Establishment of BMD reference curves at different skeletal sites in women, using a Cartesian coordinate numeration system

The BMD reference curve is the reference value used for diagnosing osteoporosis and assessing bone mass changes. Its accuracy would affect the correctness of T -score and Z -score values and thus the reliability of diagnostic results. In this paper, we report the use of a new method, a Cartesian coordinate numeration system, to establish BMD reference curves at different skeletal sites in women. In a reference population of 3,919 women ranging in age from 5–85 years, we used the dual X-ray absorptiometry (DXA) bone densitometer to measure BMD at the posteroanterior spine (PA; vertebrae L1–L4), followed by a paired PA/lateral spine scan of the vertebral bodies of L2–L4, expressed in g/cm² and g/cm³, and of the hip and forearm. We chose the cubic regression model to best fit BMD curves that varied with age at different skeletal sites. We then referred the BMD of the fitting curves established by the method of the coordinate numeration system as reference curves, compared them to BMD reference curves derived from the fitting curve equation or age cross-section, and calculated the deflection degrees of the BMD reference curves acquired from the fitting curve equation. At the PA spine, lateral spine (expressed in g/cm³), femoral neck, Wards triangle and radius + ulna ultradistal, the reference curves calculated from the equation were significantly lower than those confirmed by the method of the coordinate numeration system; whereas, at the lateral spine (expressed in g/cm²), total hip, and radius + ulna 1/3 sites, the reference curves derived from the equation were markedly higher than those acquired from the coordinate numeration system. The differences in the two kinds of reference curves calculated by these two different methods gradually increased along with the increment in ages of the women. At the peak value of the reference curves, the BMD calculated from the equation deflected from 2.02% to –10.0% from the BMD acquired from the coordinate numeration system at different skeletal sites, and from 21.5% to –121.8% until the age of 85 years. The highest positive deflection of 65.2% existed at the lateral spine (expressed in g/cm²) and the lowest positive deflection of 21.5% at the total hip. The maximum negative deflection of –121.8% was at the radius + ulna ultradistal, and the minimum negative deflection of –32.6% at the PA spine. The BMD curve acquired from age cross-section was highly positive compared with the one derived from the coordinate numeration system ( r =0.955–0.985 p =0.000) with no significant difference between them. Various analysts used such a method to obtain the coefficient of variance (CV) in BMD precision on each curve that was from 0.05–0.19%. Our study shows that the Cartesian coordinate numeration system is an accurate, precise and reliable method and can serve to reveal the serious drawbacks of using the fitting curve equation to calculate BMD. The BMD reference curves established by this coordinate numeration system maintained the authenticity of the fitting curve, whereas, using the fitting curve equation to obtain BMD reference curves at different skeletal sites led to distortion, and resulted in false increases or decreases in T -score and Z -score values.     

Early postmenopausal diminution of forearm and spinal bone mineral density: A cross-sectional study

Diminution of bone mineral density (BMD) in the spine and forearm was studied cross-sectionally in 363 women who were 6 months to 10 years postmenopausal. BMD was determined by dual-energy X-ray absorptiometry (DXA) (Hologic QDR-2000) in the lumbar spine, in both the supine lateral (LAT) and anteroposterior (AP) projections, and in the distal third of the forearm. The postmenopausal diminution of BMD was best described by an exponential fit. The initial rate of postmenopausal diminution of BMD was highest in the most trabecular sites (LAT>AP> forearm), but 10-year diminution was similar at all sites (12%–13%, corresponding to about 1.0–1.5 SD), and extrapolation suggested reverse order of the rates of diminution thereafter (forearm>AP>LAT). When bone mineral content of the entire L3 vertebra (tBMC) was measured in vivo, AP tBMC could account for only 67% of the variation in LAT tBMC, compared withr ²=0.997 in vitro. This observation suggests an accuracy problem in vivo in one of the spine measurement methods. We conclude that the initial rate of BMD diminution after the menopause seems to be highest in the spine, especially when measured laterally, but that this rate levels off within the first decade. The lower precision error of a forearm measurement (0.8% v 1.6 for AP and 3.1 for LAT) therefore implies that this method may require a shorter observation period than spine measurements for the detection of bone loss 5–10 years after menopause. Long-term longitudinal spine and forearm measurements are, however, needed to confirm these conclusions.     

