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Biomedical subjects

G S Beaupré

Publications and source records attributed to G S Beaupré.

At least 19 recordsLinked to original sources
PubMed2003

A theoretical analysis of the relative influences of peak BMD, age-related bone loss and menopause on the development of osteoporosis.

Factors that determine a post-menopausal woman's bone mineral density (BMD) include her mass at the time of skeletal maturity (peak BMD), menopause and the rate of loss she experiences as she ages. Understanding the relative influence of each of these factors may help identify important preventive treatments and provide new ways to identify women at risk for osteoporosis. In this analysis we utilize a computer model of the bone remodeling process to predict the relative influences of peak BMD, menopause and age-related bone loss on the development of osteoporosis. The delay in the onset of osteoporosis (defined as BMD <2.5 SD from the young adult mean) caused by modifying peak BMD, age-related bone loss or the age at menopause is quantified. A 10% increase in peak BMD is predicted to delay the development of osteoporosis by 13 years, while a 10% change in the age at menopause or the rate of non-menopausal bone loss is predicted to delay osteoporosis by approximately 2 years, suggesting that peak BMD may be the single most important factor in the development of osteoporosis.

Adult↗
PubMed2003

Mechanobiology of soft skeletal tissue differentiation--a computational approach of a fiber-reinforced poroelastic model based on homogeneous and isotropic simplifications.

The material properties of multipotent mesenchymal tissue change dramatically during the differentiation process associated with skeletal regeneration. Using a mechanobiological tissue differentiation concept, and homogeneous and isotropic simplifications of a fiber-reinforced poroelastic model of soft skeletal tissues, we have developed a mathematical approach for describing time-dependent material property changes during the formation of cartilage, fibrocartilage, and fibrous tissue under various loading histories. In this approach, intermittently imposed fluid pressure and tensile strain regulate proteoglycan synthesis and collagen fibrillogenesis, assembly, cross-linking, and alignment to cause changes in tissue permeability (k), compressive aggregate modulus (H(A)), and tensile elastic modulus (E). In our isotropic model, k represents the permeability in the least permeable direction (perpendicular to the fibers) and E represents the tensile elastic modulus in the stiffest direction (parallel to the fibers). Cyclic fluid pressure causes an increase in proteoglycan synthesis, resulting in a decrease in k and increase in H(A) caused by the hydrophilic nature and large size of the aggregating proteoglycans. It further causes a slight increase in E owing to the stiffness added by newly synthesized type II collagen. Tensile strain increases the density, size, alignment, and cross-linking of collagen fibers thereby increasing E while also decreasing k as a result of an increased flow path length. The Poisson's ratio of the solid matrix, nu(s), is assumed to remain constant (near zero) for all soft tissues. Implementing a computer algorithm based on these concepts, we simulate progressive changes in material properties for differentiating tissues. Beginning with initial values of E=0.05 MPa, H(A)=0 MPa, and k=1 x 10(-13) m(4)/Ns for multipotent mesenchymal tissue, we predict final values of E=11 MPa, H(A)=1 MPa, and k=4.8 x 10(-15) m(4)/Ns for articular cartilage, E=339 MPa, H(A)=1 MPa, and k=9.5 x 10(-16) m(4)/Ns for fibrocartilage, and E=1,000 MPa, H(A)=0 MPa, and k=7.5 x 10(-16) m(4)/Ns for fibrous tissue. These final values are consistent with the values reported by other investigators and the time-dependent acquisition of these values is consistent with current knowledge of the differentiation process.

Algorithms↗
PubMed2003

A theoretical analysis of the changes in basic multicellular unit activity at menopause.

Bone loss at menopause is an important contributor to the development of osteoporosis in women. Although alterations in bone remodeling are the implied process through which bone is lost at menopause, how menopause influences basic multicellular units (BMUs), the teams of cells that perform bone remodeling, is not completely clear. In this analysis we utilize a computer simulation of BMU activity to evaluate the changes that occur at menopause. Transient and maintained changes in both the rate of bone turnover (expressed as the BMU birthrate or origination frequency) and the focal bone balance (differences between the amount of bone formed and resorbed at each remodeling site) are considered. The magnitude of the change in BMU activity is determined parametrically through comparison to lumbar spine bone mineral density data present in the literature. We find that a change in bone turnover that is maintained after menopause, a transient change in focal bone balance at menopause, or a combination of the two is consistent with bone loss patterns seen clinically. Understanding the changes in BMU activity that occur at menopause could lead to improved strategies to treat and prevent postmenopausal osteoporosis.

