Biomedical subjects

J L Kuhn

Publications and source records attributed to J L Kuhn.

18 recordsLinked to original sources

PubMed1998

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).

Animals↗

PubMed1998

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.

Animals↗

PubMed1997

Characterization of regional and age-related variations in the growth of the rabbit distal femur.

Fluorochrome labeling and microcomputed tomography were used to completely characterize the regional and age-related variations in bone growth in the distal femur of the young rabbit. Use of the microcomputed tomography system, in conjunction with the more routine fluorochrome labeling, allows the investigation of changes in shape that occur during development. The growth plate in the distal femur studied here is remarkable for several reasons. First, growth rates of as much as 700 microns/day were measured, a much higher rate than those typically measured in other species or in more mature animals. In addition, regional variations in bone growth rates of as much as 300 microns/day were identified in the 6-week-old rabbit. These variations resulted in the formation of a complex curvature in the growth plate, including four mammillary processes. Identifying the factors that regulate this type of regional variation may be especially useful in understanding the causes for angular deformities such as tibia vara or developmental dysplasias.

Age Factors↗

PubMed1996

Type-I collagen mutation compromises the post-yield behavior of Mov13 long bone.

Despite recent advances in our understanding of the molecular basis of skeletal fragility, little is known about how these molecular alterations lead to whole bone brittleness. In the current study, we investigated the relationship between a type-I collagen mutation and post-yield behavior of whole bone in Mov13 transgenic mice by considering tissue-level organizational issues known to be important for normal bone fracture. Mechanical assays revealed that the post-yield deflection of Mov13 femurs was reduced by 61% relative to littermate controls. Fractographic images revealed that lamellar interfaces which were important for dissipating energy during the failure process of control femurs, were not effective in Mov13 mice. Further investigation revealed that a 22% reduction in bone collagen content, a 2-fold increase in tissue porosity, and significant alterations in collagen organization interfered with normal energy dissipation mechanisms of Mov13 microstructure. Collectively, the results provided the first evidence that the reduced ductility associated with a type-I collagen mutation was mediated by alterations in intermediate structures that normally contribute to the post-yield behavior of cortical bone. The results suggest that, to better understand the pathogenesis of skeletal fragility, it is important to consider the effects of molecular alterations on higher-level structures, particularly those structures that contribute to the failure mechanisms in normal bone.

Animals↗

PubMed1996

Relationship between bone growth rate and hypertrophic chondrocyte volume in New Zealand white rabbits of varying ages.

The dynamics of longitudinal bone growth are very complex, and potential targets for control could be any one of a number of cells or physiologic processes. Previous studies have demonstrated a linear relationship between hypertrophic cell morphology and bone growth rate in various growth plates and animals. It is unclear whether this relationship varies with age or growth plate. This study tested for significant correlations between mean terminal hypertrophic cell volume and bone growth rate as a function of age and growth plate in the New Zealand White rabbit. Three male rabbits in each of five age groups (2, 3, 5, 8, and 12 weeks old) were used to analyze growth plates from the proximal femur, proximal tibia, and proximal and distal radius. With use of tetracycline labeling and stereological techniques, bone growth rates and hypertrophic chondrocyte volumes were measured. The data were stratified by age and growth plate location and were analyzed using linear regressions. Analyses of covariance were used to test for significant differences. First, there were significant differences due to age. Linear relationships between bone growth rate and hypertrophic chondrocyte volume existed only for the older age groups (all r2 > 0.8), not for the 2 or 3-week-old groups. Also, the slope of the relationship was significantly higher in 5-week-old rabbits than in the 8 and 12-week-old groups. Second, there were significant differences between species. A comparison of the rabbit data with pig and rat data in the literature showed significant differences between all three species. Third, significant differences between growth plates were found. Although hypertrophic chondrocyte volume plays an important role in bone growth, its function may be dependent on age, species, and location.

Aging↗

PubMed1995

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)

Adult↗

PubMed1994

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.

Adult↗

PubMed1993

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.

Aging↗

PubMed1992

Aggrecan core protein is expressed in membranous bone of the chick embryo. Molecular and biomechanical studies of normal and nanomelia embryos.

