Excessive salt consumption causes systemic calcium mishandling and worsens microarchitecture and strength of long bones in rats
Open Access
- 20 January 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Scientific Reports
- Vol. 11 (1), 1-15
- https://doi.org/10.1038/s41598-021-81413-2
Abstract
Excessive salt intake has been associated with the development of non-communicable diseases, including hypertension with several cardiovascular consequences. Although the detrimental effects of high salt on the skeleton have been reported, longitudinal assessment of calcium balance together with changes in bone microarchitecture and strength under salt loading has not been fully demonstrated. To address these unanswered issues, male Sprague–Dawley rats were fed normal salt diet (NSD; 0.8% NaCl) or high salt diet (HSD; 8% NaCl) for 5 months. Elevation of blood pressure, cardiac hypertrophy and glomerular deterioration were observed in HSD, thus validating the model. The balance studies were performed to monitor calcium input and output upon HSD challenge. The HSD-induced increase in calcium losses in urine and feces together with reduced fractional calcium absorption led to a decrease in calcium retention. With these calcium imbalances, we therefore examined microstructural changes of long bones of the hind limbs. Using the synchrotron radiation x-ray tomographic microscopy, we showed that trabecular structure of tibia and femur of HSD displayed a marked increase in porosity. Consistently, the volumetric micro-computed tomography also demonstrated a significant decrease in trabecular bone mineral density with expansion of endosteal perimeter in the tibia. Interestingly, bone histomorphometric analyses indicated that salt loading caused an increase in osteoclast number together with decreases in osteoblast number and osteoid volume. This uncoupling process of bone remodeling in HSD might underlie an accelerated bone loss and bone structural changes. In conclusion, long-term excessive salt consumption leads to impairment of skeletal mass and integrity possibly through negative calcium balance.Keywords
Funding Information
- National Research Council of Thailand and Mahidol University
- Chulalongkorn University (CU_GR_63_67_23_11)
- Post-doctoral fellowship grant awarded by Mahidol University
- Thailand Research Fund (TRF)-Royal Golden Jubilee Ph.D. Program (PHD/0003/2561)
- Faculty of Allied Health Sciences, Burapha University
- Thailand Research Fund (TRF) through International Research Network Program (IRN60W0001)
- Mahidol University–Multidisciplinary Research Cluster (MU–MRC) grant
- Central Instrumental Facility (CIF/CNI), Faculty of Science Mahidol University
- Thailand Toray Science Foundation
- Mahidol University (A22/2561)
- The Medical Association of Thailand–Prasert Prasarttong-Osoth Initiative
This publication has 62 references indexed in Scilit:
- Immune cells control skin lymphatic electrolyte homeostasis and blood pressureJCI Insight, 2013
- Enhanced trabecular bone resorption and microstructural bone changes in rats after removal of the cecumAmerican Journal of Physiology-Endocrinology and Metabolism, 2012
- β2-Adrenergic Receptor Signaling in Osteoblasts Contributes to the Catabolic Effect of Glucocorticoids on BoneEndocrinology, 2011
- High-Salt Diet and Hypertension: Focus on the Renin-Angiotensin SystemKidney and Blood Pressure Research, 2010
- Changes in the mRNA expression of osteoblast‐related genes in response to β3‐adrenergic agonist in UMR106 cellsCell Biochemistry and Function, 2009
- DASH-Style Diet Associates with Reduced Risk for Kidney StonesJournal of the American Society of Nephrology, 2009
- Two-step stimulation of intestinal Ca2+absorption during lactation by long-term prolactin exposure and suckling-induced prolactin surgeAmerican Journal of Physiology-Endocrinology and Metabolism, 2009
- Macrophages regulate salt-dependent volume and blood pressure by a vascular endothelial growth factor-C–dependent buffering mechanismNature Medicine, 2009
- Sodium and Bone Health: Impact of Moderately High and Low Salt Intakes on Calcium Metabolism in Postmenopausal WomenJournal of Bone and Mineral Research, 2008
- Glycosaminoglycan polymerization may enable osmotically inactive Na+ storage in the skinAmerican Journal of Physiology-Heart and Circulatory Physiology, 2004