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.     

Sarcopenia in premenopausal and postmenopausal women with osteopenia, osteoporosis and normal bone mineral density

Sarcopenia, the decline of muscle mass with age, causes impaired gait, disability and falls. It may therefore increase the risk of fracture for osteoporotic women. The aims of this study were to determine the prevalence of sarcopenia in osteopenic and osteoporotic women, and to determine if hormone replacement therapy (HRT), diet, or physical activity (PA) has a role in the prevention of sarcopenia. One hundred and thirty-one premenopausal and 82 postmenopausal (54 taking HRT) healthy women (17–77 years) volunteered for the study. Body composition was measured by dual X-ray absorptiometry (DXA). Sarcopenia was defined as a relative skeletal muscle index (RSMI) (appendicular skeletal muscle mass divided by height) below 5.45 kg/m². Osteopenia was defined by a densitometric t -score for bone mineral density (BMD) (g/cm²) below –1.0 and osteoporosis by a t -score below –2.5. Nutrient intake was assessed using 3-day food records and physical activity (PA) was measured using the Baecke Physical Activity Questionnaire. Pearson chi-squared, independent t -tests, simple correlation and multiple regression were used to analyze the data. In premenopausal osteopenic women the prevalence of sarcopenia was 12.5%. In postmenopausal women it was 25% for those with osteopenia, and 50% for those with osteoporosis. PA was independently related to RSMI (=0.222, p =0.0001), but diet and HRT were not. After adjusting for PA, RSMI was not significantly related to BMD. These data suggest that the relationship between RSMI, BMD and risk of osteoporosis may largely be mediated through participation in PA. Sarcopenia screening simultaneous to BMD examinations by DXA, may be of value in identifying osteoporotic women with sarcopenia, a group that may be most in need of exercise interventions to increase muscle and BMD.     

Definition of a population-specific DXA reference standard in Italian women: the Densitometric Italian Normative Study (DINS)

Osteoporosis is currently defined on the basis of the T-score by dual-energy X-ray absorptiometry (DXA). Despite its limitations, this definition is applied worldwide. However, the normal values provided by manufacturers may not be fully representative of specific local populations. So far, there are no normative data in the Italian population using Hologic densitometers. The Densitometric Italian Normative Study (DINS) is an ongoing multi-center study that aims to establish reference values for bone densitometry with dual-energy X-ray absorptiometry (DXA) in the male and female Italian population. In this paper we report the results of the lumbar vertebrae (L2–L4) and proximal femur in 1,622 women aged 20–79 years. Bone mineral density (BMD) was determined using dual-energy X-ray absorptiometry (DXA) on Hologic bone densitometers (Hologic, Waltham, Mass.). Most of the subjects were examined with a QDR 4500. The BMD of the lumbar vertebrae was virtually constant between 20 and 49 years (test for trend: P=0.66); the BMD values between 20–45 in premenopausal women (mean 1.036; SD 0.109 g/cm²) were thus defined as the peak bone mass values, significantly lower compared to the Hologic reference curve (mean 1.079, SD 0.11 g/cm²). The mean BMD values of the femoral neck were virtually identical to those of the NHANES study in the first 3 decades; after the age of 50 the BMD values were slightly greater than those of the NHANES subject. The subject classification according to the WHO criteria was similar using the DINS and NHANES reference values for the femur; for the spine, the Hologic reference values classified a larger proportion of women as osteoporotic (21 vs. 16%) or osteopenic (42 vs. 38%) compared to DINS.     

Bone loss is more severe in primary adrenal than in pituitary-dependent Cushing’s syndrome

