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  • 1
    ISSN: 1432-0827
    Keywords: Key words: Cyclical etidronate therapy — Treatment withdrawal — Bone mineral measurements.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract. The objective of this study was to evaluate whether the pharmacological activity of cyclical etidronate therapy is sustained beyond the dosing period. A group of 121 postmenopausal women who had completed a 2-year, double-blind, placebo-controlled parallel study with etidronate or placebo (400 mg/day for 14 days every 3 months) and calcium agreed to participate in a 1-year open-label follow-up study to evaluate the effect of discontinuing etidronate treatment. Fifty-nine subjects in the former etidronate group and 62 in the placebo group received 500 mg/day of elemental calcium; 54/59 and 58/62 subjects, respectively, completed the study. Outcomes of the study were bone mineral density (BMD), measured by dual energy X-ray absorptiometry (DXA), and biochemical markers of bone turnover (urinary deoxypyridinoline/creatinine and serum osteocalcin). To determine whether there was a residual effect of previous therapy we compared mean percentage changes from baseline (year 0) to year 3 for both spinal and femoral neck BMD and markers of bone turnover in the former cyclical etidronate and placebo groups. To evaluate the carryover effect of treatment we compared the percent change from year 2 to year 3 for the same variables. Mean percentage change (SEM) from year 2 to year 3 for spinal BMD in the former cyclical etidronate group was −2.87% (0.48%) versus −0.99% (0.36%) in the placebo group (P= 0.0022). In the femoral neck, the BMD changes were −0.86% (0.42%) versus −1.01% (0.41%) (NS). Biochemical markers increased within 6 months toward baseline levels. Mean percentage changes from baseline (year 0) in both spinal and femoral neck BMD were significantly different between groups 1 year after treatment discontinuation. No differences between groups were maintained in deoxypyridinoline and osteocalcin. It is concluded that following withdrawal of cyclical etidronate therapy bone loss resumes at a normal and moderately accelerated rate in the proximal femur and lumbar spine, respectively. A positive effect on BMD at both cortical and trabecular sites is maintained for 1 year after treatment withdrawal.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1433-2965
    Keywords: Bone mineral measurements ; Broadband ultrasonic attenuation ; Ultrasound
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We report a study of broadband ultrasonic attenuation (BUA) in the calcaneus in 248 women. Measurements were performed with a Walker-Sonix UBA-575 ultrasonic bone analyser. The populations studied were 15 healthy young volunteers (group 1, mean age 26 years), 200 healthy pre- and postmenopausal women (group 2, mean age 53 years) and 33 osteoporotic women with vertebral crush fractures (group 3, mean age 66 years). Subjects in group 1 each had 10 repeated measurements of their right heel. Duplicate BUA measurements in the right heel were performed in 96 subjects and bilateral scans in a further 87 women in group 2. The remaining 17 subjects in group 2 and those in group 3 had a single scan of the right heel. All women in groups 2 and 3 had dual X-ray absorptiometry (DXA) scans of the lumbar spine and femoral neck. The precision study on the women in group 1 gave a root mean square (RMS) coefficient of variation (CV) of 4.2%. Individual CV results showed statistically significant differences (range 1.3%–7.6%). Duplicate scans in subjects in group 2 gave a RMS CV of 4.6% while the bilateral measurements showed no significant difference between the two heels. Linear regression analysis gave the following relationship between BUA and age: BUA=87.1−0.76 (Age −40) dB/MHz (r=−0.31,p〈0.001, SEE=14.0 dB/MHz). Multivariate regression analysis showed that, in addition to age, years since the menopause was also a significant factor in predicting BUA. In the first 5 years following the menopause BUA decreased by 2.5%/year, while in the next 5 years the decrease fell to 0.5%/year. The BUA measurements in the osteoporotic subjects in group 3 gave a mean T-score of −2.1 compared with 66 premenopausal normal women and a mean Z-score of −1.0 compared with 27 age-matched elderly normal women in group 2. In comparison the lumbar spine DXA measurements for the same women gave a mean T-score of −3.2 and a mean Z-score of −1.8. DXA therefore gave substantially better discrimination between osteoporotic and normal subjects than the BUA measurements.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1433-2965
