Pancreas fat quantification with quantitative CT: an MRI correlation analysis.

AIM: To assess the fat content of the pancreas using quantitative computed tomography (QCT) and to correlate the results with chemical-shift-encoded magnetic resonance imaging (CSE-MRI) measurements of proton density fat fraction (PDFF). MATERIAL AND METHODS: Institutional review board approval for this research was obtained and 52 participants (25 men, 27 women; mean age 35.1 years; age range 22-50 years), who were enrolled in the Prospective Urban Rural Epidemiology (PURE) Study, underwent QCT and CSE-MRI for quantification of fat content in the pancreas. Two observers placed regions of interest (area of 100-130 mm2) in the head, body, and tail of the pancreas as closely matched as possible on the two scans. Pearson correlation and Bland-Altman analysis were performed to evaluate the correlation between the QCT and CSE-MRI measurements and the systematic difference between the two techniques. RESULTS: The QCT and CSE-MRI measurements of pancreatic fat content were well correlated (r=0.805, p<0.0001), although Bland-Altman analysis showed that the QCT measurements were systematically lower by 6.3% compared to CSE-MRI PDFF. CONCLUSION: In conclusion, the results of this study suggest good correlation between QCT and CSE-MRI measurements of pancreatic fat content. Further studies are required to improve the numerical agreement of QCT measurements with PDFF.

Differences in regional bone metabolism at the spine and hip: a quantitative study using (18)F-fluoride positron emission tomography.

SUMMARY: This study showed that regional bone blood flow and (18)F-fluoride bone plasma clearance measured by positron emission tomography are three times lower at the hip than the lumbar spine. INTRODUCTION: Measurements of effective bone plasma flow (K (1)), bone plasma clearance (K ( i )) and standardised uptake values (SUV) using (18)F-fluoride positron emission tomography ((18)F-PET) provide a useful means of studying regional bone metabolism at different sites in the skeleton. This study compares the regional (18)F-fluoride kinetics and SUV at the hip and lumbar spine (LS). METHODS: Twelve healthy postmenopausal women with no history of metabolic bone disease apart from two with untreated osteoporosis were recruited. Each subject underwent 60-min dynamic (18)F-PET scans at the LS and proximal femur two weeks apart. K (1), K ( i ) and SUV were measured at the LS (mean of L(1)-L(4)), femoral neck (FN), total hip (TH) and femoral shaft (FS). Differences between sites were assessed using the nonparametric Kruskal-Wallis test with a Bonferroni correction for multiple comparisons. RESULTS: Values of K (1), K ( i ) and SUV at the FN, TH and FS were three times lower than at the LS (p = 0.003). Amongst the proximal femur sites, K ( i ) and SUV were lower at the FS compared with the FN and TH, and SUV was lower at the TH compared with the FN (all p < 0.05). The volume of distribution was lower at the TH and FS compared with the LS (p < 0.05). CONCLUSION: The lower values of K (1), K ( i ) and SUV at the hip suggest that lower bone blood flow in the proximal femur is an important factor explaining the principal reason for the differences in bone fluoride kinetics between the LS and hip sites.

Precision of ¹8F-fluoride PET skeletal kinetic studies in the assessment of bone metabolism.

UNLABELLED: We assessed the precision of lumbar spine (18)F-PET measurements based on 58 scans performed on 20 postmenopausal women. The percentage coefficient of variation (%CV) (95% confidence interval) was 9.2% (7.5-11.8) for standardised uptake values, 11.7% (9.5-14.9) for plasma clearance measurements using the Patlak method and 14.5% (11.7-18.5) for plasma clearance measurements using the Hawkins three-compartment model. INTRODUCTION: (18)F-Fluoride positron emission tomography ((18)F-PET) is a non-invasive technique that allows the assessment of regional bone turnover in patients with metabolic bone disease. Knowledge of the precision errors of (18)F-PET measurements is important for planning the number of subjects required for research studies. METHODS: Twenty osteoporotic postmenopausal women had (18)F-PET scans of the lumbar spine at 0, 6 and 12 months after stopping long-term bisphosphonate treatment. No significant changes in the PET measurements were seen over the 12-month period, and the data were deemed suitable for a precision study. Precision errors were evaluated for standardised uptake values (SUVs) and for the fluoride plasma clearance to bone mineral (K (i)) determined using the Patlak and Hawkins methods. Precision errors were expressed as the %CV and were calculated for the mean L1-L4 region and for individual vertebrae. RESULTS: %CV (95% confidence interval) for the L1-L4 region was 9.2% (7.5-11.8) for SUV, 11.7% (9.5-14.9) for K (i) measured using the Patlak method and 14.5% (11.7-18.5) for K (i) measured using the Hawkins method. There was no significant difference between precision errors obtained for the L1-L4 region and those obtained for a single vertebra. CONCLUSIONS: SUV measurements showed the smallest precision error followed by the Patlak method, while the Hawkins method gave the largest error. Measuring a smaller region of interest did not increase the precision error, suggesting that the factor determining the errors may be scanner calibration.

