[show abstract][hide abstract] ABSTRACT: To identify mechanotransductive signals for combating musculoskeletal deterioration, it is essential to determine the components and mechanisms critical to the anabolic processes of musculoskeletal tissues. It is hypothesized that the interaction between bone and muscle may depend on fluid exchange in these tissues by mechanical loading. It has been shown that intramedullary pressure (ImP) and low-level bone strain induced by muscle stimulation (MS) has the potential to mitigate bone loss induced by disuse osteopenia. Optimized MS signals, i.e., low-intensity and high frequency, may be critical in maintaining bone mass and mitigating muscle atrophy. The objectives for this review are to discuss the potential for MS to induce ImP and strains on bone, to regulate bone adaptation, and to identify optimized stimulation frequency in the loading regimen. The potential for MS to regulate blood and fluid flow will also be discussed. The results suggest that oscillatory MS regulates fluid dynamics with minimal mechanical strain in bone. The response was shown to be dependent on loading frequency, serving as a critical mediator in mitigating bone loss. A specific regimen of dynamic MS may be optimized in vivo to attenuate disuse osteopenia and serve as a biomechanical intervention in the clinical setting.
[show abstract][hide abstract] ABSTRACT: This paper studies the development of novel, non-invasive external dynamic hydraulic pressure muscle stimulation for bone quality enhancement, and the evaluation of the effects of this dynamic hydraulic pressure stimulation on muscle strength to further delineate the bone fluid flow mechanism. Trabecular bone structure of proximal metaphysis of the right tibia is scanned using ¿CT, and bone porosity of the whole tibia bones are evaluated using NMR analysis. Results show that this dynamic hydraulic pressure stimulation is an exciting intervention to be applied externally and noninvasively, as a novel treatment to improve bone structural quality. And it also has a great potential for future clinical application.
[show abstract][hide abstract] ABSTRACT: Medial tibial stress syndrome (MTSS) is pain or discomfort in the leg from repetitive running on hard surfaces or forcible excessive use of foot flexors. Early diagnosis is extremely critical for proper treatment and reduces complications. Quantitative ultrasound (QUS) has been widely used to assess bone quality non-invasively, it is also radiation free, repeatable, safe, relatively accurate, and suitable for multiple skeleton sites. QUS can provide useful information in diagnosing MTSS and predicting fracture risk. Studies have shown that ultrasound correlates not only with the bone density but also with the bone stiffness . This paper evaluates the ability of QUS in early prediction of bone attenuation under repetitive loading. Ovine tibias were scanned by a scanning confocal acoustic diagnostic (SCAD) system to determine the mechanical property changes after cyclic loading. SCAD revealed its ability of quantifying changes in mechanical properties at the tibial shell under cyclic loading.
[show abstract][hide abstract] ABSTRACT: Elucidation of the interactive mechanism between musculoskeletal circulations and bone remodeling is crucial in developing new intervention to prevent bone loss under a microgravity environment. The overall hypothesis is that dynamic muscle stimulation can enhance fluid circulation in bone, regulate osteogenic adaptation, and inhibit bone loss in a functional disuse condition. Using a hindlimb suspension rat model, electro-induced dynamic muscle contraction was induced as replacement of the normal weight-bearing activity of the hindlimb. Dynamic muscle contraction loading at 20 Hz and 50 Hz demonstrated increase of BV/TV, Conn.D, and Tb.N at the metaphyseal regions, when comparing to the hindlimb suspension control. In addition, stimulation at 20 Hz and 50 Hz can also alleviate the reduction of the cross-sectional fiber area. These results demonstrated that dynamic electro-induced muscle contraction can indeed initiate an adaptive response to inhibit bone loss and reduce muscle atrophy under a functional disuse environment.
[show abstract][hide abstract] ABSTRACT: In space, rapid losses in bone mineral density (BMD) leave astronauts at an increased risk of bone fracture. Longer microgravity missions combined with the lack of efficacy of current exercise regimes in reducing this loss leads to the need of a new treatment. This study has the goal of testing a treatment in the form of a low magnitude mechanical vibration. As an analog of space flight, 18 subjects spent 90 days in continuous 6 degree head down tilt, eight of which received 10 minutes of vibration treatment a day. Measurements of bone density and balance found that there was a 30-50% nonsignificant reduction in BMD loss in the hip, as well as a significant decrease in the loss of postural control. The combined factors of stronger bones and increased balance greatly reduce the risk of bone fracture. With a proposed multi-year planetary mission to Mars being planned by NASA, the need for improved musculoskeletal health is of increasing importance, and this device may provide the needed mode of increasing astronaut safety.
