The activity of a tartrat-resistant acid phosphatase 5B (TRACP 5b), a marker of osteoclast function, was quantified in osteoarthritic bone specimens from patients treated with Alendronate. Prior to total hip replacement, 12 patients were randomized in a bisphosphonate and a control group. The bisphosphonate group received daily oral Alendronate for 50 days before operation. After operation, the femoral heads were harvested. Samples of the anterior femoral head (A1) and the intertrochanteric area (A2) were taken, analyzed with an immunoassay and stained for TRACP 5-positive-cells. The immunoassay revealed that TRACP-5b activity of the bisphosphonate group was significantly increased in A1 compared to A2, but not of the control group. Bisphosphonate treatment decreased enzyme activity compared to the controls: 0.41 U/mg vs. 0.31 U/mg in A1 and 0.26 U/mg vs. 0.18 U/mg in A2 (p<0.05). The histological examination shows significantly less TRACP-positive cells in bisphosphonate-treated bone sections, confirming the results. Our data suggest that bisphosphonates reduce TRACP 5b activity in the intertrochanteric area rather than in the anterior femoral head. Consequently, they are more effective in areas of well-supplied bone than in osteoarthritic bone tissue.