Bone Density↗
PubMed2002

The X-ray attenuation characteristics and density of human calcaneal marrow do not change significantly during adulthood.

Changes in the material characteristics of bone marrow with aging can be a significant source of error in measurements of bone density when using X-ray and ultrasound imaging modalities. In the context of computed tomography, dual-energy computed techniques have been used to correct for changes in marrow composition. However, dual-energy quantitative computed tomography (DE-QCT) protocols, while increasing the accuracy of the measurement, reduce the precision and increase the radiation dose to the patient in comparison to single-energy quantitative computed tomography (SE-QCT) protocols. If the attenuation properties of the marrow for a particular bone can be shown to be relatively constant with age, it should be possible to use single-energy techniques without experiencing errors caused by unknown marrow composition. Marrow was extracted by centrifugation from 10 mm thick frontal sections of 34 adult cadaver calcanei (28 males, 6 females, ages 17-65 years). The density and energy-dependent linear X-ray attenuation coefficient of each marrow sample were determined. For purposes of comparing our results, we then computed an effective CT number at two GE CT/i scan voltages (80 and 120 kVp) for each specimen. The coefficients of variation for the density, CT number at 80 kVp and CT number at 120 kVp were each less than 1%, and the parameters did not change significantly with age (p > 0.2, r2 < 0.02, power > 0.8 where the minimum acceptable r2 = 0.216). We could demonstrate no significant gender-associated differences in these relationships. These data suggest that calcaneal bone marrow X-ray attenuation properties and marrow density are essentially constant from the third through sixth decades of life.

Adolescent↗
PubMed2002

Long-term predictions of the therapeutic equivalence of daily and less than daily alendronate dosing.

Less than daily alendronate dosing has been identified as an attractive alternative to daily dosing for patients and physicians. A recent 2-year study found bone mineral density (BMD) changes caused by weekly alendronate dosing therapeutically equivalent to that caused by daily dosing. There are no methods that can be used to predict how long therapeutic equivalence will be maintained after the first 2 years of treatment. In addition, it is unclear if dosing less frequently than weekly also might be therapeutically equivalent to daily dosing. In this study we use a computer simulation to develop predictions of the therapeutic equivalence of daily and less than daily dosing over time periods as long as a decade. The computer simulation uses a cell-based computer model of bone remodeling and a quantitative description of alendronate pharmacokinetics/pharmacodynamics (PK/PD). The analyses suggest that less than daily dosing regimens do not increase BMD as much as daily dosing. However, model predictions suggest that dosing as frequent as weekly still may be therapeutically equivalent to daily dosing over periods as long as 10 years. In addition, the simulations predict dosing less frequently than weekly may be therapeutically equivalent to daily dosing within the first year of treatment but may not be therapeutically equivalent after 10 years. Hypotheses based on these simulations may be useful for determining which dosing regimen may be most attractive for clinical trials.

Alendronate↗
PubMed2001

Mechanical properties of the human achilles tendon.

