Structural differences contributing to sex-specific associations between FN BMD and whole-bone strength for adult White women and men.

Hip areal BMD (aBMD) is widely used to identify individuals with increased fracture risk. Low aBMD indicates low strength, but this association differs by sex with men showing greater strength for a given aBMD than women. To better understand the structural basis giving rise to this sex-specific discrepancy, cadaveric proximal femurs from White female and male donors were imaged using nano-CT and loaded in a sideways fall configuration to assess strength. FN pseudoDXA images were generated to identify associations among structure, aBMD, and strength that differ by sex. Strength correlated significantly with pseudoDXA aBMD for females (R2 = 0.468, P < .001) and males (R2 = 0.393, P < .001), but the elevations (y-intercepts) of the linear regressions differed between sexes (P < .001). Male proximal femurs were 1045 N stronger than females for a given pseudoDXA aBMD. However, strength correlated with pseudoDXA BMC for females (R2 = 0.433, P < .001) and males (R2 = 0.443, P < .001) but without significant slope (P = .431) or elevation (P = .058) differences. Dividing pseudoDXA BMC by FN-width, total cross-sectional area, or FN-volume led to significantly different associations between strength and the size-adjusted BMC measures for women and men. Three structural differences were identified that differentially affected aBMD and strength for women and men: First, men had more bone mass per unit volume than women; second, different cross-sectional shapes resulted in larger proportions of bone mass orthogonal to the DXA image for men than women; and third, men and women had different proportions of cortical and trabecular bone relative to BMC. Thus, the proximal femurs of women were not smaller versions of men but were constructed in fundamentally different manners. Dividing BMC by a bone size measure was responsible for the sex-specific associations between hip aBMD and strength. Thus, a new approach for adjusting measures of bone mass for bone size and stature is warranted.

Genetically targeted chemical assembly of polymers specifically localized extracellularly to surface membranes of living neurons.

Multicellular biological systems, particularly living neural networks, exhibit highly complex organization properties that pose difficulties for building cell-specific biocompatible interfaces. We previously developed an approach to genetically program cells to assemble structures that modify electrical properties of neurons in situ, opening up the possibility of building minimally invasive cell-specific structures and interfaces. However, the efficiency and biocompatibility of this approach were challenged by limited membrane targeting of the constructed materials. Here, we design a method for highly localized expression of enzymes targeted to the plasma membrane of primary neurons, with minimal intracellular retention. Next, we show that polymers synthesized in situ by this approach form dense extracellular clusters selectively on the targeted cell membrane and that neurons remain viable after polymerization. Last, we show generalizability of this method across a range of design strategies. This platform can be readily extended to incorporate a broad diversity of materials onto specific cell membranes within tissues and may further enable next-generation biological interfaces.

Associations Among Hip Structure, Bone Mineral Density, and Strength Vary With External Bone Size in White Women.

Bone mineral density (BMD) is heavily relied upon to reflect structural changes affecting hip strength and fracture risk. Strong correlations between BMD and strength are needed to provide confidence that structural changes are reflected in BMD and, in turn, strength. This study investigated how variation in bone structure gives rise to variation in BMD and strength and tested whether these associations differ with external bone size. Cadaveric proximal femurs (n = 30, White women, 36-89+ years) were imaged using nanocomputed tomography (nano-CT) and loaded in a sideways fall configuration to assess bone strength and brittleness. Bone voxels within the nano-CT images were projected onto a plane to create pseudo dual-energy X-ray absorptiometry (pseudo-DXA) images consistent with a clinical DXA scan. A validation study using 19 samples confirmed pseudo-DXA measures correlated significantly with those measured from a commercially available DXA system, including bone mineral content (BMC) (R 2  = 0.95), area (R 2  = 0.58), and BMD (R 2  = 0.92). BMD-strength associations were conducted using multivariate linear regression analyses with the samples divided into narrow and wide groups by pseudo-DXA area. Nearly 80% of the variation in strength was explained by age, body weight, and pseudo-DXA BMD for the narrow subgroup. Including additional structural or density distribution information in regression models only modestly improved the correlations. In contrast, age, body weight, and pseudo-DXA BMD explained only half of the variation in strength for the wide subgroup. Including bone density distribution or structural details did not improve the correlations, but including post-yield deflection (PYD), a measure of bone material brittleness, did increase the coefficient of determination to more than 70% for the wide subgroup. This outcome suggested material level effects play an important role in the strength of wide femoral necks. Thus, the associations among structure, BMD, and strength differed with external bone size, providing evidence that structure-function relationships may be improved by judiciously sorting study cohorts into subgroups. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.