ABSTRACT
The “Guideline for preclinical evaluation and clinical trials in osteoporosis” (WHO guideline) [33] requires estimation of the effects of drugs on bone strength and fracture prevention in drug ef¢cacy tests in clinical trials, because bone mineral content and bone mineral density data are insuf¢cient for the determination of drug ef¢cacy. However, the effects of drugs on bone strength and fracture prevention cannot be measured directly or non-invasively in clinical use. Therefore, indirect estimation by long-term extensive clinical trials is used to estimate the effects on fracture risk [5]. Consequently, non-clinical tests with animal disease models are required to determine the bone strength prior to long-term extensive clinical trials. Cynomolgus monkeys were commonly used for such studies. However, minipigs are attractive as an osteoporosis model because they have several characteristics in common with humans, such as remodeling bone turnover, non-seasonal cyclic estrus, and a decrease in bone mineral density associated with estrogen de¢ciency [8,19,21,22,27]. The postmenopause model in minipigs, combining ovariectomy
and a Ca-restricted diet, developed by Mosekilde et al. [23] is well known.
