This study investigated zoledronate (CGP 42′446), a bisphosphonate, as a potential prophylactic and therapeutic agent against intracortical defects in metaphyseal bone in an experimental model of inflammatory arthritis. Inflammatory arthritis was induced in the right tibiofemoral joint of rabbits by the repeated injection of carrageenan. Three groups of animals were treated with the bisphosphonate daily, beginning at different points after the induction of arthritis. Cross sections of the right distal femoral metaphysis were prepared, and intracortical defects were examined by computerized image analysis. The percentage of total bone area with defects (the ratio of void area to total bone area) was greatly increased in the arthritic group compared with that in the normal group (p <0.001). In all groups treated with the bisphosphonate, there was a significantly lower percentage of total bone area with defects compared with that in the arthritic group (p <0.001). Treatment was likewise effective in reducing the zonal (anterior and posterior) predilection for the formation of defects observed in arthritis. Although inflammatory arthritis has a substantial effect in producing intracortical defects in metaphyseal bone, a bisphosphonate, zoledronate, was considerably effective in preventing these changes from occurring.