Diagnostic agreement at the total hip using different DXA systems and the NHANES III database.

In 1997, the National Health and Nutrition Examination Survey III (NHANES III) total hip reference database was adopted for T-score derivation in an effort to optimize diagnostic agreement among densitometers from different manufacturers. Our study was undertaken to evaluate the effectiveness of the NHANES III standardized database at achieving agreement in diagnostic classification (normal, osteopenia, or osteoporosis) based on total hip T-scores comparing 2 different dual-energy X-ray absorptiometry (DXA) systems. This was a retrospective analysis of standard bilateral hip and lumbar spine scans done in duplicate for 60 women scanned on both a GE Lunar Prodigy and Hologic Delphi DXA system. Classification based on lumbar spine T-scores using manufacturer-specific databases was also compared as no standardized lumbar spine reference database exists. Subject's mean age was 62 yr (range: 47-83 yr). There was no statistically significant difference in diagnostic classification between DXA systems (Prodigy vs Delphi), with agreement (same women classified same way) of 92% at the left total hip. Agreement was 100% when T-scores were greater than or equal to -0.8 and less than or equal to -1.2. There was 90% agreement between DXA systems at the lumbar spine. For both hip and spine, all diagnostic discrepancies occurred when the T-scores were at or near transition thresholds between normal and osteopenia or osteopenia and osteoporosis. The difference in mean T-scores between DXA systems at left total hip was 0.11 vs 0.32 for lumbar spine (p less than 0.001). Use of the NHANES III standardized database results in good diagnostic agreement at total hip between Prodigy and Delphi.     

Bone Mineral Density Discordance and Exploration of One of its Causes

Discordances between hip and spine areal density T-score values are common and incompletely understood. In a cohort of 1157 postmenopausal women, discordances of greater than 10% occurred in 91%, with spine bone mineral density (BMD) T-scores significantly less negative than femoral neck (FN) T-scores (p < 0.001). However, when T-scores based on bone mineral content (BMC) rather than BMD were used, the mean discordance was not significantly different from 0. This was largely because BMC at the FN had seemingly declined with age less rapidly than had BMD at that site. This can be explained by age-related areal expansion at the hip, which would be missed in the reported BMD output. One consequence is that if BMC-based T-scores are used to classify patients, substantially fewer individuals would have been judged osteoporotic in this cohort (two-thirds fewer for spine and three-fourths fewer for hip).     

Definition of Osteoporosis by Bone Density Criteria in Men: Effect of Using Female Instead of Male Young Reference Data Depends on Skeletal Site and Densitometer Manufacturer

Whether to use young male or young female reference data to calculate bone mineral density (BMD) T-scores in men remains controversial. The third National Health and Nutrition Examination and Survey (NHANES III) data show that the mean and standard deviation of femoral neck and total hip BMD is greater in young men than young women, and therefore differences in T-scores at these sites using NHANES III female vs male norms becomes less as BMD decreases. In contrast, manufacturer-specific reference databases generally assume similar standard deviations of BMD in men and women. Using NHANES III reference data for the femoral neck and total hip, respectively we found that men with T-scores of −2.5 when young male norms are used have T-scores of −2.4 and −2.3 when young female norms are used. Using manufacturer-specific reference data, we found that men with T-scores of −2.5 when young male norms are used at the femoral neck, total hip, lumbar spine, or one-third of the forearm would have T-scores ranging from −2.4 to −0.4 when young female norms are used, depending on skeletal site and densitometer manufacturer. The change of proportions of men diagnosed with osteoporosis when young female norms are used instead of young male reference data differs substantially according to skeletal site and densitometer manufacturer.     

Effect of precision error on T-scores and the diagnostic classification of bone status.

We quantified confidence intervals (CIs) for T-scores for the lumbar spine and hip and determined the practical effect (impact on diagnosis) of variability around the T-score cutpoint of -2.5. Using precision data from the literature for GE Lunar Prodigy dual-energy X-ray absorptiometry (DXA) systems, the 95% CI for the T-score was +/-0.23 at the lumbar spine (L1-L4), +/- 0.20 at the total hip, and +/-0.41 at the femoral neck. Thus, T-score variations of +/-0.23 or less at the spine, +/-0.20 at the total hip, and +/-0.41 at the femoral neck are not statistically significant. When diagnosing osteoporosis, T-scores in the interval -2.3 to -2.7 for spine or total hip (after rounding to conform to guidelines from the International Society for Clinical Densitometry) and -2.1 to -2.9 for femoral neck are not statistically different from -2.5. Better precision values resulted in smaller 95% CIs. This concept was applied to actual clinical data using Hologic DXA systems. The study cohort comprised 2388 white women with either normal or osteopenic spines in whom the densitometric diagnosis of osteoporosis would be determined by hip T-scores. When evaluating actual patient T-scores in the range -2.5+/-95% CI, we found that the diagnosis was indeterminate in approximately 12% of women when T-scores for femoral neck were used and in 4% of women when T-scores for total hip were used, with uncertainty as to whether the classification was osteopenia or osteoporosis. We conclude that precision influences the variability around T-scores and that this variability affects the reliability of diagnostic classification.     

