Multiscale Analysis Reveals Altered Characteristics in Femur and Mandible of Mice on a High Phosphate Diet

Excessive phosphate used as flavor enhancers and preservatives in processed foods can exacerbate cardiovascular and kidney diseases. In clinical and pre-clinical studies, chronic (over 52 weeks) high-phosphate diet (HPD) negatively affects bone health. We previously demonstrated that 12-week-HPD decreases exercise capacity and skeletal muscle metabolism in adult male mice; however, alteration of bone characteristics associated with HPD independent of disease complications is not well-characterized. Thus, we determined the effects of shorter-term-HPD on characteristics of mouse femurs and mandibles. Adult male mice were fed a normal phosphate diet (NPD) or HPD for 18 weeks, serum markers of mineral metabolism and bone formation and resorption were quantified in femurs, and histological analysis was performed on tibias. Volumetric, mineral density, and morphology parameters of femurs and mandibles were determined using micro-computed tomography, and dynamic mechanical analysis and fracture testing of the femur were conducted. Our studies revealed that 18-week-HPD significantly reduced bone quality (tissue mineral density (TMD) and cortical thickness) without changing bone quantity (total mineral content and volume) of both femurs and mandibles, and femur mechanical properties were aggravated increasing the risk of fracture. Serum markers of osteoclastic resorption and osteoblastic formation were increased with HPD, indicating active osteoclastic bone resorption and osteoblastic new bone formation. These findings provide detailed information on how excessive dietary phosphate substantially alters characteristics of bone, resulting in bone weakening.