[show abstract][hide abstract] ABSTRACT: Fluid flow that arises from the functional loading of bone tissue has been proposed to be a critical regulator of skeletal mass and morphology. To test this hypothesis, the bone adaptive response to a physiological fluid stimulus, driven by low magnitude, high frequency oscillations of intramedullary pressure (ImP), were examined, in which fluid pressures were achieved without deforming the bone tissue. The ulnae of adult turkeys were functionally isolated via transverse epiphyseal osteotomies, and the adaptive response to four weeks of disuse (n=5) was compared to disuse plus 10 min per day of a physiological sinusoidal fluid pressure signal (60 mmHg, 20Hz). Disuse alone resulted in significant bone loss (5.7+/-1.9%, p< or =0.05), achieved by thinning the cortex via endosteal resorption and an increase in intracortical porosity. By also subjecting bone to oscillatory fluid flow, a significant increase in bone mass at the mid-diaphysis (18.3+/-7.6%, p<0.05), was achieved by both periosteal and endosteal new bone formation. The spatial distribution of the transcortical fluid pressure gradients (inverted Delta P(r)), a parameter closely related to fluid velocity and fluid shear stress, was quantified in 12 equal sectors across a section at the mid-diaphyses. A strong correlation was found between the inverted Delta P(r) and total new bone formation (r=0.75, p=0.01); and an inverse correlation (r=-0.75, p=0.01) observed between inverted Delta P(r) and the area of increased intracortical porosity, indicating that fluid flow signals were necessary to maintain bone mass and/or inhibit bone loss against the challenge of disuse. By generating this fluid flow in the absence of matrix strain, these data suggest that anabolic fluid movement plays a regulatory role in the modeling and remodeling process. While ImP increases uniformly in the marrow cavity, the distinct parameters of fluid flow vary substantially due to the geometry and ultrastructure of bone, which ultimately defines the spatial non-uniformity of the adaptive process.
Journal of Biomechanics 10/2003; 36(10):1427-37. · 2.72 Impact Factor
[show abstract][hide abstract] ABSTRACT: How the material properties of trabecular bone relate to its bulk mechanical behavior is not well understood. Multiple trabeculae in four cubic samples harvested from the distal femora of sheep were evaluated using a nanoindentation testing device. The average modulus and hardness was 20.2±4.0 GPa and 1.1±0.4 GPa, respectively. These values were consistent across surface region, specimen, and feature, thereby exhibiting a very homogenous quality at this level. The source of the highly anisotropic trabecular continuum, therefore, does not directly derive from its material properties.
[show abstract][hide abstract] ABSTRACT: Osteoporosis is a common disease in USA. The consequence of this disease is reduced bone density and deteriorating bone mechanical strength. A scanning confocal acoustic scanning diagnostic (SCAD) system has been developed in our lab for characterization of not only bones' quantity but also quality. The results showed that SCAD determined broadband ultrasound attenuation (BUA) and ultrasound velocity (UV) are highly correlated with the bone density (R>0.72) and modulus (R>0.67). Linear regression tests showed that the correlation coefficients can be further improved by combining the BUA and UV (R>0.80).
[show abstract][hide abstract] ABSTRACT: The objective of this study is to determine bone pore size by using a new, non-invasive method, nuclear magnetic resonance (NMR). Current techniques, such as histomorphometry, i.e., scanning electron microscopy (SEM), used for such measurements are invasive and time consuming. Thus, we are analyzing bone porosity with NMR, and validating the data with SEM analysis. The comparison show there is a high correlation between NMR and SEM porosity. The results strongly indicate that NMR is a promising method for future bone porosity characterization.
