Biomedical subjects

I Fogelman

Publications and source records attributed to I Fogelman.

At least 55 records · Page 3Linked to original sources

PubMed2001

Development of a phantom for morphometric X-ray absorptiometry.

Morphometric X-ray absorptiometry (MXA) has recently been developed to assess vertebral deformity status using dual energy X-ray absorptiometry (DXA) machines. In contrast to bone densitometry, a vertebral morphometry phantom is not supplied by any machine manufacturer. The aim of this study was to develop a suitable phantom to quantify the accuracy and precision of the vertebral measurement software on three DXA scanners in vitro and to perform a weekly quality control (QC) scan over a 30-month period to evaluate any drift or changes in measurement accuracy over time. The phantom was constructed from Perspex and aluminium to simulate soft tissue and bone, respectively. 13 aluminium rectangles (each 30 mm wide, 25 mm high and 3 mm thick, with edges ("endplates") 6 mm thick) were set into one side of a solid Perspex block to represent the vertebral bodies from the fourth thoracic (T4) to the fourth lumbar (L4). The phantom was scanned on both the Hologic QDR2000plus and the QDR-4500A as well as the Lunar Expert-XL. Three consecutive lateral MXA scans were acquired on the Hologic machines using each of the scan modes available. On the QDR-2000plus, the lateral scan modes available are fast, array and high definition, which are all dual energy modes. These three scan modes are also available on the QDR-4500A, with the addition of a single energy scan mode. Four lateral scans were acquired on the Expert-XL machine using the single scan mode available. Each MXA scan was analysed twice by a trained operator using the standard software supplied by each manufacturer. A QC scan was performed approximately weekly over a 30-month period on only the QDR-4500A machine, and total phantom height was measured from the inferior edge of L4 to the superior edge of T4. Accuracy of "vertebral" height measurement varied between the three DXA machines and between the scan modes available. All underestimated "true" vertebral height by between 0.4% and 8.6%, with the scan modes using finer collimation producing the most accurate results. Repeat analysis precision of vertebral height measurement was best on the QDR-4500A, followed by the Expert-XL, and was poorest on the QDR-2000plus. The QC scans acquired on the QDR-4500A suggested that it was a highly stable machine, little affected by even major repairs. It must be remembered that these in vitro phantom results may not be representative of the true in vivo situation. The MXA phantom appears to be a useful tool for documenting the stability of the mechanical instruments and for checking the long-term consistency of operator precision.

Absorptiometry, Photon↗

PubMed2001

Quantitative ultrasound and bone mineral density are equally strongly associated with risk factors for osteoporosis.

Because resources do not allow all women to be screened for osteoporosis, clinical risk factors are often used to identify those individuals at increased risk of fracture who are then assessed by bone densitometry. The aim of this study was to compare calcaneal quantitative ultrasound (QUS) and axial bone mineral density (BMD) T and Z scores in a large group of women, some with no clinical risk factors and others with one or more risk factors for osteoporosis. The study population consisted of 1115 pre- and postmenopausal women. A subgroup of 530 women was used to construct reference data for calculating T and Z scores. A total of 786 women was found to have one or more of the following risk factors: (i) atraumatic fracture since the age of 25 years, (ii) report of X-ray osteopenia, (iii) predisposing medical condition or use of therapy known to affect bone metabolism, (iv) premature menopause before the age of 45 years or a history of amenorrhea of longer than 6 months duration, (v) family history of osteoporosis, (vi) body mass index (BMI) <20 kg/m2, and (vii) current smoking habit. Calcaneal broadband ultrasound attenuation (BUA) and speed of sound (SOS) measurements were performed on a Hologic Sahara and a DTUone and BMD was measured at the spine and hip using dual-energy X-ray absorptiometry (DXA). The Z score decrements associated with the seven risk factors calculated using multivariate regression analysis were similar for QUS and BMD measurements. Z score decrements (mean of BMD and QUS measurements combined) associated with a history of atraumatic fracture (-0.67), X-ray osteopenia (-0.36), a family history of osteoporosis (-0.23), and a low BMI (-0.53) were all statistically significant compared with women with no risk factors. Z score decrements associated with a medical condition or use of therapy known to affect bone metabolism, a premature menopause or prolonged amenorrhea, or those who were current smokers were not significantly different from zero. As the number of risk factors present in each individual increased, the mean Z score decrements became more negative, increasing from -0.28 for women with one risk factor to -1.19 for those with four or more risk factors. QUS and BMD measurements yielded similar mean Z scores for women with one, two, three, or more than four risk factors. Using the World Health Organization (WHO) criteria to diagnose osteoporosis for BMD measurements and revised diagnostic criteria for QUS, approximately one-third of postmenopausal women aged 50+ years with clinical risk factors were classified as osteoporotic compared with only 12% of women without clinical risk factors. Over two-thirds of postmenopausal women with risk factors were classified as osteopenic or osteoporotic and approximately 28% were classified as normal. The proportion of women classified into each diagnostic category was similar for BMD and QUS. In conclusion, clinical risk factors for osteoporosis affected calcaneal BUA and SOS Z score measurements to the same extent as axial BMD Z score measurements. Provided revised diagnostic criteria are adopted for QUS, similar proportions of postmenopausal women are identified as osteopenic or osteoporotic as with BMD.

