Biomedical subjects

D P Fyhrie

Publications and source records attributed to D P Fyhrie.

At least 19 recordsLinked to original sources

PubMed2007

On sampling bones for microcracks.

This paper addresses the problem of designing experiments to measure microcrack density in cortical bone. Microcracks are relatively scarce in bone cross-sections, and their size requires microscope settings having small fields of view. Thus, substantial time is required to count cracks in each cross-section. Consequently, most studies evaluate a relatively small cross-sectional area from each specimen, the chance of finding a crack in any given field is small, and there is a significant chance of not finding even one crack in the specimens representing a particular subject. Therefore, a statistical model for microcrack counting was created to develop guidelines for sampling bones for microcracks. Three questions were addressed. 1) What are the relationships of sample size to variability in microcrack density results and the probability of crackless specimens? 2) How can sample size be chosen a priori so as to reduce the probability of crackless specimens and the associated variability in the data to an acceptable level? 3) What are the confidence intervals for the mean density of microcracks measured using microscopic counting? Using a Poisson model for the distribution of microcracks within microscope fields the total area (mm(2)) that should be examined for each specimen is given by A(s)=-ln(F)/Cr.Dn, where Cr.Dn is the expected microcrack density for an individual sample and F is the desired probability (expressed as a fraction) that the individual sample will contain no microcracks. This equation is validated against 8 results from three different experiments.

Animals↗

PubMed2006

Comparison of the linear finite element prediction of deformation and strain of human cancellous bone to 3D digital volume correlation measurements.

The mechanical properties of cancellous bone and the biological response of the tissue to mechanical loading are related to deformation and strain in the trabeculae during function. Due to the small size of trabeculae, their motion is difficult to measure. To avoid the need to measure trabecular motions during loading the finite element method has been used to estimate trabecular level mechanical deformation. This analytical approach has been empirically successful in that the analytical models are solvable and their results correlate with the macroscopically measured stiffness and strength of bones. The present work is a direct comparison of finite element predictions to measurements of the deformation and strain at near trabecular level. Using the method of digital volume correlation, we measured the deformation and calculated the strain at a resolution approaching the trabecular level for cancellous bone specimens loaded in uniaxial compression. Smoothed results from linearly elastic finite element models of the same mechanical tests were correlated to the empirical three-dimensional (3D) deformation in the direction of loading with a coefficient of determination as high as 97% and a slope of the prediction near one. However, real deformations in the directions perpendicular to the loading direction were not as well predicted by the analytical models. Our results show, that the finite element modeling of the internal deformation and strain in cancellous bone can be accurate in one direction but that this does not ensure accuracy for all deformations and strains.

Anisotropy↗

PubMed2005

Matrix concentration of insulin-like growth factor I (IGF-I) is negatively associated with biomechanical properties of human tibial cancellous bone within individual subjects.

Insulin-like growth factor-I (IGF-I), abundant in bone matrix, is believed to play an important role during bone development and remodeling. To our knowledge, however, few studies have addressed the relationship between the concentration of IGF-I in bone matrix and the biomechanical properties of bone tissue. In this study, forty-five cylindrical specimens of cancellous bone were harvested from six human tibiae and scanned using micro-computed tomography (microCT). The bone volume fraction (BV/TV) was calculated from three-dimensional (3D) microCT images. Mechanical tests were then performed on a servohydraulic testing system to determine the strength and stiffness of cancellous bone. Following mechanical testing, the concentration of IGF-I in bone matrix was measured by using an enzyme-linked immunoabsorbent assay (ELISA). Within each subject, the concentration of IGF-I in bone matrix had significant (P<0.01) negative correlations with the bone volume fraction, strength, and stiffness of cancellous bone. In particular, the anterior quadrant of the proximal tibia was significantly (P<0.02) greater in IGF-I matrix concentration and marginally significantly lower in strength (P=0.053) and stiffness (P=0.059) than the posterior quadrant. The negative correlations between the cancellous bone matrix concentration of IGF-I and cancellous bone biomechanical properties within subjects found in this study may help us understand the variation of the biomechanical properties of cancellous bone in proximal human tibiae.

