Proposed model for the effects of imatinib on bone metabolism and serum calcium and phosphate metabolism. Decreased dissolution of calcium and phosphate from the bone, or increased deposition of calcium and phosphate in newly formed bone, may result in decreased serum calcium and phosphate levels in imatinib-treated patients. The decrease in serum phosphate results in increased 1,25 dihydroxyvitamin D₃ production, which in turn stimulates increased phosphate and calcium resorption by the gut and decreases phosphate excretion by the kidneys. Decreased serum calcium causes increased PTH production, increasing calcium reabsorption and phosphate excretion by the kidney and stimulating a further increase in 1,25 dihydroxyvitamin D₃. PTH also stimulates bone resorption to release calcium and phosphate from bone; however, this may be inhibited by imatinib. Decreased absorption of phosphate and calcium resulting from gastrointestinal problems and decreased tubular resorption of phosphate may, in some cases, also contribute to the decreased levels of serum calcium and phosphate in imatinib-treated patients (not shown).