How well do the FRAX (Australia) and Garvan calculators predict incident fractures? Data from the Geelong Osteoporosis Study.

This study reports that both FRAX and Garvan calculators underestimated fractures in Australian men and women, particularly in those with osteopenia or osteoporosis. Major osteoporotic fractures were poorly predicted, while both calculators performed acceptably well for hip fractures. INTRODUCTION: This study assessed the ability of the FRAX (Australia) and Garvan calculators to predict fractures in Australian women and men. METHODS: Women (n = 809) and men (n = 821) aged 50-90 years, enrolled in the Geelong Osteoporosis Study, were included. Fracture risk was estimated using FRAX and Garvan calculators with and without femoral neck bone mineral density (BMD) (FRAXBMD, FRAXnoBMD, GarvanBMD, GarvannoBMD). Incident major osteoporotic (MOF), fragility, and hip fractures over the following 10 years were verified radiologically. Differences between observed and predicted numbers of fractures were assessed using a chi-squared test. Diagnostics indexes were calculated. RESULTS: In women, 115 MOF, 184 fragility, and 42 hip fractures occurred. For men, there were 73, 109, and 17 fractures, respectively. FRAX underestimated MOFs, regardless of sex or inclusion of BMD. FRAX accurately predicted hip fractures, except in women with BMD (20 predicted, p = 0.004). Garvan underestimated fragility fractures except in men using BMD (88 predicted, p = 0.109). Garvan accurately predicted hip fractures except for women without BMD (12 predicted, p < 0.001). Fractures were underestimated primarily in the osteopenia and osteoporosis groups; MOFs in the normal BMD group were only underestimated by FRAXBMD and fragility fractures by GarvannoBMD, both in men. AUROCs were not different between scores with and without BMD, except for fragility fractures predicted by Garvan in women (0.696, 95% CI 0.652-0.739 and 0.668, 0.623-0.712, respectively, p = 0.008) and men, which almost reached significance (0.683, 0.631-0.734, and 0.667, 0.615-0.719, respectively, p = 0.051). Analyses of sensitivity and specificity showed overall that MOFs and fragility fractures were poorly predicted by both FRAX and Garvan, while hip fractures were acceptably predicted. CONCLUSIONS: Overall, the FRAX and Garvan calculators underestimated MOF and fragility fractures, particularly in individuals with osteopenia or osteoporosis. Hip fractures were predicted better by both calculators. AUROC analyses suggest that GarvanBMD performed better than GarvannoBMD for prediction of fragility fractures.

Increased bone mineral density in Aboriginal and Torres Strait Islander Australians: impact of body composition differences.

Bone mineral density (BMD) has been reported to be both higher and lower in Indigenous women from different populations. Body composition data have been reported for Indigenous Australians, but there are few published BMD data in this population. We assessed BMD in 161 Indigenous Australians, identified as Aboriginal (n=70), Torres Strait Islander (n=68) or both (n=23). BMD measurements were made on Norland-XR46 (n=107) and Hologic (n=90) dual-energy X-ray absorptiometry (DXA) machines. Norland BMD and body composition measurements in these individuals, and also in 36 Caucasian Australians, were converted to equivalent Hologic BMD (BMD(H)) and body composition measurements for comparison. Femoral neck (FN) and lumbar spine Z-scores were high in Indigenous participants (mean FN Z-score: Indigenous men +0.98, p<0.0001 vs. mean zero; Indigenous women +0.82, p<0.0001 vs. mean zero). FN BMD(H) was higher in Aboriginal and/or Torres Strait Islander than Caucasian participants, after adjusting for age, gender, diabetes and height and remained higher in men after addition of lean mass to the model. We conclude that FN BMD is higher in Aboriginal and/or Torres Strait Islander Australians than Caucasian Australian reference ranges and these differences still remained significant in men after adjustment for lean mass. It remains to be seen whether these BMD differences translate to differences in fracture rates.

Prognosis of fracture: evaluation of predictive accuracy of the FRAX algorithm and Garvan nomogram.

UNLABELLED: We evaluated the prognostic accuracy of fracture risk assessment tool (FRAX) and Garvan algorithms in an independent Australian cohort. The results suggest comparable performance in women but relatively poor fracture risk discrimination in men by FRAX. These data emphasize the importance of external validation before widespread clinical implementation of prognostic tools in different cohorts. INTRODUCTION: Absolute risk assessment is now recognized as a preferred approach to guide treatment decision. The present study sought to evaluate accuracy of the FRAX and Garvan algorithms for predicting absolute risk of osteoporotic fracture (hip, spine, humerus, or wrist), defined as major in FRAX, in a clinical setting in Australia. METHODS: A retrospective validation study was conducted in 144 women (69 fractures and 75 controls) and 56 men (31 fractures and 25 controls) aged between 60 and 90 years. Relevant clinical data prior to fracture event were ascertained. Based on these variables, predicted 10-year probabilities of major fracture were calculated from the Garvan and FRAX algorithms, using US (FRAX-US) and UK databases (FRAX-UK). Area under the receiver operating characteristic curves (AUC) was computed for each model. RESULTS: In women, the average 10-year probability of major fracture was consistently higher in the fracture than in the nonfracture group: Garvan (0.33 vs. 0.15), FRAX-US (0.30 vs. 0.19), and FRAX-UK (0.17 vs. 0.10). In men, although the Garvan model yielded higher average probability of major fracture in the fracture group (0.32 vs. 0.14), the FRAX algorithm did not: FRAX-US (0.17 vs. 0.19) and FRAX-UK (0.09 vs. 0.12). In women, AUC for the Garvan, FRAX-US, and FRAX-UK algorithms were 0.84, 0.77, and 0.78, respectively, vs. 0.76, 0.54, and 0.57, respectively, in men. CONCLUSION: In this analysis, although both approaches were reasonably accurate in women, FRAX discriminated fracture risk poorly in men. These data support the concept that all algorithms need external validation before clinical implementation.