The recessive mutation nanomelia blocks the synthesis of a large aggregating proteoglycan (aggrecan) by avian embryo chondrocytes. Lack of aggrecan is associated with short stature, multiple morphological defects in cartilage, and embryo lethality. Bony defects have also been described, but were assumed to be a secondary consequence of the cartilage defect. However, two lines of evidence presented in this paper indicate that the aggrecan deficiency directly affects intramembranous bone. First, the morphology (i.e. projected area and shape) of certain membranous bones of nanomelia embryos was abnormal. Second, membranous bone from nanomelia embryos proved to be significantly stiffer in biomechanical tests that measured functional properties of the extracellular matrix. These findings were unexpected because intramembranous bones normally develop from mesenchyme and not from a cartilage intermediate, and they prompted a search for evidence of aggrecan expression in the bone of normal chick embryos. We report that: 1) aggrecan mRNA was identified by PCR analysis of total RNA isolated from day-13 chick embryo calvarium, 2) the PCR method successfully amplified aggrecan mRNA from primary chick embryo osteoblasts in culture, 3) in situ hybridization of membranous bone tissue sections demonstrated aggrecan expression by chick embryo osteoblasts in vivo, and 4) the aggrecan message was identified in Northern blots of calvarial mRNA probed at high stringency. The results of the molecular and biomechanical studies provide evidence that aggrecan is indeed expressed in membranous bone as well as cartilage. Altogether, these results suggest that aggrecan may contribute to the functional properties and the normal growth and development of avian membranous bone.

Aggrecans↗

PubMed1991

Evaluation of orthogonal mechanical properties and density of human trabecular bone from the major metaphyseal regions with materials testing and computed tomography.

We evaluated the orthogonal mechanical properties of human trabecular bone from the major metaphyseal regions with materials testing and quantitative computed tomography (CT). The proximal tibia, distal femur, proximal femur, distal radius, and proximal humerus from fresh cadaver specimens between the ages of 55 and 70 years were excised and prepared for experimentation. The bones were embedded and scanned at 1 or 1.5 mm intervals on a Technicare HPS 1440 and GE 9800 CT scanner. After scanning, the bones were sectioned, producing 8-mm cubes of trabecular bone which were mechanically tested in uniaxial compression at a strain rate of 1%. The testing sequence consisted of preyield tests in two of the three orthogonal directions and failure in the third. After testing, the cubes were evaluated for apparent density and ash weight. The results of the study show that the strength and stiffness of trabecular bone varies significantly within metaphyseal regions and from metaphysis to metaphysis. The power and significance of relationships between density and modulus varied as a function of metaphyseal location. Both linear and nonlinear models were significant, suggesting that trabecular deformation occurs in response to both axial and bending loads. Finally, the need for architectural measures of trabecular bone to predict mechanical properties is emphasized.

Aged↗

PubMed1991

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.

Animals↗

PubMed1990

Morphometric and anisotropic symmetries of the canine distal femur.

The purpose of this study was to investigate the homotypical variation in morphologic and anisotropic properties of trabecular bone from paired canine distal femurs. A microcomputed tomography system was used to produce three-dimensional digital reconstructions of the trabecular bone structures. The results showed that the mean bilateral differences in all bone morphology variables were less than 5%. Differences in measures of degree of anisotropy were also less than 5% between matched sites from left and right sides. In general, the bilateral difference in angle of orientation was less than 15 degrees. These data are valuable for calculating the appropriate sample size to use in experiments using the contralateral canine femur as a control. The results and general approach of the study may have significance for the future use of other contralateral trabecular bone sites as controls.

Animals↗

PubMed1990

Evaluation of a microcomputed tomography system to study trabecular bone structure.

A new microcomputed tomography (micro-CT) system and thresholding procedure was evaluated as a tool for nondestructive analysis of trabecular bone. Images of 6-mm trabecular bone cubes acquired from the micro-CT system were compared with optical images of corresponding histologic sections to determine the accuracy of representation. The stereologic measures of bone volume fraction (PP) and trabecular plate density (PL) were used to quantify the comparisons. The results showed that the micro-CT measures of PP were not significantly different from those measured from histologic sections and therefore were very accurate. Measures of PL were different by approximately 14%, which translated into discrepancies in trabecular plate thicknesses of about 19 microns. This difference was significantly correlated to the microstructural characteristics of the specific specimen scanned. The precision of both measurements was excellent.

Bone and Bones↗

PubMed1990

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.

Bone Density↗

PubMed1989

Comparison of the trabecular and cortical tissue moduli from human iliac crests.

The purpose of this study was to design a method to produce and test mechanically microspecimens of trabecular and cortical tissue from human iliac crests, and compare their measured moduli. Rectangular beam specimens were prepared on a low-speed diamond blade saw and a miniature milling machine. The final specimen dimensions ranged from approximately 50-200 microns for base and height. The modulus of each specimen was measured using three-point bending tests across a span length of 1.04 mm and performed at a constant rate of displacement. A subset of specimens was recovered for a radiographic estimation of degree of mineralization. The results showed the mean trabecular tissue modulus of all iliac crest specimens to be 3.81 GPa, whereas cortical tissue specimens averaged 4.89 GPa. This was a significant difference according to a two-way analysis of variance that controlled for differences between donors. No strong correlations were found between modulus and mineral density. Future investigations that consider other microstructural characteristics and their contributions to modulus, and specimen size effects, are indicated.

Bone and Bones↗

PubMed1989

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.

Animals↗

PubMedDate not supplied

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.

Absorptiometry, Photon↗

PubMedDate not supplied

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

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 child's chronologic age.

Adolescent↗