OBJECTIVE: To determine whether the human Achilles tendon has higher material properties than other tendons and to test for strain rate sensitivity of the tendon. DESIGN: Mechanical testing of excised tendons. BACKGROUND: While the human Achilles tendon appears to experience higher in vivo stresses than other tendons, it is not known how the Achilles tendon's material properties compare with the properties of other tendons. METHODS: Modulus, failure stress, and failure strain were measured for excised human Achilles tendons loaded at strain rates of 1% s(-1) and 10% s(-1). Paired t-tests were used to examine strain rate effects, and average properties from grouped data were used to compare the Achilles tendon's properties with properties reported in the literature for other tendons. RESULTS: Failure stress and failure strain were higher at the faster strain rate, but no significant difference in modulus was observed. At the 1% s(-1)rate, the mean modulus and failure stress were 816 MPa (SD, 218) and 71 MPa (SD, 17), respectively. The failure strain was 12.8% (SD, 1.7) for the bone-tendon complex and 7.5% (SD, 1.1) for the tendon substance. At the 10% s(-1) rate, the mean modulus and failure stress were 822 MPa (SD, 211) and 86 MPa (SD, 24), respectively. The mean failure strain was 16.1% (SD, 3.6) for the bone-tendon complex and 9.9% (SD, 1.9) for the tendon substance. These properties fall within the range of properties reported in the literature for other tendons. CONCLUSIONS: The material properties of the human Achilles tendon measured in this study are similar to the properties of other tendons reported in the literature despite higher stresses imposed on the Achilles tendon in vivo.

Achilles Tendon↗
PubMed2001

Influence of bone mineral density, age, and strain rate on the failure mode of human Achilles tendons.

OBJECTIVE: To examine the influence of strain rate, bone mineral density, and age in determining the mode by which human Achilles tendons fail. DESIGN: Dual-energy X-ray absorptiometry and mechanical testing of excised Achilles tendon-calcaneus specimens. BACKGROUND: The Achilles tendon can fail by tendon rupture or bony avulsion. These injuries are caused by similar loading mechanisms and can present similar symptoms. It is important to understand when each mode of injury is likely to occur so that accurate diagnoses can be made and appropriate treatments selected. METHODS: Excised human Achilles tendons were loaded to failure at strain rates of 1% s(-1) and 10% s(-1) following dual-energy X-ray absorptiometry examination to determine bone mineral density near the tendon insertion. Calcaneal bone mineral density, donor age, and strain rate were compared between specimens that failed by avulsion and those that failed by tendon rupture. RESULTS: While strain rate was not observed to affect failure mode, the calcaneal bone mineral density of specimens that failed by avulsion was significantly lower than the bone mineral density of specimens that failed by tendon rupture (P=0.004). There was a significant decrease in bone mineral density with age (P=0.004), and the difference in age between the avulsed and ruptured specimens was close to statistical significance (P=0.058). For the avulsed specimens, there was a significant linear relationship between failure load and bone mineral density squared (P=0.002). Logistic regression indicated that the effect of age on failure mode is secondary to the primary effect of bone mineral density. CONCLUSIONS: The avulsions were primarily "premature" failures associated with low bone mineral density. Since bone mineral density decreases with age, older individuals are more likely to experience avulsions while younger individuals are more likely to experience tendon ruptures.

Absorptiometry, Photon↗
PubMed2001

Mechanobiology of initial pseudarthrosis formation with oblique fractures.

Mechanical stresses play an important role in regulating tissue differentiation in a variety of contexts during skeletal development and regeneration. It has been shown that some intermittent loading at a fracture site can accelerate secondary fracture healing. However, it has not been shown how the stress and strain histories resulting from mechanical loading of a fracture might, in some cases, inhibit normal fracture healing and induce pseudarthrosis formation. In this study, finite element analysis is used to calculate hydrostatic stress and maximum principal tensile strain patterns in regenerating tissue around the site of an oblique fracture. Using a mechanobiologic view on tissue differentiation, we compared calculated stress and strain patterns within the fracture callus to the histomorphology of a typical oblique pseudarthrosis. Tissue differentiation predictions were consistent with the characteristic histomorphology of oblique pseudarthrosis: in the interfragmentary gap. tensile strains led to "cleavage" of the callus; at the ends of both fracture fragments, hydrostatic pressure and tensile strain caused fibrocartilage formation, and, at discrete locations of the periosteum at the oblique fracture ends, mild hydrostatic tension caused bone formation. We also found that discrete regions of high hydrostatic pressure correlated with locations of periosteal bone resorption. When previous findings with distraction osteogenesis are considered with these observations, it appears that low levels of hydrostatic pressure may be conducive to periosteal cartilage formation but high hydrostatic pressure may induce periosteal bone resorption during bone healing. We concluded that tissue differentiation in pseudarthrosis formation is consistent with concepts previously presented for understanding fracture healing, distraction osteogenesis, and joint formation.

