title: Sex-specific differences in progressive glucose intolerance and hip geometry: the Baltimore Longitudinal Study of Aging.
abstract: Fracture risk is increased in type 2 diabetes mellitus (T2DM). The effect of pre-diabetes and T2DM on bone macroarchitecture and strength has not been well investigated. In this study, we show that in women only, both pre-diabetes and T2DM are associated with decreased hip bending strength and mineralization which might lead to skeletal weakness.
  
  
  BACKGROUND
  Older men and women with T2DM are at increased risk for fracture despite normal bone mineral density (BMD). The discordance between bone quantity and skeletal fragility has driven investigation into additional determinants of fracture resistance in T2DM. Additionally, the effect of pre-diabetes on bone strength has not been well described. The aim of this study was to determine differences in bone macroarchitecture and strength, measured by hip geometry, in persons with normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and T2DM.
  
  
  METHODS
  We performed cross-sectional analyses of older (age >55 years) men (n = 472) and women (n = 473) participating in the Baltimore Longitudinal Study of Aging (BLSA) classified as NGT, IGT, or T2DM based on oral glucose tolerance testing. Bone strength measures included the hip geometry parameters of section modulus (Z), cross-sectional area (CSA), and buckling ratio (BR). Sex-stratified analyses were conducted using adjusted stepwise regression models.
  
  
  RESULTS
  In women, IGT and T2DM were negatively associated with hip geometry parameters including mineralization in cross section (CSA, ß -0.076 and -0.073, respectively; both p < 0.05) and hip bending strength (Z, ß -0.097 and -0.09, respectively; both p < 0.05); conversely, IGT and T2DM were associated with improved compressive strength (BR, ß -0.31 and -0.29, respectively; both p < 0.05). There was no significant association between glycemic status and hip geometry in men.
  
  
  CONCLUSIONS
  In women only, both IGT and T2DM were inversely associated with bone macroarchitecture and measures of bone mineralization and bending strength. The same association between worsening glycemic status and bone strength was not observed in men. These data suggest a differential effect of sex on hip geometry with evolving glucose intolerance.
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Johns Hopkins School of Medicine, Baltimore, MD, USA, kmosele4@jhmi.edu.
authors.forename: K F
authors.initials: KF
authors.lastname: Moseley
authors.forename: C W
authors.initials: CW
authors.lastname: Chia
authors.forename: E M
authors.initials: EM
authors.lastname: Simonsick
authors.forename: J M
authors.initials: JM
authors.lastname: Egan
authors.forename: L
authors.initials: L
authors.lastname: Ferrucci
authors.forename: D E
authors.initials: DE
authors.lastname: Sellmeyer
mesh_terms: D000368:Aged; D000375:Aging / Q000473:pathology* / Q000502:physiology; D000886:Anthropometry / Q000379:methods; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology / Q000503:physiopathology; D018450:Disease Progression; D005260:Female; D005272:Femur Neck / Q000503:physiopathology; D018149:Glucose Intolerance / Q000473:pathology* / Q000503:physiopathology; D005951:Glucose Tolerance Test / Q000379:methods; D006621:Hip Joint / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D008137:Longitudinal Studies; D008159:Lumbar Vertebrae / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D012727:Sex Characteristics