standard deviation in bone mineral density, there was an increased risk of incident stroke among women (pooled relative risk 1.22; 95% confidence intervals, 1.09-1.37; I2=0%, 3 studies) but not in men (pooled relative risk 1.05; 95% confidence intervals, 0.94-1.17; I(2)=0%, 2 studies).
  
  
  CONCLUSIONS
  Bone mineral density predicts total stroke risk. The evidence is stronger in women with regard to the continuous relationship.
authors.affiliation: From the AGEING (Aberdeen Gerontological & Epidemiological INterdisciplinary Research Group), Institute of Applied Health Sciences, School of Medicine & Dentistry, University of Aberdeen, Aberdeen, UK (P.K.M., C.S.K.); Norwich Medical School, Norwich Research Park Cardiovascular Research Group, University of East Anglia, Norwich Research Park, Norwich, UK (P.K.M., A.B.C., Y.K.L., J.K.-Y.Y.); Clinical Gerontology Unit, Department of Public Health and Primary Care, School of Clinical Medicine, University of Cambridge, Cambridge, UK (P.K.M., R.N.L., K.-T.K.); Institute of Cardiovascular Sciences, University of Manchester, Manchester, UK (C.S.K.); and MRC Epidemiology Unit, Cambridge, UK (N.J.W.).
authors.forename: Phyo Kyaw
authors.initials: PK
authors.lastname: Myint
authors.forename: Allan B
authors.initials: AB
authors.lastname: Clark
authors.forename: Chun Shing
authors.initials: CS
authors.lastname: Kwok
authors.forename: Yoon Kong
authors.initials: YK
authors.lastname: Loke
authors.forename: Jessica Ka-Yan
authors.initials: JK
authors.lastname: Yeong
authors.forename: Robert N
authors.initials: RN
authors.lastname: Luben
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Wareham
authors.forename: Kay-Tee
authors.initials: KT
authors.lastname: Khaw
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D015519:Bone Density / Q000502:physiology*; D015331:Cohort Studies; D005060:Europe / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D064887:Observational Studies as Topic; D011153:Population; D016016:Proportional Hazards Models; D012044:Regression Analysis; D012306:Risk; D012737:Sex Factors; D012907:Smoking / Q000009:adverse effects / Q000453:epidemiology; D020521:Stroke / Q000000981:diagnostic imaging / Q000453:epidemiology*; D014463:Ultrasonography; D006113:United Kingdom / Q000453:epidemiology
keywords: bone density; epidemiology; osteoporosis; risk factors; stroke