Methotrexate Chemotherapy Causes Growth Impairments, Vitamin D Deficiency, Bone Loss, and Altered Intestinal Metabolism—Effects of Calcitriol Supplementation
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Animal Studies
2.1.1. MTX Treatment Time Course Study
2.1.2. MTX Treatment and Vitamin D Supplementation Trial
2.2. Serum Biochemistry Assays
2.3. Histomorphometric and Micro-Computed Topographical (μ-CT) Analyses of Tibial Trabecular Bone
2.4. RT-PCR Analyses of Vitamin D Metabolism Markers and Ca-Carrier Proteins in Jejunum
2.5. Analyses of MTX-Induced Small Intestine Mucosal Damage and Recovery
2.6. Statistical Analyses
3. Results
3.1. MTX Chemotherapy Caused Body Weight Loss and Decreased Total Body Length Gain and Tibial Length
3.2. MTX Chemotherapy Reduced Serum Vitamin D Levels, Altered Bone Turnover, and Decreased Tibial Trabecular Bone Volume
3.3. MTX Chemotherapy Altered Intestinal Expression of Key Vitamin D Metabolism Enzymes and Ca-Carrier Proteins, which Was Associated with MTX-Induced Intestinal Mucosa Damage
3.4. Vitamin D Supplementation Inhibited MTX Chemotherapy-Induced Bone Loss due to Its Effect in Suppressing Bone Resorption
4. Discussion
4.1. Vitamin D Deficiency, Bone Turnover, Bone Loss, and Ca Homeostasis following MTX Chemotherapy
4.2. Vitamin D Deficiency, Bone Loss, and Altered Intestinal Vitamin D Metabolism Are Linked with MTX-Induced Intestinal Mucositis
4.3. Potential Protective Effect of Vitamin D Supplementation and Action Mechanism
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Su, Y.-W.; Lee, A.M.C.; Xu, X.; Hua, B.; Tapp, H.; Wen, X.-S.; Xian, C.J. Methotrexate Chemotherapy Causes Growth Impairments, Vitamin D Deficiency, Bone Loss, and Altered Intestinal Metabolism—Effects of Calcitriol Supplementation. Cancers 2023, 15, 4367. https://doi.org/10.3390/cancers15174367
Su Y-W, Lee AMC, Xu X, Hua B, Tapp H, Wen X-S, Xian CJ. Methotrexate Chemotherapy Causes Growth Impairments, Vitamin D Deficiency, Bone Loss, and Altered Intestinal Metabolism—Effects of Calcitriol Supplementation. Cancers. 2023; 15(17):4367. https://doi.org/10.3390/cancers15174367
Chicago/Turabian StyleSu, Yu-Wen, Alice M. C. Lee, Xukang Xu, Belinda Hua, Heather Tapp, Xue-Sen Wen, and Cory J. Xian. 2023. "Methotrexate Chemotherapy Causes Growth Impairments, Vitamin D Deficiency, Bone Loss, and Altered Intestinal Metabolism—Effects of Calcitriol Supplementation" Cancers 15, no. 17: 4367. https://doi.org/10.3390/cancers15174367