G. Lowet

Assessment of the strength of proximal femur in vitro : Relationship to femoral bone mineral density and femoral geometry

Femoral neck axis length, neck width, and neck-shaft angle were measured on radiographs of right proximal femora from 64 cadavers (28 female, 36 male). Bone mineral density (BMD) was measured using dual energy X-ray absorptiometry (DXA) for various regions of interest, and quantitative computed tomography (QCT) was used to determine BMD and bone areas for cortical and trabecular bone at the trochanter and femoral neck. The strength of the femur was determined by a mechanical test simulating a fall on the greater trochanter, and the fracture type (cervical or trochanteric) was subsequently determined from radiographs. Twenty-six cervical fractures and 38 trochanteric fractures were observed, with no significant sex difference in the distribution of fracture types. Femoral strength was significantly elevated in males compared to females. DXA trochanteric BMD was more strongly (p < 0.05) correlated with femoral strength (r2 = 0.88) than were any of the other DXA BMD measurements (r2 = 0.59-0.76). In multiple regression models, a combination of different DXA BMD measurements produced only a small increase (1%) in the explained variability of femoral strength. Of the QCT measurements, trochanteric cortical area yielded the optimal correlation with femoral strength (r2 = 0.83). Weak, but significant, correlations were observed between femoral strength and cortical BMD at trochanteric (r2 = 0.28) and neck regions (r2 = 0.07). In multiple regression models, combining QCT parameters yielded, at best, an r2 of 0.87. Of the geometrical parameters, both neck axis length and neck width were significantly correlated with femoral strength (r2 = 0.24, 0.22, respectively), but no significant correlation was found between strength and the neck-shaft angle. Combining DXA trochanteric BMD with femoral neck width resulted in only a small increase in the explained variability (1%) compared to trochanteric BMD alone. The results demonstrated that DXA and QCT had a similar ability to predict femoral strength in vitro. Trochanteric BMD was the best DXA parameter, and cortical area (not cortical BMD) was the optimal QCT parameter. Geometric measurements of the proximal femur were only weakly correlated with the mechanical strength, and combinations of DXA, QCT, and geometric parameters resulted in only small increases in predictive power compared to the use of a single explanatory variable alone.

Do quantitative ultrasound measurements reflect structure independently of density in human vertebral cancellous bone

Ultrasonic measurements were made in three orthogonal directions on 70 vertebral bone cubes. Apparent density (rho) was determined, and microcomputed tomography was used to derive a range of microstructural parameters. Qualitatively different ultrasonic behavior was observed in the craniocaudal (CC) axis, in which two distinct waves propagated. In this direction, only attenuation correlated strongly with rho (r2 = 80%), whereas, in the anteroposterior (AP) and mediolateral (ML) axes, there were significant correlations between all ultrasonic parameters and rho (r2 = 57%-79%). Microstructural parameters were, in general, correlated with ultrasonic properties, but when adjusted for rho, few significant relationships remained and the additional variance explained by individual microstructural parameters was relatively small (< 25% for CC axis, < 3% for AP, 0% for ML). In stepwise regression analysis including rho and all of the microstructural parameters, rho remained the primary determinant of ultrasonic properties in the transverse axes: Combinations of structural parameters explained, at most, an additional of 6% of the variability in ultrasonic properties in the AP axis, but failed to contribute significantly in the ML axis. In the CC axis, structural parameters played a greater role, but the pattern of associations was complex and the predictive power of the models was generally much less than that for the transverse axes. These data indicate that the ability of ultrasound to reflect aspects of trabecular structure is strongly dependent on the direction in which ultrasonic measurements are made, and provide only qualified support for the hypothesis that ultrasound reflects cancellous bone structure independently of bone density.

A comparison of time-domain and frequency-domain approaches to ultrasonic velocity measurement in trabecular bone

Different methods for ultrasonic velocity determination using broad-band pulse transmission have been investigated in 70 human calcanae in vitro. The work took place within the context of the EC BIOMED1 concerted action Assessment of Quality of Bone in Osteoporosis. Ultrasonic velocities were determined using three different transit time definitions: first arrival (TTV1), thresholding (TTV2), and first zero crossing (TTV3). Phase velocity (PV) was determined over a range of frequencies from 200 to 800 kHz using a new phase spectral analysis technique. The different velocity measurements were compared in terms of their magnitudes and their inter-correlations. There were significant differences of up to 260 m s-1 between different transit time velocities (p < 0.0001), indicating the sensitivity of the measurement to the arrival criteria used. Phase velocities were lower than all of the transit time velocities (p < 0.0001) and decreased with increasing frequency (p < 0.005). A strong correlation (r2 = 0.968) was observed between PV at 400 kHz (PV400) and TTV3, with much weaker correlations between PV and the other transit time velocities. Reproducibility for transit time velocity measurement was optimal for TTV3 (coefficient of variation, cv = 0.41%), and for PV it was optimal at 600 kHz (cv = 0.34%). These data indicate that transit time measurements may be subject to errors due to the modification of the pulse shape during propagation through bone by attenuation and dispersion. Velocity measurement by phase spectral analysis appears to offer advantages over the transit time approach, and should be the method of choice for velocity measurement in trabecular bone. Where transit time velocity measurements are made, the first-zero-crossing criterion appears to be have some advantages over other arrival criteria. We also note that PV measurements provide new information on dispersion which could prove to be relevant to the structural and mechanical characterization of trabecular bone.

