1. Chapter 39 Animal Models for Osteoporosis
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FIGURE 39.1 Computer-generated voxel gradient displays of a frontal section of a proximal rat tibia from a 24-month-old male rat. (A) A frontal cutaway view of the tibia, proximal edge pointing up. The red arrows in the box point to cancellous bone that has fused completely across the proximal epiphyseal growth plate (bridges). (B) Computer-generated projection image showing all of the highlighted bridges projected onto the proximal epiphyseal growth plate of the tibia, viewed face on. Red spots indicate location of highlighted bridges. Only the frontal half of the growth plate is shown. (C) Computer-generated projection image shown in the same orientation as in part (A) (showing a frontal view of all of the highlighted bridges of the proximal tibial growth plate, proximal edge pointing up). Only the frontal half of the growth plate is shown. Source: reproduced with permission from Martin et al. (2003) [15].
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FIGURE 39.2 Periosteal resorption and cortical porosity at the tibial diaphysis in a rat model for chronic hyperparathyroidism. Compared to the control (panel A), parathyroid hormone treatment (Panel B) resulted in a dramatic increase in cortical porosity. 3
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FIGURE 39.3 Sexual dimorphism in tibia of Sprague Dawley rats resulting from gender differences in radial and longitudinal bone growth. 4
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FIGURE 39.4 Effects of estrogen on cancellous bone volume in a rapidly growing rat. Note that treatment with the hormone increases cancellous bone volume by (1) inhibiting the resorption of calcified cartilage, thereby increasing the template for deposition of new bone, and (2) suppressing the resorption of primary spongiosa. These cellular mechanisms for altering cancellous bone volume are not active in adults. 5
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FIGURE 39.5 Effects of ovariectomy on cancellous bone volume in the distal femur (A–C) and lumbar vertebra (D–F) of C57BL/6 mice. Mice were ovariectomized or sham-operated at 4 months of age and left untreated for 3 months. Note the low bone (black) volume in the distal femur of both 4- and 7-month-old mice (Von Kossa/tetrachrome stain; photographs courtesy of T. J. Wronski). 6
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FIGURE 39.6 Effects of estrogen on bone in mice. A weanling mouse was ovariectomized and administered estradiol for 6 months. Treatment was then discontinued. When analyzed 8 months later by microcomputer tomography, much of the estrogen-induced endocortical bone in the mid-shaft of the femur was still present. The pronounced osteosclerosis induced by estrogen in mice has no parallel in humans, contraindicating the use of mice as a preclinical model for pharmacological agents that may act through estrogen receptors. 7
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FIGURE 39.7 Cancellous bone area in the proximal tibia metaphysis for four cohorts (with two groups/cohort, baseline and control) of male 6-month-old Fisher 344 rats. The controls were sacrificed 2 weeks following the baseline groups (data are mean ± standard error of the mean (SE)). Although identical in age, strain, and source, mean cancellous bone area varied from 20% to 28%, a difference large enough to obscure treatment effects in multiple cohort studies. 8
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FIGURE 39.8 Microcomputed tomography images of cancellous bone in the distal femur of a mouse depicting changes in cancellous bone endpoints as a function of threshold. Note that bone volume/total volume is much more sensitive to threshold than trabecular number, which in turn is more sensitive than trabecular thickness. 9
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FIGURE 39.9 The etiology of osteoporotic fractures. 10
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