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.

Phosphorylation of the organic matrix proteins of dentin is important for the initiation of mineralization, but its relevance in later mineralization stages is controversial. The objective of this study was to analyze changes in the total matrix phosphate content during dentin development and to identify their origin. Amino acid and total matrix phosphate analyses of microdissected developing mantle and circumpulpal fetal bovine dentin specimens were performed. The amino acid composition showed few changes during mantle and circumpulpal dentin maturation. However, the total matrix phosphate content showed a significant, positive correlation with tissue maturation in both mantle and circumpulpal dentin, with a two-and a three-fold increase, respectively, being observed. The data indicate that changes occur in the pattern of phosphorylation of matrix proteins during dentin maturation, which we suggest may play a functional role in later stages of tooth mineralization. Keywordsbovine; dentin; development; matrix; phosphorylation Highly phosphorylated acidic proteins constitute a major part of the non-collagenous component of dentin matrices. They have been postulated to have critical and diverse functions in dentin mineralization, including initiating mineral nucleation and modulating mineral crystal growth (1-7). The in vitro functions of three abundant dentin phosphorylated proteins [dentin phosphoprotein (DPP), dentin sialoprotein (DSP), and dentin matrix protein 1 (DMP1)] have been shown to depend, at least in part, on the phosphorylation of their residues (8-10). While the number and sequence of phosphorylated residues is different among these proteins, study of the overall dentin matrix phosphorylation during dentin mineralization can provide insight into mineralization mechanisms. Earlier results describing variations in total matrix protein phosphorylation in dentin are conflicting, as both a decrease (11,12) and an increase (13) in matrix phosphorylation have been described. Data from these earlier studies are diffcult to interpret because of the high variability of the structure and composition of analyzed dentin as a result of sampling the whole tooth crown, which presents high histological variability (14,15), and because of the lack of normalization of the matrix phosphate changes observed (number of matrix protein residues phosphorylated vs. relative phosphorylated protein content in the matrix). The purpose of the present study was to test the hypothesis that there are variations in the organic matrix phosphate levels during dentin maturation. Dentin maturation, for the purposes of this study, was defined as the age-dependent processes occurring after deposition of the organic matrix at the mineralization front, including formation and growth of the mineral crystals, degradation of matrix proteins, changes in collagen cross-linking and other possible modifications of the organic matrix. To test the above-stated hypothesis, mantle and circumpulpal dentin specimens from various developmental st...

Mutations in the kidney NaPiIIa co-transporter are clinically associated with hypophosphatemia, hyperphosphaturia (phosphate wasting), hypercalcemia, nephrolithiasis and bone demineralization. The mouse lacking this co-transporter system was reported to recover its skeletal defects with age, but the “quality” of the bones was not considered. To assess changes in bone quality we examined both male and female NaPiIIa knockout (KO) mice at 1 and 7 months of age using micro-computed tomography (micro-CT) and Fourier transform infrared imaging (FT-IRI). KO cancellous bones at both ages had greater bone volume fraction, trabecular thickness and lesser structure model index based on micro-CT values relative to age- and sex-matched wildtype animals. There was a sexual-dimorphism in the micro-CT parameters, with differences at 7 months seen principally in males. Cortical bone at 1 month showed an increase in bone volume fraction, but this was not seen at 7 months. Cortical thickness which was elevated in the male and female KO at 1 month was lower in the male KO at 7 months.. FTIRI showed a reduced mineral and acid phosphate content in the male and female KO’s bones at 1 month with no change in acid phosphate content at 7 months. Collagen maturity was reduced in KO cancellous bone at 1 month. The observed sexual dimorphism in the micro-CT data may be related to altered phosphate homeostasis, differences in animal growth rates and other factors. These data indicate that the bone quality of the KO mice at both ages differs from the normal and suggests that these bone quality differences may contribute to skeletal phenotype in humans with mutations in this co-transporter.

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