Either exogenous or endogenous glucocorticoid excess is an established cause of osteoporosis and fractures. Glucocorticoids exert their negative effects on bone through mechanisms that are not yet completely elucidated; however, as many as 50% of patients with Cushings syndrome suffer from osteoporosis. Bone loss induced by glucocorticoids is potentially reversible after resolution of glucocorticoid excess. It is presently unknown if Cushings disease (CD) sustained by a pituitary ACTH-producing adenoma and adrenal-dependent Cushings syndrome (ACS) sustained by an adrenocortical adenoma have a different potential of inducing osteopenia. The aim of the present study was to retrospectively analyze bone mineral density (BMD) in 26 patients with CD (4 men, 22 women, aged 14–79 years), 12 patients with ACS (4 men, 8 women, aged 32–79 years) and 38 healthy subjects carefully matched for sex, age and body mass index (BMI). Measurement of BMD was performed by dual-energy X-ray absorptiometry (DXA) using the Hologic QDR 4500 W instrument. Data were analyzed using absolute BMD values (g/cm²), T-score and Z-score referred to the manufacturers normative data for the lumbar spine and to the NHANES III dataset for the hip. The patients with CD and ACS were comparable for age, BMI, estimated duration of disease, urinary free cortisol (UFC) levels, midnight serum cortisol and gonadal function. The analysis of variance demonstrated that lumbar bone densitometric parameters were significantly different among the three groups. They were more reduced in patients with ACS (BMD, 0.76±0.03 g/cm²; T-score, –2.78±0.28; Z-score, –2.25±0.30) while patients with CD (BMD, 0.87±0.02 g/cm²; T-score, –1.74±0.24; Z-score, –0.99±0.32) showed DXA values between the first group and controls (BMD, 1.02±0.02 g/cm²; T-score, –0.35±0.19; Z-score, 0.33±0.16). The difference in BMD at the spine remained statistically significant (P=0.04) after adjustment for the non-significant differences in age, UFC and fat mass between CD and ACS. Conversely, femoral bone densitometric parameters were not significantly different between patients with ACS and CD, even if they were more reduced than in controls. In patients with ACS, we observed a reduction of DHEA-S levels, expressed as standard score (Z-score) values referred to a group of 180 healthy subjects stratified by sex and different age groups (<40 years, between 40 and 60 years, >60 years) to circumvent the pronounced effect of gender and age on such hormone (ACS DHEA-S Z-score -0.88±1.4 versus CD DHEA-S Z-score 2.25±2.35, P=0.0001). DHEA-S Z-score values were significantly correlated with lumbar BMD (r=0.41, P=0.02) and femoral BMD (r=0.43, P=0.01). DHEA-S Z-score values were also significantly correlated with osteocalcin levels (r=0.45, P=0.01). Our data suggest that bone loss is greater in ACS than in CD. A plausible explanation comes from the reduced DHEA-S level in ACS since DHEA-S has well known anabolic actions on bone. However, this hypothesis needs to be confirmed in large, prospective series of patients with Cushings syndrome of different etiology.     

Association between weight cycling history and bone mineral density in premenopausal women

The hypothesis that a history of one or more weight reductions and regains (weight cycling) is associated with lower site-specific bone mineral density (BMD) was examined in 169 premenopausal women, aged 29–46 years. Data on the previous 10-years' weight cycling history, present weight-bearing physical exercise, number of deliveries, present use of contraceptive pills or hormone-releasing coils, age at menarche and present menstrual status were collected by a self-administered questionnaire. Dietary intake was calculated from food records. The areal BMD (g/cm²) was measured with dual-energy X-ray absorptiometry (norland XR-26). The lumbar spine (L2–4) BMD, adjusted to weight and age at menarche (ANCOVA), was 0.062 g/cm² (95% confidence interval: 0.015 to 0.011 g/cm²;p=0.01) higher in the non-cyclers (n=68) than in subjects with reported weight-cycling history (n=101). The corresponding difference for femoral neck BMD was 0.019 g/cm² (–0.018 to 0.056;p=0.30), for trochanter BMD 0.013 g/cm² (–0.025 to 0.05 g/cm²;p=0.50) and for distal radius BMD 0.022 g/cm² (0.006 to 0.397 g/cm²;p=0.008). A pairwise comparison of 34 weight-matched subjects (non-cycler vs cycler) gave similar BMD differences as found in the above (ANCOVA) analyses. The results suggest that weight cycling might be associated with lower spine and distal radius BMD.     

