# Dietary potassium restriction causes hypercalciuria, hypocalcemia, and bone loss in male mice

## TL;DR

Low potassium diets cause bone loss in mice due to changes in kidney calcium handling.

## Contribution

The study identifies kidney calcium absorption changes as a mechanism for potassium-induced bone loss.

## Key findings

- Low potassium diets increased urinary calcium excretion and reduced plasma calcium levels.
- Mice on low potassium diets showed increased bone resorption and decreased bone mineral density.
- Active sodium-chloride cotransporter (NCC) mitigated hypocalcemia from low potassium diets.

## Abstract

Loss of bone mass has a devastating effect on quality of life. Higher potassium (K+) intake is positively correlated with bone health. Here, we investigated whether kidney calcium (Ca2+) and phosphate (Pi) handling mechanisms mediate dietary K+ effects. Kidney Ca2+ and Pi handling proteins were altered in abundance in mice fed a 0% K+ diet for 2 weeks. In mice fed a 0.1% K+ diet for 4 or 8 weeks, urinary Ca2+ excretion increased, plasma Ca2+ levels were lower and plasma parathyroid hormone (PTH) levels were higher relative to control 1% K+ fed mice. The 0.1% K+ fed mice had greater excretion of the bone resorption marker deoxypyridinoline, increased osteoclast number, and decreased total femoral bone mineral density. During chronic low K+ intake, major changes in renal Ca2+ and Pi transport pathways were absent, except higher abundances of the sodium-potassium-chloride cotransporter (NKCC2) and the sodium-chloride cotransporter (NCC), in line with their role in kidney Ca2+ handling. Low dietary K+ induced hypocalcemia and changes in PTH were absent in mice with constitutively active NCC, supporting its role in mediating low K+ effects on Ca2+ homeostasis. Our study provides insights into the management of bone disorders in conditions of chronic electrolyte imbalance.

In this study we demonstrate that a diet low in potassium causes bone loss, effects that are attribuatble to altered calcium absorption by the kidney.