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

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.