Regional bone metabolism at the lumbar spine and hip following discontinuation of alendronate and risedronate treatment in postmenopausal women.

UNLABELLED: The aim of this study was to examine the effects of bisphosphonate discontinuation on bone metabolism at the spine and hip measured using (18) F-fluoride PET. Bone metabolism at the spine remained stable following discontinuation of alendronate and risedronate at 1 year but increased in the hip in the alendronate group only. INTRODUCTION: Bisphosphonates such as alendronate (ALN) or risedronate (RIS) have persistent effects on spine BMD following discontinuation. METHODS: Positron emission tomography (PET) was used to examine regional bone metabolism in 20 postmenopausal women treated with ALN (n = 11) or RIS (n = 9) for a minimum of 3 years at screening (range 3-9 years, mean 5 years for both groups). Subjects underwent a dynamic scan of the lumbar spine and a static scan of both hips at baseline and 6 and 12 months following treatment discontinuation. (18) F-fluoride plasma clearance (K(i)) at the spine was calculated using a three-compartment model. Standardised uptake values (SUV) were calculated for the spine, total hip, femoral neck and femoral shaft. Measurements of BMD and biochemical markers of bone turnover were also performed. RESULTS: With the exception of a significant decrease in spine BMD in the ALN group, BMD remained stable. Bone turnover markers increased significantly from baseline by 12 months for both study groups. Measurements of K(i) and SUV at the spine and femoral neck did not change significantly in either group. SUV at the femoral shaft and total hip increased significantly but in the ALN group only, increasing by 33.8% (p = 0.028) and 24.0% (p = 0.013), respectively. CONCLUSIONS: Bone metabolism at the spine remained suppressed following treatment discontinuation. A significant increase in SUV at the femoral shaft and total hip after 12 months was observed but for the ALN group only. This study was small, and further clinical studies are required to fully evaluate the persistence of BP treatment.

The effect of weight and weight change on the long-term precision of spine and hip DXA measurements.

SUMMARY: We examined the effect of weight and weight change on the long-term precision of spine and hip bone mineral density (BMD) in a group of 64 postmenopausal women studied over a 10-year period. Long-term precision errors were 50% larger than short-term errors. Over the range 50-90-kg weight was associated with a statistically significantly larger precision error when precision was expressed in BMD units, but not when expressed as the coefficient of variation (CV). Weight changes up to 5 kg had little effect on precision. INTRODUCTION: Reliable knowledge of the precision of bone mineral density (BMD) measurements is important for the interpretation of follow-up dual-energy X-ray absorptiometry (DXA) scans. In this study, we examined the effect of body weight and change in weight on the long-term precision of spine and hip BMD. METHODS: The study population was a group of 64 postmenopausal women enrolled in a 16-year trial of tibolone. We analyzed the spine, femoral neck, and total hip BMD data acquired over a 10-year period on a Hologic QDR4500A densitometer using linear regression to examine the trend of BMD with time for each subject. Precision was expressed in BMD units (g cm(-2)) (standard error of the estimate, SEE) and also as the coefficient of variation (CV). RESULTS: The long-term precision errors were in BMD (CV) units: 0.018 g cm(-2) (1.9%) for spine, 0.017 g cm(-2) (2.3%) for femoral neck, and 0.016 g cm(-2) (1.7%) for total hip BMD. An inverse relationship between CV and BMD was found for the spine (P = 0.003) and total hip (P = 0.043) sites, but none between SEE and BMD. For spine BMD, there were statistically significant correlations between SEE and weight (P = 0.025) and body thickness (P = 0.027). For femoral neck BMD, there were correlations between SEE and weight (P = 0.030), body mass index (BMI) (P = 0.023) and thickness (P = 0.021), but no correlations for total hip BMD or when precision was expressed as the CV. When study subjects were grouped in quartiles according to weight, the spine BMD SEE increased from 0.014 g cm(-2) for women in the lowest quartile (46-62 kg) to 0.018 g cm(-2) for women in the highest quartile (80-105 kg) (P = 0.008). There was a trend for SEE to be greater in individuals with larger weight changes, although these tended to be the heavier subjects. CONCLUSIONS: From the study, we were able to come up with the following conclusions: (1) long-term precision errors were 50% larger than short-term errors, (2) over the range 50 to 90 kg (BMI: 20-35 kg m(-2)), body weight had a small but statistically significant effect on precision expressed in BMD units, but not when expressed as the CV, and (3) weight changes up to 5 kg had little effect on precision. More studies of individuals >100 kg are required to fully investigate the dependence of DXA scan precision on weight.