Biomechanical Phenomena↗

PubMed2005

Long-term ovariectomy decreases ovine compact bone viscoelasticity.

Changes in bone mineral density associated with estrogen depletion in humans do not account for all of the associated change in fracture risk, and it is possible that some of this variation may lie in changes of other aspects of bone quality. The purpose of this study was to investigate changes in viscoelastic behavior of compact bone that may be associated with estrogen depletion. Changes in compact bone viscoelastic properties associated with three years of ovariectomy were investigated with dynamic mechanical analysis (low-amplitude 3-point bending at frequencies of 1-20 Hz) using beams milled from the diaphysis of the ovine radius. The viscoelastic storage modulus was significantly (5.2%) lower at the higher frequencies for the ovariectomized animals. The general anatomic variation in storage modulus, in which cranial sectors had higher values than caudal sectors, did not change with ovariectomy. The loss tangent (tandelta, a measure of damping) was also greatly decreased (up to 83%) at high frequencies in the ovariectomized animals. Anatomic variation in tandelta at low (6-12 Hz) frequencies (cranial and caudal sectors having higher values than lateral or medial sectors) was enhanced with ovariectomy. Changes in viscoelastic properties associated with long-term estrogen depletion could be responsible for a significant reduction in the toughness or strength of a bone without concomitant changes in screening modalities used to evaluate bone quality (e.g., DXA, QCT, QUA).

Animals↗

PubMed2004

Determinants of ovine compact bone viscoelastic properties: effects of architecture, mineralization, and remodeling.

Significant decreases in ovine compact bone viscoelastic properties (specifically, stress-rate sensitivity, and damping efficiency) are associated with three years of ovariectomy and are particularly evident at higher frequencies [Proc. Orthop. Res. Soc. 27 (2002) 89]. It is unclear what materials or architectural features of bone are responsible for either the viscoelastic properties themselves, or for the changes in those properties that were observed with estrogen depletion. In this study, we examined the relationship between these viscoelastic mechanical properties and features involving bone architecture (BV/TV), materials parameters (ash density, %mineralization), and histologic evidence of remodeling (%remodeled, cement line interface). The extent of mineralization was inversely proportional to the material's efficiency in damping stress oscillations. The damping characteristics of bone material from ovariectomized animals were significantly more sensitive to variation in mineralization than was bone from control animals. At low frequencies (6 Hz or less), increased histologic evidence of remodeling was positively correlated with increased damping efficiency. However, the dramatic decreases in stress-rate sensitivity that accompanied 3-year ovariectomy were seen throughout the bone structure and occurred even in areas with little or no secondary Haversian remodeling as well as in areas of complete remodeling. Taken together, these data suggest that, while the mineral component may modify the viscoelastic behavior of bone, the basic mechanism underlying bone viscoelastic behavior, and of the changes in that behavior with estrogen depletion, reside in a non-mineral component of the bone that can be significantly altered in the absence of secondary remodeling.

Animals↗

PubMed2003

Effects of vertebral bone fragility and bone formation rate on the mineralization levels of cancellous bone from white females.

