Retinoids, which are vitamin A derivatives, are known to cause hypercalcemia.[7] The precise mechanism for each vitamin A compound has not been clearly defined. Retinoic acid may regulate bone cell proliferation and differentiation by suppressing alkaline phosphatase activity, osteocalcin production, and prostaglandin-induced interleukin-6 synthesis in osteoblast cells.[8] Retinoic acid also can inhibit parathyroid hormone, suggesting that increased bone resorption may account for hypercalcemia.[7] The synthetic retinoid 13-cis-retinoic acid, or isotretinoin, regulates cell proliferation and differentiation and decreases N-myc expression.[9] In addition, 13-cis-retinoic acid enhances normal hematopoietic differentiation by increasing the responsiveness of myeloid and erythroid progenitor cells to myeloid colony-stimulating activity and erythropoietin, respectively.[10] It is highly protein bound, primarily to albumin, and is hepatically metabolized to 4-oxoisotretinoin, which is excreted in urine and feces. Whether 4-oxoisotretinoin is biologically active is unknown.[11] 7. Ahmed N, Sammons J, Khokher A, et al. Retinoic acid suppresses interleukin 6 production in normal human osteoblasts. Cytokine 2000;12:289-93. 8. Akiyama H, Nakamura N, Nagasaka S. Hypercalcemia due to all-trans retinoic acid. Lancet 1992;339(8788):308-9. 9.Thiele CJ, Reynolds CP, Israel MA. Decreased expression of N-myc precedes retinoic acid-induced morphological differen-tiation of human neuroblastoma. Nature 1985;313:404-6. 10. Sidell N, Altman A, Haussler MR, Seeger RC. Effects of retinoic acid on the growth and phenotype expression of several human neuroblastoma cell lines. Exp Cell Res 1983;148:21-30. 11. Allen JG, Bloxham DP. The pharmacology and pharmaco-kinetics of the retinoids. Pharmacol Ther 1989;40:1-27. Pharmacotherapy 22(5):645-648, 2002. © 2002 Pharmacotherapy Publications Remember we are NOT Doctors and have NO medical training. This site is like an Encylopedia - there are many pages, many links on many topics. Support our work with any size DONATION - see left side of any page - for how to donate. You can help raise awareness of CAM.