Absorptiometry, Photon↗

PubMed2001

Peripheral or central densitometry: does it matter which technique we use?

Over the past decade, bone density scans have assumed an essential role in the diagnosis of osteoporosis. Although dual X-ray absorptiometry (DXA) scans of the central skeleton remain widely used, a variety of different types of equipment for measuring peripheral sites is now available. However, the poor correlation between different types of measurement and a lack of consensus on how results from peripheral sites should be interpreted have proved a barrier to the more widespread use of these devices. These issues prompt the following questions: Which technique best identifies patients at risk of fracture? What approaches to scan interpretation ensure the closest agreement among different methods? Does it matter if different patients are selected for treatment on the basis of different techniques? The relative risk (RR)of fracture derived from prospective studies is a key parameter for comparing the clinical value of different techniques. Recent reports confirm the advantages of hip bone mineral density compared with peripheral measurements for predicting hip fracture risk, although for fractures at other sites the differences are inconclusive. Using receiver operating characteristic curves, we show that the guidelines adopted for scan interpretation are of crucial importance for ensuring that the information provided is used effectively. The closest agreement among different techniques is achieved by setting thresholds for peripheral devices that target either the same percentage of the population or the same percentage of future fracture cases as femur DXA. Different methods select different groups of individuals from the total pool of patients who will later sustain a fracture, with the most successful technique being the one with the largest RR value. The emphasis placed by many studies on validating new techniques by studying their correlation with DXA may lead to the clinical value of peripheral devices being underestimated when the key datum is the RR value inferred from prospective fracture studies.

Absorptiometry, Photon↗

PubMed2001

Detection of bone metastases in cancer patients by 18F-fluoride and 18F-fluorodeoxyglucose positron emission tomography.

The use of positron emission tomography (PET) in clinical oncology continues to increase and although there is now a large literature on the use of PET with various tracers in a wide variety of cancers, there has previously been relatively little use specifically in the evaluation of skeletal metastases. However, a number of reports on PET in this area of oncology are now becoming available. The potential advantages of PET over conventional nuclear medicine techniques, including improved spatial resolution, absolute quantitation and the acquisition of tomographic studies as a routine, are also of potential benefit in this area. The bone agent, 18F-fluoride and the tumour agent 18F-fluorodeoxyglucose, have been used to evaluate both benign and malignant skeletal disorders qualitatively and quantitatively and the current knowledge with respect to the skeleton in cancer patients is summarised in this article.

Bone Neoplasms↗

PubMed2000

Evaluation of CD4+ T cell function In vivo in HIV-infected patients as measured by bacteriophage phiX174 immunization.

Bacteriophage phiX174 immunization was used to measure CD4(+) T cell function in vivo in human immunodeficiency virus (HIV)-infected patients across all disease stages. Function was evaluated by measuring the ability of T cells to provide help to B cells in antibody production, amplification, and isotype switching. A total of 33 patients and 10 controls received 3 bacteriophage phiX174 immunizations 6 weeks apart. The patients' responses regarding bacteriophage-specific total antibody titers and IgG titers were quantitatively and qualitatively inferior to the controls' responses. Overall, 7 of 33 patients had normal T cell function. Baseline CD4 counts provided the strongest correlation with total antibody and IgG titers. HIV RNA had a weaker association with responses but had some predictive power among patients with a CD4 count >200 cells/microL. Bacteriophage phiX174 immunization seems to be a useful tool for measuring immune function in vivo, which suggests that most HIV-infected patients may have abnormal CD4(+) T cell function despite adequate antiretroviral treatment.

