PHARMACOLOGICAL INHIBITION OF PARTICULATE-INDUCED BONE-RESORPTION

In this study, a rat calvaria/macrophage co-culture model was used to study the effects of various agents upon bone resorption induced by ma crophage exposure to bone cement particles. The experimental group con sisted of calvaria bone disks set in tissue culture medium on stainles s-steel platforms into wells with macrophages adherent to the bottom w hich are exposed to the particles. Tumor necrosis factor a (TNF-alpha) , prostaglandin E(2) (PGE(2)), and calcium 45 (Ca-45) were released in significant amounts in this system. Interleukin 1 alpha (IL-1 alpha) was not detected. Indomethacin inhibited the production of PGE(2) but did not affect TNF release or inhibit the release of Ca-45. Anti-TNF a ntibody neutralized the presence of TNF to undetectable levels, but di d not affect PGE(2) release or inhibit Ca-45 release. The addition of calcitonin did not inhibit Ca-45 release by calvaria. In contrast, the addition of disodium pamidronate, a member of the bisphosphonate fami ly, was effective in inhibiting the release of Ca-45 even after 96 h o f incubation. In prior studies, incubation of calvaria in conditioned medium from macrophages exposed to cement particles led to resorption through a mechanism which is dependent upon TNF production by macropha ges, and PGE(2) production by cells in bone. In this two-way system, i n which macrophages and cells in bone are allowed to interact, this de pendency was no longer evident. Pamidronate was the only agent tested which suppressed the increase in bone resorption associated with macro phage exposure to bone cement particles to levels which were not signi ficantly different from unexposed calvaria. By delaying or preventing bone resorption associated with macrophage exposure to bone cement par ticles, bisphosphonates may have a clinical role in cemented joint art hroplasty by decreasing the rate or incidence of aseptic loosening and prolonging implant longevity. (C) 1996 John Wiley & Sons, Inc.