Animal Models for in Vivo Experimentation in Osteoporosis Research

Publisher Summary This chapter presents criteria for evaluating animal models of osteoporosis and then applies them using today's facts. The criteria are based on the knowledge about human osteoporosis; fundamental understanding of human and animal skeletons; experiments that use the same agent in different species; and recognition of unmet needs in osteoporosis research. Both the criteria and their evaluation should evolve with time as data about osteoporosis, each animal model, and new evaluation methods accumulate. The Food and Drug Administration has made a wise choice in requiring rat experiments during osteoporosis research. The ovariectomized rat is an excellent model that correctly emulates the most important clinical features of the estrogen-deplete adult human skeleton. Its site-specific development of cancellous osteopenia is one of the most certain physiologic responses in skeletal research. Ample time exists for experimental designs that either prevent estrogen-depletion bone loss or restore bone lost after estrogen depletion. Its response to estrogen replacement closely parallels that seen in humans. Rat's low levels of Haversian remodeling present little immediate problem when testing agents for their ability to prevent the loss of cancellous bone or rebuild lost cancellous bone. Investigators can compensate for the lack of fragility fractures by biomechanical testing. Rats are convenient for most investigators; unbred females aged 6–10 months are the optimal choice. Existing laboratory measurement tools of biochemistry, histomorphometry, densitometry, and mechanical testing are readily applicable.