Adolescent↗

PubMed2000

The role of positron emission tomography in the management of bone metastases.

BACKGROUND: Positron emission tomography (PET) is a nuclear medicine technique that only recently has been widely used in clinical oncology. PET, as a metabolic imaging technique, demonstrates advantages over and complements structural imaging methods and also demonstrates differences from conventional nuclear medicine, all of which has led to its enormous growth in clinical applications in recent years. METHODS: There is now a large body of literature on the use of PET with various tracers, especially (18)F-fluorodeoxyglucose ((18)FDG), in large numbers of patients with carcinoma. In the assessment of the skeleton in patients with carcinoma, early reports of PET imaging are now available with the use of (18)F-fluoride as a bone agent and the use of (18)FDG as a tumor agent, and the current knowledge is summarized in this report. RESULTS: High-quality tomographic PET bone scans are possible with (18)F-fluoride with possible advantages in sensitivity and specificity over conventional bone scintigraphy. With (18)FDG, it is possible to image tumor metabolism directly, and early studies have demonstrated a high sensitivity for the detection of skeletal metastases, although the demonstration of osteoblastic metastases may be less satisfactory. CONCLUSIONS: The clinical role of PET in the evaluation of patients with bone metastases is not yet defined; however, as described in this report, there is emerging evidence that this imaging method also may aid patient management in this area with the use of either (18)FDG or (18)F-fluoride ion.

Bone Neoplasms↗

PubMed2000

Intermittent oral disodium pamidronate in established osteoporosis: a 2 year double-masked placebo-controlled study of efficacy and safety.

The effect of oral pamidronate on bone mineral density and its adverse effect profile was investigated by a double-masked placebo-controlled study of 122 patients aged 55-75 years with established vertebral osteoporosis. Patients on active therapy received disodium pamidronate 300 mg/day (group A) for 4 weeks every 16 weeks, 150 mg/day (group B) for 4 weeks every 8 weeks or placebo (group C). All patients additionally received 500 mg of calcium and 400 IU vitamin D daily. Dual-energy X-ray absorptiometry measurements of the spine, hip, forearm and total body were performed at baseline and 6-monthly for 2 years using a Hologic QDR 1000 device at two sites. Serum osteocalcin and urinary deoxypyridinoline were measured at the above visits and at 3 months. The percentage change (SEM) in spine bone mineral density (BMD) at 2 years based on intention-to-treat analysis was 4.64 (1.01) in group A, 6.10 (0.87) in group B and 1.13 (1.32) in group C. Analysis of variance showed significant increases in group A and B compared with placebo (p < 0.01). There were also significant rises in femoral neck BMD for group A (p = 0.005), trochanter BMD for groups A and B (p < 0.01) and total-body BMD for groups A and B (p < 0.001). There was a significant reduction in serum osteocalcin and urinary deoxypyridinoline for groups A and B (p < 0.01). There was an excess of gastrointestinal side-effects in the treated groups, particularly group A. We conclude that intermittent pamidronate therapy can prevent bone loss at both the lumbar spine and femoral neck in patients with established vertebral osteoporosis, although due to gastrointestinal side-effects the 300 mg dose in particular does not appear suitable for clinical usage.

Administration, Oral↗

PubMed2000

Long-term precision of DXA scanning assessed over seven years in forty postmenopausal women.

The reproducibility of dual-energy X-ray absorptiometry (DXA) measurements of bone mineral density (BMD) is an important factor for longitudinal studies. We assessed the long-term precision of posteroanterior lumbar spine, femoral neck and total hip BMD in 40 postmenopausal women who formed the control arm of a clinical trial of tibolone. BMD was measured at 0, 6 and 12 months and thereafter every 12 months up to 7 years. For each subject the trend of BMD with time was analyzed using linear regression. Each residual was expressed as the percentage difference from predicted BMD and the validity of assuming linear change with time was checked using the mean residuals for each visit number. For spine BMD a chi-squared test showed that the mean residuals were not statistically significantly different from zero. Although statistically significant deviations from linearity were found for the femoral neck and total hip sites the weighted root mean square residuals were small compared with the precision errors. When residuals were binned into histograms a statistical test for skewness was not significant for all three sites. However, a test for kurtosis yielded a statistically significant result for each histogram due to outlying residuals. To determine the standard deviation (SD) of the core gaussian distribution, outliers were trimmed using the method of Melton et al. For lumbar spine BMD outliers with residuals exceeding +/- 3 SD arose mainly from subjects with a body mass index (BMI) >28 kg/m(2) or from subjects who had undergone a large change in BMI during the study. For femoral neck BMD and total hip BMD the outliers were frequently due to inconsistent rotation of the hip. Results for long-term precision calculated from the standard deviation of residuals using the trimmed (untrimmed) data were: lumbar spine BMD, 1.12% (1.65%); femoral neck BMD, 2.21% (2.48%); and total hip BMD, 1.32% (1.57%). These errors were only slightly worse than short-term errors despite changes of DXA scanner during the course of the study. However, obesity may have an adverse effect on precision errors in individual patients and particular care is necessary to ensure reproducible patient positioning for femur scans.