    Keywords: Bone mineral measurement ; Dual-energy X-ray absorptiometry ; Longitudinal studies ; Supine lateral DXA
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We report a study to assess whether supine lateral dual-energy X-ray absorptiometry (DXA) scans of the lumbar spine provide better data for monitoring response to treatment than alternative measurement sites such as the posteroanterior (PA) spine, hip and total body. The study population was 152 women enrolled in a placebo-controlled clinical trial of cyclical etidronate therapy. All subjects were 1–10 years after the menopause with bone mineral density (BMD) between 0 and −2 SD of age-matched normal women. Paired PA and lateral spine, left hip and total-body DXA scans were performed at baseline, 1 year and 2 years on a Hologic QDR-2000. One hundred and thirty-one subjects completed the study. Mean percentage change from baseline at 2 years in the treated (n=61) and control (n=70) groups was calculated for vertebral body, width-adjusted (WA) vertebral body, mid-vertebral body and WA mid-vertebral body BMD measurements on the lateral scans and compared with the percentage changes in PA spine, femoral neck, trochanter, Ward's triangle and total-body BMD. The long-term precision for each BMD measurement site was obtained by linear regression analysis in subjects taking placebo. Overall treatment effect, defined as the difference in the percentage change in BMD in the two treatment groups at 2 years, was divided by long-term precision to give an index of the ability of each site to monitor response to treatment. Results (and standard errors) normalized to the ratio of treatment effect/precision for PA spine BMD were as follows: PA spine, 1.00; vertebral body, 0.89 (0.14); WA vertebral body, 0.78 (0.14); mid-vertebral body, 0.65 (0.14); WA mid-vertebral body, 0.60 (0.13); femoral neck, 0.35 (0.15); trochanter, 0.45 (0.15); Ward's triangle, 0.59 (0.22); total body, 0.52 (0.19). Although treatment effect was larger for lateral than for PA spine BMD, this advantage was offset by the greater precision errors. PA spine BMD remains the optimum measurement for longitudinal studies in recently postmenopausal women.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1433-2965
    Keywords: Key words:Calibration change – Dual-energy X-ray absorptiometry, Longitudinal studies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract: Since its commercial introduction a decade ago, the technique of dual-energy X-ray absorptiometry (DXA) has been widely recognized as a useful and sensitive method of measuring changes in bone mineral density (BMD) at selected sites in the skeleton such as the spine and proximal femur. Because of their high precision and stable calibration, DXA scanners are frequently used in clinical trials to evaluate new treatments for osteoporosis. Quality assurance procedures based on regular scanning of phantoms are widely adopted in such trials, and continuity of the phantom BMD measurements is generally believed to ensure continuity in the in-vivo calibration. We report a change in calibration of a DXA scanner that occurred during a clinical trial where the calibration shift was different for the spine and femur sites and was not predicted or explained by the standard quality control procedures using phantoms. However, we show that provided patients enrolled in studies are thoroughly randomized and the statistical analysis is confined to the differences between the treated and control groups, then the effects of such calibration shifts on conclusions regarding the efficacy of treatment are considerably smaller than the random statistical errors.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1433-2965
    Keywords: Key words:Bone density – Clinical trials – Dual-energy X-ray absorptiometry – Total body DXA – Weight change
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract: In the past decade dual-energy X-ray absorptiometry (DXA) scanning has assumed an important role in the evaluation of new treatments for osteoporosis. Although the spine and hip are the sites usually chosen for monitoring bone mineral density (BMD) changes, total body DXA is also of interest because of the comprehensive view it gives of the whole skeleton. However, recent studies have reported anomalies in total body DXA in subjects undergoing weight change, suggesting that the technique may not be valid in this circumstance. The present study evaluated total body DXA in a trial of cyclical etidronate therapy in which many subjects underwent significant weight change. The study population was 152 postmenopausal women who had spine, hip and total body DXA scans performed at baseline, 1 and 2 years. The total body scans were analyzed