Evaluation of changes in trabecular bone architecture and mechanical properties of minipig vertebrae by three-dimensional magnetic resonance microimaging and finite element modeling.

The study objective was to analyze the three-dimensional (3D) trabecular architecture and mechanical properties in vertebral specimens of young and mature Sinclair minipigs to assess the relative contribution of architecture to bone strength. We used 3D magnetic resonance microimaging (MRmicroI) and direct image analysis to evaluate a set of standard structural measurements and new architectural descriptors of trabecular bone in biopsy specimens from L2, L3, and L4 vertebrae (n = 16 in each group) from young (mean age, 1.2 years) and mature (mean age, 4.8 years) minipigs. The measurements included bone volume/tissue volume (BV/TV), marrow star volume (Ma.St.V), connectivity density (ConnD), and two new parameters, percent platelike trabeculae (% plate) and percent bone in the load direction (% boneLD). The % plate, calculated from surface curvature, allowed the delineation of plates from rods. The % boneLD quantified the percentage of bone oriented along the long axis of the vertebral body. We showed that 3D MRmicroI can detect the subtle changes in trabecular architecture between the two age groups. ConnD, star volume, % plate, % boneLD, and BV/TV were found to be more effective than the model-based, derived indices (trabecular thickness [Tb.Th], trabecular separation [Tb.Sp], and trabecular number [Tb.N]) in differentiating the structural changes. BV/TV, % plate, and % boneLD significantly increased (p < 0.05) in all three vertebral sites of the mature minipigs. The significant decrease in ConnD and star volume in the mature vertebra was consistent with the concurrent increase of platelike trabecular bone (p < 0.05). Overall, ConnD, star volume, % plate, and % boneLD provided a coherent picture of the architectural changes between the two age groups. Apparent modulus and maximum stress were determined experimentally on biopsy specimens from L2 vertebrae (n = 16). When apparent modulus was predicted using 3D MRmicroI data sets as input for finite element modeling (FEM), the results were similar to the experimentally determined apparent modulus (p = 0.12). Both methods were then used to compare the young and the mature animals; the experimental and predicted apparent modulus were significantly higher for the mature group (p = 0.003 and 0.012, respectively). The experimental maximum stress in the vertebra of the mature animals was twice as high as that for the young animals (p = 0.006). Bone quantity (BV/TV or bone mineral content [BMC]) alone could explain approximately 74-85% of the total variability in stress and modulus. The inclusion of either ConnD or % boneLD with BV/TV in a multiple regression analysis significantly improved the predictability of maximum stress, indicating that architecture makes additional contributions to compressive strength in normal minipig vertebra.

The ferret as a small animal model with BMU-based remodeling for skeletal research.

UNLABELLED: The need exists for a small animal model with bone metabolic unit (BMU)-based remodeling to mimic the bone loss found in postmenopausal women. The purpose of this investigation was to evaluate the ferret as a potential model for skeletal research. Specifically, we determined whether the ferret: 1) exhibits evidence of BMU-remodeling, 2) has a skeletal response to parathyroid hormone (PTH) similar to other remodeling species, and 3) loses bone in response to reduced estrogen levels. METHODS: Using three sets of experiments, we determined the response of female ferrets to ovariectomy/light cycle manipulation or to administration of PTH. Scanning electron microscopy, light microscopy, determination of estrogen levels and/or single-photon absorptiometry (SPA) were used for evaluation. RESULTS: The ferret was found to exhibit BMU-based remodeling, and may therefore provide a small animal remodeling species for skeletal research. Ferrets reach skeletal maturity between four and seven months of age as evidenced by closure of the growth plate and maturation of trabecluae from thin rods to thick rods and plates. PTH treatment resulted in a marked increase in bone mass accompanied by the PTH-induced tunneling phenomenon known to occur in dogs and humans but not rats. The response to PTH supports the use of the ferret in studies of bone anabolic agents. Bone mass in the proximal tibia was significantly reduced when estrogen depletion was induced by either bilateral ovariectomy or short light/dark cycles (8 hour light, 16 hour dark). Maintenance of intact ferrets under short-light conditions mimiced ovariectomy in terms of serum estrogen levels, uterine weights, and tibial BMD.(ABSTRACT TRUNCATED AT 250 WORDS)

Bone architecture and image synthesis.

3-D bone architecture can now be measured by micro-computer tomography or micro-magnetic resonance imaging. The principles of the micro-computer technique is reviewed and new architectural parameters can be computed. In addition, the method allows the contruction of polymer models by stereolithography, a method that can be used to perform repetitive mechanical studies on the same bone sample. These non destructive methods are interesting in the pre-clinical studies on bone diseases and in the investigation of animal trials on new pharmacological compounds active on bone.