BACKGROUND: Mixed CLA isomers variably affect bone resorption in animals and decrease osteoclast formation and activity in murine osteoclasts. These variable effects may be due to the different isomers present in commercial preparations of CLA, and the effects of the predominant individual isomers, 9cis,11trans (9,11) and 10trans,12cis (10,12) CLA are not clear. The objectives of this study were to determine the effects of the individual CLA isomers on osteoclast formation and activity from human CD14+ monocytes, and to determine whether any changes are accompanied by changes in cathepsin K, matrix metalloproteinase-9 (MMP-9), receptor activator of NF-kappaB (RANK) and tumour necrosis factor alpha (TNFalpha) gene expression. Osteoclasts were identified as TRAP+ multinucleated cells. Osteoclast activity was quantified by the amount of TRAP in the cultured media. RESULTS: At 50 microM, 9,11 CLA inhibited osteoclast formation by approximately 70%, and both 9,11 and 10,12 CLA decreased osteoclast activity by approximately 85-90%. Both isomers inhibited cathepsin K (50 microM 9,11 by approximately 60%; 10,12 by approximately 50%) and RANK (50 microM 9,11 by approximately 85%; 50 microM 10,12 by approximately 65%) expression, but had no effect on MMP-9 or TNFalpha expression. CONCLUSION: 9,11 CLA inhibits osteoclast formation and activity from human cells, suggesting that this isomer may prevent bone resorption in humans. Although 10,12 CLA did not significantly reduce osteoclast formation, it reduced osteoclast activity and cathepsin K and RANK expression, suggesting that this isomer may also affect bone resorption.