ZOLEDRONATE PREVENTS THE DEVELOPMENT OF ABSOLUTE OSTEOPENIA FOLLOWINGOVARIECTOMY IN ADULT RHESUS-MONKEYS

This study assessed effects of the bisphosphonate zoledronate (ZLN) on bone density and biochemical markers of bone turnover in ovariectomiz ed (OVX) adult female rhesus monkeys. Forty monkeys were randomly assi gned 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 mu g/kg) by a single weekly subcutaneous injection for 69 we eks, Bone mass of the total body (TB), lumbar spine (LS), distal and c entral radius (dual-energy X-ray absorptiometry), and skeletal turnove r markers were measured at baseline and at 13, 26, 39, 52, and 69 week s of treatment. Increased skeletal turnover and decreased bone mass (L S 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 t he study duration. Long-term ZLN treatment was well tolerated and prev ented increased skeletal turnover and bone loss in a dose-dependent fa shion, Progressive turnover suppression was not observed with any ZLN dose. In conclusion, after OVX, adult rhesus monkeys develop persisten t increased bone turnover and absolute osteopenia of the LS and TB, ma king them an outstanding model of skeletal behavior in perimenopausal women, These OVX-related skeletal changes are dose-dependently blocked by ZLN.