Biomechanical Phenomena↗
PubMed2001

The influence of bone volume fraction and ash fraction on bone strength and modulus.

Although bone strength and modulus are known to be influenced by both volume fraction and mineral content (ash fraction), the relative influence of these two parameters remains unknown. Single-parameter power law functions are used widely to relate bone volume or ash fraction to bone strength and elastic modulus. In this study we evaluate the potential for predicting bone mechanical properties with two-parameter power law functions of bone volume fraction (BV/TV) and ash fraction (alpha) of the form y = a(BV/TV)(b) alpha(c) (where y is either ultimate strength or elastic modulus). We derived an expression for bone volume fraction as a function of apparent density and ash fraction to perform a new analysis of data presented by Keller in 1994. Exponents b and c for the prediction of bone strength were found to be 1.92 +/- 0.02 and 2.79 +/- 0.09 (mean +/- SE), respectively, with r(2) = 0.97. The value of b was found to be consistent with that found previously, whereas the value of c was lower than values previously reported. For the prediction of elastic modulus we found b and c to be 2.58 +/- 0.02 and 2.74 +/- 0.13, respectively, with r(2) = 0.97. The exponent related to ash fraction was typically larger than that associated with bone volume fraction, suggesting that a change in mineral content will, in general, generate a larger change in bone strength and stiffness than a similar change in bone volume fraction. These findings are important for interpreting the results of antiresorptive drug treatments that can cause changes in both ash and bone volume fraction.

Biomechanical Phenomena↗
PubMed2001

A theoretical analysis of the contributions of remodeling space, mineralization, and bone balance to changes in bone mineral density during alendronate treatment.

In patients with osteoporosis, alendronate treatment causes an increase in bone mineral density (BMD) and a decrease in fracture incidence. Alendronate acts by changing the bone remodeling process. Changes in bone remodeling resulting in decreased remodeling space, increased bone balance per remodeling cycle, and increased mineralization (ash mass/bone mass) have all been associated with alendronate treatment. Understanding the relative contributions of these parameters to BMD increases could help predict the utility of long-term (>10 years) or intermittent treatment strategies, as well as treatment strategies in which another pharmaceutical is administered concurrently. We have developed a computer simulation of bone remodeling to compare the contributions of focal bone balance and mineralization on BMD by simulating alendronate treatment using a bone balance method (decreased remodeling space, increased focal bone balance, uniform bone mineralization) and a mineralization method (decreased remodeling space, neutral focal bone balance, varying bone mineralization). Although both methods are able to predict BMD increases caused by alendronate over short periods, our findings suggest that the mineralization method may be more descriptive of long-term alendronate treatment. This implies that mineralization may be a larger contributor to BMD changes caused by alendronate than the focal bone balance. Based on this finding we offer a hypothesis to describe how remodeling space, focal bone balance, and mineralization each contribute to alendronate-induced BMD changes. Future analyses with this method could be used to identify improved dosing regimens and to predict which osteoporosis treatments would best complement each other.

Alendronate↗
PubMed2000

The effect of a silane coupling agent on the bond strength of bone cement and cobalt-chrome alloy.

Debonding of the cement-implant interface has been hypothesized to be the leading initial indicator of failed total hip prostheses. Many attempts have been made to increase the bond strength of this interface by precoating the implant, increasing the implant's surface roughness, and creating macro-grooves or channels on the implant. However, each of these approaches introduces new complications. This study introduces a unique silane coupling agent used to chemically bond the bone cement to the implant. Cylindrical cobalt-chrome samples were treated with the silane coupling agent, bonded to polymethylmethacrylate, and pushed out to failure. The mean shear strengths were compared to the failure strengths of untreated samples. Half of the specimens were tested immediately following cement curing, and the other half were tested after immersion in saline solution for 60 days. The mean shear strength of the silane-coated samples ranged from 18.2 to 24.1 MPa, and the mean shear strength of the uncoated samples ranged from 7.6 to 15.0 MPa. The increase in strength following silane coating noted in this study may increase the longevity of the implant by decreasing debonding at the interface and, therefore, subsequent failure due to loosening.

