This study assessed effects of the bisphosphonate zoledronate (ZLN) on bone density and biochemical markers of bone turnover in ovariectomized (OVX) adult female rhesus monkeys. Forty monkeys were randomly assigned to one control or four OVX groups. The control and one OVX group received saline, and the other three OVX groups received ZLN (0.5, 2.5, or 12.5 microg/kg) by a single weekly subcutaneous injection for 69 weeks. Bone mass of the total body (TB), lumbar spine (LS), distal and central radius (dual-energy X-ray absorptiometry), and skeletal turnover markers were measured at baseline and at 13, 26, 39, 52, and 69 weeks of treatment. Increased skeletal turnover and decreased bone mass (LS and TB) were demonstrable by 13 weeks post-OVX. Maximal bone loss (7-8%) at these sites occurred by 39 weeks after OVX and persisted for the study duration. Long-term ZLN treatment was well tolerated and prevented increased skeletal turnover and bone loss in a dose-dependent fashion. Progressive turnover suppression was not observed with any ZLN dose. In conclusion, after OVX, adult rhesus monkeys develop persistent increased bone turnover and absolute osteopenia of the LS and TB, making them an outstanding model of skeletal behavior in perimenopausal women. These OVX-related skeletal changes are dose-dependently blocked by ZLN.