Back-scattered electron microscopy was used to study mineralization levels of human iliac cancellous bone of white females (N = 49). Mineralization levels were assessed by converting bone pixel grayscale levels to atomic number (Z) using known calibration standards. The data set consisted of bone biopsies from normal and vertebral fracture subjects that had either high or low values for bone formation rate (BFR(s)) within their respective groups (fracture/low BFR(s), N = 12; fracture/high BFR(s), N = 10; normal/low BFR(s), N = 12; normal/high BFR(s), N = 15). The following three measures of mineralization were quantitatively determined for each specimen: an overall mean mineralization (Z(mean)), the mineralization of trabecular packets deep within the interior of trabeculae (Z(deep)), and the mineralization of superficial exterior packets (Z(superficial)). Two-way analysis of variance revealed that the high BFR(s) group had a significantly lower Z(superficial) than the low BFR(s) group [mean (SD) 10.383 (0.270) vs. 10.563 (0.289)], and there was no significant interaction. BFR(s) had no effect on Z(mean) or Z(deep). For the pooled data, Z(deep) was significantly higher than Z(superficial) [10.866 (0.242) vs. 10.471 (0.291)]. There was no significant difference in Z(mean), Z(deep), or Z(superficial) between normals and those with vertebral fracture, but the standard deviations of the mineralization measures in the fracture group were at least double that of the normal group. Frequency histograms show that the two groups have fundamentally different mineralization distributions. The normal group demonstrates typical Gaussian distributions centered around the mean, and the distributions of the fracture group are bimodal, with peaks occurring at either the high or low tails of the distributions of the normal group. We hypothesize that both low and high patterns of mineralization might detrimentally affect bone material properties, with low mineralization levels causing reduced stiffness and strength and high mineralization resulting in reduced fracture toughness. The degree to which the mineralization differences may affect strength and stiffness of individual elements is estimated. The higher standard deviations of mineralization measures in the fracture group may reflect an inability to properly regulate trabecular level stress and strain. Forward stepwise regression analysis showed significant relationships between Ob.S/OS and both Z(superficial) and Z(mean), suggesting that the osteoblast may play an important role in regulating mineralization.

Aged↗

PubMed2003

Polymer dynamics as a mechanistic model for the flow-independent viscoelasticity of cartilage.

The initial, rapid, flow independent, apparent stress relaxation of articular cartilage disks deformed by unconfined compressive displacement is shown to be consistent with the theory of polymer dynamics. A relaxation function for polymers based upon a mechanistic model of molecular interaction (reptation) appropriately approximated early, flow independent relaxation of stress. It is argued that the theory of polymer dynamics, with its reliance on mechanistic models of molecular interaction, is an appropriate technique for application to and the understanding of rapid, flow independent, stress relaxation in cartilage.

Animals↗

PubMed2002

Determination of bone volume by osteocyte population.

During development and growth, biological tissues and organisms can control their size and mass by regulating cell number (Raff, 1992; Conlon and Raff, 1999). Later in life both cell number and organ mass decrease (Buetow, 1985). We demonstrate that the number density of bone cells buried in the calcified matrix (osteocyte lacunar density) predicts extracellular matrix volume for both cancellous and cortical bone in a broad cross-section of the population (males and females, age range 23-91 years, r(2) = 0.98). Our hypothesis is that bone mass is determined by the control of osteocyte number, and that this is a particular instance of the control of organ size through the social controls on cell survival and death (Raff, 1992; Conlon and Raff, 1999).

Adolescent↗

PubMed2002

Fatigue damage-fracture mechanics interaction in cortical bone.

Fatigue loading causes accumulation of damage that may lead to the initiation of a macrocrack and result in a catastrophic failure of bone. The objective of this study was to examine the influence of fatigue damage on crack growth parameters in bovine cortical bone. Nineteen rectangular beam specimens (4 x 4 x 48 mm) were machined from bovine tibiae. The long axis of the beams was aligned with the long axis of bones. Using a four-point bending fatigue setup, ten specimens were fatigue-damaged to different levels as indicated by stiffness loss. A through-thickness notch was machined at the center of each damaged and undamaged beam. The notched specimens were then monotonically loaded beyond failure using a three-point bending protocol. Critical stress intensity factor, K(I), and work to critical load, W(Q), were significantly lower in the damaged group than in the undamaged group (p < 0.03). When the undamaged specimens were assigned a percent stiffness loss of zero and pooled with the damaged group, significant negative correlations of percent stiffness loss with K(I) (R = 0.58, p < 0.01), W(Q) (R = 0.54, p < 0.02), maximum load, P(max) (R = 0.59, p < 0.008), deflection at maximum load, Delta(max) (R = 0.48, p < 0.04), structural stiffness, S(max) (R = 0.53, p < 0.02), W(max) (R = 0.55, p < 0.02), and load at 1.4 mm deflection (a value beyond failure but without complete fracture), P(1.4) (R = 0.47, p < 0.05), were found. Post hoc analysis revealed that the average load-deflection curve from the damaged group was transformable into that from the undamaged group through a special shift on the load-deflection plane. Fatigue damage reduces bone stiffness and resistance to crack initiation, maximum load-carrying capacity, and deflection before and after failure in cortical bone. The data suggest there is a single rule that governs the overall effect of fatigue damage on the fracture behavior of cortical bone.

