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 7. months 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 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.