using two software options referred to as “standard” and “enhanced”. The following variables were studied: total body BMD, total body bone mineral content (BMC), and subregional BMD values for the following seven sites: lumbar spine, thoracic spine, pelvis, head, ribs, arms and legs. The percentage change from baseline was analyzed in a multivariate regression analysis to derive the treatment effect (defined as the difference in changes between the etidronate and placebo groups) and a coefficient that described the effect of weight change on the total body DXA variable. Mean weight change after 2 years was +1.1 kg (range −9.3 to +16.8 kg). Results for the weight change coefficient were significantly different from zero for five of nine total body variables using the standard analysis and seven of nine for the enhanced analysis with values (and standard errors) that varied from +0.67 (0.04) %/kg for standard total body BMC to −0.32 (0.11) %/kg for enhanced arm BMD. Results for the treatment effect at 2 years were significantly different from zero for total body BMD, total body BMC and for the lumbar spine, thoracic spine and pelvis BMD subregions, but were not significant for head, rib, arm or leg BMD. Findings for the standard and enhanced analyses agreed closely and the size of the treatment effect was related to the proportion of trabecular bone at the measurement site. We conclude that in a randomized study the effects of weight change can be corrected and total body DXA can give useful information about the response to treatment across the whole skeleton.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1433-2965
    Keywords: Calcaneus ; Precision ; Ultrasound ; Velocity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The assessment of skeletal integrity by the measurement of ultrasonic velocity through the calcaneus has only recently become widely available and is usually made in conjunction with the measurement of broadband ultrasonic attenuation. Using data obtained with a contact ultrasonic bone analyser (CUBA) system, this report examines whether ultrasonic studies of the heel require the measurement of true velocity of sound in the calcaneus (Vbone), or whether heel velocity (Vheel, defined as the mean velocity through bone and soft tissue) or time of flight velocity (Vtof, defined as the mean velocity between the two transducers) are adequate surrogates. The populations selected for study were 15 healthy young women (group 1, mean age 26 years), 231 healthy peri- and postmenopausal women (group 2, mean age 52 years) and 33 osteoporotic women with confirmed vertebral fracture (group 3, mean age 66 years). Precision was studied by performing 10 repeated scans on the subjects in group 1 and duplicate scans on 144 women randomly selected in groups 2 and 3. Precision was expressed as the percentage coefficient of variation (CV). Both precision studies yielded similar results. The precisions (and 5% to 95% ranges) for all groups combined were: Vbone 2.71% (1465–1809 m/s); Vheel, 1.10% (1511–1646 m/s); Vtof, 0.70% (1349–1425 m/s). Although the precision data suggest Vtof should be preferred, when the range of clinical values is taken into account the smaller CV is exactly cancelled by the narrower range. To demonstrate this numerically it is proposed to introduce a new measure of precision, the standardized coefficient of variation (SCV), defined as the percentage CV divided by the percentage ratio of the range over the mean. SCV had a value of 12.7% for Vtof and 12.8% for Vbone and Vheel. For comparison a SCV of 2.2% was estimated for dual X-ray absorptiometry (DXA). Thus the measurement of ultrasonic velocity through the calcaneus compares equally in terms of CV, but not in terms of SCV. A scatter plot of Vbone against Vtof gave a significantly poorer correlation (r=0.828) than that of Vbone against Vheel (r=0.984). This latter correlation can be explained by theoretical studies demonstrating convergence of the two measurements when the velocity through the bone equals that through soft tissue (1540 m/s). Since the measurement of Vheel dispenses with the need to determine soft tissue thickness over the calcaneus, it is the optimum velocity parameter for the CUBA system.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Calcified tissue international 61 (1997), S. 393-399 
    ISSN: 1432-0827
