Effect of Vitamin D Metabolites on Bone Resorption in Tissue Culture

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This chapter describes the effect of vitamin D metabolites on bone resorption in tissue culture. Many of the phenomena that have been observed using PTH in organ culture can be produced with 25–HCC. Both agents can induce prolonged resorptive response after brief application, a phenomenon that is termed as induction. Using either agent, a parallel inhibition of induction has been demonstrated by decreasing the calcium concentration in the medium during induction, by adding inhibitors of RNA and protein synthesis, including actinomycin D, mithramycin, camptothecin and cycloheximide during induction and by treating the bones with glucocorticoids before and during induction. These results indicate that the coupling of excitation to response in induction is calcium-dependent and involves a transcriptional effect on bone cells. PTH and 25-HCC appear to differ from a group of stimulators of bone resorption that do not induce and usually produce their effects less rapidly; these include vitamin A, prostaglandins, and AMP. In the search for therapeutic agents, vitamin D metabolites that selectively stimulate bone resorption would be useful in the treatment of hypoparathyroidism, while metabolites that enhance the intestinal absorption of calcium but do not stimulate bone resorption or that block the effects of active metabolites and of PTH on bone could be useful in the treatment of osteoporosis, renal osteodystrophy, and other disorders where resorption is increased.