Stress governs tissue phenotype at the femoral insertion of the rabbit MCL.
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Animals↗
Biomedical subjects
D R Carter
Publications and source records attributed to D R Carter.
Body mass is the primary determinant of midfemoral bone acquisition during adolescent growth.
To study the determinants of bone mass and structure during adolescence, we analyzed the femoral mid-diaphysis of 375 healthy adolescents and young adults, ages 9-26 years, from four ethnic cohorts (African-American, Asian-American, Caucasian, and Hispanic). Whole-body dual-energy X-ray absorptiometry (DXA) scans were used to determine diaphyseal length and mid-diaphyseal diameter of the left femur, as well as linear bone mineral content (BMCL) of a region at the mid-diaphysis. Cross-sectional geometric properties were estimated and used to calculate two structural strength indicators: the section modulus and the whole bone strength index. When the relationships between the bone measurements and age, pubertal group, height, or body mass were evaluated, all cross-sectional femoral measures correlated most strongly with body mass. Multiple regressions accounting for gender and ethnicity provided little additional predictive value over the simple regressions with body mass alone. Furthermore, accounting for all developmental parameters (age, pubertal group, body mass, lean body mass, calcium intake, physical activity level) as well as ethnicity and gender in a single saturated model also did not generally significantly improve the predictive results achieved using only body mass. Our results indicate that increases in midfemoral bone mass and cross-sectional properties during adolescence are primarily related to increases in mechanical loading as reflected by body mass.
Adolescent↗
Developmental mechanics determine long bone allometry.
Evolutionary and developmental factors responsible for the scaling relationships observed in animal skeletons are poorly understood. We have created a mathematical model for long bone cross-sectional development which incorporates both intrinsic growth and extrinsic, adaptive bone modeling in response to changes in bone mechanical strains during ontogeny. The model successfully simulates the developing morphology in individual animals and the bone geometric allometric relationships among adults across many species (range from mouse to elephant in size). Our results suggest that long bone scaling characteristics are not a result of intrinsic genetic factors but are the results of highly conserved, extrinsic biophysical processes whereby bone tissue strains modulate skeletal morphogenesis.
Biomechanical Phenomena↗
Hindlimb suspension diminishes femoral cross-sectional growth in the rat.
Growth, functional adaptation, and torsional strength were examined in the femora of 39-day-old male Sprague-Dawley rats subjected to hindlimb suspension for 0, 1, 2, 3, or 4 weeks and were compared with measurements for age-matched control animals. Our goal was to understand the effect of reduced loading on the normal age-related changes in femoral properties during growth. The control animals exhibited growth-related increases in all geometric and torsional properties of the femur. The mean body mass and femoral length of the hindlimb-suspended rats were similar to those of the controls throughout the experiment. Over 4 weeks, the femoral cross-sectional and torsional measurements from the hindlimb-suspended rats demonstrated increases in comparison with the basal values (+33% cross-sectional area, +64% polar moment of inertia, +67% ultimate torque, and +181% torsional rigidity), but the age-matched controls showed significantly greater growth-related increases (+71% cross-sectional area, +136% polar moment of inertia, +127% ultimate torque, and +367% torsional rigidity). The differences in femoral structural strength between the hindlimb-suspended animals and the age-matched controls were attributable to differences in altered cross-sectional geometry.
Adaptation, Physiological↗
Effects of fluid-induced shear on articular chondrocyte morphology and metabolism in vitro.
This study tested the effects of fluid-induced shear on high density monolayer cultures of adult articular chondrocytes. Fluid-induced shear (1.6 Pa) was applied by cone viscometer to normal human and bovine articular chondrocytes for periods of 24, 48, and 72 hours. At 48 and 72 hours, fluid-induced shear caused individual chondrocytes to elongate and align tangential to the direction of cone rotation. Fluid-induced shear stimulated glycosaminoglycan synthesis by 2-fold (p < 0.05) and increased the length of newly synthesized chains in human and bovine chondrocytes. In human chondrocytes, the hydrodynamic size of newly synthesized proteoglycans also was increased. After 48 hours of fluid-induced shear, the release of prostaglandin E2 from the chondrocytes was increased 10 to 20-fold. In human chondrocytes, mRNA signal levels for tissue inhibitor of metalloproteinase increased 9-fold in response to shear compared with the controls. In contrast, mRNA signal levels for the neutral metalloproteinases, collagenase, stromelysin, and 72 kD gelatinase, did not show such major changes. This study demonstrated that articular chondrocyte metabolism responds directly to physical stimulation in vitro and suggests that mechanical loading may directly influence cartilage homeostasis in vivo.