Distribution of bone mineral density in the lumbar spine in health and osteoporosis

The significance of variability in bone mineral density (BMD) between lumbar vertebrae L1 to L4 in the same individual was investigated by dual-energy X-ray absorptiometry in 1000 normal women aged 40–60 years (average 52 years) and 145 women aged 45–80 years (average 65 years) with vertebral osteoporosis. The mean BMD increased from L1 to L4 in normal women from 0.841 g/cm² to 1.017 g/cm², and in osteoporotics from 0.562 g/cm² to 0.709 g/cm².Z scores for osteoporotic women (Z = osteoporotic BMD — age-normal BMD/normal SD) were significantly lower for individual vertebrae compared with Ll–4 and at L4 compared with L1, L2 and L3 (p<0.001). The mean difference betweenZ scores for the highest and lowest vertebrae in an individual was 0.70 for normals (SD=0.40) and 0.64 for osteoporotics (SD=0.36). The mean Z score difference between the L1–4Z score and the lowest individual vertebralZ score was 0.36 for normals (SD=0.23) and 0.06 for osteoporotics (SD=0.31). However, receiver operating analysis (ROC) curves showed that the lowestZ score for any individual vertebra did not provide improved discrimination between normals and osteoporotics when compared with the L1–4Z score. The area under the ROC curve for L1–4 was significantly greater than for individual vertebrae (p<0.05) and that for L4 was significantly smaller than for L1, L2 or L3 (p<0.001). In conclusion, L1–4 BMD gives greater diagnostic sensitivity for osteoporosis than individual vertebrae, and L1, L2 and L3 are better than L4. Although there is considerable individual variation inZ scores for different vertebrae in the same individual, the lowest vertebralZ score does not offer improved diagnostic sensitivity over the L1–4Z score.     

Can radial bone mineral density and quantitative ultrasound measurements reduce the number of women who need axial density skeletal assessment?

The purpose of this study was to investigate the clinical usefulness of forearm bone mineral density (BMD) and speed of sound (SOS) at the phalanx and radius as pre-selection tests to identify women with low BMD at the axial skeleton. BMD was measured by dual-energy X-ray absorptiometry (DXA) in the forearm, lumbar spine and femoral neck. SOS at the radius and phalanx was measured using a multisite quantitative ultrasound (QUS) device. Measurements were performed on 524 consecutive women referred for the assessment of BMD. Women with a T-score <–1 and T-score –2.5 at either spine or femoral neck were identified, and T-score cut-off values for the forearm DXA and QUS variables were determined. Cut-off values for the forearm BMD estimated to detect normal women and those with T-score <–1 at the axial skeleton identified a total of 82% of subjects with 91% certainty. Cut-off values for the forearm BMD determined to detect women with T-score >–2.5 and those with osteoporosis allowed the identification of 62% of the study population with 90% certainty. Cut-off values for the phalangeal and radial SOS estimated to detect normal women and those with T-score <–1 at the axial skeleton identified a total of 49% and 1% of subjects, respectively. Cut-off values estimated for QUS variables to detect women with T-score >–2.5 and those with osteoporosis at the axial skeleton either failed to detect subjects with sufficient certainty (phalangeal SOS) or detected a negligible percentage of patients (radial SOS). In conclusion, forearm BMD may be used as a pre-selection test to identify women with low BMD at the axial skeleton, thus enabling reduction of the number of women who need axial BMD assessment. SOS of the phalanges and radius appears to have less value in the detection of the women with low axial BMD.     

Densitometry of the radius using single and dual energy absorptiometry

Though spinal and femoral measurements are typically preferred for evaluating skeletal density, an abundance of forearm data exists, primarily from single photon absorptiometry (SPA) devices. Most dual X-ray absorptiometry (DXA) scanners are capable of scanning the forearm and provide analysis tools to duplicate conventional SPA measurements. In this study, we have compared the radius density measurements from three commonly available densitometers: a Norland 278 SPA, a Lunar DPX-L, and a Hologic 1000/W. Radius bone mineral density (BMD) on the nondominant forearm was measured in 28 volunteers (21 women and 7 men) aged 24–78, with an average age of 51±17 years. Values were compared and regression relationships derived at corresponding measurement sites. SPA and DXA BMD values were found to be highly correlated (r=0.99) with small standard errors (0.014 g/cm²–0.021 g/cm²), though significant absolute differences were observed at most measurement regions. Correlation slopes ranged from 0.85 to 1.04, with intercepts from 0.01 to 0.08 g/cm². Using the resultant regression equations, SPA BMD values can be converted to DXA values with an expected error of roughly 3%. DXA BMD can also be interconverted between Lunar and Hologic with a similar expected error. In situations where this level of imprecision is acceptable, patient forearm measurements obtained on different systems can be interconverted.     