Absorptiometry, Photon↗

PubMed2000

The effect of weight change on total body dual-energy X-ray absorptiometry: results from a clinical trial.

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.

Absorptiometry, Photon↗

PubMed2000

Visual assessment of vertebral deformity by X-ray absorptiometry: a highly predictive method to exclude vertebral deformity.

The accurate identification of prevalent vertebral fractures is important in both the clinical and research setting as they are associated with increased risk of further fracture and irreversible clinical consequences. This study reports a direct comparison of prevalent vertebral deformity identification using X-ray absorptiometry (XA) scans, acquired on a dual-energy X-ray absorptiometry (DXA) machine, and conventional radiographs in a diverse group of 161 postmenopausal women, ranging from healthy subjects with normal bone mineral density (BMD) to osteoporotic subjects with multiple vertebral deformities. Deformities were identified by a trained operator by visual assessment of the XA scans (VXA) and semiquantitatively by an experienced radiologist on the conventional radiographs (XSQ). Subjects were recruited prospectively and were triaged according to their VXA results into normal, equivocal and definite deformity groups. VXA and XSQ demonstrated good agreement (96.3%, K = 0.79) in classifying vertebrae as normal or deformed in the 1978 of 2093 vertebrae deemed analyzable on both the XA scans and conventional radiographs. VXA showed good sensitivity (91.9%) in the identification of moderate/severe XSQ deformities and an excellent negative predictive value (98.0%) was produced when VXA was used to distinguish subjects without vertebral deformities from those with possible or definite deformities on a per subject basis. The majority of disagreement between the two methods resulted from different classification of mild wedge and endplate deformities and the poor visualization of upper thoracic vertebrae on the XA scans. Agreement improved, particularly on a per subject basis, when analysis was restricted to the vertebral levels from L4 to T7. Visual triage of XA scans by a trained operator would seem to be swift, convenient and cost-effective method, with excellent negative predictive value, to distinguish subjects with very low risk of vertebral deformities from those with possible deformities. These 'normal' subjects can then be excluded prior to performing conventional radiographs and further time-consuming and costly methods of vertebral deformity assessment such as XSQ by an experienced radiologist and/or quantitative morphometry. VXA may prove useful in the clinical evaluation of patients at risk of osteoporosis as an adjunct to BMD scans or in the selection of subjects for osteoporosis-related clinical trials.

Absorptiometry, Photon↗

PubMed2000

Vertebral morphometry: repeat scan precision using the Lunar Expert-XL and the Hologic 4500A. A study for the 'WISDOM' RCT of hormone replacement therapy.