Comparison of T-scores from different skeletal sites in differentiating postmenopausal women with and without prevalent vertebral fractures.

It is not clear how bone mineral density (BMD) measurements from several regions of lumbar spine and proximal femur should be utilized in assessing fracture risk. We examined how well the newest ISCD recommendations differentiate subjects with and without prevalent vertebral fractures in 187 postmenopausal women presenting for routine bone densitometry. The association between T-scores from proximal femur and lumbar spine sites and the probability of having a vertebral fracture was modeled via logistic regression with adjustment for age. The lowest T-score of any hip or spine sites (the current ISCD recommendation) and the proximal femur measurements, particularly the femoral neck and total hip, displayed the strongest association with the probability of vertebral fractures.Subjects with a T-score < -2.5 at multiple hip sites had a higher probability of having a vertebral fracture. The sensitivity and specificity associated with particular T-score cutoff values varied greatly depending on the site of measurement.Consequently, T-score values from different sites that had comparable sensitivity/specificity for detecting the presence of vertebral fractures differed by as much as 1.5 T-score units. This finding implies that a single cutoff value, such as -2.5, might not be clinically acceptable when applied to T-scores from different sites.     

The prevalence of significant left-right differences in hip bone mineral density

Introduction We determined the prevalence of left-right differences in hip bone mineral density (BMD) by dual-energy x-ray absorptiometry (DXA) and the resultant consequence, namely: the frequency at which patients would be classified differently if lumbar spine and only one hip (rather than both hips) were measured.Methods This was a retrospective DXA scan reanalysis of 3012 white women ≥50 yrs who had scans of both hips using Hologic DXA systems. The difference between left and right hips was considered significant if it exceeded the least significant change (LSC) for any of three hip subregions (total hip, femoral neck, trochanter). The number of women with osteoporosis in both hips, the left hip only, or the right hip only was determined by lowest T-score from total hip, femoral neck, or trochanter.Results Despite high left-right correlations of subregion BMD, significant left-right differences in BMD were common: the difference exceeded the LSC for 47% of women at total hip, 31% at femoral neck, and 56% at trochanter. Left-right differences in BMD that exceeded the LSC affected the percent agreement of left-right hip classification: for all women irrespective of spine status, there was 77% classification (diagnostic) agreement in hip pairs in which the left-right hip BMD difference exceeded the LSC versus 87% agreement in which LSC was not exceeded (significant difference in proportions, P<0.0001). The greatest risk of different classification would occur in women with normal spines as the diagnosis might be determined by hip T-scores. Using L1-4 lumbar spine T-scores, 1229 women were normal at the spine. Twenty-four (2%) were osteoporotic at both hips. However, 12 women (1%) were osteoporotic only in the left hip (significantly different from zero, P<0.001) and 11 (1%) only in the right hip (P<0.001); of these 23 women, the difference in BMD between the osteoporotic hip and the contralateral hip exceeded the LSC in 16 (70% of those with osteoporosis in only one hip). Using L1-4 lumbar spine T-scores, 1159 women were osteopenic at the spine. Of these, 126 (11%) were osteoporotic at both hips, 54 (5%) only in the left hip (P<0.001), and 42 (4%) only in the right hip (P<0.001); of these 96 women, the difference in BMD between the osteoporotic hip and the contralateral hip exceeded the LSC in 56 (58% of those with osteoporosis in only one hip).Conclusions A statistically significant number of women with osteoporosis are potentially classified differently when scanning only one hip as a result of the high prevalence of left-right differences in BMD. Although the percentages are low, the total number of women affected may be large. From a public health perspective, the practice of scanning both hips could potentially identify more women with osteoporosis and may help prevent future hip fractures.     

Recalculation of the NHANES database SD improves T-score agreement and reduces osteoporosis prevalence.

