Wang ZX, Lloyd AA, Donnelly E. Altered distributions of bone tissue mineral and collagen properties in women with fragility fractures. Bone. 2016


Heterogeneity of bone tissue properties is emerging as a potential indicator of altered bone quality in pathologic tissue. The objective of this study was to compare the distributions of tissue properties in women with and without histories of fragility fractures using Fourier transform infrared (FTIR) imaging. We extended a prior study that examined the relationship of the mean FTIR properties to fracture risk by analyzing in detail the widths and the tails of the distributions of FTIR properties in biopsies from fracture and non-fracture cohorts. The mineral and matrix properties of cortical and trabecular iliac crest tissue were compared in biopsies from women with a history of fragility fracture (+Fx; n = 21, age: mean 54 ± SD 15 y) and with no history of fragility fracture (−Fx; n = 12, age: 57 ± 5 y). A subset of the patients included in the −Fx group were taking estrogen-plusprogestin hormone replacement therapy (HRT) (−Fx + HRT n = 8, age: 58 ± 5 y) and were analyzed separately from patients with no history of HRT (−Fx − HRT n = 4, age: 56 ± 7 y). When the FTIR parameter mean values were examined by treatment group, the trabecular tissue of −Fx−HRT patients had a lower mineral:matrix ratio (M:M) and collagen maturity (XLR) than that of −Fx + HRT patients (−22% M:M, −18% XLR) and +Fx patients (−17% M:M, −18% XLR). Across multiple FTIR parameters, tissue from the −Fx − HRT group had smaller lowtail (5th percentile) values than that from the −Fx + HRT or +Fx groups. In trabecular collagen maturity and crystallinity (XST), the −Fx − HRT group had smaller low-tail values than those in the –Fx + HRT group (−16% XLR, −5% XST) and the + Fx group (−17% XLR, −7% XST). The relatively low values of trabecular mineral:matrix ratio and collagen maturity and smaller low-tail values of collagen maturity and crystallinity observed in the −Fx − HRT group are characteristic of younger tissue. Taken together, our data suggest that the presence of newly formed tissue that includes small/imperfect crystals and immature crosslinks, as well as moderately mature tissue, is an important characteristic of healthy, fracture-resistant bone. Finally, the larger mean and low-tail values of mineral:matrix ratio and collagen maturity noted in our −Fx + HRT vs. −Fx−HRT biopsies are consistent with greater tissue age and greater BMD arising from decreased osteoclastic resorption in HRT-treated patients.

DOI: 10.1016/j.bone.2016.01.012

Lloyd AA, Wang ZX, Donnelly E. Multiscale Contribution of Bone Tissue Material Property Heterogeneity to Trabecular Bone Mechanical Behavior. J Biomech Eng. 2015.


Heterogeneity of material properties is an important potential contributor to bone fracture resistance because of its putative contribution to toughness, but establishing the contribution of heterogeneity to fracture risk is still in an incipient stage. Experimental studies have demonstrated changes in distributions of compositional and nanomechanical properties with fragility fracture history, disease, and pharmacologic treatment. Computational studies have demonstrated that models with heterogeneous material properties predict apparent stiffness moderately better than homogeneous models and show greater energy dissipation. Collectively, these results suggest that microscale material heterogeneity affects not only microscale mechanics but also structural performance at larger length scales.