On radiation safety grounds there is concern about the morbidity attributable to routine radiographs of the spine for the identification of new fractures in large-scale trials of fracture prevention. However, the role of the potentially safer low-radiation-dose technique of vertebral morphometry performed by third generation dual-energy X-ray absorptiometry equipment requires evaluation for use in clinical trials. We have therefore investigated the short-term inter-scan imprecision as well as the imprecision attributable to different-day analyses by the same operator and differences in analyses by different operators. The volunteer subjects were participants in a pilot study for a randomized controlled trial of hormone replacement therapy (Women's International Study of long Duration Oestrogen after Menopause, WISDOM). Each subject had two morphometric X-ray analysis scans separated by 2-4 weeks. Exclusions were women with densitometrically defined osteoporosis, as defined by the WHO criterion, and women with a body mass index exceeding 30.9 kg/m2. On average, the women were 58.7 years of age and had bone mineral density values in the lumbar spine which were about 0.7 SD units higher than a reference US female age-matched population. Scans were assessed from vertebrae T7 through L4. In the study there were no clinically significant differences in performance between the Hologic QDR 4500A and the Lunar Expert XL equipment. Between-scan imprecision was significantly worse than imprecision attributable to reanalysis of the same scan by a different operator or the same operator after an interval. Vertebral level had an effect on measurement uncertainty, especially at the level of the diaphragm and at T7. Coefficients of variation, expressed as percentages of mean values, were better for absolute height measurements than for height ratios, ranging from 1.75% to 3.40% for the three heights measured on three separate machines and from 2.34% to 4.11% for the two height ratios. These results compared favorably with the equivalent figures from a parallel study of morphometry precision undertaken using standard lateral radiographs of the thoracic and lumbar spine (3.1-3.6% and 3.8-3.9%, respectively). We conclude that in trials of prevention therapy in women (or men) selected for not having osteoporosis, low-dose vertebral morphometry using the Hologic 4500A, the Lunar Expert XL or similar equipment is preferable on safety grounds to the classical technique based on standard radiographs, although conventional radiology may still be required in those with prevalent or incident deformities to exclude causes other than osteoporosis. The place of this low-dose technique in trials performed on patients with osteoporosis requires further study.

Absorptiometry, Photon↗

PubMed2000

Does quantitative ultrasound imaging enhance precision and discrimination?

The aim of this study was to compare quantitative ultrasound (QUS) measurements obtained using a new calcaneal QUS imaging device with a conventional non-imaging device using fixed transducers. The study group consisted of 340 healthy women with no risk factors associated with osteoporosis (176 premenopausal and 164 postmenopausal) and 83 women with one or more vertebral fractures. All women had QUS measurements performed on the Osteometer DTU-one (imaging) and Walker-Sonix UBA575+ (non-imaging) devices and bone mineral density (BMD) measurements performed at the spine and hip. A subgroup of 81 women had additional dual-energy X-ray absorptiometry (DXA) scans at the calcaneus. Short-term standardized precision (SP = SD/young adult SD) based on duplicate measurements was significantly better on the DTU for broadband ultrasound attenuation (BUA) (SP: DTU 0.15 vs UBA 0.21,p = 0.01) and speed of sound (SOS) (SP: DTU 0.14 vs UBA 0.18, p = 0.01). However, long-term SP of the DTU was comparable to or significantly poorer than the SP of the UBA device. The BUA and SOS measurements obtained on the DTU and UBA were significantly correlated (r = 0.76 and 0.89 for BUA and SOS measurements respectively). The correlations between QUS and BMD measurements were all significant, ranging from 0.53 to 0.72. No significant improvements in the correlation with axial or peripheral BMD were observed using the imaging device. All the QUS measurement parameters showed a significant negative relationship between age and years since menopause in the postmenopausal group. Annual losses were lower for the DTU for BUA (DTU 0.22 dB/MHz per year vs UBA 0.44 dB/MHz per year) but comparable for SOS (DTU 0.29 m/s per-year vs UBA 0.22 m/s per year). However, when these figures were standardized to take into account the clinical range, the annual losses were similar on the DTU and UBA. Age-adjusted odds ratios for each SD decline were similar on the DTU for BUA (DTU 3.2 vs UBA 3.3) and SOS (DTU 3.4 vs UBA 5.1). The corresponding odds ratios for BMD at the lumbar spine, femoral neck and total hip were 2.7, 2.9 and 3.3 respectively. Age-adjusted receiver-operating characteristics analysis yielded values for the area under the curve (AUC) ranging from 0.74 to 0.83. The DTU BUA AUC of 0.83 was significantly greater than the AUC obtained for UBA BUA and BMD measurements at the lumbar spine and femoral neck. Ultrasound imaging at the calcaneus was found to improve the standardized precision of BUA and SOS measurements in the short term but not in the long term. Neither the correlation with BMD nor the discriminatory ability of QUS was improved by utilizing QUS images at the calcaneus. The inconsistencies of the imaging system used for this study demonstrate that further development is required before it will be possible to show improvements in long-term precision.

Absorptiometry, Photon↗

PubMed2000

Can the WHO criteria for diagnosing osteoporosis be applied to calcaneal quantitative ultrasound?

