Kenneth G. Faulkner

Racial differences in hip axis lengths might explain racial differences in rates of hip fracture

Compared with white women, Asian women have about a 40%–50% and blacks a 50%–60% lower risk of hip fracture, but the reason for this racial difference is not known. Women with a shorter hip axis have a lower risk of hip fracture. To test the hypothesis that a shorter hip axis length could account for the lower risk of hip fracture among Asian and black women, we measured hip axis length in 135 Caucasian, 74 Asian and 50 black women. The mean hip axis lengths of Asian and black women were significantly shorter (1.2 and 0.7 standard deviations, respectively) than that of the whites (p<0.0001). We estimate that, compared with white women, Asians would have a 47% lower risk (95% confidence interval: 32%–63%) and blacks would have a 32% (15%–45%) lower risk of hip fracture because of their shorter hip axis. We conclude that a shorter hip axis length might be a major factor accounting for Asian womens lower risk of hip fracture and might contribute to the lower risk in black women.

Bone matters : Are density increases necessary to reduce fracture risk?

As aconsequence of the exponential BMD/fracture risk relationship,very small increases in BMD can be expected to have very largeeffects on reducing fracture rates (Fig. 1). It is not necessary todouble BMD to reduce fractures by a factor of 2.On the basis of the established relationships betweenBMD, bone strength, and fracture risk, current therapies forreducing fractures have been targeted at reversing bone lossto increase bone strength. Several different therapies havebeen shown to increase bone density and reduce frac-tures.

Precision and Discriminatory Ability of Calcaneal Bone Assessment Technologies

To determine if measuring skeletal status at the calcaneus is a potentially valuable technique for diagnosing osteoporosis, we examined five calcaneal assessment techniques in 53 young normal women and 108 postmenopausal women with osteoporosis and compared these measurements to dual‐energy X‐ray absorptiometry (DEXA) at the calcaneus, hip, and spine. The five instruments, including single‐energy X‐ray absorptiometry (SEXA) and four quantitative ultrasound (QUS) instruments, were evaluated for precision, ability to discriminate osteoporotic from young normal subjects, and correlation to the other instruments. The coefficient of variation (%CV) for instrument, positioning, interobserver, and short‐term precision of the five calcaneal instruments ranged from 1.34–7.76%, 1.63–7.00%, 1.84–9.44%, and 1.99–7.04%, respectively. The %CVs for positioning, interobserver, and short‐term precision were similar for calcaneal DEXA, calcaneal SEXA, and stiffness (as measured by Achilles). The %CVs for instrument precision were similar between calcaneal DEXA and SEXA. The ability of the five calcaneal instruments to discriminate osteoporotic from young normal subjects was similar based on the analysis of area under the receiver operating characteristic curves (range 0.88–0.93) and equivalent to DEXA of the calcaneus and hip (0.88–0.93). The correlations between the measurements of five calcaneal instruments were strong (0.80 ≤ r ≤ 0.91, p < 0.001). These data suggest that although the precision is variable, the calcaneal QUS and SEXA instruments can discriminate between osteoporotic patients and young normal controls and appear to be a useful technique for assessment of osteoporosis.

Discrepancies in normative data between Lunar and Hologic DXA systems.

Many studies have shown the high correlation between Lunar and Hologic DXA bone mineral density (BMD) measurements despite differences in absolute calibration. However, in clinical practice, raw BMD values (in g/cm2) are not normally used for assessing skeletal status and fracture risk. Instead, the BMD values are expressed in terms of the number of standard deviations above or below the young normal value (commonly referred to as theT-score). If the normative populations of the various systems are consistent, the standard deviation scores should also be consistent. For this reason, the World Health Organization (WHO) recently established diagnostic criteria for osteoporosis based onT-scores and not BMD. However, few studies have compared the instruments in terms of their standard deviation scores. In this study, we used linear regression to compareT-scores in 83 women at L1–4 and 120 women at the femoral neck obtained on a Lunar DPX and a Hologic QDR-1000/W system. Patient BMD andT-score measurements were highly correlated between the two systems (r>0.95). No clinically significant difference in L1–4T-scores was seen (less than 0.1 SD). However, linear regression analysis confirmed a systematic difference of 0.9 SD between the femoral neck T-scores. This discrepancy is caused by: (1) differences in the normal populations, and (2) differences in statistical models used to determine the young normal mean and standard deviation. In an attempt to correct the discrepancy, the female young normal mean and standard deviation were recalculated for the femoral neck using published epidemiological data from NHANES and existing DXA cross-calibration equations. The Hologic young normal value (mean ± SD) was redefined as 0.85±0.11 g/cm2, while the Lunar value was redefined as 1.00±0.11 g/cm2. When the femoral neckT-scores for the study population were recalculated on the basis of these new values, the results were equivalent between manufacturers, effectively eliminating the discrepancy. However, the revised values should be confirmed by additional measurements in young normal adults.

