Bone quality in animal models of osteoporosis

The use of animal models is a very powerful tool for the preclinical assess ment of potential therapies for osteoporosis. However, the effective use of animal models has two prerequisites. The first is the use of appropriate t echniques to assess the overall effects of therapy on bone. As spontaneous fractures do not occur in any species other than humans, the efficacy of a therapy cannot be assessed by its impact on fracture incidence. Instead, a suite of parameters (collectively referred to as 'bone quality'), including bone architecture, mineralization and mechanical properties, is examined. While techniques such as histomorphometry and dual-energy x-ray absorptiome try are useful for elucidating specific effects of therapies on bone, mecha nical testing is crucial to integrate all the changes into parameters which can serve as a proxy for fracture risk. The second prerequisite is an unde rstanding of the similarities and differences between various animal models of osteoporosis and the human case. Two important animal models of postmen opausal osteoporosis are discussed here: the ovariectomized (OVX) rat and t he non-human primate (NHP) model. The OVX rat is convenient, inexpensive an d responds rapidly to ovariectomy and to therapy at a number of cancellous sites, which is congruent to the human case. However, the OVX-induced chang es are largely confined to cancellous bone. Non-human primates, however, ar e biologically much more similar, particularly in terms of their reproducti ve physiology, to humans. The response of cortical bone of skeletally matur e NHPs to ovariectomy and other stimuli closely parallels that in humans, b ut this is not mirrored in the cancellous bone in younger animals. This sug gests that these two animal models complement each other as models for oste oporosis in humans. Drug Dev. Res. 49:146-158, 2000. (C) 2000 Wiley Liss, I nc.