# A High Fat/High Sucrose Diet Alters the Skeletal Response to Adenine-Induced Chronic Kidney Disease in Male Rats

## TL;DR

A high fat and sugar diet changes how rat bones respond to chronic kidney disease, compared to a standard diet.

## Contribution

This study reveals diet-specific skeletal responses in a rat model of chronic kidney disease.

## Key findings

- Rats on a standard diet with CKD had worse bone mechanical properties and higher cortical porosity.
- A high fat/high sucrose diet reduced PTHR1 and RANKL osteocyte markers but increased TNF-α and osteoclasts.
- Diet influences skeletal outcomes in CKD through complex systemic interactions.

## Abstract

Chronic kidney disease (CKD) impacts a large and growing proportion of the population. Fracture rates are high in individuals with CKD compared to the non-CKD population. Dietary patterns consisting of higher fat and sugar intake are associated with higher risk of developing CKD, but the impact of different dietary patterns on the skeleton in the setting of CKD is largely unknown.

To assess the impact of a high fat/high sucrose diet (HFHS) in male Sprague Dawley rats with adenine-induced CKD (Ad).

Rats were given the HFHS or standard diet (SD) for 4 weeks followed by 8 weeks with adenine incorporated into those diets for the Ad groups.

All Ad rats, regardless of diet, had high circulating blood urea nitrogen and parathyroid hormone (PTH). Ad + SD rats had greater femoral volumetric cortical porosity and pore number and lower mechanical properties than Ad + HFHS rats. Ad + HFHS had a lower percentage of cortical bone osteocytes positive for PTHR1 and RANKL matching trends in porosity; however, the HFHS diet led to greater TNF-α-positive osteocytes and trabecular osteoclast numbers.

There were differences in the skeletal response to adenine-induced CKD based on diet with the standard diet leading to a skeletal phenotype more associated with high PTH. These data demonstrate both the complexity of systemic alterations impacting bone in CKD and highlight the importance of understanding the influence of dietary factors on skeletal outcomes.

The online version contains supplementary material available at 10.1007/s00223-026-01479-w.