The purpose of this study was to assess the validity, as well as to test novel approaches to improving the reliability, of mechanical response tissue analysis (MRTA). Twenty composite tibiae underwent MRTA testing on three separate days to determine intra- and inter-day reliability of bending stiffness. The bones were then subjected to three-point bending tests to directly determine elastic modulus. Within- and between-day reliability of tibial bending stiffness with MRTA was moderate (CV = 24%) and poor (CV = 74%), respectively. No relationship was observed between the two testing methods due to the wide variation in tibial bending stiffness values with MRTA. The second part of the study sought to determine within- and between-day reliability of MRTA in young women with the current testing protocol and compare the results with those from newly-designed protocols. Twelve women (23 ± 2 yr, 162 ± 7 cm, 57 ± 7kg, 19 ± 4 % fat) were tested for tibial bending stiffness with MRTA over 5 days. The current protocol was compared to protocols where day-to-day subject positioning was quantified, subjects were tested in a supine position, and various bending stiffness prediction models were used. Within- (CV = 20%) and between-day (CV = 19%) reliability of tibial bending stiffness with MRTA was moderate using the original methodology. Modifications to this protocol either resulted in similar or worse reliability. / Ph. D.

Mechanical response tissue analysis (MRTA) provides a noninvasive means of estimating the cross-sectional bending stiffness (EI) of long bones, and thus can serve as a predictor of bone strength. Estimates of bone bending stiffness are derived from the point impedance response of a long bone to low frequency (70-500Hz) stimulation according to beam vibration theory. MRTA has demonstrated the ability to reliably estimate human ulnar bending stiffness with between-test coefficients of variation of 5%, and in vivo measurements of monkey tibiae have been validated with ex vivo 3-point mechanical bending tests. Human tibial MRTA measurement has achieved between-trial coefficients of variation of only 12%, so a new physical MRTA configuration and improved computer algorithms have been developed in an attempt to improve upon this level of reliability. The new configuration removes the rigid proximal and distal tibial restraints and models the tissue behavior with a 12-parameter algorithm that accounts for free vibration at the ankle and knee joints. Initial testing with only the hardware changes and application of the 7-parameter model of tissue behavior used in earlier systems yielded unacceptable variation. Subsequent reliability testing with application of 6-, 9-, and 12-parameter models demonstrated modest improvements, prompting the development of the more robust 12-parameter model used in the present study. Evaluation of 110 college-age females (age 20.2±1.8 yr, height 163.3±5.9 cm, weight 60.7±9.3 kg, BMI 22.8±3.1 kg·m⁻²) with the current MRTA system has demonstrated an improvement in within-trial reliability for unsupported tibial EI measurement with a coefficient of variation of 11.2%. These results demonstrate the ability of the system to measure tibial response characteristics when both proximal and distal ends are free of rigid support. Long-term measurement reliability is still problematic with a coefficient of variation of 36.5% for a set of 4 measurements spanning 21 months. / Ph. D.

The purpose of this randomized controlled trial was to investigate temporal skeletal responses to short-term high intensity physical activity. Twenty-eight normal active females [age: 20.7 +/- 2.1 yr (mean +/- SD)] were randomized into exercise (EX, n = 15) or control (CN, n = 13) groups. The exercise group trained 6 days/wk for 6 wk, which consisted of maximal isokinetic knee flexion/extension 3 days/wk, combined with 3 days/wk running. The purpose was to expose the tibiae to a period of abruptly increased loading forces. Tibial bending stiffness (EIMRTA), and serum concentrations of biochemical markers of bone formation [osteocalcin (OC)], and bone resorption [n-telopeptide of type I collagen (NTx)] were measured at baseline, 2 wks, 4 wks, and 6 wks. Isokinetic concentric knee extension/flexion peak torque, as well as total body and site-specific bone mineral density (BMD) were measured at baseline and 6 wk. After training, the exercise group significantly increased (p < 0.05) isokinetic concentric peak torque for the dominant (13.6%) and non-dominant (5.7%) quadriceps, as well as dominant (7.7%) and non-dominant (9.5%) hamstrings, compared to the controls. No differences for total body or site-specific BMD were noted. A two-way multivariate repeated measures ANOVA revealed no timeâ ¢group interactions for composite tibial bending stiffness [(EIMRTA); p = 0.57] or the biochemical markers of bone turnover [(OC and NTx); p = 0.15] across the four sampling periods. While there were no main effects for group, a trend for time (p = 0.051) for composite EIMRTA was observed. The exercise group demonstrated a 20% increase in EIMRTA from baseline (74.8 +/- 22.3 Nm2) to 6 wk (89.8 +/- 24 Nm2), compared to controls who demonstrated a 4% increase (Baseline 86.5 +/- 23.8 Nm2; 6 wk 90 +/- 23.7 Nm2). Significant group differences (p = 0.05) were noted for OC, but not NTx. Differences (p < 0.05) for OC were observed at baseline [13.2 +/- 2.4 ng/ml (CN), 15.6 +/- 2.7 ng/ml (EX)], and follow-up ANCOVA revealed no differences for subsequent sampling periods. Main effects for time were found for OC and NTx (p < 0.001). Main effects for time in OC were attributable to changes in the exercise group (p < 0.01) and NTx (p < 0.01), but not the control group. / Ph. D.