Cross-calibration of DXA equipment: Upgrading from a hologic QDR 1000/W to a QDR 2000

SummaryIn this study, the cross-calibration of a fan beam DXA system (Hologic QDR-2000) to a pencil beam scanner from the same manufacturer (Hologic QDR-1000/W) is described. The scanners were calibrated by the manufacturer using the same anthropomorphic spine phantom at installation. To verify consistent machine calibration, a group of 69 female subjects, aged 46–75, had anteroposterior (AP) spine and proximal femur scans on the QDR-1000/W followed by pencil and array scans of the same sites on the QDR-2000 during the same visit. Many of the subjects had bilateral examinations of the proximal femur for a total of 123 hip scans. Pencil and array area, bone mineral content (BMC), and bone mineral density (BMD) from the QDR-2000 were compared with the values obtained on the QDR-1000/W, and linear regression equations were derived for relating the two instruments. At the spine, no differences were found between the QDR-1000/W BMD values and the QDR-2000 array BMD values. A slight difference between pencil beam modes was detected but was not deemed clinically significant. Linear regression models relating the QDR-2000 and QDR-1000/W AP spine BMD measurements showed correlation coefficients greater than 0.99, with slopes of 1.00, intercepts equivalent to zero, and small root mean square errors. Comparisons at the proximal femur showed equivalency at the femoral neck and trochanter regions for the two machines in pencil mode, but slight increases in BMC and BMD at the other femoral sites on the QDR-2000 in both pencil and array mode. Correlation coefficients were 0.97–0.99 for all measurement regions except for Wards. Regression slopes relating the BMD for the femoral regions were 1.00–1.04, with intercepts not significantly different from zero and small residual errors. As with the spine, the differences were small enough that they were not of clinical significance. However, in longitudinal drug trials requiring highly precise determination of spinal and femoral BMD changes, these differences may be important.

Bilateral comparison of femoral bone density and hip axis length from single and fan beam DXA scans.

Dominant/nondominant differences in bone mineral density (BMD) have been observed in the upper extremities. However for the proximal femur, the distinction between dominant and nondominant hips is not clear. The purpose of this study is to evaluate left/right variations in femoral BMD and hip axis length (HAL) in both single beam and fan beam dual x-ray absorptiometry (DXA) scans. A total of 36 women aged 41–76 years (average age 60±10 years) received single beam and fan beam DXA scans of both proximal femora with a Hologic QDR-2000 scanner. Femoral BMD and hip axis length were determined for each scan. Left/right and single beam/fan beam correlations were determined and differences were evaluated using a two-way analysis of variance. Femoral BMD at corresponding measurement regions in opposing femora were highly correlated (r=0.81–0.96). No significant left/right differences were detected. At the femoral neck, the mean BMD difference (± standard deviation) was 1.5%±4.7% in a single beam mode and-0.6%±6.3% in fan beam mode. Though mean values of femoral BMD were equivalent, the observed individual left/right differences were occasionally large (as high as 26% in the femoral neck). The hip axis length of the left and right hips were highly correlated and statistically equivalent. However, hip axis length using fan beam was significantly larger (7.5%) than the single beam measurement with a larger observed variation. We conclude that measurement of a single proximal femur will usually be sufficient for clinical evaluation of BMD and/or hip axis length. However, bilateral BMD measurements are indicated in subjects where unilateral degeneration or disease are suspected. If possible, hip axis length should be measured in single beam mode to avoid magnification errors.

Cross-calibration of liquid and solid QCT calibration standards: corrections to the UCSF normative data

Quantitative computed tomography (QCT) has been shown to be a precise and sensitive method for evaluating spinal bone mineral density (BMD) and skeletal response to aging and therapy. Precise and accurate determination of BMD using QCT requires a calibration standard to compensate for and reduce the effects of beam-hardening artifacts and scanner drift. The first standards were based on dipotassium hydrogen phosphate (K2HPO4) solutions. Recently, several manufacturers have developed stable solid calibration standards based on calcium hydroxyapatite (CHA) in water-equivalent plastic. Due to differences in attenuating properties of the liquid and solid standards, the calibrated BMD values obtained with each system do not agree. In order to compare and interpret the results obtained on both systems, cross-calibration measurements were performed in phantoms and patients using the University of California San Francisco (UCSF) liquid standard and the Image Analysis (IA) solid standard on the UCSF GE 9800 CT scanner. From the phantom measurements, a highly linear relationship was found between the liquid- and solid-calibrated BMD values. No influence on the cross-calibration due to simulated variations in body size or vertebral fat content was seen, though a significant difference in the cross-calibration was observed between scans acquired at 80 and 140 kVp. From the patient measurements, a linear relationship between the liquid (UCSF) and solid (IA) calibrated values was derived for GE 9800 CT scanners at 80 kVp (IA=[1.15×UCSF]-7.32). The UCSF normative database for women and men obtained with the liquid standard was corrected for use with the solid standard. Proper procedures for cross-calibrating QCT measurements and the appropriate uses of normative data are discussed.