Aged↗
Bone strain gage data and theoretical models of functional adaptation.
The in vivo implantation of strain gages on the surface of bones has proven to be a very useful technique for studying the relationship between in vivo loading and bone growth and adaptation. However, data from such experiments have yet to be well incorporated within the context of theoretical models of bone adaptation. Methods for analyzing bone rosette strain gage recordings within the framework of strain energy density-based computational modeling/remodeling theories are presented. A new strain energy density based parameter, energy equivalent strain, is proposed as a single scalar measure of cyclic strain magnitudes and the concept of a daily strain stimulus is also introduced. As an illustrative example, the approach is applied to analyze previously reported in vivo data from the anteromedial human tibia (Lanyon et al., 1975, Acta orthop. Scand. 46, 256-268).
Adaptation, Physiological↗
Numerical instabilities in bone remodeling simulations: the advantages of a node-based finite element approach.
Long bone structure occurs in two distinct forms. The bone mass near the joint is primarily found in a distributed, porous trabecular structure, while in the diaphyses a tubular cortical structure is formed. It seems likely that these two observed morphologies come about, at least in part, as a mechanical adaptation to the different mechanical demands in the two regions. Mathematical formulations of this dependency have been proposed, thus facilitating numerical simulations of bone adaptation. Recently two types of discontinuities have been observed in these simulations. The first type (near-field) appears in areas near distributed load application and is characterized by a 'checkerboard' pattern of density wherein adjacent remodeled elements alternate between low and high density. The second type of discontinuity (far-field) appears remote from the load application and is characterized by strut or column-like regions of elements which become fully compact bone while adjacent regions are fully resorbed. In fact, the far-field discontinuity is an accurate representation of bone physiology and morphology since it is consistent with the appearance of cortical bone in the diaphysis. On the other hand, the near-field discontinuity, appears in a region where continuous distributions of intermediate apparent densities (trabecular bone) are expected. This finding may cause some to question whether a single continuum formulation of bone remodeling can predict both discontinuous far-field behavior and continuous near-field behavior. We describe a node-based implementation of current continuum bone remodeling theories which eliminates the spurious near-field discontinuities and preserves the anatomically correct far-field discontinuities, thus indicating that a single biological process may be at work in forming and maintaining both far-field and near-field morphologies.
Algorithms↗
Computational method for determination of bone and joint loads using bone density distributions.
Because bone structure is influenced by mechanical loading during ontogeny, the geometry and density distribution of bones contain information about their loading histories. Based on a mathematical theory relating stress history to bone remodeling, we have developed a method to determine dominant bone loading conditions using an optimization procedure. We applied this load determination method using a simplified two-dimensional bone-end finite element model, for which a standard density distribution had been calculated under a given set of loading conditions. With this density distribution, the optimization procedure was used to determine the original loads from a broad set of many plausible basic load distributions and locations. The optimization procedure adjusted the magnitude of each basic load to achieve the desired tissue level attractor stress stimulus throughout the model. The results show that the density-based bone load determination method yields accurate results for basic test cases and, thus, may have potential for estimating in vivo bone loads for both extant and extinct animals.
Animals↗
Mechanical influences on tissue differentiation at bone-cement interfaces.
Retrieval studies have shown that tissue at the bone-cement or bone-implant interface can develop into fibrous tissue, fibrocartilage, and bone, and that tissue differentiation appears to be mechanically influenced. A prior histologic analysis of retrieved interface tissues supporting cemented Marmor unicondylar knee components found that beneath the central portion of these implants, a thick, mature layer of fibrocartilage consistently developed, whereas fibrous tissue formed beneath the prosthesis periphery and adjacent to the bone beneath the tibial spine. Finite-element analysis was used to model the interface tissue supporting a cemented Marmor tibial component and interpreted patterns of stress and strain generated in the interface according to a mechanically based tissue differentiation theory. Distortional strain and hydrostatic stress, mechanical stimuli that are hypothesized to be associated with fibrous matrix and cartilaginous matrix production, respectively, were found to correlate well with the previous histologic findings. Given the biologic environments in which the retrieved interface tissues developed, frequently applied hydrostatic stress of approximately 0.7 MPa may be sufficient to stimulate cartilaginous extracellular matrix production in the interface tissue, and frequently applied distortional strain of 10% may be sufficient to stimulate fibrous extracellular matrix production.
Biomechanical Phenomena↗
Long bone geometry and strength in adult BMP-5 deficient mice.