Bone mineral content (BMC) and bone mineral density (BMD), measured by dual x-ray absorptiometry are used clinically to diagnose osteoporosis and estimate risk for fragility fractures. Bone mineral explains up to 70% of bone strength; however, it does not take into account bone geometry. Mechanical Response Tissue Analysis is a method of non-invasively measuring the bending stiffness (EI) of bone which is determined by the product of Young's modulus of elasticity (E) and the areal cross sectional moment of inertia (I). The aim of the current study was to determine if high intensity strength training will increase ulnar bending stiffness in young women. Forty-nine women aged 19.9 ± 1.7 yrs, trained their nondominant arm either concentrically or eccentrically in the Isokinetic modality on the Biodex® system III 3d/wk for 32 wks. The dominant arm served as the control limb (untrained). Analysis of all subjects regardless of training mode demonstrated a significant increase in ulnar EI (22% ↑, P=0.01) with no significant difference in the untrained arm. When EI results were assessed by training mode, subjects who trained eccentrically showed a significant increase for ulnar EI in the trained limb (40% ↑, P=0.01) with no significant effect on the untrained limb while concentric training demonstrated no significant gain in either the trained or untrained arm. There was no effect of time x mode of training interaction for either the trained or untrained limb. Bone mineral density and bone mineral content of the ulna increased significantly in the trained arm in both concentric and eccentric training modes (P<0.05). These findings suggest support for the hypothesis that a critical threshold of mechanical bending loads may be necessary to effect an adaptation in bone strength and thus, eccentric training may be a novel approach to increase ulnar EI in young women. / Master of Science

Mechanical Response Tissue Analysis (MRTA) is an emerging technology for assessing maximal bending stiffness (EI) of human long bones in vivo. The MRTA variable, EI, is the product of Young's modulus of elasticity (E) and cross-sectional moment of inertia (I). EI quantifies material and architectural/geometric properties of bone. Published human research using MRTA to measure EI has been limited to the ulna; however, the tibia requires further investigation due to its central involvement in many human activities and exercise-related clinical problems, e.g. stress fracture of the lower leg. To evaluate the inter- and intra-reliability of tibial EI, 22 healthy women (X + SD: 20.8 + 1.8 yr) were assessed twice daily for three non-consecutive days. Each daily session consisted of five repeated trials. The ulnar EI protocol of McCabe et al. [J Bone and Mineral Res. 1991;6(1):53-59] was adapted to assess tibial EI via MRTA. A significant difference was not found in scores for five repeated trials taken consecutively on the same day. Mean scores for EI were higher on day 1 (59.1 &#177; 35.5 N&#183;m², p < 0.05), compared to day 2 (46.9 &#177; 22.3) and day 3 (49.9 &#177; 18.3). Individual trial mean scores for EI on each day (mean of 5 trials) were highly correlated, R² = 0.84, 0.62, and 0.79 (set 1 vs. 2, for day 1,2,3, respectively) and the average percent change between sets 1 and 2 on each day was 5.3. The inter-test (between day) reproducibility was found to be low and unacceptable, 11.7, 18.3, and 1.3%, for day 1 vs. 2, 1 vs. 3, and 2 vs. 3. Poor inter-day reliability may be a result of the inability, at the time of this study, to apply the best computational EI model. It is concluded that tibial bone stiffness measurements with the MRTA are in the range of acceptability for same day inter- and intra-trial reliability when the 7-parameter analytic model of vibratory properties developed by McCabe et al. is used. / Master of Science

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