title: Volumetric femoral BMD, bone geometry, and serum sclerostin levels differ between type 2 diabetic postmenopausal women with and without fragility fractures.
abstract: While type 2 diabetes (T2D) is associated with higher skeletal fragility, specific risk stratification remains incompletely understood. We found volumetric bone mineral density, geometry, and serum sclerostin differences between low-fracture risk and high-fracture risk T2D women. These features might help identify T2D individuals at high fracture risk in the future.
  
  
  BACKGROUND
  Diabetic bone disease, an increasingly recognized complication of type 2 diabetes mellitus (T2D), is associated with high skeletal fragility. Exactly which T2D individuals are at higher risk for fracture, however, remains incompletely understood. Here, we analyzed volumetric bone mineral density (vBMD), geometry, and serum sclerostin levels in two specific T2D subsets with different fracture risk profiles. We examined a T2D group with prior history of fragility fractures (DMFx, assigned high-risk group) and a fracture-free T2D group (DM, assigned low-risk group) and compared their results to nondiabetic controls with (Fx) and without fragility fractures (Co).
  
  
  METHODS
  Eighty postmenopausal women (n = 20 per group) underwent quantitative computed tomography (QCT) to compute vBMD and bone geometry of the proximal femur. Additionally, serum sclerostin, vitamin D, parathyroid hormone (PTH), HbA1c, and glomerular filtration rate (GFR) levels were measured. Statistical analyses employed linear regression models.
  
  
  RESULTS
  DMFx subjects exhibited up to 33 % lower femoral neck vBMD than DM subjects across all femoral sites (-19 % ≤ ΔvBMD ≤ -33 %, 0.008 ≤ p ≤0.021). Additionally, DMFx subjects showed significantly thinner cortices (-6 %, p = 0.046) and a trend toward larger bone volume (+10 %, p = 0.055) relative to DM women and higher serum sclerostin levels when compared to DM (+31.4 %, p = 0.013), Fx (+25.2 %, p = 0.033), and control (+22.4 %, p = 0.028) subjects.
  
  
  CONCLUSIONS
  Our data suggest that volumetric bone parameters by QCT and serum sclerostin levels can identify T2D individuals at high risk of fracture and might therefore show promise as clinical tools for fracture risk assessment in T2D. However, future research is needed to establish diabetes-specific QCT- and sclerostin-reference databases.
authors.affiliation: Musculoskeletal Quantitative Imaging Research Group, Department of Radiology & Biomedical Imaging, University of California San Francisco, 185 Berry Street, Lobby 6, Suite 350, San Francisco, CA, 94158, USA, Ursula.Heilmeier@ucsf.edu.
authors.forename: U
authors.initials: U
authors.lastname: Heilmeier
authors.forename: D R
authors.initials: DR
authors.lastname: Carpenter
authors.forename: J M
authors.initials: JM
authors.lastname: Patsch
authors.forename: R
authors.initials: R
authors.lastname: Harnish
authors.forename: G B
authors.initials: GB
authors.lastname: Joseph
authors.forename: A J
authors.initials: AJ
authors.lastname: Burghardt
authors.forename: T
authors.initials: T
authors.lastname: Baum
authors.forename: A V
authors.initials: AV
authors.lastname: Schwartz
authors.forename: T F
authors.initials: TF
authors.lastname: Lang
authors.forename: T M
authors.initials: TM
authors.lastname: Link
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000368:Aged; D000886:Anthropometry / Q000379:methods; D015415:Biomarkers / Q000097:blood; D015519:Bone Density / Q000502:physiology*; D019485:Bone Morphogenetic Proteins / Q000097:blood*; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000503:physiopathology*; D005260:Female; D005269:Femur / Q000000981:diagnostic imaging / Q000503:physiopathology*; D005272:Femur Neck / Q000000981:diagnostic imaging / Q000503:physiopathology; D005819:Genetic Markers; D006801:Humans; D008875:Middle Aged; D058866:Osteoporotic Fractures / Q000097:blood / Q000000981:diagnostic imaging / Q000209:etiology / Q000503:physiopathology*; D018570:Risk Assessment / Q000379:methods; D014057:Tomography, X-Ray Computed / Q000379:methods
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015415:Biomarkers; D019485:Bone Morphogenetic Proteins; D005819:Genetic Markers; C422903:SOST protein, human