Bone morphogenetic proteins (BMPs) play a critical role in early skeletal development. BMPs are also potential mediators of bone response to mechanical loading, but their role in later stages of bone growth and adaptation has yet to be studied. We characterized the postcranial skeletal defects in mature mice with BMP deficiency by measuring hind-limb muscle mass and long bone geometric, material, and torsional mechanical properties. The animals studied were 26-week-old short ear mice (n = 10) with a homozygous deletion of the BMP-5 gene and their heterozygous control litter mates (n = 15). Gender-related effects, which were found to be independent of genotype, were also examined. The femora of short ear mice were 3% shorter than in controls and had significantly lower values of many cross-sectional geometric and structural strength parameters (p < 0.05). No significant differences in ash content or material properties were detected. Lower femoral whole bone torsional strength was due to the smaller cross-sectional geometry (16% smaller section modulus) in the short ear mice. The diminished cross-sectional geometry may be commensurate with lower levels of in vivo loading, as reflected by body mass (-8%) and quadriceps mass (-11%). While no significant gender differences were found in whole bone strength or cross-sectional geometry, males had significantly greater body mass (+18%) and quadriceps mass (+15%) and lower tibio-fibular ash content (-3%). The data suggest that adult female mice have a more robust skeleton than males, relative to in vivo mechanical demands. Furthermore, although the bones of short ear mice are smaller and weaker than in control animals, they appear to be biomechanically appropriate for the in vivo mechanical loads that they experience.
Analysis of Variance↗
The effect of dowel lubrication on retention of resin-cemented dowels.
Threaded dowels were cemented into prepared canals of extracted human teeth by use of unfilled Bis-GMA resin cement. One half the dowels were lubricated before cementation, unscrewed partially, and reseated to original length after cement had set, to assure retrievability. There was no significant difference in mean tensile force required to dislodge the dowels cemented with or without prior lubrication. Lubrication of dowels makes them predictably and easily retrievable with no short-term effect on tensile strength of the cemented lubricated dowels. Long-term effects of the lubricant on the resin are unknown.
Bisphenol A-Glycidyl Methacrylate↗
Cellular shape and pressure may mediate mechanical control of tissue composition in tendons.
In vivo studies have suggested that mechanical factors are involved in the regulation of the morphology and biochemical composition of tendons that wrap around bones. In these tendons, fibrocartilage is found in the segment wrapped around the bone, and tendon far from the bone displays normal tendon histomorphology. Recent in vitro studies have shown that intermittently loaded connective tissue cells are sensitive to changes in cellular shape and hydrostatic pressure: stretching and distortion of the cells enhances production of fibrous matrix and hydrostatic pressure enhances production of cartilaginous matrix. We used finite-element analysis to determine whether the regions of increased development of cartilaginous matrix in tendons that wrap around bones correspond to regions in which tendon cells are subjected to higher pressures, and whether the maintenance and rearrangement of fibrous extracellular matrix in these tendons is associated with regions of stretching and distortion of cells. We found that regions of cartilaginous matrix and fibrous matrix formation and turnover correlate well with patterns of hydrostatic compressive stress and distortional strain in the tendon. Although further experiments clearly are needed to establish the predictive value of our approach, hydrostatic stress and distortional strain history--parameters intimately related to changes in cellular pressure and shape, respectively--appear to be important tissue-level mechanical stimuli that regulate cartilaginous and fibrous matrix composition of connective tissues.
Animals↗
Computer simulations of stress-related bone remodeling around noncemented acetabular components.
The authors have used computer modeling techniques to examine stress-related bone changes in the acetabular region. Using a previously developed theory for bone development and adaptation, the authors simulated the distribution of bone density in the natural pelvis as well as changes in bone density following total hip arthroplasty. The geometry of the finite element model was based on a two-dimensional slice through the pelvis. Starting from a solid, homogeneous structure, the computer simulations predicted the distribution of bone density throughout the natural pelvis. The predicted bone density distribution in this first simulation agreed well with the actual bone density distribution only when loads representing multiple activities were incorporated. Using the predicted density distribution as a starting point the authors modified the finite element models to study two designs of noncemented, metal-backed acetabular cups. The simulations with fully fixed bone-implant interfaces predicted extensive loss of bone density medial and inferior to the prosthetic components. The simulations with loose interfaces led to more moderate losses of bone density, indicating a load transfer more similar to that which occurs in the natural joint. The differences in simulated bone remodeling between the two component designs were quite minimal. These results indicate that acetabular components with full bony ingrowth may induce significant stress-related bone remodeling due to a nonphysiologic transfer of load.
Bone Density↗
Genes for the establishment and maintenance of lysogeny by the temperate coliphage 186.
