title: Women Build Long Bones With Less Cortical Mass Relative to Body Size and Bone Size Compared With Men.
abstract: BACKGROUND
  The twofold greater lifetime risk of fracturing a bone for white women compared with white men and black women has been attributed in part to differences in how the skeletal system accumulates bone mass during growth. On average, women build more slender long bones with less cortical area compared with men. Although slender bones are known to have a naturally lower cortical area compared with wider bones, it remains unclear whether the relatively lower cortical area of women is consistent with their increased slenderness or is reduced beyond that expected for the sex-specific differences in bone size and body size. Whether this sexual dimorphism is consistent with ethnic background and is recapitulated in the widely used mouse model also remains unclear.
  
  
  OBJECTIVE
  We asked (1) do black women build bones with reduced cortical area compared with black men; (2) do white women build bones with reduced cortical area compared with white men; and (3) do female mice build bones with reduced cortical area compared with male mice?
  
  
  METHODS
  Bone strength and cross-sectional morphology of adult human and mouse bone were calculated from quantitative CT images of the femoral midshaft. The data were tested for normality and regression analyses were used to test for differences in cortical area between men and women after adjusting for body size and bone size by general linear model (GLM).
  
  
  RESULTS
  Linear regression analysis showed that the femurs of black women had 11% lower cortical area compared with those of black men after adjusting for body size and bone size (women: mean=357.7 mm2; 95% confidence interval [CI], 347.9-367.5 mm2; men: mean=400.1 mm2; 95% CI, 391.5-408.7 mm2; effect size=1.2; p<0.001, GLM). Likewise, the femurs of white women had 12% less cortical area compared with those of white men after adjusting for body size and bone size (women: mean=350.1 mm2; 95% CI, 340.4-359.8 mm2; men: mean=394.3 mm2; 95% CI, 386.5-402.1 mm2; effect size=1.3; p<0.001, GLM). In contrast, female and male femora from recombinant inbred mouse strains showed the opposite trend; femurs from female mice had a 4% larger cortical area compared with those of male mice after adjusting for body size and bone size (female: mean=0.73 mm2; 95% CI, 0.71-0.74 mm2; male: mean=0.70 mm2; 95% CI, 0.68-0.71 mm2; effect size=0.74; p=0.04, GLM).
  
  
  CONCLUSIONS
  Female femurs are not simply a more slender version of male femurs. Women acquire substantially less mass (cortical area) for their body size and bone size compared with men. Our analysis questions whether mouse long bone is a suitable model to study human sexual dimorphism.
  
  
  CONCLUSIONS
  Identifying differences in the way bones are constructed may be clinically important for developing sex-specific diagnostics and treatment strategies to reduce fragility fractures.
authors.affiliation: Department of Orthopaedic Surgery, University of Michigan, 109 Zina Pitcher Place, Room 2001 BSRB, Ann Arbor, MI, 48109, USA, kjepsen@med.umich.edu.
authors.forename: Karl J
authors.initials: KJ
authors.lastname: Jepsen
authors.forename: Erin M R
authors.initials: EM
authors.lastname: Bigelow
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Schlecht
mesh_terms: D000328:Adult; D001741:Black or African American; D000818:Animals; D001696:Biomechanical Phenomena; D049628:Body Size / Q000208:ethnology; D005260:Female; D005269:Femur / Q000000981:diagnostic imaging / Q000254:growth & development*; D054624:Health Status Disparities; D006801:Humans; D016014:Linear Models; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D023421:Models, Animal; D010012:Osteogenesis; D012727:Sex Characteristics; D012737:Sex Factors; D013045:Species Specificity; D014057:Tomography, X-Ray Computed; D044465:White People; D055815:Young Adult