[show abstract][hide abstract] ABSTRACT: Conclusive evidence indicates that osteopenia occurs due to a lack of physical activity in the skeleton such as in microgravity and long-term bed rest. Early diagnosis of these skeletal disorders (i.e., osteoporosis), leads to prompt treatment and could dramatically reduce the risk of complications. Using our newly developed scanning confocal acoustic diagnostic (SCAD) system, we evaluated the ability of quantitative ultrasound to non-invasively predict trabecular bone quantity and quality on 63 sheep bone samples. The structural and strength of bone were confirmed using μCT and mechanical testing in three orthogonal directions. While there are fair correlations between broadband ultrasonic attenuation and μCT determined parameters such as bone volume fraction (BV/TV) (R=0.68), as well as tissue bulk modulus (R=0.31), strong correlations exist between ultrasound velocity and bone strength and structural parameters such as bulk modulus (R=0.82), and BV/TV (R=0.93). The correlations between SCAD prediction and bone quantity and quality parameters were improved by using a parameter to combine BUA and UV in a linear regression analysis, yielding R=0.96 (BV/TV) and R=0.82 (bulk modulus). These results suggest that SCAD has the capability to non-invasively assess bone mass and strength.
Engineering in Medicine and Biology, 2002. 24th Annual Conference and the Annual Fall Meeting of the Biomedical Engineering Society EMBS/BMES Conference, 2002. Proceedings of the Second Joint; 11/2002
[show abstract][hide abstract] ABSTRACT: Ultrasound velocity (UV) is one of the most popular ultrasound properties in the assessment of bone status. The defining of the arrival time of ultrasound pulse transmitted through the bone is critical to the accuracy of UV measurement. The adaptive phase tracking method can measure the accurate arrival time of a specific frequency component from the broadband ultrasonic pulse through the detection of time dependent phase information. The phase UV derived from the method is objective and robust. When correlated with the stiffness of the trabecular bone from sheep femoral condyle, the phase UV in the trabecular bone obtained through this method has the highest correlation coefficient (r=0.84) compared to the group velocity (r=0.76) and the phase velocity from FFT analysis (r=0.14).
Engineering in Medicine and Biology, 2002. 24th Annual Conference and the Annual Fall Meeting of the Biomedical Engineering Society EMBS/BMES Conference, 2002. Proceedings of the Second Joint; 11/2002
[show abstract][hide abstract] ABSTRACT: Noticeable changes in bone density are often first evident in trabecular bone. Moreover, qualities beyond density are important in identifying fracture risk. This study seeks to identify the degree to which the variability in trabecular material properties can be explained by using micro-CT (μCT) imaging. The material properties studied include stiffness, yield strength, and ultimate strength, while the μCT parameters analyzed include bone volume fraction, mean intercept length analysis, and degree of anisotropy. Trabecular bone was harvested from both the medial and lateral condyle of the left distal femur of 38 adult female sheep. The maximum correlation was found by combing all the μCT properties to explain approximately majority of the variability in modulus, yield, and ultimate strength (r2=0.87). In the principal loading direction, a lower amount of the variability in modulus is explained (r2=0.83), which is slightly less than the mediolateral direction but more than the anteroposterior direction. As the goal is to identify changes and potential fracture risk at the earliest possible time, the remaining variability should be identified. Further work with nano-indentation, fractals, and finite element modeling may yield the desired specificity.
[show abstract][hide abstract] ABSTRACT: The objective of this work is to evaluate the newly developed scanning confocal acoustic diagnostic (SCAD) system in the assessment of bone mineral density (BMD) of human calcaneus and femoral neck. Results show that ultrasound attenuation (ATT) image obtained from SCAD represents bone mass distribution. High correlation (R=0.82) exists between SCAD determined broadband ultrasound attenuation (BUA) and dual energy X-ray absorptiometry (DEXA) determined bone mineral density (BMD) for calcaneus. The BUA data from the calcaneus region is also highly correlated with BMD results for femoral neck (R=0.81), which is generally a site for assessing osteoporosis and predicting risk of bone fracture. These results demonstrate that the newly developed SCAD system can improve ultrasound performance and provide enough resolution in the region of interest (ROI) for non-invasive diagnosis of bone mass changes.
[show abstract][hide abstract] ABSTRACT: The objective of this study was to investigate ultrasound propagation in trabecular bone by considering the wave reflection and transmission in a multilayered medium. The use of ultrasound to identify those at risk of osteoporosis is a promising diagnostic method providing a measure of bone mineral density (BMD). A stratified model was proposed to study the effect of transmission and reflection of ultrasound wave within the trabecular architecture on the relationship between ultrasound and BMD. The results demonstrated that ultrasound velocity in trabecular bone was highly correlated with the bone apparent density (r=0.97). Moreover, a consistent pattern of the frequency dependence of ultrasound attenuation coefficient has been observed between simulation using this model and experimental measurement of trabecular bone. The normalized broadband ultrasound attenuation (nBUA) derived from the simulation results revealed that nBUA was nonlinear with respect to trabecular porosity and BMD. The curve of the relationship between nBUA and BMD was parabolic in shape, and the peak magnitude of nBUA was observed at approximately 60% of bone porosity. These results agreed with the published experimental data and demonstrated that according to the stratified model, reflection and transmission were important factors in the ultrasonic propagation through the trabecular bone.
