Janet L. Kuhn

The relationship between the structural and orthogonal compressive properties of trabecular bone

In this study, cubes of trabecular bone with a wide range of structural properties were scanned on a micro-computed tomography system to produce complete three-dimensional digitizations from which morphological and architectural parameters could be measured in a nondestructive manner. The cubes were then mechanically tested in uniaxial compression in three orthogonal directions and to failure in one direction to find the orthogonal tangent elastic moduli and ultimate strengths. After testing, the cubes were weighed and ashed to determine the apparent and ash densities. A high correlation between the basic stereologic measurements was found, indicating that there is a relationship between the amount of bone and number of trabeculae in cancellous bone. Regression analysis was used to estimate the modulus and ultimate strength; these regressions accounted for 68-90% of the variance in these measures. These relationships were dependent on the metaphyseal type and donor, with the modulus also dependent on the direction of testing. This indicates that the properties of the individual trabeculae, as well as their amount and organization, may be important in predicting the mechanical properties of cancellous bone.

The elastic moduli of human subchondral, trabecular, and cortical bone tissue and the size-dependency of cortical bone modulus☆

The elastic moduli of human subchondral, trabecular, and cortical bone tissue from a proximal tibia were experimentally determined using three-point bending tests on a microstructural level. The mean modulus of subchondral specimens was 1.15 GPa, and those of trabecular and cortical specimens was 4.59 GPa and 5.44 GPa respectively. Significant differences were found in the modulus values between bone tissues, which may have mainly resulted from the differences in the microstructures of each bone tissue rather than in the mineral density. Furthermore, the size-dependency of the modulus was examined using eight different sizes of cortical specimens (heights h = 100-1000 microns). While the modulus values for relatively large specimens (h greater than 500 microns) remained fairly constant (approximately 15 GPa), the values decreased as the specimens became smaller. A significant correlation was found between the modulus and specimen size. The surface area to volume ratio proved to be a key variable to explain the size-dependency.

Trabecular bone remodeling: An experimental model

An experimental model, capable of inducing controlled stress fields to the distal femoral metaphyses of large dogs, is presented. This model utilized an implantable hydraulic device incorporating five loading cylinders and platens in direct contact with an exposed plane of trabecular bone. A microprocessor controls the loading characteristics, and finite element models were created to calculate the induced stress and strain fields. The trabecular remodeling response is measured using serial in vivo computed tomography, in vitro microcomputed tomography, and histologic analysis. The results of the experiment indicate that significant remodeling can be induced by the activated implant. An increase in trabecular orientation toward the loaded platens was observed, and a statistically significant decrease in connectivity was documented. The greatest effect was associated with a change in the loading rate. A fast rise time (70 ms) loading waveform induced significant bone ingrowth at the implant interface when compared to a slow rise time waveform (700 ms), and demonstrated high correlations with the calculated stress fields as remodeling approached an equilibrium state.

Type I collagen mutation alters the strength and fatigue behavior of Mov13 cortical tissue

Despite advances in understanding the molecular basis of Osteogenesis Imperfecta, the mechanisms by which type I collagen mutations compromise whole bone function are not well understood. Previously, we have shown that a heterozygous type I collagen mutation is associated with increased brittleness of long bones from Mov13 transgenic mice, a model of the mild form of Osteogenesis Imperfecta. In the current study, we investigated tissue-level damage processes by testing the hypothesis that the fatigue properties of Mov13 tissue were significantly compromised relative to littermate controls. We also quantified tissue structure and mineral content to explain variations in the fatigue behavior. Micro-beam specimens were machined from the anterior and posterior quadrants of Mov13 and control femurs and subjected to cyclic bending at one of four stress levels. Mov13 tissue exhibited a 22-25% reduction in tissue bending strength and a similar reductions in fatigue life and the stress level at which damage was apparent. These results provided tissue-level evidence that damage accumulation mechanisms were significantly compromised in Mov13 cortical tissue. Given that significant alterations in tissue structure were observed in Mov13 femurs, the results of this study support the idea that Mov13 femurs were brittle because alterations in tissue structure associated with the mutation interfered with normal damage processes. These results provide new insight into the pathogenesis of Osteogenesis Imperfecta and are consistent with bone behaving as a damaging composite material, where damage accumulation is central to bone fracture.

A murine skeletal adaptation that significantly increases cortical bone mechanical properties. Implications for human skeletal fragility.

Mov13 mice carry a provirus that prevents transcription initiation of the alpha 1(I) collagen gene. Mutant mice homozygous for the null mutation produce no type I collagen and die at mid-gestation, whereas heterozygotes survive to adulthood. Dermal fibroblasts from heterozygous mice produce approximately 50% less type I collagen than normal littermates, and the partial deficiency in collagen production results in a phenotype similar to osteogenesis imperfecta type I (an inherited form of skeletal fragility). In this study, we have identified an adaptation of Mov13 skeletal tissue that significantly improves the bending strength of long bone. The adaptive response occurred over a 2-mo period, during which time a small number of newly proliferated osteogenic cells produced a significant amount of matrix components and thus generated new bone along periosteal surfaces. New bone deposition resulted in a measurable increase in cross-sectional geometry which, in turn, led to a dramatic increase in long bone bending strength.

