The kidney sodium-phosphate co-transporter alters bone quality in an age and gender specific manner.

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 7months of age using micro-computed tomography (micro-CT) and Fourier transform infrared imaging (FTIRI). 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 7months seen principally in males. Cortical bone at 1month showed an increase in bone volume fraction, but this was not seen at 7months. Cortical thickness which was elevated in the male and female KO at 1month was lower in the male KO at 7months. FTIRI showed a reduced mineral and acid phosphate content in the male and female KO's bones at 1month with no change in acid phosphate content at 7months. Collagen maturity was reduced in KO cancellous bone at 1month. 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.

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.

After the age of 60 years, hip fracture risk strongly increases, but only a fifth of this increase is attributable to reduced bone 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 nonfractured 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 with controls. Although our treatment-naive 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.

Changes in matrix phosphorylation during bovine dentin development.

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.