In attempt to improve diagnostic agreement between manufacturers, a recent software update incorporated NHANES III data in GE Lunar densitometers. As a result, the femur neck and trochanter T-scores were lowered, and osteoporosis prevalence was increased. Use of a recalculated young-normal SD for the GE Lunar-adjusted NHANES III database improved diagnostic agreement and is recommended. INTRODUCTION: Use of manufacturer-specific normative databases for T-score derivation leads to discordance in T-score values and differences in diagnostic classification. To address this issue, the International Committee for Standards in Bone Measurement (ICSBM) recommended the NHANES III database for femur T-score derivation. Acquired on Hologic (Hol) instruments, this database requires conversion equations for application to other DXA systems. NHANES III total femur (TF) conversions for GE Lunar (GE) have previously been available, and femoral neck (FN) and trochanter (TR) equations were reported recently. Per the ICSBM recommendation, GE Lunar incorporated these values into their female database. This should produce T-score and diagnostic agreement between Hol and GE instruments; however, this has not been evaluated. MATERIALS AND METHODS: We compared GE femur scans in 115 postmenopausal women using software before and after the NHANES III software update. Subsequently, T-scores derived from femur scans obtained on GE and Hol densitometers were compared in a different group of 89 postmenopausal women. RESULTS: The NHANES III software update had no effect on measured BMD (g/cm2) at any femur region. However, because of changes in values used for T-score calculation (increase in the mean young-normal BMD at the FN and TR and a reduction in SD at the TR), the T-scores were lower (mean, 0.48 and 0.68, respectively) at the FN and TR using post-NHANES III software. Consequently, this update increased femur osteoporosis prevalence in these 115 women from 7.8% to 18.3%. Comparison of GE with Hol total proximal femur T-scores revealed a minimal difference (<0.1) and equal diagnoses of osteoporosis. FN and TR differences were larger, with mean GE T-scores lower than Hol (p < 0.001) by 0.17 and 0.50, respectively, thereby introducing osteoporosis diagnostic disagreement (13 [GE] versus 9 [Hol]). Our evaluation suggested that this disparity resulted from direct application of published NHANES III SDs at the FN and TR. As such, we applied the conversion formulae to the NHANES III published Hologic data and found the FN and TR SDs were greater than assumed by GE. Using our recalculated SD to derive T-scores reduced the mean GE/Hol T-score difference to 0.03 at the FN and 0.32 at the TR and resolved osteoporosis diagnostic disagreement. CONCLUSION: The GE NHANES III software update leads to lower FN and TR T-scores than obtained with Hol or prior GE software. Recalculation of the young-normal SD reduces this difference and is recommended. Clinicians are advised to avoid using the TR for diagnosis or, at a minimum, use caution when making treatment decisions based solely on T-score at this site.     

A Comparison of a Peripheral DXA System with Conventional Densitometry of the Spine and Femur

Because of the perceived high cost of dual-energy X-ray absorptiometry (DXA) studies of the spine and femur, there is renewed interest in small, low-cost X-ray devices for scanning the peripheral skeleton. We have compared forearm bone mineral density (BMD) measurements (distal and ultradistal sites) performed on a DTX-200 (Osteometer MediTech, Hoersholm, Denmark) with spine (L1-L4) and femur (femoral neck and total hip sites) scans performed on a QDR-4500 (Hologic, Waltham, MA) in 172 white UK women aged 22-84 yr with a view to establishing differences caused by inconsistent reference ranges and different age-related changes in BMD. All BMDs were expressed as T-scores using the manufacturers' reference ranges for the forearm and spine, and the National Health and Nutrition Examination Survey (NHANES) ranges for the femur. Linear regression between peripheral and axial sites gave correlation coefficients r = 0.71-0.74 and roof mean standard errors (RMSE) 0.88-1.14 in T-score units. Subjects were divided into the following five age groups: <40 yr; 40-49 yr; 50-59 yr; 60-69 yr and >/=70 yr. A large systematic difference between distal and ultradistal T-scores (mean DeltaT = 0.59, SEM = 0.05) was found affecting all age groups. When the mean difference in T-score between each forearm site (distal, ultradistal) and each axial site (spine, femoral neck, total hip) was examined for premenopausal subjects (n = 58) the mean difference between forearm and axial T-score showed a consistent negative offset (DeltaT = -0.41 to -0.48) for the distal forearm site and a consistent positive offset (DeltaT = +0.30 to +0.37) for the ultradistal site. When interpreting results in postmenopausal women, age-related T-score changes in the forearm were in close agreement with the femoral neck region of exterest (ROI), but systematic differences were found between the forearm and the spine and total hip sites. The two forearm and three axial sites were compared to evaluate the number of postmenopausal subjects identified as osteoporotic on the basis of the World Health Organization (WHO) Study Group criteria (T-score <-2.5). Although forearm and spine T-scores identified approximately equal numbers of subjects as osteoporotic (distal 38/114; ultradistal 31/114; spine 30/114), the two femur sites identified fewer subjects as osteoporotic (femoral neck 25/114; total hip 16/114). The number for the total hip site was statistically significantly smaller than the spine and forearm sites.     

