Amphotericin B: Stimulation of Bone Resorption in Organ Culture 1

Abstract

Abstract

Organ culture studies of 5-day-old mouse calvaria show that amphotericin B, a polyene antibiotic, is a potent bone resorption-stimulating agent, as measured by calcium release into the medium, residual calcium, and hydroxyproline in the calvaria at the end of the 7-day culture period, and by histological examination. Nystatin and filipin, two other polyene antibiotics, also induce bone resorption in the same system. Amphotericin B and nystatin are thought to act on natural and artificial membrane systems by binding to cholesterol or other steroids thereby forming aqueous pores that permit the passage of ions and some other solutes. Such alteration of cell membrane permeability may be a crucial initial step in the chain of events leading to bone resorption by these two agents. Inhibition of polyene antibiotic-stimulated bone resorption by indomethacin and dexamethasone suggest that polyene antibiotic-stimulated resorption is mediated by prostaglandin biosynthesis.