Region-specific associations among tissue-level mechanical properties, porosity, and composition in human male femora.

Region-specific differences in age-related bone remodeling are known to exist. We therefore hypothesized that the decline in tissue-level strength and post-yield strain (PYS) with age is not uniform within the femur, but is driven by region-specific differences in porosity and composition. Four-point bending was conducted on anterior, posterior, medial, and lateral beams from male cadaveric femora (n = 33, 18-89 yrs of age). Mid-cortical porosity, composition, and mineralization were assessed using nano-computed tomography (nanoCT), Raman spectroscopy, and ashing assays. Traits between bones from young and elderly groups were compared, while multivariate analyses were used to identify traits that predicted strength and PYS at the regional level. We show that age-related decline in porosity and mechanical properties varied regionally, with highest positive slope of age vs. Log(porosity) found in posterior and anterior bone, and steepest negative slopes of age vs. strength and age vs. PYS found in anterior bone. Multivariate analyses show that Log(porosity) and/or Raman 1246/1269 ratio explained 46-51% of the variance in strength in anterior and posterior bone. Three out of five traits related to Log(porosity), mineral crystallinity, 1246/1269, mineral/matrix ratio, and/or hydroxyproline/proline (Hyp/Pro) ratio, explained 35-50% of the variance in PYS in anterior, posterior and lateral bones. Log(porosity) and Hyp/Pro ratio alone explained 13% and 19% of the variance in strength and PYS in medial bone, respectively. The predictive performance of multivariate analyses was negatively impacted by pooling data across all bone regions, underscoring the complexity of the femur and that the use of pooled analyses may obscure underlying region-specific differences.

State of the mineralized tissue comprising the femoral ACL enthesis in young women with an ACL failure.

Despite poor graft integration among some patients that undergo an anterior cruciate ligament (ACL) reconstruction, there has been little consideration of the bone quality into which the ACL femoral tunnel is drilled and the graft is placed. Bone mineral density of the knee decreases following ACL injury. However, trabecular and cortical architecture differences between injured and non-injured femoral ACL entheses have not been reported. We hypothesize that injured femoral ACL entheses will show significantly less cortical and trabecular mass compared with non-injured controls. Femoral ACL enthesis explants from 54 female patients (13-25 years) were collected during ACL reconstructive surgery. Control explants (n = 12) were collected from seven donors (18-36 years). Injured (I) femoral explants differed from those of non-injured (NI) controls with significantly less (p ≤ 0.001) cortical volumetric bone mineral density (vBMD) (NI: 736.1-867.6 mg/cm3 ; I: 451.2-891.9 mg/cm3 ), relative bone volume (BV/TV) (NI: 0.674-0.867; I: 0.401-0.792) and porosity (Ct.Po) (NI: 0.133-0.326; I: 0.209-0.600). Injured explants showed significantly less trabecular vBMD (p = 0.013) but not trabecular BV/TV (p = 0.314), thickness (p = 0.412), or separation (p = 0.828). We found significantly less cortical bone within injured femoral entheses compared to NI controls. Lower cortical and trabecular bone mass within patient femoral ACL entheses may help explain poor ACL graft osseointegration outcomes in the young and may be a contributor to the osteolytic phenomenon that often occurs within the graft tunnel following ACL reconstruction.

External Bone Size Is a Key Determinant of Strength-Decline Trajectories of Aging Male Radii.

Given prior work showing associations between remodeling and external bone size, we tested the hypothesis that wide bones would show a greater negative correlation between whole-bone strength and age compared with narrow bones. Cadaveric male radii (n = 37 pairs, 18 to 89 years old) were evaluated biomechanically, and samples were sorted into narrow and wide subgroups using height-adjusted robustness (total area/bone length). Strength was 54% greater (p < 0.0001) in wide compared with narrow radii for young adults (<40 years old). However, the greater strength of young-adult wide radii was not observed for older wide radii, as the wide (R2 = 0.565, p = 0.001), but not narrow (R2 = 0.0004, p = 0.944) subgroup showed a significant negative correlation between strength and age. Significant positive correlations between age and robustness (R2 = 0.269, p = 0.048), cortical area (Ct.Ar; R2 = 0.356, p = 0.019), and the mineral/matrix ratio (MMR; R2 = 0.293, p = 0.037) were observed for narrow, but not wide radii (robustness: R2 = 0.015, p = 0.217; Ct.Ar: R2 = 0.095, p = 0.245; MMR: R2 = 0.086, p = 0.271). Porosity increased with age for the narrow (R2 = 0.556, p = 0.001) and wide (R2 = 0.321, p = 0.022) subgroups. The wide subgroup (p < 0.0001) showed a significantly greater elevation of a new measure called the Cortical Pore Score, which quantifies the cumulative effect of pore size and location, indicating that porosity had a more deleterious effect on strength for wide compared with narrow radii. Thus, the divergent strength-age regressions implied that narrow radii maintained a low strength with aging by increasing external size and mineral content to mechanically offset increases in porosity. In contrast, the significant negative strength-age correlation for wide radii implied that the deleterious effect of greater porosity further from the centroid was not offset by changes in outer bone size or mineral content. Thus, the low strength of elderly male radii arose through different biomechanical mechanisms. Consideration of different strength-age regressions (trajectories) may inform clinical decisions on how best to treat individuals to reduce fracture risk. © 2019 American Society for Bone and Mineral Research.

The relationship between whole bone stiffness and strength is age and sex dependent.

Accurately estimating whole bone strength is critical for identifying individuals that may benefit from prophylactic treatments aimed at reducing fracture risk. Strength is often estimated from stiffness, but it is not known whether the relationship between stiffness and strength varies with age and sex. Cadaveric proximal femurs (44 Male: 18-78 years; 40 Female: 24-95 years) and radial (36 Male: 18-89 years; 19 Female: 24-95 years) and femoral diaphyses (34 Male: 18-89 years; 19 Female: 24-95 years) were loaded to failure to evaluate how the stiffness-strength relationship varies with age and sex. Strength correlated significantly with stiffness at all sites and for both sexes, as expected. However, females exhibited significantly less strength for the proximal femur (58% difference, p < 0.001). Multivariate regressions revealed that stiffness, age and PYD were significant negative independent predictors of strength for the proximal femur (Age: M: p = 0.005, F: p < 0.001, PYD: M: p = 0.022, F: p = 0.025), radial diaphysis (Age: M = 0.055, PYD: F = 0.024), and femoral diaphysis (Age: M: p = 0.014, F: p = 0.097, PYD: M: p = 0.003, F: p = 0.091). These results indicated that older bones tended to be significantly weaker for a given stiffness than younger bones. These results suggested that human bones exhibit diminishing strength relative to stiffness with aging and with decreasing PYD. Incorporating these age- and sex-specific factors may help to improve the accuracy of strength estimates.