Phosphate: boon or bane?

Disturbed phosphate homeostasis and its consequences for health(y aging)

Phosphorus has many important functions in the human body. PhosphoNorm represented a collaboration between Erasmus University Medical Center and Kyowa Kirin Pharma, exploring phosphorus homeostasis. The aim of our research was to extend the knowledge on phosphate homeostasis and on causes and clinical consequences of phosphate disturbances.

Using a range of laboratory studies on bone cells, we revealed that the hormone fibroblast growth factor (FGF)23, which regulates serum phosphate, responds to organic phosphates from healthy foods, but not to inorganic phosphates from fast food. Moreover, novel molecules were discovered as potential phosphate sensors. These findings could impact dietary policies and strategies to address rising inorganic phosphate intake.

Our population studies aimed to deepen understanding of phosphate homeostasis and the impact of phosphate disturbances. Key findings included sex and age differences in serum phosphate levels from the Rotterdam Study and UK Biobank, with adult women having higher levels than men, so we propose sex-specific reference ranges for individuals over 45. In addition, a higher body mass index (BMI) correlated with lower serum phosphate levels, suggesting that BMI impacts on phosphate more than vice versa. Studies on use of diuretics revealed that loop diuretics lower serum phosphate in women only, while thiazide diuretics lower it in both sexes. We also explored Cushing's syndrome (overproduction of stress hormone cortisol), linking it to previously unrecognized hypophosphatemia. Finally, higher serum phosphate was associated with coronary artery calcifications, particularly in men, indicating potential cardiovascular risks even within normal phosphate ranges.

Our initiated patient registry (ORPHOS-NED) for X-linked hypophosphatemia (XLH) includes 80 Dutch patients, with detailed disease manifestations. A literature review on tumor-induced osteomalacia (TIO) highlighted its clinical characteristics and treatments in 895 cases.

Altogether, PhosphoNorm has significantly enhanced our understanding of phosphate homeostasis and its disturbances, spanning from molecular mechanisms to patient-specific insights and population-level findings

Summary

Phosphorus homeostasis is crucial for many processes in our body and when this is disturbed, many systems in our body are affected. In this project, the consequence of too little or too much phosphorus has been investigated in laboratory experiments and in human population studies.

Technology Readiness Level (TRL)

1 - 3

Time period

54 months

Partners