title: Serum sclerostin and risk of hip fracture in older Caucasian women.
abstract: BACKGROUND
  Sclerostin, a protein secreted by osteocytes, inhibits bone formation. Individuals with genetic mutations that decrease the availability of sclerostin have very high bone mass.
  
  
  OBJECTIVE
  The aim of this study was to examine the hypothesis that elevated serum sclerostin levels are associated with increased risk of hip fracture in older women.
  
  
  METHODS
  This was a case-cohort study of a prospective, community-based cohort of 9704 women aged 65 yr or older. Sclerostin levels were measured in serum collected in 1989-1990 in 228 women with incident hip fractures and 227 women in a randomly selected sample; average follow-up time was 9.8 yr.
  
  
  RESULTS
  Serum sclerostin levels were correlated with total hip bone mineral density (BMD; r = 0.27, P < 0.001). The risk of hip fracture increased across quartiles of serum sclerostin (test for trend, P < 0.001) and was significantly elevated among those in the fourth quartile (hazard risk 3.4, 95% confidence interval 1.7-7.0) compared with women in the lowest quartile, after adjusting for age, body mass index, estrogen use, history of fracture since age 50 yr, and total hip BMD. When dividing the cohort into eight groups by sclerostin quartile and median hip BMD, women with lower total hip BMD in the highest sclerostin quartile had a 22.3-fold (95% confidence interval 5.8-86.3) increased risk of fracture compared with women with higher total hip BMD in the lowest sclerostin quartile.
  
  
  CONCLUSIONS
  We conclude that higher serum sclerostin levels are associated with a greater risk of hip fractures in older women. In addition, the risk of hip fracture is amplified when high sclerostin levels are combined with lower BMD.
authors.affiliation: Department of Medicine, University of California, San Francisco, USA. aarthi.arasu@ucsf.edu
authors.forename: Aarthi
authors.initials: A
authors.lastname: Arasu
authors.forename: Peggy M
authors.initials: PM
authors.lastname: Cawthon
authors.forename: Li-Yung
authors.initials: LY
authors.lastname: Lui
authors.forename: Thy P
authors.initials: TP
authors.lastname: Do
authors.forename: Puneet S
authors.initials: PS
authors.lastname: Arora
authors.forename: Jane A
authors.initials: JA
authors.lastname: Cauley
authors.forename: Kristine E
authors.initials: KE
authors.lastname: Ensrud
authors.forename: Steven R
authors.initials: SR
authors.lastname: Cummings
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000368:Aged; D000369:Aged, 80 and over; D015519:Bone Density; D019485:Bone Morphogenetic Proteins / Q000097:blood*; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D005819:Genetic Markers; D006620:Hip Fractures / Q000453:epidemiology* / Q000503:physiopathology*; D006801:Humans; D015994:Incidence; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D044465:White People / Q000706:statistics & numerical data*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D019485:Bone Morphogenetic Proteins; D005819:Genetic Markers; C422903:SOST protein, human