Bone Cements↗
PubMed2000

Calcaneal loading during walking and running.

PURPOSE: This study of the foot uses experimentally measured kinematic and kinetic data with a numerical model to evaluate in vivo calcaneal stresses during walking and running. METHODS: External ground reaction forces (GRF) and kinematic data were measured during walking and running using cineradiography and force plate measurements. A contact-coupled finite element model of the foot was developed to assess the forces acting on the calcaneus during gait. RESULTS: We found that the calculated force-time profiles of the joint contact, ligament, and Achilles tendon forces varied with the time-history curve of the moment about the ankle joint. The model predicted peak talocalcaneal and calcaneocuboid joint loads of 5.4 and 4.2 body weights (BW) during walking and 11.1 and 7.9 BW during running. The maximum predicted Achilles tendon forces were 3.9 and 7.7 BW for walking and running. CONCLUSIONS: Large magnitude forces and calcaneal stresses are generated late in the stance phase, with maximum loads occurring at approximately 70% of the stance phase during walking and at approximately 60% of the stance phase during running, for the gait velocities analyzed. The trajectories of the principal stresses, during both walking and running, corresponded to each other and qualitatively to the calcaneal trabecular architecture.

Adult↗
PubMed2000

Reconstruction algorithm for polychromatic CT imaging: application to beam hardening correction.

This paper presents a new reconstruction algorithm for both single- and dual-energy computed tomography (CT) imaging. By incorporating the polychromatic characteristics of the X-ray beam into the reconstruction process, the algorithm is capable of eliminating beam hardening artifacts. The single energy version of the algorithm assumes that each voxel in the scan field can be expressed as a mixture of two known substances, for example, a mixture of trabecular bone and marrow, or a mixture of fat and flesh. These assumptions are easily satisfied in a quantitative computed tomography (QCT) setting. We have compared our algorithm to three commonly used single-energy correction techniques. Experimental results show that our algorithm is much more robust and accurate. We have also shown that QCT measurements obtained using our algorithm are five times more accurate than that from current QCT systems (using calibration). The dual-energy mode does not require any prior knowledge of the object in the scan field, and can be used to estimate the attenuation coefficient function of unknown materials. We have tested the dual-energy setup to obtain an accurate estimate for the attenuation coefficient function of K2 HPO4 solution.

Algorithms↗
PubMed2000

Interpretation of calcaneus dual-energy X-ray absorptiometry measurements in the assessment of osteopenia and fracture risk.

Dual-energy X-ray absorptiometry (DXA) of the calcaneus is useful in assessing bone mass and fracture risk at other skeletal sites. However, DXA yields an areal bone mineral density (BMD) that depends on both bone apparent density and bone size, potentially complicating interpretation of the DXA results. Information that is more complete may be obtained from DXA exams by using a volumetric density in addition to BMD in clinical applications. In this paper, we develop a simple methodology for determining a volumetric bone mineral apparent density (BMAD) of the calcaneus. For the whole calcaneus, BMAD = (BMC)/ADXA3/2, where BMC and ADXA are, respectively, the bone mineral content and projected area measured by DXA. We found that ADXA3/2 was proportional to the calcaneus volume with a proportionality constant of 1.82 +/- 0.02 (mean +/- SE). Consequently, consistent with theoretical predictions, BMAD was proportional to the true volumetric apparent density (rho) of the bone according to the relationship rho = 1.82 BMAD. Also consistent with theoretical predictions, we found that BMD varied in proportion to rho V1/3, where V is the bone volume. We propose that the volumetric apparent density, estimated at the calcaneus, provides additional information that may aid in the diagnosis of osteopenia. Areal BMD or BMD2 may allow estimation of the load required to fracture a bone. Fracture risk depends on the loading applied to a bone in relation to the bone's failure load. When DXA is used to assess osteopenia and fracture risk in patients, it may be useful to recognize the separate and combined effects of applied loading, bone apparent density, and bone size.

Absorptiometry, Photon↗
PubMed1999

Mechanically modulated cartilage growth may regulate joint surface morphogenesis.

