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It is the first such model to incorporate recent findings regarding the role of the calcium-sensing receptor (CaSR) in the kidney, the presence of a rapidly exchangeable pool in bone, and the delayed response of vitamin D<jats:sub>3<\/jats:sub>synthesis. Accounting for two (fast and slow) calcium storage compartments in bone allows the model to properly predict the effects of bisphophonates on the plasma levels of Ca<jats:sup>2+<\/jats:sup>([Ca<jats:sup>2+<\/jats:sup>]<jats:sub>p<\/jats:sub>), PTH, and vitamin D<jats:sub>3<\/jats:sub>. Our model also suggests that Ca<jats:sup>2+<\/jats:sup>exchange rates between plasma and the fast pool vary with both sex and age, allowing [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>p<\/jats:sub>to remain constant in spite of sex- and age-based hormonal and other differences. Our results suggest that the inconstant hypercalciuria that is observed in primary hyperparathyroidism can be attributed in part to counterbalancing effects of PTH and CaSR in the kidney. Our model also correctly predicts that calcimimetic agents such as cinacalcet bring down [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>p<\/jats:sub>to within its normal range in primary hyperparathyroidism. In addition, the model provides a simulation of CYP24A1 inactivation that leads to a situation reminiscent of infantile hypercalcemia. In summary, our model of calcium handling can be used to decipher the complex regulation of calcium homeostasis.<\/jats:p>","DOI":"10.1152\/ajprenal.00230.2016","type":"journal-article","created":{"date-parts":[[2016,6,30]],"date-time":"2016-06-30T02:39:18Z","timestamp":1467254358000},"page":"F1047-F1062","source":"Crossref","is-referenced-by-count":20,"title":["A model of calcium homeostasis in the rat"],"prefix":"10.1152","volume":"311","author":[{"given":"David","family":"Granjon","sequence":"first","affiliation":[{"name":"Sorbonne Universit\u00e9s, UPMC Univ Paris 06, Universit\u00e9 Paris Descartes, Sorbonne Paris Cit\u00e9, INSERM UMRS 1138, CNRS ERL 8228, Centre de Recherche des Cordeliers, Paris, France; and"},{"name":"Department of Pharmacology and Toxicology, University of Lausanne, and Service of Nephrology, Lausanne University Hospital, Lausanne, 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