Bone mineral density (BMD) assessment of central skeletal sites from peripheral BMD and ultrasonographic measurements: an improved solution employing age and weight in type 3 regression.

The objective of this study was to develop a method whereby bone mineral density measurements of the heel and finger, as well as ultrasonographic measurements of calcaneal sound transmission, could identify individuals with a diagnosis of osteoporosis or osteopenia by the World Health Organization criteria for these diagnoses in the central skeleton (i.e., the lumbar spine (LS) and hip [femoral neck] [FN]). Two hundred and forty-four women in a university hospital laboratory setting had dual-energy X-ray absorptiometry measurements of bone mineral density (BMD) in the calcaneus, finger, hip, and spine, and quantitative ultrasound of the calcaneus. Regression equations were developed to predict central bone mineral T-scores from T-scores of peripheral measurements, adjusted by age and weight. Equations were validated by predicting the cut point for osteopenia at the lumbar spine and hip (T-score=-1.0). Ninety-five percent confidence intervals of the mean predicted LS or FN T-score from each peripheral site included -1.0. We conclude that our derived regression equations (taking into account interaction of peripheral BMD with patient age and weight) are useful for predicting T-scores in the central skeleton. This approach reduces the potential for misdiagnosis, which can result if one uses unadjusted peripheral T-scores, which are only moderately correlated with the central measurements of BMD.     

Utility of heel ultrasound bone density in men.

In women, heel ultrasound (US) bone mineral density (BMD) has been shown to predict fracture risk, but the usefulness of this screening tool in men is not known. We measured the heel quantitative ultrasound index (QUI( in a convenience sample 185 of men (136 Caucasian, 1 Asian, and 48 African-American) with an average age of 63 yr (range of 25-85) undergoing BMD of the spine and hip by dual X-ray absorptiometry (DXA) to determine whether the heel measurement could predict central BMD. The average DXA T-score was -0.97, -1.20, and -1.61 for the spine, total hip, and femoral neck, respectively. The mean heel US BMD T-score (using the only available T-score, which was defined for Caucasian postmenopausal women) was -0.92. There were significant correlations among the various DXA measurements and the heel US BMD T-score (r = 0.373-0.483, p < 0.001). We defined arbitrarily osteopenia as a spine, total hip, or femoral neck T-score by DXA of < -1.5. We also made two different arbitrary definitions of osteoporosis by DXA: < -2.0 and < -2.5. Using these numbers as disease definitions, we determined the specificity, sensitivity, as well as positive and negative predictive values of using the heel US T-score to predict osteopenia or osteoporosis. Using various cutoffs for the heel T-score, we found that increasing the cutoff toward 0 increased the sensitivity but lowered the specificity. No cutoff was found that provided both good sensitivity and specificity. By analyzing the men by ethnic and age groups, we found that the best set of receiver operating characteristic (ROC) curves was derived from data using heel US to predict osteopenia and osteoporosis in men younger than age 65, although the areas under the ROC curve were approx 0.8. In conclusion, despite a strong correlation between the heel QUI and the spine and hip BMD by DXA, no heel T-score could predict osteopenia or osteoporosis with satisfactory sensitivity and specificity. It is possible that the use of risk factor assessment plus heel QUI might have better predictive value, and further studies are needed to determine whether heel QUI or other US determination is an independent risk factor for fracture in men.     

Geographic and other determinants of BMD change in European men and women at the hip and spine. a population-based study from the Network in Europe for Male Osteoporosis (NEMO)