The limitations of canine trabecular bone as a model for human: A biomechanical study

Distal canine femurs were sectioned into 8 mm cubic specimens. Orthogonal compression tests were performed to preyield in two or three directions and to failure in a third. Apparent density and ash weight density were measured for a subset of specimens. The results were compared to the human distal femur results of Ciarelli et al. (Transactions of the 32nd Annual Meeting of the Orthopaedic Research Society, Vol. 11, p. 42, 1986). Quantitative similarities existed in the fraction of components comprising the trabecular tissue of the two species. Qualitative similarities were seen in the positional and anisotropic variation of the mechanical properties, and also in the form and strength of the relationships between the mean modulus and bone density, ultimate stress and density, and ultimate stress and modulus. However, significantly different regression equations resulted for the mean modulus-density, and ultimate stress modulus relationships, indicating that for the same density, canine trabecular bone displays a lower modulus than human, and may achieve greater compressive strains before failure.

STATIC AND FATIGUE FAILURE PROPERTIES OF THORACIC AND LUMBAR VERTEBRAL BODIES AND THEIR RELATION TO REGIONAL DENSITY

This study investigated (1) whether a characterization of the macroscopic architecture within the vertebral centrum would improve predictions of vertebral strength, (2) if regions in the centrum where least bone loss with age occurs are more predictive of vertebral strength, and (3) whether different patterns of the macroscopic architecture are predictive of static as compared to fatigue strength. To characterize the vertebral macroscopic architecture, a regional bone mineral density (rBMD) technique was used that estimated the cancellous density distribution (in 18 specific regions of the vertebral centrum) for vertebrae T7-L4, from spines of 20 female cadavers. Static and fatigue failure properties of whole vertebrae were obtained, and predictive models of static and fatigue failure properties of whole vertebrae were examined. We found that (1) vertebral failure properties were better predicted by combinations of vertebral regional cancellous density (multiple linear regressions) rather than by any individual region of cancellous density alone (simple linear regressions); (2) models using regions of density that demonstrated minimum decline with age [from the data of Flynn and Cody (Calcif. Tissue Int. 53, S170-S175 (1993))] resulted in better correlations with ex vivo vertebral static failure properties than models using density regions that showed maximum decline with age, and (3) static and fatigue characteristics required different density regions to reach significance. (A comparison of models predictive of static and fatigue failure properties revealed that anterior density regions were most often included in predictive models of the static properties while posterior regions were more predictive of the fatigue properties).(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of the mechanical environment during distraction osteogenesis

Physical forces have been hypothesized to direct the process of bone regeneration during distraction osteogenesis. However, despite significant clinical experience, relatively little is known about how the mechanics of distraction influence bone formation. This study investigated net fixator forces and strains in the distraction callus during bilateral lengthening of tibiae in New Zealand White rabbits. Distractions yielded a classic viscoelastic response with a sharp increase in fixator force, followed immediately by significant relaxation. Tension acting on mesenchymal gap tissue caused by distraction was estimated to reach more than 30 N by the time full lengthening was achieved. Average maximum cyclic strains within the distraction zone during ambulation were estimated to be 14% to 15% and supported by the results of fluoroscopic imaging. Paradigms for fracture healing have hypothesized that such strains are incompatible with new bone formation. The documented clinical success of distraction osteogenesis at stimulating large volumes of new bone suggests that other mechanisms that warrant additional investigation may be at work during distraction.

Narrow window of bone age in children with slipped capital femoral epiphyses

Summary Pelvis radiographs of 30 children with slipped capital femoral epiphyses (SCFE) were reviewed by four readers to determine the skeletal age. The average chronologic age for girls was 12.1 ± 1.0 years and that for boys was 14.4 ± 1.3 years; the average pelvic bone age was 13.2 ± 0.6 for girls and 15.1 ± 0.6 years for boys. The chronologic age range was 98 months, and skeletal age range was only 50 months. Pelvis bone age was advanced in the youngest children, normal in most children, and mildly delayed in older children. We conclude that there is a uniform skeletal age or “narrow window” during which epiphyseal slipping occurs, regardless of the childs chronologic age.

Are regional variations in bone growth related to mechanical stress and strain parameters

A three-dimensional finite element analysis was used to quantify the patterns of mechanical stresses within the rabbit distal femur growth plate, and test the hypothesis that these patterns are correlated to measured patterns of bone growth rates. This investigation of normal development is the first step toward improving our understanding of the role of mechanical factors in bone growth abnormalities. Rabbits from five age groups ranging from 1 to 42 days were evaluated, and four different loading conditions were analyzed, representing specific time points in the normal gait cycle. Finite element models generated directly from micro-computed tomography images of the distal femurs identified regional variations in stress and strain parameters, similar to the variations in bone growth rates measured using fluorochrome labeling. A linear regression analysis supports the hypothesis that high compressive stresses are correlated with lower bone growth rates. However, for the loading conditions considered in this study, the variations in mechanical stress and strain parameters explain no more than 15% of the overall variations in bone growth rates. The greatest variations in both growth rates and mechanical stresses were present in the anterior frontal plane from the 42 day age group, in which correlations between reduced bone growth rates and compressive stresses were much stronger (r2 up to 0.80).