Significant differences in UK and US female bone density reference ranges.

UNLABELLED: In the United Kingdom (UK), T- and Z-scores are usually calculated using reference ranges derived from United States (US) populations. In the UK arm of a recent randomised trial (International Breast Cancer Intervention Study II (IBIS-II)), substantially, fewer women than expected were recruited into the osteopenic (-2.545 years with a typical body mass index of 28 kg m(-2) have spine and hip bone mineral density (BMD) 0.6 standard deviation higher than their US counterparts. INTRODUCTION: Dual energy X-ray absorptiometry (DXA) is widely used for the diagnosis of osteoporosis and to investigate the effect of pharmacological treatments on BMD. In both routine and research settings, it is important that DXA results are correctly interpreted. METHODS: T- and Z-scores for the first 650 UK Caucasian women enrolled in the IBIS-II study were compared with data from two independent studies of unrelated, unselected UK Caucasian women: (1) 2,382 women aged 18 to 79 recruited to the Twins UK Adult Twin Registry; (2) 431 women aged 21 to 84 with no risk factors for osteoporosis recruited at Guy's Hospital. All DXA measurements were performed on Hologic densitometers. Subjects were divided into six age bands, and T- and Z-scores were calculated using the manufacturer's US reference range for the spine and the National Health and Nutrition Examination Survey III reference range for the femoral neck and total hip. RESULTS: The overall mean Z-scores for the IBIS-II, Twin, and Guy's groups were: spine: +0.61, +0.29, +0.33; femoral neck: +0.42, +0.36, +0.45; total hip: +0.65, +0.38, +0.39 (all p<0.001 compared with the expected value of 0). The mean body weight of subjects in the three studies was 74.4, 65.5, and 65.4 kg, respectively. Analysis revealed a highly significant relationship between Z-score and weight at each BMD site with a slope of 0.03 kg(-1). CONCLUSIONS: In general, US spine and hip reference ranges are not suitable for the calculation of Z-scores in UK women. For some research study designs, the differences may significantly influence the pattern of subject recruitment.

Genetic and environmental determinants on bone loss in postmenopausal Caucasian women: a 14-year longitudinal twin study.

SUMMARY: This longitudinal twin study documented that genetic factors explain 44-56% of the between-individual variance in bone loss at femoral neck, lumbar spine, and forearm in postmenopausal Caucasian women, providing a rationale for identifying the specific genes involved. INTRODUCTION: Although there is a significant genetic effect on peak BMD, until recently, no substantive studies on heritability of bone loss in human were available. The aim of the study was to estimate the heritability of the bone loss at multiple sites in postmenopausal Caucasian women. METHODS: Postmenopausal female monozygotic (MZ) and dizygotic (DZ) twins aged 40 or above at baseline were selected from the TwinsUK registry and followed up for an average of 8 years (range 5-14 years). All twins were noncurrent hormone replacement therapy users and not on any osteoporosis treatment. They had dual-energy X-ray absorptiometry (DXA) scans of their hip, lumbar spine, and forearm several times (range 2-9) during the follow-up period. Individual bone losses at femoral neck, lumbar spine, and forearm were estimated by linear regression modeling. Structural equation modeling was utilized to estimate the heritability of the bone loss. RESULTS: A total of 712 postmenopausal Caucasian female twins (152 MZ and 204 DZ pairs) were included. MZ twins were older and had slightly lower BMD at all sites than DZ twins. DZ twins had slightly higher bone loss at lumbar spine, but similar at femoral neck and forearm compared to MZ twins. Intraclass correlation coefficients (ICC) for the bone loss at all sites were significantly higher in MZ than DZ twin pairs (p = 0.0045, 0.0003, and 0.0007 for femoral neck, lumbar spine, and forearm, respectively), indicating a significant genetic influence on bone loss at these sites. After adjustment for age at baseline and weight change during the follow-up, the heritability estimate was 47% (95% CI 27-63%) for bone loss at femoral neck, 44% (95% CI 27-58%) for lumbar spine, and 56% (95% CI 44-65%) for forearm. CONCLUSIONS: Our data suggest that up to 56% of the between-individual variance in bone loss is due to genes, providing a rationale to identify specific genetic factors for bone loss.