INTRODUCTION: While the determinants of BMD change have been studied in women, there have been few longitudinal studies in men. As part of the Network in Europe for Male Osteoporosis (NEMO) study, data were analysed from 1337 men and 1722 women aged 50-86y (mean=67 years) from 13 centres across Europe to assess determinants of BMD change and between-gender contrasts. METHODS: BMD was measured at the femoral neck, trochanter and/or L2-L4 spine on 2 occasions 0.8-8 years apart (mean=3.5 years) using DXA densitometers manufactured by Hologic (n=6), Lunar (n=5) and Norland (n=2). Each was cross-calibrated using the European Spine Phantom and annual rates of BMD change (g/cm(2)/year) were calculated from the standardised paired BMD values. The EPOS risk factor questionnaire was administered at baseline. RESULTS: In multivariate linear regression models, there were large between centre differences in the mean rates of BMD change in all 3 sites for both genders (P<0.0001) with the standard deviation of the between centre heterogeneity in the adjusted means being 0.005 g/cm(2)/year at the femoral neck. The overall adjusted mean annual rates of BMD change in g/cm(2)/year (95% CI) pooled across centres by random effects meta-analysis in men were: femoral neck -0.005 (-0.009, -0.001); trochanter -0.003 (-0.006, -0.001); and spine 0.000 (-0.004, 0.004). In women the respective estimates were: -0.007 (-0.009, -0.005); -0.004 (-0.006, -0.003); and -0.005 (-0.008, -0.001). The I(2) statistic for heterogeneity was between 81% and 94%, indicating strong evidence of between centre heterogeneity. Higher baseline BMD value was associated with subsequent greater decline in BMD (P<0.001). Preserved BMD was associated with higher baseline body weight in all 3 sites in men (P<0.012) but not in women. Weight gain preserved BMD (P<0.039) in all 3 sites for both genders, except the male spine. Increasing age was associated with faster BMD decline at the trochanter in both genders (P<0.026) and with a slower rate of decline at the female spine (P=0.002). Effects of lifestyle, physical activity, medications, and reproductive factors were not consistent across sites or between genders. CONCLUSION: These results show major geographic variations in rates of BMD change in men and women over 50 years of age across diverse European populations and demonstrate that body weight and weight gain are key determinants of BMD change in men.     

Use of a Swedish T-score reference population for women causes a two-fold increase in the amount of postmenopausal Swedish patients that fulfill the WHO criteria for osteoporosis

The WHO criteria for osteoporosis are based on bone mineral density (BMD) values in comparison to a reference population of healthy young adults. The aim of this study was to create BMD references for ethnic Swedish women, and to investigate whether the use of these T-score measurements influence the amount of Swedish postmenopausal patients that are diagnosed as having osteoporosis. A bone density reference was created by measuring a population-based sample of 335 randomly selected Swedish women aged 20-39yr. BMD was measured by dual-energy X-ray absorptiometry (DXA) at the lumbar spine, proximal femur, and total body. These locally derived T-score values were subsequently used to diagnose a sample of 300 consecutive postmenopausal Swedish patients referred to the Uppsala Osteoporosis Unit. There was a slight age-dependent decrease in femoral neck BMD, whereas no age effect was seen at other sites such as total hip, lumbar spine, or total body. This suggests that the cohort represents the steady state BMD at the ages of expected peak bone mass in Swedish women. The correlation between BMD measures at different sites differed from r=0.55 (lumbar spine BMD vs femoral neck BMD [FNBMD]) to r=0.92 (total hip BMD vs FNBMD). Central DXA-generated T-scores were calculated from this cohort, and these were significantly higher (0.3-0.5 SD) as compared with manufacturers and NHANESIII reference populations. This indicates that young Swedish women have a higher peak bone mass than the subjects included in the reference populations currently used for clinical measurements. The T-score in total hip derived from the investigated cohort was subsequently used to diagnose 300 clinical patients (mean age 63yr) referred for a DXA scan by their physicians. The use of this locally established and ethnic representative, T-score reference increased the prevalence of osteoporosis in femoral neck and total hip with 53-106%. A Swedish female BMD reference representing peak bone mass has been established and the normative data are presented. Notably, this cohort has considerably higher BMD as compared to the NHANESIII and manufacturer's reference populations. The use of the present T-score reference therefore causes approximately a 2-fold increase in the amount of Swedish postmenopausal women that fulfill the WHO criteria for osteoporosis. This demonstrates the problems with using T-score as diagnostic threshold for osteoporosis and is an argument for future strategies to obtain standardized densitometric cut-offs, for example, mg/cm(2).     

Discordance in patient classification using T-scores.

