ABSTRACT
I. Introduction ............................................................................. 32
II. Human Bone — Vertebrae ....................................................... 32 A. Peak Bone Mass and Strength......................................... 32 B. Normal Age-Related Changes ........................................ 33 C. Structural Determinants of Vertebral Strength and
Mechanisms Responsible for Loss of Strength .............. 34 D. Osteoporosis .................................................................... 38
III. Measurement of Vertebral Bone Mass and Quality In Vivo and In Vitro .................................................................................. 40 A. Vertebral Bone Mass Measurements In Vivo .................. 40 B. Vertebral Bone Mass Measurements In Vitro ................. 41 C. Vertebral Bone Quality Measurements In Vivo .............. 42 D. Vertebral Bone Quality Measurements In Vitro ............. 42
IV. Rationale for Using Animal Models ....................................... 43
V. Animal Models as Preclinical Osteoporosis Models .............. 43 A. The Rat Model ................................................................. 44 B. The Large Animal Model ................................................ 44
VI. Rationale for Testing Anabolic Agents in Animal Models .... 46
VII. Effects of PTH Monotherapy on Bone Biomechanical Competence in Animal Models ............................................... 47 A. Vertebral Body ................................................................. 47 B. Femoral Neck................................................................... 47 C. Femoral Cortical Bone ..................................................... 49
VIII. Effects of PTH Cotherapy with Antiresorptive Agents ......... 49
IX. Comparison Between PTH and Other Bone Anabolic Agents ....................................................................... 51
X. Summary .................................................................................. 51
References ........................................................................................... 53
In order to develop optimum animal models for osteoporosis research, an extensive knowledge of human bone quality is needed. Bone quality is a combination of bone mass, architecture, and material strength. And all these factors change during aging, the menopause, development of osteoporosis, and also during different treatment regimens. In the following sections, normal age-related changes in human vertebral bodies will be described. Particular attention has been paid to the vertebral bodies, because vertebral fractures are the first and also the most common osteoporotic fractures. Thereafter, the need to develop animal models for osteoporosis research is described. Finally, the anabolic effects of PTH on bone quality in animal models is discussed in detail.
