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Bone Resorption Activity of All-trans Retinoic Acid Is Independent of Vitamin D in Rats¹

Department of Biochemistry, University of Wisconsin-Madison, College of Agricultural of Life Sciences, Madison, WI 53706

³To whom correspondence should be addressed. No reprints will be available from the authors. E-mail: deluca{at}biochem.wisc.edu.

The mechanism by which all-trans retinoic acid (ATRA) induces bone resorption is unknown. However, an interaction between vitamin A and vitamin D has been established. In fact, although the mechanism is still unclear, vitamin A has been shown to be a weak antagonist of the actions of vitamin D. Taking into account this interaction and the influence of vitamin D on other calcitropic hormones, such as parathyroid hormone, the effect of vitamin D on ATRA-induced bone resorption was investigated. Vitamin D–deficient rats were fed diets containing 0 or 150 µg of ATRA/g of diet. The rats then were orally administered 0 or 625 ng of cholecalciferol (vitamin D₃) daily. Various bone parameters were measured after 3–8 wk. Regardless of the presence or absence of vitamin D₃, ATRA was able to cause bone resorption. In addition to examining the effect of vitamin D on ATRA-induced bone resorption under normal conditions, this effect also was studied under conditions that inhibit bone mineralization or growth by altering dietary calcium (Ca) and phosphorus (P) levels. Changes in dietary levels of Ca and P did not affect the ability of ATRA to cause bone resorption. Interestingly, despite its ability to stimulate bone resorption, ATRA did not affect serum calcium or phosphorus levels. Overall, the ability of ATRA to cause bone resorption is not dependent on vitamin D₃, dietary Ca or dietary P.

KEY WORDS: • retinoids • osteoclasts • osteoblasts • vitamin A and bone

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