Annals of Biomedical Engineering 10/2001; 29(9):781-90. · 2.58 Impact Factor
[show abstract][hide abstract] ABSTRACT: The identification of anabolic agents for the treatment of metabolic bone disease is a highly prized, and elusive, goal. In searching for the osteogenic (bone-producing) constituents within mechanical stimuli, it was determined that high frequency (10-100 Hz) and low magnitude (<10 microstrain) stimuli were capable of augmenting bone mass and morphology, thereby benefiting both bone quantity and quality. Using animal models, it is shown that these mechanical signals can double bone-formation rates, inhibit disuse osteoporosis and increase the strength of trabecular bone by 25%. Considering that the magnitude of these mechanical signals are several orders of magnitude below those which cause damage to the bone tissue, it is proposed that this modality could be useful in the treatment of metabolic bone diseases.
Drug discovery today 08/2001; 6(16):848-858. · 6.63 Impact Factor
[show abstract][hide abstract] ABSTRACT: Stress fractures have been proposed to arise from repetitive activity of training inducing an accumulation of microfractures in locations of peak strain. However, stress fractures most often occur long before accumulation of material damage could occur; they occur in cortical locations of low, not high, strain; and intracortical osteopenia precedes any evidence of micro-cracks. We propose that this lesion arises from a focal remodeling response to site-specific changes in bone perfusion during redundant axial loading of appendicular bones. Intramedullary pressures significantly exceeding peak arterial pressure are generated by strenuous exercise and, if the exercise is maintained, the bone tissue can suffer from ischemia caused by reduced blood flow into the medullary canal and hence to the inner two-thirds of the cortex. Site specificity is caused by the lack, in certain regions of the cortex, of compensating matrix-consolidation-driven fluid flow which brings nutrients from the periosteal surface to portions of the cortex. Upon cessation of the exercise, re-flow of fresh blood into the vasculature leads to reperfusion injury, causing an extended no-flow or reduced flow to that portion of the bone most strongly denied perfusion during the exercise. This leads to a cell-stress-initiated remodeling which ultimately weakens the bone, predisposing it to fracture.
Medical Hypotheses 11/1999; 53(5):363-8. · 1.05 Impact Factor
[show abstract][hide abstract] ABSTRACT: IM pressure induced intracortical fluid flow has been evaluated by pore-elastic FEM and measured streaming potentials. The results suggest that oscillating IM P can initiate spatial fluid flow in bone without matrix deformation, and may play an important role in bone adaptation
[show abstract][hide abstract] ABSTRACT: The daily stress stimulus theory of bone adaptation was formulated to describe the loading conditions necessary to maintain bone mass. This theory identifies stress/strain magnitude and loading cycle number as sufficient to define an appropriate maintenance loading signal. Here, we extend the range over which loading cycle number has been evaluated to determine whether the daily stress stimulus theory can be applied to conditions of very high numbers of loading cycles at very low strain magnitudes. The ability of a relatively high-frequency (30-Hz) and moderate-duration (60-minute) loading regimen to maintain bone mass in a turkey ulna model of disuse osteopenia was evaluated by correlating the applied strain distributions to site-specific remodeling activity. Changes in morphology were investigated following 8 weeks of disuse compared with disuse plus daily exposure to 108,000 applied loading cycles sufficient to induce peak strains of approximately 100 microstrain. A strong correlation was observed between the preservation of bone mass and longitudinal normal strain (R = 0.91) (p < 0.01). The results confirm the strong antiresorptive influence of mechanical loading and identify a threshold near 70 microstrain for a daily loading cycle regimen of approximately 100,000 strain cycles. These results are not consistent with the daily stress stimulus theory and suggest that the frequency or strain rate associated with the loading stimulus must also play a critical role in the mechanism by which bone responds to mechanical strain.
Journal of Orthopaedic Research 08/1998; 16(4):482-9. · 2.88 Impact Factor