In their original study report, "Assessment of Fracture Risk and Its Application to Screening for Postmenopausal Osteoporosis," the World Health Organization (WHO) explicitly stated that any T-score criterion for osteoporosis is sensitive to bone mineral density (BMD) measurement site and technique, as well as the young adult reference population. Yet, the T = -2.5 criterion introduced by WHO is used for many different BMD techniques, despite the fact that it was based primarily on the relationship between forearm measurements and prevalent hip fracture in postmenopausal Caucasian females. It is reasonable to expect that a T-score threshold of -2.5 may be inappropriate for different skeletal sites and measurement techniques. This may explain the large variation in osteoporosis prevalence observed when different skeletal sites are measured. In this study, we compared the prevalence of osteoporosis (based on the T = -2.5 criterion) at different skeletal sites using the manufacturer's normative data. We determined the expected mean T-score for a 60-yr-old Caucasian female at the heel (ultrasound), hip (dual X-ray absorptiometry [DXA]), spine (PA DXA, lateral DXA, and quantitative computed tomography [QCT]), and forearm (DXA). Assuming a normal distribution of T-scores at a fixed age, we computed the expected percentage of 60-yr-old Caucasian women that would be classified as osteoporotic using the -2.5 standard deviation criterion for each technique. At age 60 yr, the expected mean T-score ranged from -2.5 (spine QCT) to -0.7 (heel). Prevalence estimates ranged from 3% at the heel to 50% for spinal QCT. It was also noted that the sites with the strongest relationship to hip fracture risk (the hip and heel) showed the least age-related T-score decline and lowest estimated prevalence. We conclude that a single T-score criterion cannot be universally applied to all BMD measurements. The discrepancies in the prevalence of osteoporosis are the result of several factors, including differences in age-related bone loss at different skeletal sites, differences in the young adult reference populations used by the various bone densitometry devices, and technology-related differences. Using estimated BMD by heel ultrasound, few patients will have T-scores below -2.5, whereas most postmenopausal women will fall below this level for spine bone density measurements performed by lateral DXA or QCT. Based on these data, it may be necessary to provide a T-score criterion specific to the type of densitometric evaluation performed.     

Age-Specific Values and Cutoff Levels for the Diagnosis of Osteoporosis in Quantitative Ultrasound Measurements at the Calcaneus with SAHARA in Healthy Japanese Women: Japanese Population-Based Osteoporosis (JPOS) Study

To establish the reference values of the quantitative ultrasound (QUS) indices in healthy Japanese women and to propose a diagnostic criterion for osteoporosis by means of the QUS indices, 659 healthy women aged 20-79 years recruited from a larger cohort study (JPOS study), were examined for bone mass measurements by QUS at the calcaneus (SAHARA, Hologic Inc., USA) and by dual-energy X-ray absorptiometry at the spine, hip, and distal forearm. We presented 10-year age-specific mean values and T-scores of the QUS indices. The pattern of decrease in the T-score appeared to be linear in the QUS indices and total hip BMD but not in BMD at the spine. The T-score of the QUS of indices of the subjects in their 70s were significantly higher than that of BMD at the spine. The prevalence rates of osteoporosis in the subjects aged 50 and older diagnosed by QUS (8.7% for SOS, 10.7% for BUA) were similar to that diagnosed by total hip BMD (11.5%) and significantly lower than that by the spine BMD (36.1%) when the WHO criteria were applied. We performed receiver-operating characteristic analysis to set a cutoff level of the QUS indices for the diagnosis of osteoporosis to accurately identify the subjects diagnosed by either the spine or total hip BMD. The highest likelihood ratios for SOS and BUA were obtained at the cutoff levels of 1,517.7 m/sec (T-score: -1.58) with the sensitivity of 0.65 and the specificity of 0.65 and 59.5 dB/MHz (T-score: -1.52) with 0.66 and 0.69, respectively. The diagnostic accuracy of QUS indices for osteoporosis was not superior to that of age. However, the QUS indices showed a significant contribution to forming the diagnosis of osteoporosis independently of age and body size in multivariate diagnostic models developed by the logistic regression analysis. Therefore, the cutoff values presented in this study may be used as a tentative criterion until the cutoff levels for the QUS indices are set according to the fracture risk.     

International variation in proximal femur bone mineral density

Summary

We observed higher proximal femur bone mineral density (BMD) in European women compared to average values derived from US Caucasian women in the National Health and Nutrition Examination Survey (NHANES) study. Across European centres, Parisian women had lower proximal femur BMD compared to women from Kiel or Sheffield.

Introduction

Proximal femur BMD of US adults (NHANES III) may not accurately reflect that of European women. We examined the heterogeneity of BMD across European and US Caucasian women and across different European populations.

Methods

Proximal femur BMD was measured in women ages 20–39 years (n?=?258) and 55–79 years (n?=?1,426) from three European centres. Cross-calibrated BMD for total hip, femoral neck, trochanter and intertrochanter were examined. International variation in BMD was assessed by comparing means and SDs in the European data with those from the US NHANES III study. European populations were stratified into 5-year age bands to establish individual centre reference intervals. Between-centre differences were assessed using ANOVA and post hoc Fisher’s least significant difference tests.