Effect of increasing vertebral marrow fat content on BMD measurement, T-Score status and fracture risk prediction by DXA.

Quantitative examination of iliac crest bone biopsies shows that as subjects become older bone and functional marrow are replaced by adipose tissue. Studies of vertebral marrow fat using nuclear magnetic resonance spectroscopy ((1)H-MRS) show that subjects with lower spine T-scores have significantly higher marrow fat content. These findings suggest that the ability of DXA scans to determine fracture risk may be partly explained by the effect of increased marrow fat on BMD. However, a proper evaluation of the relationship between WHO spine T-score status and marrow fat content requires that the BMD data are first corrected for the bias caused by a selection effect in which subjects with higher marrow fat are more likely to be identified as having osteoporosis. In this study we have therefore reanalysed previously published data for 185 elderly Hong Kong Chinese subjects (103 women, mean age 73 y; 82 men, mean age 73 y) who had spine DXA scans and (1)H-MRS measurements of L3 marrow fat. The effect of varying marrow fat on BMD was modelled using vertebral body thicknesses measured in 50 men and women. Spine T-scores in each individual were adjusted for the measured marrow fat. Subjects were assigned to WHO categories based on their corrected T-scores, and the relationship between marrow fat and T-score status evaluated using regression analysis and analysis of variance. The average change in percent marrow fat per T-score unit was used to infer the fraction of the spine BMD fracture discrimination explained by marrow composition. The mean (SD) of the L1-L4 vertebral body thickness was 30.2 (2.1) mm for Hong Kong women and 33.4 (2.5) mm for men. A change in marrow fat content from 0 to 100% was estimated to produce a BMD decrease of 0.14 g/cm(2) (1.3 T-score units) in women and 0.16 g/cm(2) (1.3 T-score units) in men. Although adjusting spine BMD for marrow fat reduced the significance of the correlation, there was still a trend for marrow fat to increase with decreasing T-score with a slope of -1.2+/-0.7% per T-score unit (p=0.078) for women and -1.4+/-0.6% per T-score unit (p=0.023) for men. When the effect of marrow composition on fracture discrimination was evaluated the results showed that the higher vertebral marrow fat content found in osteoporotic subjects made a negligible contribution to the ability of spine BMD measurements to predict fracture risk.

Peripheral and central measurements of bone mineral density are equally strongly associated with clinical risk factors for osteoporosis.

The aim of this study was to determine whether forearm bone mineral density (BMD) measurements are affected by clinical risk factors for osteoporosis to the same extent as spine and hip BMD. The study population consisted of 1,009 female patients and volunteers, of whom 238 were premenopausal. Women were placed into seven groups according to which clinical risk factor they had (women could be placed in more than one group): (1) atraumatic fracture since the age of 25 years, (2) report of X-ray osteopenia, (3) predisposing medical condition or use of therapy known to affect bone metabolism, (4) premature menopause before the age of 45 years or a history of amenorrhea of longer than 6 months' duration, (5) family history of osteoporosis, (6) body mass index (BMI) <20 kg/m(2), and (7) current smoking habit. Forearm BMD was measured using an Osteometer DTX-200 peripheral dual-energy X-ray absorptiometry scanner, and spine and hip BMD measurements were obtained on a Hologic QDR-4500 scanner. Manufacturers' reference ranges were used to calculate Z scores for the spine and forearm, and the NHANES III reference range was used to calculate Z scores for the hip. Multivariate regression analysis was used to estimate the mean decrease in Z score associated with each clinical risk factor. The Z-score reductions associated with the seven risk factors were similar for forearm and central BMD measurements. For forearm measurements, Z-score decreases associated with a history of atraumatic fracture (-0.25), a medical condition or therapy known to affect bone metabolism (-0.26), premature menopause or history of amenorrhea (-0.30), and BMI <20 kg/m(2) (-0.82) were all statistically significantly different from zero (P < 0.05). With an increasing number of risk factors in each individual, the mean Z score at each measurement site became progressively more negative. In conclusion, clinical risk factors for low BMD affect forearm BMD measurements to a similar extent as central BMD.