Animals↗

PubMed2001

Trabecular shear stress in human vertebral cancellous bone: intra- and inter-individual variations.

Correlation of the mean and standard deviation of trabecular stresses has been proposed as a mechanism by which a strong relationship between the apparent strength and stiffness of cancellous bone can be achieved. The current study examined whether the relationship between the mean and standard deviation of trabecular von Mises stresses can be generalized for any group of cancellous bone. Cylindrical human vertebral cancellous bone specimens were cut in the infero-superior direction from T12 of 23 individuals (inter-individual group). Thirty nine additional specimens were prepared similarly from the T4-T12 and L2-L5 vertebrae of a 63 year old male (intra-individual group). The specimens were scanned by micro-computed tomography (microCT) and trabecular von Mises stresses were calculated using finite element modeling. The expected value, standard deviation and coefficient of variation of the von Mises stress were calculated form a three-parameter Weibull function fitted to von Mises stress data from each specimen. It was found that the average and standard deviation of trabecular von Mises shear stress were: (i) correlated with each other, supporting the idea that high correlation between the apparent strength and stiffness of cancellous bone can be achieved through controlling the trabecular level shear stress variations, (ii) dependent on anatomical site and sample group, suggesting that the variation of stresses are correlated to the mean stress to different degrees between vertebrae and individuals, and (iii) dependent on bone volume fraction, consistent with the idea that shear stress is less well controlled in bones with low BV/TV. The conversion of infero-superior loading into trabecular von Mises stresses was maximum for the tissue at the junction of the thoracic and lumbar spine (T12-L1) consistent with this junction being a common site of vertebral fracture.

Adult↗

PubMed2001

Finite element calculated uniaxial apparent stiffness is a consistent predictor of uniaxial apparent strength in human vertebral cancellous bone tested with different boundary conditions.

Strong correspondence between the uniaxial apparent strength and stiffness of cancellous bone allows the use of stiffness as a predictor of bone strength. Measured values of mechanical properties in cancellous bone can be different between experiments due to different experimental conditions. In the current study, bone volume fraction, experimentally determined and finite element (FE) predicted stiffness were examined as predictors of cancellous bone ultimate strength in two different groups each of which was tested using a different end constraint. It is demonstrated that, although always significant, the relationships of strength with bone volume fraction and experimentally determined stiffness are different between test groups. Apparent stiffness, estimated by FE modeling, predicts the ultimate strength of human cancellous bone consistently for all examined experimental protocols.

Adult↗

PubMed2001

Influence of nonenzymatic glycation on biomechanical properties of cortical bone.

In this study, the influence of nonenzymatic glycation (NEG) on the mechanical properties of bone and bone collagen were investigated. Bovine cortical bone specimens were incubated in ribose to cause collagen cross-links in vitro, and nondestructive mechanical testing was used to determine tensile and compressive elastic modulus as a function of incubation time. Mechanical properties associated with yield, postyield, and final fracture of bone were determined at the end of the incubation period. The stiffness of the collagen network was measured using stress relaxation tests of demineralized bone cylinders extracted periodically throughout the incubation period. It was found that accumulation of nonenzymatic glycation end-products in cortical bone caused stiffening of the type I collagen network in bone (r2 = 0.92; p < 0.001) but did not significantly affect the overall stiffness of the mineralized bone (p = 0.98). The ribosylated group had significantly more NEG products and higher yield stress and strain than the control group (p < 0.05). Postyield properties including postyield strain and strain energy were lower in the ribosylated group but were not significantly different from the control group (p = 0.24). Compared with the control group, the ribosylated group was characterized by significantly higher secant modulus and lower damage fraction (p < 0.05). Taken together, the results of this study suggest that collagen in bone is susceptible to the same NEG-mediated changes as collagen in other connective tissues and that an increased stiffness of the collagen network in bone due to NEG may explain some of the age-related increase in skeletal fragility and fracture risk.