Ultrasound velocity measurement in long bones: Measurement method and simulation of ultrasound wave propagation

A new method for the measurement of ultrasound velocity in long bones is presented. The method can be applied in vitro as well as in vivo. It automatically corrects for the influence of soft tissue, such that the real velocity in bone is obtained. In a series of simulation experiments, hypotheses on the followed wave path were verified. A very good agreement was found between the measurement obtained in the experimental set-up and the values calculated for the hypothesised wave path in the experimental structure. These simulations revealed the feasibility of the technique to determine the velocity in a local site of the structure. Clinical applications of this technique include the monitoring of callus consolidation after fracture and the detection of bone degenerative diseases such as osteoporosis.

Structural and material mechanical properties of human vertebral cancellous bone

The structural Youngs modulus (i.e. that of the cancellous framework) was determined by non-destructive compressive mechanical testing in the three orthogonal axes of 48 vertebral bone cubes. In addition, the material Youngs modulus (i.e. of the trabeculae themselves) was estimated using an ultrasonic technique. Apparent and true density were determined by direct physical measurements. Significant mechanical anisotropy was observed: mean structural Youngs modulus varied from 165 MPa in the supero-inferior direction to 43 MPa in the lateral direction. Structural Youngs modulus correlated with apparent density, with power-law regression models giving the best correlations (r2 = 0.52-0.88). Mechanical anisotropy increased as a function of decreasing apparent density (p < 0.001). Material Youngs modulus was 10.0 +/- 1.3 GPa, and was negatively correlated with apparent density (p < 0.001). In multiple regression models, material Youngs modulus was a significant independent predictor of structural Youngs modulus only in the supero-inferior direction. The data suggest the presence of two effects in vertebral bone associated with decreasing apparent density and, by implication, bone loss in general: (a) increased mechanical anisotropy, such that there is relative conservation of stiffness in the axial direction compared with the transverse directions; and (b) increased stiffness of the trabeculae themselves.

Age-Associated Decline in Human Femoral Neck Cortical and Trabecular Content of Insulin-Like Growth Factor I: Potential Implications for Age-Related (Type II) Osteoporotic Fracture Occurrence

Abstract. Recent evidence suggests that regulatory peptides such as insulin-like growth factor-I (IGF-I) are released locally from bone during resorption, and may then act in a sequential manner to regulate the cellular events required for the coupling of bone formation to resorption. Among other factors, a decrease in bone-associated IGF-I levels could therefore result in remodeling imbalance and contribute to the gradual loss of bone that occurs with age. As the femoral neck region is of primary concern for the clinical manifestations of osteoporosis, the current study was intended to assess the IGF-I contents in femoral neck cortical and trabecular bone from aging individuals. Bone samples from the neck region were obtained at postmortem from 39 females and 35 males, aged 23–92 years. Concentrations of IGF-I and osteocalcin were measured by radioimmunoassay in the supernatants obtained after EDTA and guanidine hydrochloride extraction. The total amount of protein present in the extracts was determined by spectrophotometry. IGF-I levels were significantly lower in trabecular compared with cortical bone. Though femoral neck total protein did not vary with donor age, both IGF-I and osteocalcin were found to decline markedly. Between the ages of 23 and 92 years, average yearly rates of loss of 0.30 and 0.21 ng IGF-I/mg protein were observed in cortical and trabecular bone, respectively, corresponding with net losses of nearly 35% of the cortical skeletal content of IGF-I and 41% of the trabecular skeletal content of IGF-I. These changes in bone-associated IGF-I paralleled those of osteocalcin, consistent with an overall decrease in osteoblast function with aging. In women, the rate of decline was significantly faster for trabecular than for cortical IGF-I, however in men, age-dependent changes in cortical and trabecular IGF-I were similar. These findings support the hypothesis that changes in the local IGF regulatory system over time could be a pathophysiologic component of the age-related (type II) femoral neck osteoporotic syndrome.

Assessment of the strength of the proximal femur in vitro: relationship with ultrasonic measurements of the calcaneus