The effect of overlying calcification on lumbar bone densitometry

Summary We studied bone mineral density (BMD) of the spine using dual photon absorptiometry, as well as standard anterior-posterior and lateral lumbar spine X-ray film in 113 ambulatory elderly male volunteers with a mean age of 72 years (range 66–91 years). Each subject had three measurements taken for lumbar vertebrae 1 through 4: BMD, length of aortic calcification (AC), and degenerative facet sclerosis graded 0–3. A separate statistical model was fit to BMD for each vertebra using analysis of covariance. AC did not contribute significantly to BMD. BMD was increased by 0.28–0.03 g/cm² (L1–L4) with a sclerosis score of 2, and by 0.47–0.25 g/cm² with a sclerosis score of 3,P<0.001. The association between increased BMD and overlying facet sclerosis may be related to the bone density within the sclerosis itself or to an association between degenerative joint disease and a generalized increase in subchondral bone.     

Dual-energy X-ray absorptiometry at the lumbar spine in German men and women: A cross-sectional study

A cross-sectional, population-based study of 238 randomly selected females and 224 males with German ethnic background (aged 20–80 years) was carried out to establish lumbar spine bone mineral density (BMD) values, using dual X-ray absorptiometry (DXA), for a German population. Comparison was made to the reference range provided by the manufacturer of the DXA equipment. No sex difference in peak spine BMD was found in our study (1.091±0.114 g/cm² for males versus 1.070±0.113 g/cm² for females, n.s.). Different patterns of bone loss could be detected in both sexes. In premenopausal women there was no significant correlation between age and BMD (y = 1.044 + 0.00047x, r=0.03, P=0.73) whereas reduction of female BMD at the spine was demonstrated in postmenopausal women (y = 1.189–0.0041x, r=-0.28, P=0.01), underscoring the important role of the menopause for later manifestation of spinal osteoporosis in women. In contrast, in males we found no significant change of BMD with aging (y = 1.071–0.0007x, r=-0.08, P=0.25). Employing commonly used exclusion criteria, BMD values of the study subjects were found mostly within the normal range of BMD. The major finding of our study was good concordance between female data of our study population and the reference data provided by the manufacturer. Clinically significant discrepancies between our data and the Hologic reference range for males could be detected. Our data on males (30–39 years of age) were up to 7% lower than those provided by the manufacturer, probably due to differences in sampling procedures.     

Correlations of dual-energy X-ray absorptiometry,quantitative computed tomography,and single photon absorptiometry with spinal and non-spinal fractures

Controversy continues as to which method of measuring bone mineral density (BMD) best detects osteoporosis and best correlates with fractures of the spine, hip and elsewhere. To answer these questions the prevalence of fractures was carefully determined among 90 subjects (70 with osteoporosis, 6 with mild primary hyperparathyroidism, 1 with osteomalacia and 13 normals) and simultaneous measurements were made using spinal computed tomography (QCT), spinal anteroposterior (AP) and supine lateral dual X-ray absorptiometry (DXA), femoral neck and total hip DXA, and distal third radial DXA and single photon absorptiometry (SPA). The DXA measurements which had the greatest sensitivity in detecting osteoporosis (defined as a BMD lower than –2.5 SD of peak bone mass at age 30 years) were the supine lateral spine DXA (84%) and femoral neck DXA (75%); less sensitive were the DXA measurements of the distal third of the radius (61%) and AP spine (51%). DXA measurements of the femoral neck and distal third of the radius were more useful than spinal measurements in detecting the osteopenia of mild primary hyperparathyroidism. Vertebral compression fractures (VCF) correlated well with spinal QCT (r=–0.38) and lateral spine DXA (r=–0.41), but poorly with AP spine DXA (r=–0.17) and distal third radial DXA (r=–0.02). Non-spinal fractures correlated best with the distal third radial DXA (r=–0.42). In conclusion, spinal QCT, supine lateral spine DXA and femoral neck DXA are the best BMD methods to screen for osteoporosis, whereas AP spine DXA is a poor screening method in women over 60 years of age. Spinal QCT and lateral spine DXA correlate well with VCFs, whereas correlations of VCFs with AP spine DXA, femoral neck DXA and distal third radial DXA are poor.     

