Bone and Kidney Alterations in Diabetic Akita Mice: Evaluating FGF23 Secretion and Urinary Calcium and Phosphate Excretion
6 affiliations
- 1Dipartimento di Medicina e Chirurgia, Università degli Studi di Milano-Bicocca, 20900 Monza, Italy
- 2Unità Complicanze del Diabete, IRCCS Istituto Scientifico San Raffaele, 20132 Milano, Italy
- 3Laboratorio di Endocrinologia e Metabolismo Osseo, Istituto di Endocrinologia e Scienze Metaboliche, IRCCS Istituto Scientifico San Raffaele, 20132 Milano, Italy
- 4Laboratorio Analisi Chimico Cliniche, IRCCS San Gerardo dei Tintori, 20900 Monza, Italy
- 5Clinica Ortopedica, IRCCS San Gerardo dei Tintori, 20900 Monza, Italy
- 6Ospedale San Raffaele-Respighi, 20121 Milano, Italy
Abstract
A growing body of evidence indicates that bone is a target for diabetic complications. Hyperglycemia is associated with bone fragility and increased risk of fractures. In type 1 diabetes, which typically develops in children and adolescents, bone alterations already occur in the skeleton during the growth processes. In type 1 diabetic Akita mice, we analyzed with a pQCT scan the volumetric bone mineral density (vBMD) changes caused by hyperglycemia starting from 10 to 40 weeks of age. The results showed lower cortical vBMD at 20, 30 and 40 weeks of age, whereas cortical thickness and area were lower compared with control mice at all observation times from late growth (10 weeks of age) to aging (40 weeks of age). Fibroblast growth factor 23 (FGF23), synthetized mainly in osteocytes, is considered a ‘bone hormone’, that is critical to the maintenance of phosphate homeostasis. Diabetic Akita mice showed a persistent increase in the urinary calcium-to-creatinine ratio throughout the experimental period. In the presence of renal histological alterations, the urinary phosphate-to-creatinine ratio varied at different ages; its significantly lower value at 30 weeks of age, compared to wild-type mice, was associated with significantly lower plasma FGF23 levels. This study shows that in the Akita mice, the alterations in bone structure, caused by the high plasma glucose levels, are associated with a modulation of urinary calcium and phosphate excretion over time; the latter was only partially associated with the adjustment of FGF23 secretion.
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BibTeX
@article{castoldi2026bone,
title = {{Bone and Kidney Alterations in Diabetic Akita Mice: Evaluating FGF23 Secretion and Urinary Calcium and Phosphate Excretion}},
author = {Giovanna Castoldi and Ilaria Viganò and Barbara Vergani and Isabella Villa and Silvia Ippolito and Marco Casati and Silvia Galbiati and Daniela Gabellini and Alessia Montorfano and Francesco Giordano and Biagio E. Leone and Giovanni Zatti and Alessandro Rubinacci and Gianpaolo Zerbini},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = nov,
doi = {10.3390/ijms27219989},
url = {https://www.mdpi.com/1422-0067/27/21/9989},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Bone and Kidney Alterations in Diabetic Akita Mice: Evaluating FGF23 Secretion and Urinary Calcium and Phosphate Excretion
AU - Giovanna Castoldi
AU - Ilaria Viganò
AU - Barbara Vergani
AU - Isabella Villa
AU - Silvia Ippolito
AU - Marco Casati
AU - Silvia Galbiati
AU - Daniela Gabellini
AU - Alessia Montorfano
AU - Francesco Giordano
AU - Biagio E. Leone
AU - Giovanni Zatti
AU - Alessandro Rubinacci
AU - Gianpaolo Zerbini
PY - 2026
DA - 2026/11/07
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219989
UR - https://www.mdpi.com/1422-0067/27/21/9989
AB - A growing body of evidence indicates that bone is a target for diabetic complications. Hyperglycemia is associated with bone fragility and increased risk of fractures. In type 1 diabetes, which typically develops in children and adolescents, bone alterations already occur in the skeleton during the growth processes. In type 1 diabetic Akita mice, we analyzed with a pQCT scan the volumetric bone mineral density (vBMD) changes caused by hyperglycemia starting from 10 to 40 weeks of age. The results showed lower cortical vBMD at 20, 30 and 40 weeks of age, whereas cortical thickness and area were lower compared with control mice at all observation times from late growth (10 weeks of age) to aging (40 weeks of age). Fibroblast growth factor 23 (FGF23), synthetized mainly in osteocytes, is considered a ‘bone hormone’, that is critical to the maintenance of phosphate homeostasis. Diabetic Akita mice showed a persistent increase in the urinary calcium-to-creatinine ratio throughout the experimental period. In the presence of renal histological alterations, the urinary phosphate-to-creatinine ratio varied at different ages; its significantly lower value at 30 weeks of age, compared to wild-type mice, was associated with significantly lower plasma FGF23 levels. This study shows that in the Akita mice, the alterations in bone structure, caused by the high plasma glucose levels, are associated with a modulation of urinary calcium and phosphate excretion over time; the latter was only partially associated with the adjustment of FGF23 secretion.
SN - 1422-0067
ER -