Results

European women had higher BMD than US women: The differences were 7.1% to 14.2% (p?<?0.001) and 0% to 3.9% (p?<?0.05) in the older and younger women, respectively. Standard deviations for BMD at the different sites were comparable to those for US women. Among older, but not younger European women, proximal femur BMD was significantly lower in French women (Paris) than in women from Germany (Kiel) or the UK (Sheffield) (difference?=?5.0% to 9.6%, p?<?0.05).

Conclusions

International variation in hip BMD does exist, with international and between-centre differences being less evident at the femoral neck.     

Heterogeneity of Bone Mineral Density Across Skeletal Sites and Its Clinical Implications

Low trauma fractures in the elderly are highly predictable by measurement of bone mineral density (BMD). Preventive measures for low BMD, such as hormone replace therapy (HRT), have potential risks. Thus, a rational decision on HRT or other therapy critically depends on an accurate diagnosis of osteopenia/osteoporosis. We assessed the degree of diagnostic heterogeneity based on spine and hip BMD for 2313 women. We found: 1. In ~30.0% of cases, the difference between spine and hip Z- and T-scores was >1.0, and in 20.8% (Z-scores) and 15.2% (T-scores) the difference was >2.0. 2. With increasing age, the proportions of women with Z- or T-scores greater at the hip than the spine generally decreased. 3. The correlation between hip and spine and Z- and T-scores ranged from 0.50 to 0.72, and generally decreased with increasing age. 4. If screened only at the hip or spine, 17.9/27.3% with osteopenia and 1.3/2.9% with osteoporosis at either site would be diagnosed as normal. Corresponding analyses of 143 men yielded similar results. Therefore, if possible, dual X-ray absorptiometry (DXA) of both the spine and hip should be performed for an accurate assessment of osteoporosis at these two most frequently fractured sites. If only one site is chosen, measurement of the hip is preferred to measurement of the spine.     

The impact of hip subregion reference data on osteoporosis diagnosis

Manufacturers of bone densitometry devices have been moving from manufacturer-specific reference values to data derived from larger population-based cohorts such as the National Health and Nutrition Evaluation Survey (NHANES) III. One bone densitometer manufacturer has released software that provides hip subregion T-score calculations based upon four slightly different versions of hip reference data. Our aim was to determine how changes in hip reference data affect diagnostic classification based on minimum T-scores in older women. We extracted results for lumbar spine and hip bone density measurements from the Manitoba Bone Density database for women aged 50 years or older who had baseline scans on the manufacturers equipment ( n =17,053). T-scores were calculated using manufacturer-specific non-NHANES data and three software implementations of NHANES reference data. One software version gave results at subregions of the hip that were significantly lower than with the three other sets of reference data from the same manufacturer (mean femoral neck T-score absolute difference 0.23–0.48, P <0.00001; mean trochanter T-score absolute difference 0.49–0.70, P <0.00001). As a result the proportion of measurements with a T-score of –2.5 or lower almost doubled at the femoral neck (14.3 versus 27.7%, P <0.00001) and approximately tripled at the trochanter (8.1 versus 24.0%, P <0.00001). The final patient classification of osteoporosis based on a minimum T-score of –2.5 or lower from all four measured sites differed significantly between the four versions (absolute difference 7.9 to 10.4%, P <0.00001). Small changes in the reference data used in T-score calculations had large effects on patient categorization and the calculated prevalence of osteoporosis. The impact of changes in reference data need to be carefully evaluated by users and manufacturers before widespread clinical dissemination.     

How Often Does Lateral Spine DXA Detect Low Bone Mass in Patients with Both Normal PA Spine and Hip?

The clinical utility of lateral bone mineral density (BMD) measurement for the diagnosis of osteoporosis remains controversial. Since both posterior-anterior (PA) spine and hip scans are universally performed, the true clinical utility of lateral dual-energy X-ray absorptiometry (DXA) should lie in its ability to detect low bone mass independent of both PA spine and hip. We examined lateral, PA and hip BMDs in 2134 referred Caucasian females aged 25-89 using the Hologic 2000. Compared only to PA scans, the additional percentages of women with very low BMD (T-score below -2.5 utilizing the National Health and Nutrition Examination Survey [NHANES] III normative database) on lateral were 7.3, 16.4, 28.2, 33.7, and 26.2% for age groups 25-49, 50-59, 60-69, 70-79, and 80-89, respectively. When the results from both PA and total hip measurements were combined, lower but still significant percentages were found: 5.4, 14.9, 24.4, 26.6, and 17.8% for age groups 25-49, 50-59, 60-69, 70-79, and 80-89, respectively. Utilizing the original Hologic normative database, the additional yield in women with a nonosteoporotic PA spine and femoral neck was quite low: 4.6, 8.5, 13.3, 10.0, and 2.5% for women age 25-49, 50-59, 60-69, 70-79, and 80-89, respectively. Thus, the lateral scans now add more additional patients into the very low BMD category. Whether the relationship to future fracture risk of low BMD and T-scores on lateral is similar to that of PA spine remains to be established.     