Predicting the risk of fracture at any site in the skeleton: are all bone mineral density measurement sites equally effective?

The ability to assess a patient's risk of fracture is fundamental to the clinical role of bone densitometry. Fracture discrimination is quantified by the relative risk (RR), defined as the increased risk of fracture for a 1 standard deviation decrease in bone mineral density (BMD). The larger the value of RR, the more effective measurements are at identifying patients at risk of fracture. Epidemiological studies show that RR values for predicting the risk of any fracture are approximately the same for all BMD measurement sites. In this study, we show theoretically that this interesting observation is predictable and a consequence of two related observations: (1) that fracture prediction by BMD measurement sites distant from the fracture site is quantitatively explained by the correlation of BMD measurements and (2) that all correlation coefficients between distant BMD sites are comparable, with values in the range r = 0.55-0.65. The first of these conditions (referred to as the correlation hypothesis) is important because it sets a lower limit on the RR values at distant BMD sites on the assumption that measurements at these sites contain no independent information about fracture risk over and above that provided by their correlation with the fracture site BMD. If the correlation hypothesis is true, the present study points to the importance of the correlation coefficient between BMD sites as a key index that is indicative of the ability of different types of measurement to predict fracture risk. If, on the contrary, the correlation hypothesis is not valid, there is scope to improve bone densitometry by further studies to better identify those measurements that do provide independent information about fracture risk and how best to integrate this information with existing techniques to improve decision making.

The influence of implant design on periprosthetic bone remodelling of two types of uncemented HA-coated hip stems. A two-year follow-up study using DEXA.

UNLABELLED: Proximal bone resorption and an increased fracture rate in the ABG-I stem has been shown. For these reasons the ABG-I stem design was changed to the ABG-II. In this study periprosthetic bone loss around the ABG-I vs ABG-II is compared to verify if the design changes resulted in improved proximal bone preservation. METHODS: 51 patients were randomised to either the ABG-I or ABG-II hip prosthesis. Periprosthetic BMD change at various time points was measured using DEXA. Between the two groups (age, gender, weight etc.) no statistical difference was encountered. Compared to the baseline at two years the ABG-II preserved bone better proximally (e.g. zone 7: ABG-II: -3.7%, ABG-I: -11.9%, p=0.05) than the ABG-I. Distally, the trend was opposite and less bone loss was measured for the ABG-I than the ABG-II in zones 3, 4 and 5 (n.s.). CONCLUSION: this study confirms the philosophy behind the design changes from the ABG-I to ABG-II stem where increased elasticity, more proximal HA-coating, a shorter and distally polished stem, were meant to reduce proximal bone resorption. In future this may lead to fewer periprosthetic fractures and to less complicated revision surgery.

A list of device-specific thresholds for the clinical interpretation of peripheral x-ray absorptiometry examinations.

The UK National Osteoporosis Society (NOS) has recently issued new guidelines on the use of peripheral x-ray absorptiometry (pDXA) devices in managing osteoporosis. The NOS guidelines recommend a triage approach in which patients' bone mineral density (BMD) measurements are interpreted using upper and lower thresholds specific to each type of pDXA device. The thresholds are defined so that patients with osteoporosis at the hip or spine are identified with 90% sensitivity and 90% specificity. Patients with a pDXA result below the lower threshold are likely to have osteoporosis at the hip or spine, patients with a result above the upper threshold are unlikely to have osteoporosis, while those between the two thresholds require a hip and spine BMD examination for a definitive diagnosis. This report presents data from a multicenter study to establish the triage thresholds for a range of pDXA devices in use in the UK. The subjects were white female patients aged 55-70 years who met the normal referral criteria for a BMD examination. For each device, at least 70 women with osteoporosis at the hip or spine and 70 women without osteoporosis were enrolled. All women had hip and spine BMD measurements using axial DXA systems that were interpreted using the National Health and Nutrition Examination Survey (NHANES) reference range for the hip and the manufacturers' reference ranges for the spine. Data are presented for five different devices: the Osteometer DTX-200 (forearm BMD), the Schick AccuDEXA (hand BMD), the GE Lunar PIXI (heel BMD), the Alara MetriScan (hand BMD), and the Demetech Calscan (heel BMD). The clinical measurements were supplemented by theoretical modeling to estimate the age dependence of the triage thresholds and the effect of the correlation coefficient between pDXA and axial BMD on the percentage of women referred for an axial BMD examination. In summary, this study provides thresholds for implementing the new NOS guidelines for managing osteoporosis using pDXA devices. The figures reported apply to postmenopausal white women aged 55-70 years who meet the conventional criteria for a BMD examination. The results confirm that the thresholds are specific to each type of pDXA device and that the NOS triage algorithm requires 40% of women to have an axial DXA examination.

