The effect of the bisphosphonate zoledronate (CAS 118072-93-8, CGP 42446) on trabecular bone in two rat models of osteopenia, i.e. the ovariectomized rat and the adjuvant arthritic rat, was tested and compared to the activity of alendronate and pamidronate. All three bisphosphonates prevented bone loss in the distal femur and in the lumbar vertebrae in both animal models, as measured by chemical analysis and/or bone densitometry. Zoledronate was the most potent bisphosphonate, 10-30 times more potent than alendronate and 120 times more potent than pamidronate.