Interactions between bacterial endotoxin and other stimulators of bone resorption in organ culture.

Abstract

Four agents which have been implicated in the pathogenesis of alveolar bone loss. In periodontaI disease, endotoxin, prostagandin E2 (PGE2), parathyroid hormone (PTH) and osteoclast activating factor (OAF), were studied for their effects on bone resorption as measured by the release of previously incorporated 45Ca from long bone shafts of 19 day fetal rats. Endotoxin at concentrations of 4 to 25 ng/ml caused little increase in 45Ca release but was able to enhance the response to submaximal concentrations of PGE2, PTH, and OAF. The response appeared synergistic, that is, it was greater than the sum of the individual responses when the agents were added singly. PTH and PGE2 do not show such apparent synergism when added together. The effects of endotoxin were not inhibited by three structurally unrelated inhibitors of prostaglandin synthesis, indomethacin, flufenamic acid and RO 20–5720, and synergistic responses were similar when PGE2 and endotoxin were added in the presence of indomethacin. We conclude that interactions between endotoxin and other bone resorbers can produce unexpectedly large resorptive responses and suggest that these interactions may be important in the pathogenesis of bone loss in periodontaJ disease and other forms of pathologic osteolysis.