Fourier transform infrared imaging of femoral neck bone: Reduced heterogeneity of mineral-to-matrix and carbonate-to-phosphate and more variable crystallinity in treatment-naive fracture cases compared with fracture-free controls

Abstract

After age 60 hip fracture risk strongly increases, but only a fifth of this increase is attributable to reduced mineral density (BMD, measured clinically). Changes in bone quality, specifically bone composition as measured by Fourier Transform Infrared spectroscopic imaging (FTIRI), also contribute to fracture risk. Here, FTIRI was applied to study the femoral neck and provide spatially derived information on its mineral and matrix properties in age-matched fractured and non-fractured bones. Whole femoral neck cross sections, divided into quadrants along the neck’s axis, from 10 women with hip fracture and 10 cadaveric controls were studied using FTIRI and micro-computed Tomography. Although 3-dimensional micro-CT bone mineral densities were similar, the mineral-to-matrix ratio was reduced in the cases of hip fracture, confirming previous reports. New findings were that the FTIRI microscopic variation (heterogeneity) of the mineral-to-matrix ratio was substantially reduced in the fracture group as was the heterogeneity of the carbonate-to-phosphate ratio. Conversely, the heterogeneity of crystallinity was increased. Increased variation of crystallinity was statistically associated with reduced variation of the carbonate-to-phosphate ratio. Anatomical variation in these properties between the different femoral neck quadrants was reduced in the fracture group compared to controls. While our treatment-naïve patients had reduced rather than increased bending resistance, these changes in heterogeneity associated with hip fracture are in another way comparable to the effects of experimental bisphosphonate therapy, which decreases heterogeneity and other indicators of bone’s toughness as a material.

Towards new material biomarkers for fracture risk

“…When age matched, the mineral to organic ratio was not significantly different between the fracture and non-fracture group, although the values for the fracture group were lower. In contrast, previous studies have shown a decrease in the mineral to organic ratio in ovariectomized animal and osteoporotic human tissue [18,30,33,45,74], suggesting either a lower mineral content and/ or a greater collagen content. The consensus tends to be that in osteoporotic bone, a decrease in mineral content is observed [18,19], resulting in a reduction in mechanical strength [11].…”

“…For example, Gourion-Arsiquaud et al reported greater cortical mineral/organic and trabecular crystallinity values associated with increased fracture risk when iliac crest specimens were analysed [32]. However, more recently, when investigating material properties of femoral neck specimens, a decrease in the mineral: organic ratio for both cortical and trabecular fractured bone was observed whilst no change in crystallinity was reported [33] by the same research group. Such differences can also be found between local geographic anatomies as demonstrated by Donnelly et al [80].…”

“…Processing involving aqueous solutions has been shown to modify the physicochemical characteristics of bone [83][84][85] although in our study the tissues were frozen. Our approach of quadrant sampling randomisation would have increased the variability in any of the characteristics measured and thus, given the previously reported variation between quadrant values [33], we may have expected a reduction in the power of our experiments.…”

Are Changes in Composition in Response to Treatment of a Mouse Model of Osteogenesis Imperfecta Sex-dependent?

“…Without a complex statistical analysis requiring larger numbers, we can only suggest that no treatment corrected any FTIR-determined material property parameters in oim/oim of either sex to WT values. The increased heterogeneity discussed may be beneficial, because increased heterogeneity has been correlated with reduced fracture risk in untreated osteoporotic humans [6,14,20]. The lack of change in collagen maturity, noted to be slightly elevated in untreated male and female oim/oim cortical and cancellous bone, merits comment.…”

“…The distribution (heterogeneity) of each parameter is calculated based on the full width at half maximum of the pixel histogram for spatial distribution in each individual image. Heterogeneity in adult human bone has been shown to decrease with bisphosphonate treatment [6,14,20]. These compositional parameters, taken together, provide an index of bone quality.…”