Bone Mineral Density of Opposing Hips Using Dual Energy X-Ray Absorptiometry in Single-Beam and Fan-Beam Design

Bone densitometry focuses on bone mineral area density (BMD in g/cm²) of the proximal femur and spine in anterior-posterior (AP) projections. Artifacts, such as osteoarthritis and osteophytic calcifications (OC) influence spine BMD, especially in AP scans. If only two sites are measured, as is usual in clinical practice, there may be advantages to measuring both femora rather than one femur and the spine. This would not be useful, however, if there was strong symmetry between the two sides. Furthermore, fan beam (FB) techniques have become available for measuring BMD with less data acquisition time. We compared densitometry of opposing femora in 421 patients (369 women, mean age 59.0 ± 4.8; 52 men, mean age 56.9 ± 7.4) using dual-energy X-ray absorptiometry (DXA): both single-beam (SB) and FB modes were evaluated. The precision errors in vivo (short- and midterm) of total BMD were 0.7% for both SB and FB. The total BMD and BMC of the left hip (0.817 ± 0.124 g/cm², 31.3 ± 6.4 g) were significantly (P < 0.001) higher (2–3%) than the corresponding values of the right hip (0.801 ± 0.125 g/cm², 30.3 ± 6.3 g) in both SB and FB (left BMD 0.802 ± 0.117 g/cm², BMC 30.0 ± 6.2 g versus right BMD 0.795 ± 0.117 g/cm², BMC 29.3 ± 6.3 g) modes. However, BMD of the femoral neck and Ward's triangle were not significantly (P > 0.05) different between the two sides. The FB results were generally 2% lower than SB results. There were highly significant (P < 0.001) correlations (r > 0.9) between both hips using both SB and FB. For diagnostic procedures and longitudinal studies, one should consider that there are bilateral differences of femur BMD, as well as differences between FB and SB scan modes.     

A Comparative Study of Computed Digital Absorptiometry and Conventional Dual-Energy X-ray Absorptiometry in Postmenopausal Women

The aim of the study was to evaluate whether computed digital absorptiometry (CDA) of the hand might be a useful screening technique for identifying patients with postmenopausal osteoporosis and to compare the results of CDA with those of dual-energy X-ray absorptiometry (DXA) of the lumbar spine and femoral neck. We studied 230 postmenopausal women (mean age 58.4 ± 7.9 years). For CDA, bone mineral density (BMD) was measured with an AccuDEXA Schick densitometer in the third middle phalanx of the nondominant hand. For DXA, BMD of the lumbar spine and upper femur was assessed using a DXA Hologic QDR-1000 densitometer. We did a comparative analysis (ANOVA) and linear correlation tests. Sensitivity and specificity of CDA and receiver operating characteristic (ROC) curves for the diagnosis of osteoporosis were calculated. The mean BMD with CDA was 0.445 ± 0.084 (T-score: −1.27 ± 1.29). The mean BMD (g/cm²) with DXA at the lumbar spine was 0.877 ± 0.166 (T-score: −1.52 ± 1.59) and 0.708 ± 0.127 at the femoral neck (T-score: −1.12 ± 1.25). BMD at the lumbar spine and femoral neck correlated positively with CDA of the hand (r= 0.66 and r= 0.65 respectively, p<0.001). When using as cut-off a T-score of −2.5, according to WHO criteria, 76 women (33%) had osteoporosis of the lumbar spine and/or femoral neck with DXA and 42 (18%) with CDA (p<0.001). The kappa score for osteoporosis was 0.33 for CDA versus spinal DXA and 0.35 for CDA versus femoral DXA. With the cut-off level used, sensitivity and specificity of CDA in detecting osteoporosis at the lumbar spine were 0.39 and 0.90, respectively; sensitivity and specificity of CDA in identifying osteoporosis at the femoral neck were 0.58 and 0.87, respectively. The positive predictive value of CDA for osteoporosis was 69% and the negative predictive value was 75%. The area under the ROC curve for osteoporosis was 0.822 ± 0.028. We conclude that: (a) CDA assessment has a moderate correlation with BMD measured by DXA at the lumbar spine and femoral neck; (b) CDA has a low sensitivity for the diagnosis of osteoporosis compared with spinal and femoral DXA; and (c) predictive values for osteoporosis at both the lumbar spine and femoral neck are acceptable. Received: September 2000 / Accepted: January 2001     

