BISPHOSPHONATE INHIBITION OF BONE-RESORPTION INDUCED BY PARTICULATE BIOMATERIAL-ASSOCIATED MACROPHAGES

Aseptic loosening of total joint replacements is associated with bone resorption. A heavy infiltrate of foreign body macrophages in response to biomaterial wear particles is commonly found in the fibrous membra ne surrounding loose components. It has recently been shown that forei gn body macrophages can differentiate into osteoclastic cells. To dete rmine whether pharmacological inhibitors of bone resorption have a rol e to play in controlling the osteolysis of aseptic loosening, we analy zed the effect of a bisphosphonate, disodium ethane-1, 1-diphosphonate (EHDP) on this process. Murine monocytes and foreign body macrophages (derived from granulomas formed by subcutaneous implantation of parti cles of prosthetic biomaterials) were co-cultured with UMR106 osteobla st-like cells in the presence of 1,25 dihydroxyvitamin D-3 for 14 days on glass coverslips and bone slices. EHDP significantly inhibited bon e resorption in these co-cultures. There was little or no expression o f the osteoclast-associated enzyme, tartrate-resistant acid phosphatas e (TRAP) in EHDP-treated co-cultures. Addition of EHDP to monocyte-UMR 106 co-cultures after the appearance of TRAP-positive cells did not ab olish bone resorption, indicating that EHDP, in addition to its known inhibitory effect on osteoclast function, suppresses differentiation o f osteoclast precursors. EHDP inhibition of the osteolysis induced by particulate biomaterial-associated macrophages shows that pharmacologi cal inhibition of bone resorption might be used to control the osteoly sis of aseptic loosening.