Implications in the use of T-scores for the diagnosis of osteoporosis in men.

Osteoporosis is recognized as a disorder of both men and women. However, the World Health Organizations (WHO) definition of osteoporosis (a bone mineral density [BMD] T-score of -2.5 or less) was formulated for use with postmenopausal women only. In the absence of a BMD-based definition for male osteoporosis, the WHO definition is often applied to men as well. Several important questions exist when considering the use of T-scores in men. First, is the WHO definition appropriate for men? What is the impact of using a -2.5 criteria, in terms of the number of men that would be identified as osteoporotic? When calculating T-scores in men, should male or female young normal values be used? Can the same T-score criteria be used for all skeletal sites and technologies? To address these questions, osteoporosis prevalence estimates for men aged 50 yr and over were generated using WHO methods and manufacturer normative data from dual-energy X-ray absorptiometry (DXA), quantitative computed tomography (QCT), and ultrasound. Estimates were determined for several skeletal sites and technologies using both male and female young normal values. Prevalence estimates were compared to published fracture risk estimates. Mean T-scores declined with age at all measurement sites. Discrepancies were found between the different skeletal sites and techniques, similar to the previously reported differences in women. A -2.5 criterion (based on young normal males or females) appeared to underestimate the prevalence of osteoporosis, except for QCT, which seemed to overestimate risk. Depending on the technique used, 0 to 12.5 million US men 50 yr of age and older would be classified as osteoporotic using the WHO definition. T-Scores based on male norms were less discordant across skeletal sites than female-based T-scores. Male-based T-scores between -1.8 and -2.3 using DXA and ultrasound and -3.1 for QCT provided osteoporosis prevalence estimates that approximated the likelihood of common fractures in men 50 and over. We conclude that the use of single T-score-based criterion for the diagnosis of osteoporosis in men has many potential difficulties. BMD measurement techniques provide discrepant estimates of prevalence and may underestimate the size of the male population at risk for fracture. Based on available normative data, a -2.5 criterion underestimates osteoporosis prevalence in men, whether based on male or female norms. Prospective studies are needed to further refinement to the BMD definition of osteoporosis in men.

Quality assurance for bone densitometry research studies: concept and impact.

A concept for quality assurance (QA) in bone densitometry has been developed for clinical multicenter studies. Major elements provided by a coordinating center comprise (1) consulting services and certification of participating centers in the start-up phase of the study, (2) review of scan data acquired on QA standards for cross-calibration and longitudinal assessment of scanner stability, (3) review of selected patient data as well as of problem cases during the study, and (4) comprehensive review and correction of patient results based on QA data after conclusion of the study. Limitations of phantom-based QA data should be acknowledged. Typical problems encountered during research studies and guidelines for solutions are presented. Successful implementation of QA measures may yield substantial enhancement of statistical power. Depending on the study design and the variability of response within patient groups, improvement in precision due to QA measures may reduce the smallest detectable difference between subject groups or, alternatively, sample size by a few to more than 50%, and thus may contribute to a substantial reduction in study cost. Formulae for calculation of the magnitude of these effects are presented. To maximize the net benefit, QA efforts have to be limited to levels that assure reliability of the data at acceptable QA cost. While QA programs at individual clinical sites or for local practitioners may not need to be as extensive as for multicenter clinical trials, awareness of the potential problems and implementation of basic QA measures will help in obtaining high-quality bone densitometry results.

Measurement of bone mineral density: Current status

0 steoporosis has been traditionally defined as a condition of low bone mass accompanied by atraumatic fractures. Recently, more emphasis has been placed on patient bone mineral density in the attempt to identify those at high risk for osteoporotic fracture before these fractures have occurred. As a result, bone densitometry techniques have become increasingly important. Four general methods have been developed and are currently being used for noninvasively measuring bone mineral density at various anatomic sites, both in the axial and in the peripheral skeleton (Table I). While differing in the particular anatomic sites they measure and in their precision, accuracy, and fracture discrimination, all of these methods provide clinically useful measurements of skeletal status and represent major advances in our ability to noninvasively measure bone mass.