Phf Nicholson

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.

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.

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.

Factors Associated with Cortical and Trabecular Bone Loss as Quantified by Peripheral Computed Tomography (pQCT) at the Ultradistal Radius in Aging Women

Abstract. Peripheral quantitative computed tomography (pQCT) allows the separate determination of cortical and trabecular bone mineral density in the peripheral skeleton. This cross-sectional study was designed to examine the effects of healthy aging on pQCT measurements at the ultradistal radius. In a well-defined sample of 129 community-based women, aged 70–87 years, the differences in cortical and trabecular density over the age range were equivalent to losses of −0.41% and −0.65% per year, respectively. To investigate the mechanism of this age-related decline, we assessed relationships between both parameters and height, weight, body mass index, dietary calcium intake, grip strength, and serum concentrations of insulin-like growth factor-I (IGF-I), calcidiol (25(OH)D3), calcitriol (1,25(OH)2D3), parathyroid hormone (PTH), and sex hormone binding globulin (SHBG). Multiple regression was used to adjust for potential confounders. Age was not significant after controlling for other covariables. Body mass index, grip strength, serum IGF-I, 25(OH)D3, and PTH (1–84) were found to be independent predictors of total bone density. Including (total or free) 1,25(OH)2D3 did not improve the model precision. These findings provide evidence that, among other factors, the activity of the growth hormone-IGF-I-axis is of importance for skeletal integrity. Grip strength, serum IGF-I, and PTH (1–84) were discovered to be significantly related to cortical but not to trabecular density, suggesting that different mechanisms may be involved in compact and cancellous bone loss.

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.

Measurements of vertebral shape by radiographic morphometry : sex differences and relationships with vertebral level and lumbar lordosis

Abstract Objective. To examine sex-related and vertebral-level-specific differences in vertebral shape and to investigate the relationships between the lumbar lordosis angle and vertebral morphology. Design and patients. Lateral thoracic and lumbar spine radiographs were obtained with a standardized protocol in 142 healthy men and 198 healthy women over 50 years old. Anterior (Ha), central (Hc) and posterior (Hp) heights of each vertebra from T4 to L4 were measured using a digitizing technique, and the Ha/Hp and Hc/Hp ratios were calculated. The lumbar lordosis angle was measured on the lateral lumbar spine radiographs. Results. Ha/Hp and Hc/Hp ratios were smaller in men than women by 1.8% and 0.7%, respectively, and these ratios varied with vertebral level. Significant correlations were found between vertebral shape and the lumbar lordosis angle. Conclusions. These results demonstrate that vertebral shape varies significantly with sex, vertebral level and lumbar lordosis angle. Awareness of these relationships may help prevent misdiagnosis in clinical vertebral morphometry.

Radiological prevalence of lumbar intervertebral disc calcification in the elderly : an autopsy study

Abstract Objective. The objective of this study was to investigate the in vitro radiological prevalence of lumbar intervertebral disc calcification (IDC) in the elderly and its relation to osteoarthritis (OA). Materials and methods. Lumbar spine segments comprising L2–4 were resected from 60 cadavers (30 males, 30 females; average age 67 years) and investigated with high-contrast radiography and computed tomography (CT). Results and conclusions. IDC was found in 58.3% of the patients using high-contrast radiography and in 46.7% of the patients using CT. IDC prevalence and OA grades in the lumbar spine and right hand were found to increase with age. IDC prevalence and OA grades for L2–3 were not significantly different from those for L3–4. No significant sex difference was found for IDC prevalence and OA grades. The results indicate that IDC is significantly underestimated in vivo by conventional radiography and that intervertebral disc calcification may be a common phenomenon in aging. The exact relation of IDC to OA remains undetermined.

The accuracy of peripheral skeletal assessment at the radius in estimating femoral bone density as measured by dual-energy X-ray absorptiometry : a comparative study of single-photon absorptiometry and computed tomography

Boonen S, Cheng X, Nicholson PHF, Verbeke G, Broos P, Dequeker J (Katholieke Universiteit Leuven, Leuven, Belgium). The accuracy of peripheral skeletal assessment at the radius in estimating femoral bone density as measured by dual‐energy X‐ray absorptiometry: a comparative study of single‐photon absorptiometry and computed tomography. J Intern Med 1997; 242: 323–8.

Prevalence of Trabecular Microcallus Formation in the Vertebral Body and the Femoral Neck

Abstract. Trabecular microcallus formation (TMF) has been described previously in the human vertebra and femur, but the difference in TMF prevalence at these two sites has not been studied and the role of TMF remains controversial. In this study, the 4th lumbar vertebra (L4) and right proximal femur were removed from 27 male and 23 female cadavers. A 2 cm cube cut from the center of L4 and a 1 cm-thick slice cut from the femoral neck were cleaned, defatted, and dried. The apparent density of the L4 cubes was determined as dry weight/bulk bone volume. Using a dissecting microscope at low magnification (4–60×), TMF were identified and counted in both the vertebral and femoral samples. A 8 mm diameter core was then cut from the center of the L4 cubes in the vertical direction, and selected histomorphometric parameters of the core were evaluated with an X-ray microcomputed tomography system (μ-CT). There was a significantly greater prevalence of TMF in vertebral cubes (82%) than in the femoral slices (11%) (P < 0.001). TMF prevalence did not differ significantly between males and females, but the mean number of TMF in the vertebra was significantly (P < 0.05) greater in females (15.0/vertebra) than in males (7.7/vertebra). In the vertebra, the majority of the observed TMF were in vertical trabeculae. Subjects over 60 years old had a higher TMF prevalence than those under 60 years old (P < 0.01). TMF numbers increased with decreasing apparent density (P < 0.05), whereas no significant correlations were found between TMF and bone volume (BV/TV), trabecular number (Tb.N), or trabecular thickness (Tb.Th) as assessed by μ-CT. In two fractured vertebra, very few TMFs (2 and 4, respectively) were observed. These results demonstrated that the occurrence of TMF is strongly related to the anatomical site, probably due to differences in the applied loads and the trabecular structure between sites. The results were consistent with the hypothesis that TMF is a mechanism acting to maintain bone strength, but further studies are needed to clarify this important issue.