With the increasing number of quantitative ultrasound (QUS) devices in use worldwide it is important to develop strategies for the clinical use of QUS. The aims of this study were to examine the age-dependence of T-scores and the prevalence of osteoporosis using the World Health Organization Study Group criteria for diagnosing osteoporosis and to examine the T-score threshold that would be appropriate to identify women at risk of osteoporosis using QUS. Two groups of women were studied: (i) 420 healthy women aged 20-79 years with no known risk factors associated with osteoporosis; (ii) 97 postmenopausal women with vertebral fractures. All subjects had dual-energy X-ray absorptiometry (DXA) measurements of the spine and hip and QUS measurements on three calcaneal ultrasound devices (Hologic Sahara, Hologic UBA575+, Osteometer DTUone). A subgroup of 102 (76 on the DTUone) healthy women aged 20-40 years was used to estimate the young adult mean and SD for each QUS and DXA measurement parameter to calculate T-scores. The age-related decline in T-scores for QUS measurement parameters was half the rate observed for the bone mineral density (BMD) measurements. The average T-score for a woman aged 65 years was -1.2 for QUS measurements and -1.75 for the BMD measurements. When osteoporosis was defined by a T-score < or = -2.5 the prevalence of osteoporosis in healthy postmenopausal women was 17%, 16% and 12% for lumbar spine, femoral neck and total hip BMD respectively. When the same definition was used for QUS measurements the prevalence of osteoporosis ranged from 2% to 8% depending on which ultrasound device and measurement parameter was used. Four different approaches, based on DXA-equivalent prevalence rates of osteoporosis, were utilized to examine which T-score threshold would be appropriate for identifying postmenopausal women at risk of osteoporosis using QUS measurements. These ranged from -1.05 to -2.12 depending upon the approach used to estimate the threshold and on which QUS device the measurements were performed, but all were significantly lower than the threshold of -2.5 used for BMD measurements. In conclusion, the WHO threshold of T = -2.5 for diagnosing osteoporosis requires modification when using QUS to assess skeletal status. For the three QUS devices used in this study, a T-score threshold of -1.80 would result in the same percentage of postmenopausal women classified as osteoporotic as the WHO threshold for BMD measurements. Corresponding T-score thresholds for individual measurement parameters on the two commercially available devices were -1.61, -1.94 and -1.90 for Sahara BUA, SOS and estimated heel BMD respectively and -1.45 and -2.10 for DTU BUA and SOS respectively Additional studies are needed to determine suitable T-score thresholds for other commercial QUS devices.

Absorptiometry, Photon↗

PubMed2000

Cyclical etidronate therapy for prevention of postmenopausal bone loss: a 1-year open-label follow-up study.

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.

Amino Acids↗

PubMed2000

The time of day that etidronate is ingested does not influence its therapeutic effect in osteoporosis.

To investigate whether the therapeutic effect of etidronate is affected by the time of ingestion we have retrospectively studied 110 osteoporotic patients. They had been taking etidronate according to the manufacturer's instructions for a mean duration of 2.6 years either on waking (n=47), on retiring (n=47), or during the day (n= 16). No significant differences were found between the three groups with respect to percentage change in bone mineral density at all sites either for the first year of treatment or for the mean yearly percent change throughout the total course of treatment. These findings suggest that the time of ingestion of etidronate does not influence the therapeutic effect if a two hour fast before and after ingestion is adhered to.

Administration, Oral↗

PubMed2000

Alendronate in early postmenopausal women: effects on bone mass during long-term treatment and after withdrawal. Alendronate Osteoporosis Prevention Study Group.

We studied the effect on bone mass of alendronate treatment for 5 yr and its withdrawal. Four hundred and forty-seven postmenopausal women with normal bone mass entered a 3-yr randomized trial followed by a 2-yr open label extension. Three hundred and eleven women completed the first 3 yr, and 263 consented to continue and completed the extension. We are reporting data from groups using the dose of alendronate currently approved for osteoporosis prevention (5 mg) or from the group in which alendronate treatment was withdrawn: 52 women received alendronate (5 mg) for 5 yr (group I), 56 received 3 yr of placebo followed by alendronate (5 mg) for 2 yr (group II), and 52 received alendronate (20 mg) for 2 yr followed by 3 yr off therapy (group III). In group I, alendronate (5 mg) increased bone mineral density (BMD) at the spine and trochanter by 2.5-3.2% (P < 0.001 vs. baseline) and stabilized total body and femoral neck BMD (change vs. baseline, P = NS) over 5 yr. By the end of 5 yr, BMD was comparable at the spine, hip, and total body in groups I and III. The 3-yr decrease in BMD after withdrawal of alendronate (20 mg) in group III was 1.8-5.7% (P < 0.01 vs. baseline) and similar to the 3-yr decrease in BMD in group II during the initial 3 yr. In conclusion, alendronate (5 mg) for 5 yr or alendronate (20 mg) for 2 yr followed by 3 yr off therapy prevented postmenopausal bone loss. After withdrawal of alendronate (20 mg), bone loss resumed at the normal early postmenopausal rate.

