The long-term objectives of this study are to evaluate, in surgically menopausal (SM) monkeys, the therapeutic effectiveness of an anabolic steroid (nandrolone decanoate) for postmenopausal bone loss (osteoporosis) and to evaluate the compound for cardiovascular disease risks. Surgically menopausal cynomolgus monkeys develop rapidly progressive osteopenia and coronary artery atherosclerosis in patterns highly analogous to those of postmenopausal women. Any compound used for the treatment of osteoporosis should consider both skeletal and cardiovascular effects.
The specific aims are: (1) to determine if anabolic steroid treatment prevents the bone loss that occurs in SM cynomolgus; (2) determine if this treatment has lasting beneficial effects; (3) determine if anabolic steroid treatment increases bone volume, density, and strength in osteopenic macaques; (4) study mechanisms by which these compounds prevent bone loss and/or restore bone; and (5) evaluate whether anabolic steroid treatment has adverse effects on the cardiovascular system. Seventy-five young adult female cynomolgus macaques will be divided into 5 groups of 15 animals each: (Group A) sham-ovariectomized; (Group B) ovariectomized (OVX), untreated; (Group C) OVX, treated with nandrolone decanoate for 24 months; (Group D) OVX, untreated for 12 months and then treated with nandrolone decanoate for 12 months; and (Group E) OVX, treated with nandrolone decanoate for the initial 12 months and then untreated for 12 months. Throughout the 24-month trial, serum markers of bone turnover, bone densitometry, plasma lipids, bone biopsies (for histomorphometry, immunocytochemistry, in situ hybridization), serum chemistry measurements, sex hormone levels, and body measurements will be evaluated. At the end of the trial, all monkeys will be necropsied and the groups compared for bone changes, cardiovascular disease risk factors and atherosclerosis.
