Clint Rubin

Whole-body vibration in the skeleton: Development of a resonance-based testing device

Whole-body vibration (WBV) has been demonstrated to have a strong influence on physiological systems, ranging from severely destructive to potentially beneficial. Unfortutely, the study of WBV in a controlled manner is commonly constrained by space and budgetary factors, particularly where vibration in the low frequency range is considered. In the work presented here, a small, low-cost device for performing WBV of the human skeleton is developed to assist in studies of vertical acceleration in a clinical setting. The device design consists of a spring-supported plate driven by an 18N peak-force electromagnetic actuator, and the associated driving and monitoring electronics. Animal and human lumped-mass models have been coupled with a model of the loading device to seek a resonance response in the vicinity of 30Hz. This approach minimizes the loading requirements of such a device, and thus a major component of the cost, yet can provide peak accelerations of 0.15 g at a frequency of 30 Hz in a small, lightweight package capable of use in a clinical or laboratory setting.

Tetracycline Prevents Cancellous Bone Loss and Maintains Near-Normal Rates of Bone Formation in Streptozotocin Diabetic Rats

The skeletal consequences of streptozotocin-induced (STZ) diabetes in the rat are characterized by decreased bone formation and, consequently, reductions in bone mass. Given the ability of tetracyclines to inhibit the breakdown of connective tissue collagen in experimental diabetes (and in other diseases), we examined the potential of this drug to prevent the osteopenia associated with STZ diabetes. To evaluate drug efficacy, the cortical and trabecular bone histomorphometry were analyzed and compared between vehicle-treated control and diabetic rats and control and diabetic rats treated orally with 20 mg/day of minocycline, a semisynthetic tetracycline. In addition, blood and urine glucose, body weight change, tibia lengths, cortical bone densities, and bone ash content were compared. At the end of the 26 day experimental period, diabetic (D) and minocycline-treated diabetic (MTD) rats were polyuric with reduced body weights and significantly elevated blood and urinary glucose levels (p < 0.01). Compared to control (C) and minocycline-treated control (MTC) animals, the periosteal and cancellous bone formation in the D rats had virtually ceased (p < 0.001), and the cancellous bone mass in the tibial metaphysis was reduced 47% (p < 0.01). In contrast, bone formation rates in the MTD animals were increased compared to the D rats (p < 0.001), while cancellous bone areas in the MTD animals were essentially equivalent to those observed in the C and MTC groups. Moreover, growth plate thickness, reduced 43% in the D rats, was preserved in the diabetic animals treated with minocycline. These results demonstrate that minocycline treatment of the streptozotocin diabetic rat maintains normal bone formation, normalizes growth plate thickness, and prevents cancellous bone loss.

Osteoblastic networks with deficient coupling : Differential effects of magnetic and electric field exposure

A gap junction-deficient cell line was utilized to test whether intercellular coupling plays a significant role in modulating the influence of biophysical stimuli such as extracellular electrical currents. ROS 17/2.8 cells, an osteosarcoma cell line, along with a control transfected cell line and a connexin 43-gap junction-deficient cell line, were exposed to a time-changing magnetic flux (30 Hz, 1.8 milliTesla) sufficient to induce an electric field in the cultures on the order of 2 mV/m. Field exposure inhibited cell growth independent of gap junctional coupling, while alkaline phosphatase activity was found to be dependent on gap junctional coupling. These findings can be interpreted to suggest that magnetic and electric field exposures have differential effects on cell cultures, with magnetic field exposure inhibiting cell growth through a mechanism independent of gap junctional coupling, while the alteration in enzyme activity appears to be stimulated by the induced electric field in a gap junction-dependent manner.

Intramedullary pressure induced fluid flow in bone

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.

Noninvasive ultrasound imaging for bone quality assessment using scanning confocal acoustic diagnosis, µCT, DXA measurements, and mechanical testing

Osteoporosis is a disease characterized by decreased bone mass and progressive deterioration of the microstructure, affecting both mineral density and bones fragility. Current diagnoses are only measuring apparent bone mineral density (AppBMD). Using our newly developed scanning confocal acoustic diagnostic (SCAD) system, we evaluated the ability of quantitative ultrasound in noninvasively predicting bones quantity and quality on 19 human cadaver calcanei. Results show that ultrasound attenuation image on intact calcaneus represents bone mass distribution. High correlation (R=0.82) exists between SCAD determined broadband ultrasound attenuation (BUA) and DXA determined AppBMD at the calcaneus, as well as in the AppBMD result at femoral neck (R=0.81). SCAD determined BUA and ultrasound velocity (UV) are highly correlated with the micro-CT and mechanical testing determined bone quantity and quality parameters. These results suggest that image-based quantitative ultrasound is able to identify ROI and predict both bone mass and strength.

Longitudinal assessment of human bone quality using scanning confocal quantitative ultrasound

of calcaneus bone loss in a 90-day bedrest. QUS scanning was performed at proximal femur (cadaver) and calcaneus (bedrest subjects) regions with QUS images of 80x80 mm2 for hip and 40x40 mm2 for calcaneus. QUS was processed to calculate the ultrasound attenuation (ATT; dB), wave ultrasound velocity (UV), and the broadband ultrasound attenuation (BUA; dB/MHz). Human cadaver proximal femurs have been measured with the SCAD, micro-CT, DXA, and mechanical strength test. Human calcaneus of bedrest subjects were measured using SCAD and DXA in day 0 (baseline), day 60 and day 90. Results demonstrated that QUS measurement has the capability to predict bone BMD, microstructure and mechanical properties in human bone, and indicated significant sensitivity to the progressive change of bone quality, particularly in the trabecular bone region with remodeling activities.

Retention of bone density and postural status with a non-invasive extremely low level mechanical signal: A ground based evaluation of efficacy

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.

Non-invasive Bone Quality Assessment Using Quantitative Ultrasound Imaging and Acoustic Parameters

Musculoskeletal complications, i. e., osteoporosis, affect not only bone’s mineral density, but also quality. Early diagnosis of such poor bone quality leads to prompt treatment and thus will dramatically reduce the risk of complications. Using a newly developed scanning confocal acoustic diagnostic (SCAD) system, trabecular bone quality was evaluated by quantitative ultrasound on 63 sheep bone samples. The structural and strength properties of bone were confirmed using µCT and mechanical testing in three orthogonal directions. While there are good correlations between broadband ultrasonic attenuation and µCT determined parameters, such as bone volume fraction (BV/TV; R = −0.68), 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). 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 has been observed between simulation using this model and experimental measurement of trabecular bone, in which the peak magnitude of nBUA was observed at approximately 60% of the bone porosity. These results suggest that image-based quantitative ultrasound has demonstrated the potentials to predict not only the bone mass, but also bone’s mechanical strength in the region of interests of bone.

Determination of bone porosity by non-invasive nuclear magnetic resonance

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.

Characterization of human trabecular bone quantity and quality using confocal acoustic scanning

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.