Publications

Journal Article Epublish

PubMed: 40573160 DOI: 10.3390/nu17122049

High Dietary Phosphorus Impairs Bone Microarchitecture and Induces Alterations in the LGR4-R-Spondins Axis in Rats with Normal Renal Function.

Nutrients 17(12)

Authors: Sara Fernández-Villabrille, Francisco Baena-Huerta, Laura Suárez-Fernández, Elena Nefyodova, Paula Calvó, Nerea González-García, Helena Gil-Peña, Carlos Gómez-Alonso, Cristina Alonso-Montes, Manuel Naves-Díaz, Christa Maes, Natalia Carrillo-López, Sara Panizo

Affiliations

  • Metabolismo Óseo, Vascular y Enfermedades Inflamatorias Crónicas, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), 33011 Oviedo, Spain.
  • Redes de Investigación Cooperativa Orientadas a Resultados en Salud, RICORS2040-Renal, 33011 Oviedo, Spain.
  • Unidad de Metabolismo Óseo, Unidad de Gestión Clínica de Medicina Interna, Hospital Universitario Central de Asturias, 33011 Oviedo, Spain.
  • Laboratory of Skeletal Cell Biology and Physiology (SCEBP), Skeletal Biology and Engineering Research Center (SBE), Department of Development and Regeneration, KU Leuven, 3000 Leuven, Belgium.
  • Metabolismo Óseo, Vascular y Enfermedades Inflamatorias Crónicas, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), 33011 Oviedo, Spain. Redes de Investigación Cooperativa Orientadas a Resultados en Salud, RICORS2040-Renal, 33011 Oviedo, Spain. Unidad de Metabolismo Óseo, Unidad de Gestión Clínica de Medicina Interna, Hospital Universitario Central de Asturias, 33011 Oviedo, Spain.
  • Area de Gestión Clínica de la Infancia y Adolescencia, Hospital Universitario Central de Asturias (HUCA), Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), 33011 Oviedo, Spain.
  • Programa de Doctorado en Ciencias de la Salud, Universidad de Oviedo, 33006 Oviedo, Spain.

Abstract

Background: The increasing prevalence of processed foods has significantly elevated dietary phosphorus intake globally, posing a risk to skeletal health. Elevated serum phosphate promotes parathyroid hormone (PTH) release, leading to bone resorption and decreased bone formation. Objective: This study investigated the influence of chronically elevated phosphorus intake on bone structure in rats with normal renal function, focusing on the Receptor Activator of Nuclear factor Kappa-B (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) pathway and its related components, leucine rich repeat containing G protein-coupled receptor 4 (LGR4), and R-spondins (RSPOs). Methods: Rats were fed a high-phosphorus diet, followed by assessment of the bone microstructure and of the expression of key signalling molecules. Results: Elevated phosphorus intake induced significant bone deterioration, particularly in the trabecular bone compartment, associated with alterations in the RANK/RANKL/OPG pathway and in the LGR4 and RSPO1 and RSPO4 signalling components in bone. Moreover, we also observed changes in RANKL, RSPO1 and RSPO4 serum levels in the rats that had received a high-phosphorus diet. Conclusions: These findings highlight the detrimental impact of excessive dietary phosphorus on skeletal health, even without renal impairment, and suggest that components of this pathway, particularly RSPO1 and RSPO4, could serve as potential biomarkers of bone deterioration. The widespread consumption of phosphorus-rich processed foods underscores the importance of nutritional education to mitigate these skeletal risks in industrialized populations.

MeSH

Parathyroid Hormone, Osteoprotegerin, Serum, Phosphorus, Dietary, Diet, Food, Cancellous Bone, Food, Processed