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. Questions/purposes 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 mm 2 ; 95% confidence interval [CI], 347.9-367.5 mm 2 ; men: mean = 400.1 mm 2 ; 95% CI, 391.5-408.7 mm 2 ; 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 mm 2 ; 95% CI, 340.4-359.8 mm 2 ; men: mean = 394.3 mm 2 ; 95% CI, 386.5-402.1 mm 2 ; 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 mm 2 ; 95% CI, 0.71-0.74 mm 2 ; male: mean = 0.70 mm 2 ; 95% CI, 0.68-0.71 mm 2 ; effect size = 0.74; p = 0.04, GLM).

How Does Bone Strength Compare Across Sex, Site, and Ethnicity?

“…However, it had yet to be determined whether this difference in strength is the result of fundamental differences in the manner by which men and women construct bone. Mapping the sex-specific differences in skeletal traits for all the long bones confirmed what we reported for the femur in our companion manuscript [10], that women's bones are not merely a more slender version of men's, but that women also have significantly less bone mass (cortical area) than expected for their slenderness. This leads to an even greater structural deficit than expected that may functionally impact how well their bones can resist potentially catastrophic mechanical loads.…”

“…First, the slopes and y-intercepts of a series of regressions among bone strength index, robustness, and body size of men and women were compared through an analysis of covariance (ANCOVA) to determine whether men consistently build stronger and wider bones throughout their skeleton. Second, the slope and y-intercepts of a series of regressions among robustness, and cortical area, all adjusted for body size, were compared using ANCOVA to determine whether all long bones for women demonstrate the same reduced cortical area previously reported for the femur [10]. Third, a general linear model (GLM) was performed to compare group mean differences in bone strength between men and women.…”

“…Therefore, these traits can now be used to evaluate whether black and white men and women construct their bones in fundamentally different manners, because these coordinated traits provide a general assessment of whole bone strength and stiffness. Jepsen et al [10] found that the femora of black and white women accumulate significantly less cortical area for their body size and robustness compared with their male counterparts. We investigate whether this reduction in cortical area among the femora of black and white women is present throughout the appendicular skeleton.…”

Establishing Biomechanical Mechanisms in Mouse Models: Practical Guidelines for Systematically Evaluating Phenotypic Changes in the Diaphyses of Long Bones

“…On an absolute basis, female mice typically have lower bone properties compared to male mice given their smaller body size. However, after adjusting bone properties for body size, female mice have greater femoral maximum load, a similar robustness, larger cortical area, and higher tissue‐mineral density (TMD) compared to male mice . Thus, sex‐specific differences in bone properties on an absolute and relative basis preclude combining data in most experiments.Can I combine data across different ages?The answer depends on whether bone morphology and/or composition vary across the age range of interest.…”

Morphological profile of atypical femoral fractures: age‐related changes to the cross‐sectional geometry of the diaphysis

“…Sex differences in the cross‐sectional morphologies of human long bones with aging were reported in native Americans (Ruff & Hayes, ) and in blacks and whites (Jepsen et al. ; Schlecht et al. ).…”