Animals↗

PubMed2001

Estimation of bone matrix apparent stiffness variation caused by osteocyte lacunar size and density.

The role of osteocyte lacunar size and density on the apparent stiffness of bone matrix was predicted using a mechanical model from the literature. Lacunar size and lacunar density for different bones from different gender and age groups were used to predict the range of matrix apparent stiffness values for human cortical and cancellous tissue. The results suggest that bone matrix apparent stiffness depends on tissue type (cortical versus cancellous), age, and gender, the magnitudes of the effects being significant but small in all cases. Males had a higher predicted matrix apparent stiffness than females for vertebral cancellous bone (p< I0(-7)) and the difference increased with age (p =0.0007). In contrast, matrix apparent stiffness was not different between males and females forfemoral cortical bone and increased with age in both males (p < 0.0001) and females (p < 0.0364). Osteocyte lacunar density and size may cause significant gender and age-related variations in bone matrix apparent stiffness. The magnitude of variations in matrix apparent stiffness was small within the physiological range of lacunar size and density for healthy bone, whereas the variations can be profound in certain pathological cases. It was proposed that the mechanical effects of osteocyte density be uncoupled from their biological effects by controlling lacunar size in normal bone.

Adolescent↗

PubMed2000

Femoral structure and stiffness in patients with femoral neck fracture.

Bone morphological characteristics may relate to the risk of hip fracture. We applied finite element modeling to radiologic data for two groups of women in vivo to address two questions: (a) Do individuals who have just sustained a femoral neck fracture exhibit reduced three-dimensional structural stiffness? and (b) Are victims of hip fracture disproportionately more susceptible to loads sustained in a fall than to stance-type loads? Ten white women (age: 64-76 years) who had just sustained a femoral neck fracture and 18 female volunteers (age: 65-76 years), matched as groups for race, age. and body mass index, were evaluated. From quantitative computed tomography scans, femoral morphometric and volumetric cancellous density measurements were obtained and a finite element model was constructed. Two load conditions were simulated: single-stance phase and lateral fall. Global stiffness values were determined for each model. The cancellous bone density was significantly lower at the femoral neck and the femoral neck and head diameters were significantly larger in the women in the fracture group than in those in the control group. The stiffness of the proximal femur did not differ significantly between the groups for either load condition. An apparently linear relationship was found for stiffness at stance load compared with stiffness at fall load (r = 0.84, p < 0.001). and slopes did not differ significantly between the groups. Although cancellous density was reduced at the fracture site in patients with femoral neck fractures. this did not result in a reduction in the predicted bone stiffness. Previous studies have established a very strong relationship between the stiffness and strength of bone. Since these modeling methods were thoroughly validated ex vivo, we conclude that although decreased bone density at the femoral neck may predict where fracture initiates, the risk of hip fracture per se may be more strongly dependent on issues such as the risk of falling and fall biomechanics than on the structural characteristics of bone.

Accidental Falls↗

PubMed2000

Decline in osteocyte lacunar density in human cortical bone is associated with accumulation of microcracks with age.