Fractal analysis of trabecular bone in knee osteoarthritis (OA) is a more sensitive marker of disease status than bone mineral density (BMD).

The purpose of this study was to determine whether fractal analysis (FSA) of macroradiographs or bone mineral density (BMD) is more sensitive in detecting disease-related cancellous bone alterations in knee osteoarthritis (OA). Differences in BMD between 11 OA (6 females) and 11 non-OA reference (7 females) tibiae were compared with differences in trabecular organization measured by computerized method of fractal signature analysis (FSA) of digitized macroradiographs (x3.5 to x5). OA knees had anatomic and radiographic evidence of medial compartment disease. FSA measured cancellous bone organization at 4 regions of interest (ROI): medial and lateral subchondral (Sc) and subarticular (Sa) sites, dual X-ray absorptiometry (DXA) measured BMD at the same ROIs. Compared to non-OA, OA tibiae had significant increased (P < 0.05) in FSA of vertical trabeculae in the medial Sa region (trabecular size range: 0.42-0.54; 0.90-1.98 mm) and significant decrease (P < 0.05) in FSA for some horizontal trabeculae in the Sc region (trabecular size range: medial side 0.12-0.18 mm; lateral side 0.12-0.24 mm). Compared to non-OA, BMD of OA tibiae was not significantly different at any ROI. BMD was not sensitive to changes in trabecular organization detected by FSA. The increase in FSA of vertical trabeculae in the medial Sa region was consistent with trabecular fenestration and thinning, which may have been detected as decreased BMD in a larger sample. For studies involving small sample sizes, quantifying changes in trabecular organization is more sensitive than BMD for detecting bone alterations in knee OA.

Dual X-ray absorptiometry: clinical evaluation of a new cone-beam system.

The DMS Lexxos is the first cone-beam dual X-ray absorptiometry (DXA) system capable of performing bone mineral density (BMD) measurements of the spine and hip. By using a two-dimensional (2-D) detector array rather than the linear array used with conventional fan-beam DXA systems, image acquisition time on Lexxos is only 1.5 s. However, the need to correct for the large signal from scattered radiation reaching the detector is a potential source of error in cone-beam DXA. The aim of this clinical evaluation of the Lexxos bone densitometer was to investigate the relative accuracy of cone-beam BMD measurements compared with conventional DXA by performing an in vivo cross-calibration study with an established fan-beam system, the Hologic QDR-4500. Spine (L1-L4) and hip BMD measurements were performed in 135 patients (111 women, 24 men) referred for a bone densitometry examination. Duplicate Lexxos measurements were performed in 27 female patients to evaluate precision. On average, Lexxos spine and femoral neck BMD measurements were 2% lower than those on the QDR-4500, whereas total hip BMD was 5% higher. Larger differences were found for the trochanter and Ward's triangle regions. For all sites, Lexxos BMD measurements showed a strong linear relationship with those measured on the QDR-4500 with correlation coefficients in the range r = 0.95 to 0.97 for the clinically important spine, femoral neck, and total hip regions. The root mean standard error (RMSE) between Lexxos and QDR-4500 BMDs ranged from 0.037 g/cm(2) for the femoral neck to 0.060 g/cm(2) for the spine, whereas Lexxos precision was 1.3% for total hip, 2.0% for femoral neck, and 2.3% for spine BMD. Although for the hip BMD sites the RMSE and precision of Lexxos measurements were similar to studies of pencil-beam and fan-beam DXA systems, the results for the spine were poorer than expected. The findings of this study suggest that Lexxos corrects accurately for the effects of scattered radiation at the detector, but that the precision of spine BMD measurements may be limited by involuntary patient movement between the high and low energy X-ray exposures.

16-detector multislice CT: dosimetry estimation by TLD measurement compared with Monte Carlo simulation.