Absorptiometry, Photon↗

PubMed2000

Risedronate reverses bone loss in postmenopausal women with low bone mass: results from a multinational, double-blind, placebo-controlled trial. BMD-MN Study Group.

Our objective was to investigate the efficacy and tolerability of risedronate in postmenopausal women with low bone mass. Women with a mean lumbar spine T-score of -2 or less (n = 543) received 24 months of placebo or risedronate (2.5 or 5 mg/day). All received calcium (1 g/day). The principal outcome measures were bone mineral density (BMD) at the lumbar spine, femoral neck, and femoral trochanter. At 24 months, lumbar spine BMD increased from baseline by 4% with 5 mg risedronate and 1.4% in the 2.5-mg group, compared with no change with placebo. Efficacy was similar in women who were less than 5 yr and more than 5 yr postmenopausal. At 24 months, risedronate (5 mg) had also increased BMD at the femoral neck and trochanter, whereas BMD decreased in the placebo group. BMD increases were seen at all three sites with risedronate (5 mg) after only 6 months of therapy. Risedronate was well tolerated; upper gastrointestinal adverse events were similar to placebo. We conclude that risedronate (5 mg) increases BMD rapidly and effectively and is well tolerated in postmenopausal women with low bone mass, regardless of time since menopause.

Aged↗

PubMed2000

Morphometric X-ray absorptiometry and morphometric radiography of the spine: a comparison of prevalent vertebral deformity identification.

Prevalent vertebral deformities are associated with a substantially increased risk of subsequent vertebral and nonvertebral fractures. Knowledge of vertebral fracture status is an important component in the prediction of further fractures in patients with osteoporosis. This study reports a comparison of the quantitative identification of vertebral deformities on morphometric X-ray absorptiometry (MXA) scans and conventional radiographs (MRX) in 161 postmenopausal women (mean age +/- SD, 64 +/- 7.1 years) recruited from patients referred by their family doctor for bone density measurement (n = 119) and osteoporotic subjects with known vertebral deformities attending an osteoporosis clinic (n = 42). Each subject had MXA scans and MRXs of the thoracolumbar spine, to image the vertebrae from T4-L4, at a single visit. The scans and radiographs were analyzed by two trained observers using six points to quantify the shape of each vertebral body. From these points, three vertebral heights were measured: anterior, middle, and posterior. Vertebral deformities were identified using the algorithms proposed by Eastell and by McCloskey. Generally good to excellent agreement (per vertebra, kappa = 0.87-0.93; per subject, kappa = 0.81-0.91) was observed between the two algorithms used for quantitative vertebral deformity identification using MXA or MRX. More moderate agreement (per vertebra, kappa = 0.70-0.79; per subject, kappa = 0.67-0.75) was seen when comparing the same algorithm between MXA and MRX. Agreement between MXA and MRX for the McCloskey algorithm was better than for the Eastell algorithm, largely because of the lower number of false positives produced by the McCloskey methodology. Deformity identification by MXA was limited because of poor image quality, primarily in the upper thoracic spine. One in six MRX deformities were missed by MXA as they occurred in vertebrae not visualized sufficiently for analysis on the MXA scans. Deformity identification was poorer in the upper thoracic spine in analyzable vertebrae with a sensitivity of 50.0% for MXA in terms of MRX using the Eastell algorithm for the vertebral levels T4-T7, compared with 80.6% for L1-L4A. MXA proved to be more effective at identifying moderate to severe MRX deformities producing a sensitivity of 22.0% for MXA in terms of identifying MRX grade 1 deformities using the Eastell algorithm, compared with 81.6% for grade 2 deformities. Although MXA image quality is inferior to that of conventional radiographs, MXA has distinct advantages such as a substantially reduced effective dose to the patient and acquisition of a single image of the spine. MXA is a potentially useful, relatively fast, low-radiation technique to identify prevalent vertebral deformities, particularly moderate to severe deformities in the middle/lower thoracic and lumbar spine, in conjunction with morphometric radiography in some patients.

Absorptiometry, Photon↗