Estradiol (E,) and testosterone(T) effectively prevent orchidectomy (orx) induced osteoporosis. T, however, Stimulates prostate proliferation which may lead to malignancy. We showed that a Cimicifuga racemosa (CR) preparation had bone-sparing effects without exerting estrogenic effects in the uterus. We Studied therefore whether a CR preparation has also antiosteoporotic effects in orx rats substituted with E-2, T or CR via pelleted food over a period of 3 months. Average daily intake per animal was: T: 25 mg; E-2: 0.325 mg, CR low close: 33 CR high dose: 133 mg, E-2 T and CR a, the high dose partially prevented development of osteoporosis as measured by quantitative computer tomography in the metaphysis of the tibia. E-2, but not T or CR reduced serum osteocalcin and the metabolic products of collagen-1 alpha 1. Gene expression of collagen-1 alpha 1 and tartrate-resistant acid phosphatase was decreased by E-2 and the higher dose of the CR extract but increased in the T-treated animals. In the prostate T inhibited androgen receptor, estrogen receptor alpha and insulin-like growth factor-1 gene expression but Stimulated the expression of the ERP gene. These effects were not shared by E-2 or both doses of the CR extract. It is concluded that E-2 T and CR exert antiosteoporotic effects in the metaphysis of the tibia of orx rats. T has profound effects in the prostate which were not seen in the E-2- and CR-treated animals. Therefore, the Cimicifuga racemosa extract BNO 1055 may be useful to prevent osteoporosis in aged male patients with reduced testosterone production. (c) 2004 Elsevier Ireland Ltd. All rights reserved.