Computer simulations are widely used to estimate effective doses from CT examinations. The raw data often used in their estimations were obtained some years ago and made certain assumptions regarding CT unit design. At that time multidetector CT units were unavailable. Changes in design will limit the accuracy of computer simulated dosimetry on these machines. We therefore estimated CT dose on a 16-detector unit directly using thermoluminescent dosemeters (TLDs) and an anthropomorphic phantom. We found that the dose measured directly was 18% higher than the computer simulated dosimetry, in keeping with the previously recognised underestimation by computer simulation techniques compared with TLD measurements.

Dual X-ray absorptiometry: cross-calibration of a new fan-beam system.

The high precision and stable calibration of dual X-ray absorptiometry (DXA) scanners have led to their widespread use in longitudinal studies for research and the follow-up of individual patients who are receiving treatment for osteoporosis. However, difficulties in maintaining the continuity of the bone mineral density (BMD) calibration scale can arise when an old DXA system is replaced by a newer model. We report the results of an in vivo cross-calibration study performed when a GE-Lunar Prodigy fan-beam system replaced a DPX-L pencil-beam scanner. Lumbar spine and hip DXA scans were performed in 133 patients (104 female, 29 male) attending long-term BMD monitoring. On average, lumbar spine BMD measurements on the two systems agreed closely, with Prodigy values 1% lower than those on the DPX-L. However, after allowing for this difference, the root mean square error (RMSE) of 0.037 g/cm2 was larger than in previous cross-calibration studies reported in the literature, and was 3 times the value expected from the precision of the BMD measurements. Mean femoral neck BMD also agreed closely between the two systems, although for Prodigy, the spread of measurements was 10% smaller than that for the DPX-L. For the trochanter and Ward's triangle regions, mean BMD was 4% and 6% lower, respectively, on the Prodigy system, and the results were affected by a similar compression of the range of values. RMSE values were 0.037 g/cm2, 0.044 g/cm2, and 0.044 g/cm2, respectively, for the femoral neck, trochanter, and Ward's triangle sites. When the high value of the RMSE was investigated, it was found that for lumbar spine BMD, patient body weight and the difference between the two systems in the percentage fat reported in the soft tissue reference region explained 40% of the variance. This enabled equations to be developed that significantly improved the agreement between scans performed on the two systems. Smaller improvements were obtained for the femur BMD measurements.

Evaluation of the Cockroft-Gault, Jelliffe and Wright formulae in estimating renal function in elderly cancer patients.

BACKGROUND: More elderly patients are being treated with chemotherapy. Reliable and accurate measures of renal function are needed to obtain predictable, safe and effective exposure to renally excreted drugs. The Jelliffe, Cockroft-Gault and Wright formulae have been used to evaluate renal function, although they have not been validated in elderly oncology patients. We performed a retrospective evaluation of these formulae using the [51Cr]-ethylenediamine tetraacetic acid ([51Cr]-EDTA) method of measuring glomerular filtration rate (GFR) as the 'gold standard'. PATIENTS AND METHODS: Inclusion criteria were age > or = 70 years and serum creatinine <250 micromol/l, performed within 4 weeks of glomerular filtration rate (GFR) measurement. Creatinine clearance was calculated using the Cockroft-Gault, Jelliffe and Wright formulae. The precision and accuracy of the three formulae were compared with the gold standard. RESULTS: Two hundred and twenty-five patients were evaluated: median age, 74 years (range 70-89); males, 108; females, 117; median creatinine, 84 micromol/l (range 44-186). Correlation coefficients of the Jelliffe, Cockroft-Gault and Wright formulae were similar. In the specific GFR ranges of 50-70, 70-90 and 90-120 ml/min, the bias [mean percentage error (MPE)] was +8%, -4% and -13%, respectively. The degree of bias was greater with the Cockroft-Gault and Jelliffe formulae across the same range of GFR with the MPE being -15%, -25%, -32% and -12%, -19% and -23%, respectively. All three formulae have reduced precision and greater bias at the extremes of GFR. CONCLUSIONS: The Wright formula is the most accurate, precise and least biased formula for the calculation of GFR in elderly patients with a GFR >50 ml/min. These results allow the physician to make a decision regarding the use of the formula based on an expected degree of bias.

Can the WHO definition of osteoporosis be applied to multi-site axial transmission quantitative ultrasound?