Despite osteocytes' ideal position to sense the local environment and thereby influence bone remodeling, the function of osteocytes in bone remains controversial. In this study, histomorphometric examination of male and female femoral middiaphyseal cortical bone was conducted to determine if bone's remodeling response, indicated by tissue porosity and accumulation of damage, is associated with osteocyte lacunar density (number of osteocyte lacunae per bone area). The results support the sensory role of the osteocyte network as the decline in osteocyte lacunar density in human cortical bone is associated with the accumulation of microcracks and increase in porosity with age. Porosity and microcrack density increased exponentially with a decline in osteocyte lacunar density indicating that a certain minimum number of osteocytes is essential for an "operational" network. No gender-related differences were found in the relationship of osteocyte lacunar density to age, porosity, or microcrack density. The coefficient of variation of osteocyte lacunar density increased linearly with age, indicating that aging bone tissue is characterized by increased heterogeneity in the spatial organization of osteocytes. Osteocyte lacunar density, porosity, and microcrack density exhibited the same exponential probability density distribution in the donor population, indicating their regulation by similar biological phenomena.

Adolescent↗

PubMed2000

Bone stiffness predicts strength similarly for human vertebral cancellous bone in compression and for cortical bone in tension.

The yield strength and ultimate strength of cortical and cancellous bone tissue are very highly correlated to bone stiffness. For samples of human vertebral cancellous bone in compression and for bovine cortical bone in tension, the coefficient of determination (r2) for regression between ultimate strength and stiffness was 0.89 and 0.92, and between yield strength and stiffness it was 0.94 and 0.93, respectively. The slope of the regression for human vertebral cancellous bone ultimate strength predicted by stiffness was not statistically different from similar regressions for cortical bone in tension in either a bovine sample or in published data from multiple species. We believe that the observed correlation results from the evolutionary need to build sufficiently strong bones using cells that are sensitive to deformation and that directly control bone stiffness, but not strength. The practical significance of this work is that an in vivo estimate of bone stiffness (e.g., from ultrasound measurement) may be a surrogate for bone strength.

Adaptation, Physiological↗

PubMed2000

In vivo diffuse damage in human vertebral trabecular bone.

Accumulation of microdamage in vivo may lead to loss of bone quality. Until recently, linear microcracks were the only known form of in vivo microdamage, but through the use of confocal microscopy an additional level of damage (diffuse damage) has been identified. In this study, in vivo diffuse damage was characterized and quantified in human vertebral trabecular bone as a function of tissue morphology, age, race, gender, and previously quantified in vivo linear microcracks. Presence of diffuse damage in human vertebral tissue was confirmed and validated by simultaneous use of polarized, ultraviolet, and laser confocal microscopy. Diffuse damage was found to occur preferentially within trabecular packets rather than in interstitial bone (p < 0.05). It was consistently higher in men compared with women (p < 0.05), but was not different by race or age group. Diffuse damage did not correlate with linear microcracks, but both exhibited the same probability distribution in which the percentage of individuals having a particular amount of damage decreased exponentially as damage content increased. These findings suggest that diffuse damage accumulation and repair are governed by the same biological phenomena as microcracks, but diffuse damage contributes independently to the microdamage content of bone.

Adult↗

PubMed2000

Shear stress distribution in the trabeculae of human vertebral bone.

The statistical distribution of von Mises stress in the trabeculae of human vertebral cancellous bone was estimated using large-scale finite element models. The goal was to test the hypothesis that average trabecular von Mises stress is correlated to the maximum trabecular level von Mises stress. The hypothesis was proposed to explain the close experimental correlation between apparent strength and stiffness of human cancellous bone tissue. A three-parameter Weibull function described the probability distribution of the estimated von Mises stress (r2>0.99 for each of 23 cases). The mean von Mises stress was linearly related to the standard deviation (r2=0.63) supporting the hypothesis that average and maximum magnitude stress would be correlated. The coefficient of variation (COV) of the von Mises stress was nonlinearly related to apparent compressive strength, apparent stiffness, and bone volume fraction (adjusted r2=0.66, 0.56, 0.54, respectively) by a saturating exponential function [COV = A + B exp(-x/C)]. The COV of the stress was higher for low volume fraction tissue (<0.12) consistent with the weakness of low volume fraction tissue and suggesting that stress variation is better controlled in higher volume fraction tissue. We propose that the average stress and standard deviation of the stress are both controlled by bone remodeling in response to applied loading.

Adult↗