Accuracy of DXA scanning of the thoracic spine: cadaveric studies comparing BMC, areal BMD and geometric estimates of volumetric BMD against ash weight and CT measures of bone volume

Biomechanical studies of the thoracic spine often scan cadaveric segments by dual energy X-ray absorptiometry (DXA) to obtain measures of bone mass. Only one study has reported the accuracy of lateral scans of thoracic vertebral bodies. The accuracy of DXA scans of thoracic spine segments and of anterior-posterior (AP) thoracic scans has not been investigated. We have examined the accuracy of AP and lateral thoracic DXA scans by comparison with ash weight, the gold-standard for measuring bone mineral content (BMC). We have also compared three methods of estimating volumetric bone mineral density (vBMD) with a novel standard–ash weight (g)/bone volume (cm³) as measured by computed tomography (CT). Twelve T5–T8 spine segments were scanned with DXA (AP and lateral) and CT. The T6 vertebrae were excised, the posterior elements removed and then the vertebral bodies were ashed in a muffle furnace. We proposed a new method of estimating vBMD and compared it with two previously published methods. BMC values from lateral DXA scans displayed the strongest correlation with ash weight (r=0.99) and were on average 12.8% higher (p<0.001). As expected, BMC (AP or lateral) was more strongly correlated with ash weight than areal bone mineral density (aBMD; AP: r=0.54, or lateral: r=0.71) or estimated vBMD. Estimates of vBMD with either of the three methods were strongly and similarly correlated with volumetric BMD calculated by dividing ash weight by CT-derived volume. These data suggest that readily available DXA scanning is an appropriate surrogate measure for thoracic spine bone mineral and that the lateral scan might be the scan method of choice.     

Reproducibility of bone mineral density measurements using dual X-ray absorptiometry in daily clinical practice

Bone mineral density (BMD) measurements are frequently performed repeatedly for each patient. Subsequent BMD measurements allow reproducibility to be assessed. Previous studies have suggested that reproducibility may be influenced by age and clinical status. The purpose of the study was to examine the reproducibility of BMD by dual energy X-ray absorptiometry (DXA) and to investigate the practical value of different measures of reproducibility in three distinct groups of subjects: healthy young volunteers, postmenopausal women and patients with chronic rheumatic diseases. Two hundred twenty-two subjects underwent two subsequent BMD measurements of the spine and hip. There were 60 young healthy subjects, 102 postmenopausal women and 60 patients with chronic rheumatic diseases (33 rheumatoid arthritis, 10 ankylosing spondylitis and 10 other systemic diseases). Forty-five patients (75%) among the third group were receiving corticosteroids. Reproducibility was expressed as the smallest detectable difference (SDD), coefficient of variation (CV), least significant change (LSC) and intraclass correlation coefficient (ICC). Sources of variation were investigated by linear regression analysis. The median interval between measurements was 0 days (range 0–7). The mean difference (SD) between the measurements (g/cm²) was –0.0001 (±0.003) and –0.0004 (±0.002) at L1-L4 and the total hip, respectively. At L1-L4 and the total hip, SDD (g/cm²) was ±0.04 and ±0.02, CV (%) was 2.02 and 1.29, and LSC (%) 5.60 and 3.56, respectively. The ICC at the spine and hip was 0.99 and 0.99, respectively. Only a minimal difference existed between the groups. Reproducibility in the three groups studied was good. In a repeated DXA scan, a BMD change, the least significant change (LSC) or the SDD should be regarded as significant. Use of the SDD is preferable to use of the CV and LSC because of its independence from BMD and its expression in absolute units. Expressed as SDD, a BMD change of at least ±0.04 g/cm² at L1-L4 and ±0.02 g/cm² at the total hip should be considered significant. This reproducibility seems independent from age and clinical status and improved in the hips by measuring the dual femur.     