Osteoporosis is a highly prevalent but preventable disease and, as such, it is important that there are appropriate diagnostic criteria to identify those at risk of low trauma fracture. In 1994 the World Health Organization (WHO) introduced definitions of osteoporosis and osteopenia using T-scores, which identified 30% of all Caucasian post-menopausal women as having osteoporosis. However, the use of the WHO T-score thresholds of -2.5 for osteoporosis and -1.0 for osteopenia may be inappropriate at skeletal sites other than the spine, hip and forearm or when other modalities, such as quantitative ultrasound (QUS) are used. The aim of this study was to evaluate the age-dependence of T-scores for speed of sound (SOS) measurements at the radius, tibia, phalanx and metatarsal by use of the Sunlight Omnisense, to evaluate the prevalence of osteoporosis and osteopenia at these sites by use of the WHO criteria, and calculate appropriate equivalent T-score thresholds. The study population consisted of 278 healthy pre-menopausal women, 194 healthy post-menopausal women and 115 women with atraumatic vertebral fractures. All women had SOS measurements at the radius, tibia, phalanx and metatarsal and bone mineral density (BMD) measurements at the lumbar spine and hip. A group of healthy pre-menopausal women aged 20-40 years from the pre-menopausal group were used to estimate the population mean and SD for each of the SOS and BMD measurement sites. Healthy post-menopausal women were classified into normal, osteopenic or osteoporotic, based upon the standard WHO definition of osteoporosis and expressed as a percentage. We investigated the age-related decline in T-scores from 20-79 by stratifying the healthy subjects into 10-year age groups and calculating the mean T-score for each of these groups. Finally, we estimated appropriate T-score thresholds, using five different approaches. The prevalence of osteoporosis in the post-menopausal women aged 50 years and over ranged from 1.4 to 12.7% for SOS and 1.3 to 5.2% for BMD. The age-related decline in T-scores ranged from -0.92 to -1.80 for SOS measurements in the 60 to 69-year age group and -0.60 to -1.19 for BMD measurements in the same age group. The WHO definition was not suitable for use with SOS measurements, and revised T-score thresholds for the diagnosis of osteoporosis of -2.6, -3.0, -3.0 and -2.2 and for osteopenia of -1.4, -1.6, -2.3, and -1.4, for the radius, tibia, phalanx and metatarsal, respectively, were recommended.

Periprosthetic bone remodelling of two types of uncemented femoral implant with proximal hydroxyapatite coating: a 3-year follow-up study addressing the influence of prosthesis design and preoperative bone density on periprosthetic bone loss.

Periprosthetic bone loss is a major cause of concern in patients undergoing total hip arthroplasty (THA). Further studies are required to identify the factors determining the pattern of bone remodelling following THA and obtain improvements in the design and durability of prostheses. In this study, we monitored periprosthetic bone loss around two different types of hydroxyapatite coated femoral implant over a 3-year period to evaluate their design and investigate the relationship with the preoperative bone mineral density (BMD) at the spine, hip and forearm. Sixty patients (35 F, 25 M, mean age 63 years, range 46-75 years) undergoing THA were randomised to either the Anatomic Benoist Girard (ABG) or Mallory-Head (MH) femoral stem. Preoperative dual-energy X-ray absorptiometry (DXA) scans were acquired of the posteroanterior (PA) and lateral lumbar spine, the contralateral hip and the non-dominant forearm. Postoperative DXA scans were performed to measure periprosthetic BMD at 10 days (treated as baseline), 6 weeks, and 3, 6, 12, 24 and 36 months after THA using a standard Gruen zone analysis. Results were expressed as the percentage change from baseline and the data examined for the differences in bone loss between the different Gruen zones, between the ABG and MH stems, and the relationship with preoperative BMD. A total of 50 patients (24 ABG, 26 MH) completed the study. Three months after THA there was a statistically significant BMD decrease in every Gruen zone that varied between 5.6% and 13.8% for the ABG prosthesis and between 3.8% and 8.7% for the MH prosthesis. Subsequently, in most zones BMD reached a plateau or showed a small recovery. However, BMD continued to fall in Gruen zones 1 and 7 in ABG patients and Gruen zone 1 in MH patients. Bone loss was less in every Gruen zone in MH patients compared with ABG with the largest difference (10%, P=0.018) in Gruen zone 7. Highly significant relationships were found between periprosthetic bone loss and preoperative BMD measured at the PA spine ( P<0.001), total hip ( P=0.004) and total distal radius ( P<0.001). This study showed differences between two different designs of hydroxyapatite-coated implant that confirmed that prosthesis design influences periprosthetic bone loss. The study also showed that patients' bone density measured at the spine, hip or forearm at the time of operation was a major factor influencing bone loss around the femoral stem.