    Keywords: Key words: Bone mineral measurements — Dual X-ray absorptiometry — Weight change — Clinical trials.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract. Variation in soft tissue composition is a potential cause of error in dual X-ray absorptiometry (DXA) measurements of bone mineral density (BMD). We investigated the effect of patients' change of weight on DXA scans in 152 women enrolled in a 2-year trial of cyclical etidronate therapy. Scans of the spine, hip, and total body were performed at baseline, 1 and 2 years on a Hologic QDR-2000. The study was completed by 135 subjects (64 on etidronate, 71 on placebo). Results were expressed as the percentage change in BMD (spine, femoral neck, total body) or bone mineral content (BMC) (total body only) at 2 years. Total body scans were analyzed using the manufacturer's `standard' and `enhanced' algorithms. Analysis was performed using multivariate regression with percentage change in BMD or BMC as the dependent variable, and treatment group and percentage change in weight as the independent variables. Weight change varied between −14.4% and +16.7%. All DXA variables showed a statistically significant treatment effect. Standard total body BMD and BMC and enhanced total body BMC all showed a significant dependence on weight change (P 〈 0.01, P 〈 0.001 and P 〈 0.01, respectively). No effect of weight change was seen on spine, femoral neck, or enhanced total body BMD. In order to investigate the effects of weight on long-term precision, patients were allocated to two groups according to baseline body mass index (BMI 〈25 and 〉25 kg/m2, respectively). For femoral neck BMD the root mean square (RMS) residual percentage change was statistically significantly larger in the high BMI group (P 〈 0.05) but all other bone density variables showed no significant difference. With patients allocated to two groups according to their absolute percentage change in weight (〈5% and 〉5%, respectively) the RMS residual percentage changes in the bone density variables were statistically significantly larger in the large weight change group for femoral neck BMD (P 〈 0.05) and for standard and enhanced total body BMC (P 〈 0.01 and P 〈 0.05, respectively). With the exception of the standard total body algorithm, weight change in a longitudinal study of postmenopausal women was not found to cause systematic errors in the results of DXA studies but may adversely affect precision.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-0827
    Keywords: Bone mineral measurements ; Broadband ultrasonic attenuation ; Calcaneus ; Ultrasonic velocity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Measurements of broadband ultrasonic attenuation (BUA) and velocity of ultrasound through the heel (heel velocity, HV) were performed with a Contact Ultrasonic Bone Analyzer (CUBA-Research model) in 229 women. The subjects consisted of 16 healthy young volunteers (Group 1, mean age 26 years), 170 healthy pre- and postmenopausal women (Group 2, mean age 53 years), and 43 osteoporotic women with radiographically defined vertebral crush fracture (Group 3, mean age 66 years). Subjects in Group 1 had 10 repeated measurements in a study of short-term precision. Women in Groups 2 and 3 also had dual X-ray absorptiometry (DXA) scans to measure lumbar spine and femoral neck bone mineral density (BMD). The BUA and HV measurements for all 229 women showed a significant correlation (r = 0.75,P 〈 0.001). The precision study on the subjects in Group 1 gave a root mean square coefficient of variation of 6.3% for BUA and 1.04% for HV. Linear regression analysis gave the following relationship between BUA and age for the 170 normal women in Group 2: BUA = 83.6 − 0.86 (age 40) dB/MHz (r = −0.31,P 〈 0.001, SEE = 16.3 dB/MHz). The relationship between HV and age was as follows: HV = 1614 − 2.3 (age 40) m/s (r = −0.33,P 〈 0.001, SEE = 42 m/s). Multivariate regression analysis showed that in addition to age, years since the menopause was also a significant factor in determining both BUA and HV. In the first 5 years following the menopause, BUA and HV decreased by 2.2% and 0.3%/year, respectively, whereas in the next 10 years the rates of decrease fell to 0.5% and 0.03%/year. The BUA and HV measurements on the 43 osteoporotic subjects in Group 3 gave mean T-scores of −2.1 and −1.9 compared with 59 premenopausal women, and mean Z-scores of −1.3 and −0.9 compared with 26 age-matched normal women in Group 2, respectively. In comparison, the lumbar spine and femoral neck DXA measurements in the same subjects gave mean T-scores of −2.9 and −2.1 and mean Z-scores of −1.7 and −1.0, respectively. Lumbar spine BMD gave the best discrimination between women with osteoporotic vertebral fractures and normal subjects. However, the difference between the lumbar spine and BUA Z-scores was not statistically significant. Femoral neck BMD was equivalent to the ultrasound parameters in T-score and Z-score values.
    Type of Medium: Electronic Resource
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