Matched pairs of the right proximal femur and right calcaneus were obtained from 64 cadavers (28 female, 36 male). Ultrasonic velocity and broadband ultrasonic attenuation were measured in the calcaneus using a laboratory ultrasound system. Bone mineral density (BMD) was measured at the calcaneus and at the trochanteric and neck regions of the femur using dual-energy X-ray absorptiometry. Femoral strength was determined in a mechanical test simulating a fall onto the greater trochanter. Femoral BMD was more strongly correlated with femoral strength (r2 = 0.71, 0.88 for neck BMD and trochanteric BMD, respectively) than were any of the other predictive variables investigated (p < 0.05). Calcaneal ultrasonic measurements alone produced correlations with femoral strength of r2 = 0.40-0.47, with no significant differences observed in predictive ability between the various ultrasonic parameters. In multiple regression analysis, ultrasound was, in general, not a significant additional independent predictor of femoral strength when combined with either femoral or calcaneal BMD, and combining ultrasonic parameters did not improve the ability to predict femoral strength. Calcaneal width was found to be significantly correlated with both femoral strength and femoral BMD, and this explained the slightly better correlations with femoral strength found for those ultrasonic parameters which were not effectively normalized for calcaneal width. In summary, calcaneal ultrasound did not significantly enhance the prediction of femoral strength compared to femoral BMD measurements alone. Given the substantial differences between the in vitro and in vivo situations, this finding does not necessarily contradict emerging clinical data indicating that ultrasound and BMD have comparable and independent predictive ability for hip fracture risk. Reasons for the apparent discrepancy are discussed, including the enhanced accuracy of DXA in vitro. Nevertheless, it is suggested that further fundamental investigations into the efficacy of current ultrasonic techniques are warranted.

The relation between resonant frequencies and torsional stiffness of long bones in vitro. Validation of a simple beam model.

The results of vibration analysis experiments and impact torsion tests performed on excised animal long bones were used to validate a simple beam model for the prediction of torsional stiffness from resonant frequencies. Resonant frequency data on two mutually perpendicular bending vibration modes of 142 excised long bones were evaluated. Torsional stiffness of the same bones had been determined by an impact torsion test. Using a simple beam model, a theoretical relation between resonant frequencies and torsional stiffness was derived. If total bone mass and bone length are known, the formula thus derived allows one to calculate torsional stiffness from resonant frequencies. Linear regression analysis shows a strong correlation between the measured and the calculated torsional stiffness for sheep femora (r2 = 0.63, n = 24), dog femora (r2 = 0.94, n = 34), dog tibiae (r2 = 0.79, n = 18) and monkey radii (r2 = 0.77, n = 66). It was found that this linear relation was valid not within one bone type alone. Linear regression analysis on the combined data of all bones demonstrated that all bones obeyed the same global linear relation between measured and the calculated torsional stiffness (r2 = 0.98, n = 142). This implies that one and the same beam model is valid for the different bone types investigated. The calculation of stiffness from resonant frequencies, however, requires total bone mass, m, and length to be known. In view of in vivo applications, the feasibility of using total bone mineral content (TBMC) as a measure for m was investigated.(ABSTRACT TRUNCATED AT 250 WORDS)

In vivo assessment of bone mechanical properties by vibration and ultrasonic wave propagation analysis

Vibration analysis and ultrasonic wave propagation analysis were evaluated as noninvasive techniques for the in vivo assessment of bone mechanical properties. The relation between the resonant frequencies, obtained by vibration analysis, and geometrical and material properties of long bones is explained using a simple beam model. This simple beam model was validated experimentally in previous work on excised animal bones. In vitro measurements were performed on human and animal excised bones from specific osteopenic cases and control groups. Using specific protocols for in vivo vibration and ultrasound measurements of the tibia, a population of osteoporotic patients and age-matched controls were tested. From these measurements, it was concluded that the bending rigidity, calculated from the resonant frequencies, in osteoporotic tibiae had decreased as compared to the control group. Also the ultrasound velocity in the tibial cortex was lower in the osteoporotic group. The latter indicates a change in the bone tissue material properties. On the other hand, immobilization osteoporosis appeared to lead to a decrease in bending rigidity without an observable change in bone tissue material properties. By the combination of vibration analysis and ultrasound velocity measurements, the whole bones mechanical characteristics as well as the bone tissue properties can be assessed in vivo. Since both techniques are noninvasive, they can be used in longitudinal studies for the assessment of bone response on physical loading.

The effect of fracture and fracture fixation on ultrasonic velocity and attenuation

Measurement of the velocity of propagation and attenuation of ultrasound (200 kHz) is believed to be a useful non-invasive technique for assessing the mechanical properties of bone. A new method for the determination of ultrasound velocity and attenuation of longitudinal waves in cortical bone was used in vivo and in situ on intact and fractured human tibiae. The measured ultrasound attenuation and velocity were found to be unaffected by the soft tissue between transducers and bone. The ultrasound velocity in vivo on control tibiae was 3614 +/- 32 m s-1 and the attenuation was 5.52 +/- 0.43 dB MHz-1 cm-1. The ultrasound velocity in fractured tibiae was considerably lower 1 week after fracture (2375 +/- 82 m s-1), but had significantly increased after 3 weeks (to 2882 +/- 90 m s-1). A higher attenuation was measured 1 week after fracture (17.81 +/- 3.91 dB MHz-1 cm-1), but it had decreased again 3 weeks after fracture (10.42 +/- 3.56 dB MHz-1 cm-1). In situ studies under well-defined conditions confirmed the in vivo results. The effects of internal plate fixation and gradually cutting through the cortex on the ultrasound velocity and attenuation were studied in situ. These results demonstrate the clinical potential of this technique for the non-invasive assessment of bone fracture healing.