Enhanced prediction of fracture risk combining vertebral fracture status and BMD

Summary Prevalent vertebral fractures are associated with increased fracture risk, but the magnitude of this effect across a range of BMD T-scores has not been quantified. In this analysis, for any given BMD T-score, incident fracture risk varied up to twelve fold when information regarding prevalent radiographic vertebral fracture status was considered. Background Clinical fracture risk evaluation of older women usually includes assessment of bone mineral density (BMD) but often not vertebral fracture status. In this analysis, we quantified the impact of vertebral fracture burden on two year fracture risk across a range of BMD T-scores. Methods Data were from 2,651 postmenopausal women who were assigned to the placebo groups of the Fracture Prevention Trial (median observation 21 months) and the Multiple Outcomes of Raloxifene Evaluation Trial (MORE; observation 2 years). Using the Genant visual semiquantitative criteria, we defined prevalent vertebral fracture status as: a) presence or absence of fracture; b) fracture number; c) maximum semi-quantitative (SQ) score (normal=0, mild fracture=1, moderate fracture=2, severe fracture=3); and d) spinal deformity index (SDI) score (sum of SQ scores of T4 to L4 vertebrae). Incident fractures over two years were identified via lateral spine radiographs and outside the spine by questioning of patients and review of radiographs or radiographic reports. Results Femoral neck BMD T-score provided significant information regarding fracture risk. Across the range of T-scores, vertebral fracture status provided additional prognostic information. The risk increased with increasing number and severity of prevalent vertebral fractures and SDI, a summary measure of spine fracture burden. Across a range of BMD values, prevalent spine fracture burden as assessed by SDI increased the risk of incident vertebral fractures by up to 12-fold, nonvertebral fractures by about twofold, and any fractures by up to sevenfold. Conclusions These findings indicate that at any given BMD T-score, the risk of incident vertebral, non-vertebral, and any fracture depended heavily on prevalent radiographic vertebral fracture status. Assessment of vertebral fracture status, in addition to BMD, provides practical and relevant clinical information to aid in predicting fracture risk in postmenopausal women. This study was supported by Eli Lilly and Company.     

Applying ethnic-specific bone mineral density T-scores to Chinese women in the USA

Summary

Caucasian reference data are used to classify bone mineral density in US women of all races. However, use of Chinese American reference data yields lower osteoporosis prevalence in Chinese women. The reduction in osteoporosis labeling may be relevant for younger Chinese women at low fracture risk.

Introduction

Caucasian reference data are used for osteoporosis classification in US postmenopausal women regardless of race, including Asians who tend to have lower bone mineral density (BMD) than women of white race. This study examines BMD classification by ethnic T-scores for Chinese women.

Methods

Using BMD data in a Northern California healthcare population, Chinese women aged 50–79 years were compared to age-matched white women (1:5 ratio), with femoral neck (FN), total hip (TH), and lumbar spine (LS) T-scores calculated using Caucasian versus Chinese American reference data.

Results

Comparing 4039 Chinese and 20,195 white women (44.8 % age 50–59 years, 37.5 % age 60–69 years, 17.7 % age 70–79 years), Chinese women had lower BMD T-scores at the FN, TH, and LS (median T-score 0.29–0.72 units lower across age groups, p?<?0.001) using Caucasian reference data. Using Chinese American BMD reference data resulted in an average +0.47, +0.36, and +0.48 units higher FN, TH, and LS T-scores, respectively, reducing the prevalence of osteoporosis (T-score?≤??2.5) in Chinese women at the FN (16.7 to 6.6 %), TH (9.8 to 3.2 %), and LS (23.2 to 8.9 %); osteoporosis prevalence at any one of three sites fell from 29.6 to 12.6 % (22.4 to 8.1 % for age 50–64 years and 43.2 to 21.0 % for age 65–79 years).

Conclusion

Use of Chinese American BMD reference data yields higher (ethnic) T-scores by 0.4–0.5 units, with a large proportion of Chinese women reclassified from osteoporosis to osteopenia. The reduction in osteoporosis labeling with ethnic T-scores may be relevant for younger Chinese women at low fracture risk.