To identify the genes in coliphage 186 that are required for lysogeny, we isolated clear-plaque mutants. Complementation studies and DNA sequencing identified two genes, the cI gene for the immunity maintenance repressor and the cII gene, which is required only for the establishment of lysogeny. One mutant carried a change in the LexA-binding site controlling expression of the antirepression protein Tum.
Bacterial Proteins↗
New approaches for interpreting projected bone densitometry data.
Bone densitometry using dual-photon absorptiometry (DPA) or dual-energy x-ray absorptiometry (DXA) has become a standard method for assessing bone mineral content in the spine and other skeletal regions. A projected areal density, referred to as bone mineral density (BMD,g/cm2), is normally calculated to assess regional bone density and strength. We demonstrate that this measure can be misleading when used to compare bones of different sizes due to inherent biases caused by bone thickness differences. For example, assuming that volumetric bone density remains constant and bony linear dimensions are proportional to height, a 20% increase in height would result in a 20% increase in both the thickness and the BMD of any bone. We describe new analysis methods to reduce the confounding effect of bone size, and we introduce a parameter, bone mineral apparent density (BMAD, g/cm3), that better reflects bone apparent density. Using this parameter, we calculate a quantity that serves as an index of bone strength (IBS, g2/cm4) for whole vertebral bodies. These analyses were applied to lumbar spine (L2-4) DXA measurements in a population of women 17-40 years old and appear to offer advantages to conventional techniques.
Absorptiometry, Photon↗
Effects of resistance and endurance exercise on bone mineral status of young women: a randomized exercise intervention trial.
A substantial body of cross-sectional data and a smaller number of intervention trials generally justify optimism that regular physical activity benefits the skeleton. We conducted an 8 month controlled exercise trial in a group of healthy college women (mean age = 19.9 years) who were randomly assigned to a control group or to progressive training in jogging or weight lifting. We measured the following variables: bone mineral density (BMD) of the spine (L2-4) and right proximal femur using dual-energy x-ray absorptiometry, dynamic muscle strength using the 1-RM method, and endurance performance using the 1.5 mile walk/run field test. A total of 31 women completed the 8 month study. For women completing the study, compliance, defined as the percentage of workout sessions attended, was 97% for the runners (range 90-100%) and 92% (range 88-100%) for the weight trainers. Body weight increased by approximately 2 kg in all groups (p less than 0.05). Weight training was associated with significant increases (p less than 0.01) in muscle strength in all muscle groups. Improvement ranged from 10% for the deep back to 54% for the leg. No significant changes in strength scores were observed in the control or running groups. Aerobic performance improved only in the running group (16%, p less than 0.01). Lumbar BMD increased (p less than 0.05) in both runners (1.3 +/- 1.6%) and weight trainers (1.2 +/- 1.8%). These results did not differ from each other but were both significantly greater than results in control subjects, in whom bone mineral did not change.(ABSTRACT TRUNCATED AT 250 WORDS)
Absorptiometry, Photon↗
Skeletal development and bone functional adaptation.
The role of in vivo mechanical loading histories in normal skeletogenesis is related to the process of adaptive, stress-regulated bone remodeling in the adult. The results of many previous computer models for endochondral ossification and bone modeling and remodeling are reviewed. These studies support the view that simple stress-related mathematical algorithms or "construction rules" can be used to emulate normal skeletal development and architectural construction. Such mathematical rules presumably represent the net result of biophysical phenomena influencing cell metabolism and biosynthetic activity. These rules are also successful in describing the adaptation of adult bone to changes in tissue stresses. The findings suggest that stress-related functional adaptation in mature bones may be merely the adult manifestation of the same mechanical construction rules that guide and constrain normal development.
Adaptation, Physiological↗
Rabbit knee immobilization: bone remodeling precedes cartilage degradation.
This study analyzed processes underlying osteoporosis and osteoarthrosis after short-term immobilization of the right hind limb of postadolescent (2.8 kg) and mature (4.0 kg) rabbits. After 3 weeks, the lateral posterior aspect of the lateral tibial plateau and the lateral femoral condyle of the immobilized limb exhibited prominent subchondral vascular eruptions. Femoral metaphyseal bone density decreased 27 and 18% in the immobilized limbs of postadolescent and mature rabbits, respectively. Calcein green fluorescence increased 1.9-fold (p less than 0.001) in the metaphyseal trabeculae of immobilized femurs. With immobilization, sulfate incorporation into femoral cartilage glycosaminoglycan increased, although total cartilage glycosaminoglycan and hydroxyproline levels were unchanged. Thymidine incorporation into DNA increased four- to fivefold in tibial and femoral cartilage of the immobilized limb. In this study, bone loss and remodeling preceded erosive cartilage degradation.
Animals↗