The development of normal joints depends on mechanical function in utero. Experimental studies have shown that the normal surface topography of diarthrodial joints fails to form in paralyzed embryos. We implemented a mathematical model for joint morphogenesis that explores the hypothesis that the stress distribution created in a functional joint may modulate the growth of the cartilage anlagen and lead to the development of congruent articular surfaces. We simulated the morphogenesis of a human finger joint (proximal interphalangeal joint) between days 55 and 70 of fetal life. A baseline biological growth rate was defined to account for the intrinsic biological influences on the growth of the articulating ends of the anlagen. We assumed this rate to be proportional to the chondrocyte density in the growing tissue. Cyclic hydrostatic stress caused by joint motion was assumed to modulate the baseline biological growth, with compression slowing it and tension accelerating it. Changes in the overall shape of the joint resulted from spatial differences in growth rates throughout the developing chondroepiphyses. When only baseline biological growth was included, the two epiphyses increased in size but retained convex incongruent joint surfaces. The inclusion of mechanobiological-based growth modulation in the chondroepiphyses led to one convex joint surface, which articulated with a locally concave surface. The articular surfaces became more congruent, and the anlagen exhibited an asymmetric sagittal profile similar to that observed in adult phalangeal bones. These results are consistent with the hypothesis that mechanobiological influences associated with normal function play an important role in the regulation of joint morphogenesis.

Biomechanical Phenomena↗
PubMed1999

Computer model of endochondral growth and ossification in long bones: biological and mechanobiological influences.

Endochondral growth and ossification, the processes by which cartilage increases in size and is replaced by bone, are affected by biological factors such as intrinsic genetic makeup and systemic chemical agents. In addition, these processes are affected by epigenetic mechanical factors: they may be accelerated in regions of intermittent high shear stress and decelerated in regions of intermittent high hydrostatic pressure. Previous models of bone development have not incorporated both biological and mechanobiological influences on endochondral growth and ossification. We have implemented a finite element analysis to model a developing bone rudiment from 8 weeks of gestational development to approximately 2 years after birth. As a function of time, we calculated a maturity index that reflects the progression of a region of cartilage through the endochondral ossification sequence of proliferation, hypertrophy, mineralization, and replacement by bone. We calculated a specific growth rate for each region of cartilage and estimated overall longitudinal growth of the rudiment. Regions of cartilage replaced by bone were remodeled. The results from the maturity index can be compared with distributions of proliferative, hypertrophic, and mineralized cartilage seen on histology at various stages in development. The results of the simulation predicted prenatal and postnatal developmental events, including formation of a secondary ossific nucleus, a layer of articular cartilage, and a growth plate. Our results demonstrate the necessity to include biological and mechanobiological influences when endochondral growth and ossification are considered.

Animals↗
PubMed1999

Modeling of polychromatic attenuation using computed tomography reconstructed images.

This paper presents a procedure for estimating an accurate model of the CT imaging process including spectral effects. As raw projection data are typically unavailable to the end-user, we adopt a post-processing approach that utilizes the reconstructed images themselves. This approach includes errors from x-ray scatter and the nonidealities of the built-in soft tissue correction into the beam characteristics, which is crucial to beam hardening correction algorithms that are designed to be applied directly to CT reconstructed images. We formulate this approach as a quadratic programming problem and propose two different methods, dimension reduction and regularization, to overcome ill conditioning in the model. For the regularization method we use a statistical procedure, Cross Validation, to select the regularization parameter. We have constructed step-wedge phantoms to estimate the effective beam spectrum of a GE CT-I scanner. Using the derived spectrum, we computed the attenuation ratios for the wedge phantoms and found that the worst case modeling error is less than 3% of the corresponding attenuation ratio. We have also built two test (hybrid) phantoms to evaluate the effective spectrum. Based on these test phantoms, we have shown that the effective beam spectrum provides an accurate model for the CT imaging process. Last, we used a simple beam hardening correction experiment to demonstrate the effectiveness of the estimated beam profile for removing beam hardening artifacts. We hope that this estimation procedure will encourage more independent research on beam hardening corrections and will lead to the development of application-specific beam hardening correction algorithms.

Algorithms↗