Differential effects of estrogen treatment on bone mineral density of the spine,hip, wrist and total body in late postmenopausal women

It is commonly believed that estrogen is effective only in preventing menopause-related loss of bone mineral. However, recent studies found significant increases in bone mineral density (BMD) of the spine in response to estrogen, particularly in older women. The degree to which estrogen can restore BMD of the hip is uncertain. In the present study, changes in BMD of the lumber spine (L2–4), hip (neck, trochanter and Ward's triangle), wrist (ultradistal) and total body in response to 1 year of hormone replacement therapy (HRT) were evaluated by dual-energy X-ray absorptiometry (DXA) in women 10 or more years past menopause. Twelve women, aged 61–74 years, received conjugated estrogens 0.625 mg and cyclic medroxyprogesterone acetate 5 mg; 12 women who did not receive HRT were controls. Calcium intake was adjusted to approximately 1500 mg/day in all subjects. There were no differences between the groups in BMD prior to treatment. Increases in BMD of the lumbar spine (mean±SD, 0.041±0.030 g/cm²), hip (neck, 0.019±0.018 g/cm²; trochanter, 0.017±0.012 g/cm²; Ward's triangle, 0.026±0.029 g/cm²) and total body (0.013±0.016 g/cm²) occurred in response to HRT, and these changes were significantly different from those in controls (spine, 0.005±0.020 g/cm²; neck, –0.007±0.026 g/cm²; trochanter, 0.002±0.014 g/cm²; Ward's triangle, 0.003±0.019 g/cm²; total body, –0.001±0.017 g/cm²). HRT appears to be most effective at weight-bearing sites that have a high cancellous bone content. This study demonstrates that HRT significantly increases bone mass of the lumbar spine and proximal femur in osteopenic, late postmenopausal women, and may, therefore, be effective in preventing osteoporotic fractures at these sites in this population.     

Does Osteoporosis Classification Using Heel BMD Agree Across Manufacturers?

The lack of standardization in bone mineral density (BMD) measurements is known. Several studies have been carried out to cross-calibrate the axial dual X-ray absorptiometry (DXA) devices. Recently, a number of peripheral DXA (pDXA) densitometers have been introduced. In this study we evaluated the agreement between two heel DXA devices on BMD and T-scores. A total of 99 females aged 21–78 years (ca. 16 per decade) had their non-dominant heel BMD measured using the PIXI (Lunar Inc.) and the Apollo (Norland Medical) pDXA scanners. The mean BMD values were 0.492 and 0.607 g/cm² and the mean T-scores using manufacturers’ specified reference data were −0.07 and −0.25 for the PIXI and Apollo, respectively. Both the BMD and T-score intermachine relationships were highly correlated but showed significant nonidentity slopes and non-zero offsets. The diagnostic comparison on T-scores resulted in 86% agreement between the instruments (weighted kappa score of 0.550). Normalizing the reference peaks and SDs using this study’s young adult population BMD results removed the systematic T-score disagreement. We found that PIXI and Apollo are highly correlated. Differences in BMD values are mainly due to different region of interest (ROI) definitions and additional T-score disagreement reflects the difference in normative databases. Received: 9 July 2001 / Accepted: 12 March 2002     

Monofluorophosphate increases lumbar bone density in osteopenic patients: A double-masked randomized study

To assess the efficacy of combined sodium monofluorophosphate and calcium therapy (FC) in increasing lumbar bone mineral density (BMD) in patients with low bone mass, we conducted a prospective double-masked randomized study in 94 patients aged 50–70 years. Patients were selected on the basis of a lumbar BMD at least 2 standard deviations (SD) below the young adult mean (T-score) but without evidence of previous vertebral fracture (severe osteopenia). They were randomly assigned to receive for 2 years, twice a day, either FC (13.2 mg F^–, i.e. 100 mg sodium monofluorophosphate, and 500 mg Ca²⁺) or C (500 mg Ca²⁺). Vertebral BMD was measured by dual photon absorptiometry from L2 to L4. Comparison at final assessment in the 76 eligible patients (Student'st-test) showed a statistically significant difference between the two groups in the mean BMD increase in favour of FC. Furthermore, Student'st-test showed a significantly greater increase in lumbar BMD in FC-treated patients at 1 year, at 18 months and after 2 years (mean increase of 7.1%/year). These results were confirmed by ANOVA at 1 year, at 18 months and after 2 years of treatment. Of the FC-treated patients, 71.4% were considered to have responded (i.e. they showed an increase in lumbar BMD of more than 0.034 g/cm²). The dosage of 26.4 mg fluoride ion/day (i.e. 200 mg monofluorophosphate/day) therefore appears to be safe and to increase the BMD effectively in patients with low bone mass prior to vertebral fracture.