Direct comparison of 18F-fluorodeoxyglucose coincidence gamma camera tomography with gallium scanning for the staging of lymphoma.

BACKGROUND: The present study compared the performance of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) using a coincidence dual-head gamma camera (FDG Co-PET) with 67gallium scinti graphy (GS) in pretreatment staging of lymphoma. METHODS: A total of 46 patients underwent FDG Co-PET, computed tomography (CT) scanning and GS for pretreatment staging of lymphoma (40 newly diagnosed and recurrence) between November 1997 and December 1999. RESULTS: Histological subgroups comprised low grade (8 patients), intermediate grade (25) high-grade (3) non-Hodgkin's lymphoma and Hodgkin's disease (10). Based on clinical assessment, CT scan findings and biopsy, 100 nodal sites and 15 extra-nodal sites were deemed positive. FDG Co-PET was superior to GS in nodal site positivity rate (97%vs 79%, P < 0.0001). Compared with GS, FDG Co-PET detected 39 more abnormal sites in 22 patients (48%), of which 28 sites were validated by biopsy, CT and/or progress FDG Co-PET scanning. There was only one proven false negative FDG site in the spleen. CT + FDG Co-PET led to upstaging in 2 patients (4%), compared to CT + GS. CONCLUSION: FDG Co-PET shows potential for providing an accurate means for pretreatment staging of lymphoma and can detect extra sites of disease activity compared to GS.

Reference ranges for bone densitometers adopted Australia-wide: Geelong osteoporosis study.

Bone densitometry reports a measure of fracture risk in comparison with young adults (T-scores) and age-matched peers (Z-scores). To date, each manufacturer has provided its own reference range resulting in lack of uniformity. The Australia and New Zealand Bone and Mineral Society and Osteoporosis Australia have recognized the need to standardize the reference range and have recommended that data generated by the Geelong Osteoporosis Study (GOS) be used Australia-wide. The GOS recruited a random, population-based sample of adult women and measured bone mineral density (BMD) at the proximal femur and spine using a Lunar DPX-L. These data were used to establish reference ranges for Lunar machines and, using conversion equations, for Norland and Hologic machines. The new standardized Australian reference ranges for BMD will enable consistent diagnosis of osteoporosis and categorization of fracture risk across different types of densitometers.

The effect of room temperature on dual-energy X-ray absorptiometry.

There has been little published data on the effects of temperature on the performance of dual-energy X-ray absorptiometry (DXA) machines. We examined the effect of changes in ambient room temperature on the performance of three DXA scanners (DPXL, Expert-XL and Prodigy). The study involved repeat measurements of bone mineral density (BMD) using three different spine phantoms scanned at different ambient room temperatures, both before and after calibration procedures. The calibration or quality assurance (QA) scan calibrates the scanner, adjusting for the ambient room temperature at the time of calibration. There was a moderate correlation between change in temperature and change in BMD measured prior to recalibration for the Expert-XL ( r=0.58) during normal clinical scanning conditions. There was no observed change in phantom BMD with change in temperature measured using the DXPL or Prodigy. After temperature change, without repeat calibration measurements, there was a strong correlation between temperature change and change in BMD measured using the Expert-XL ( r=0.96, p<0.001). From the regression equation, a change of 2.5 degrees C could alter the calculated BMD result measured by the Expert-XL by 1.5%, which would significantly affect the precision of the DXA system. There was no significant correlation between temperature and BMD in the DXPL or Prodigy. The observed differences between the densitometers and the effect of temperature change are most likely due to the differing types of detector systems used. Operators must be made aware that solid state detectors of the sort used in the Expert-XL (charge-coupled devices, CCDs) are significantly affected by changes in ambient room temperature.

Coincidence detection FDG PET in the management of oncological patients: attenuation correction versus non-attenuation correction.

The aim of this study was to determine if attenuation correction (AC) in a dual-head, coincidence, positron emission tomography imaging system (Co-PET) improved image quality, lesion detection, patient staging and management of various malignant neoplasms, compared to non-attenuation corrected (NAC) images. Thirty patients with known or suspected malignant neoplasms underwent fluorodeoxyglucose (FDG) Co-PET, which was correlated with histopathology, computed tomography (CT) and other conventional imaging modalities and clinical follow-up. The number and location of FDG avid lesions detected on the AC images and NAC Co-PET images were blindly assessed by two independent observers. Semi-quantitative grading of image clarity and lesion-to-background quality was performed. This revealed markedly improved image clarity and lesion-to-background quality in the AC versus NAC Co-PET images. AC Co-PET was statistically superior to NAC Co-PET in relation to lesion detection (P<0.01) and tumour staging (P<0.01). NAC Co-PET demonstrated 51 of the 65 lesions (78%) detected by AC Co-PET. AC Co-PET altered tumour staging in five additional patients (16%) compared to NAC Co-PET. Management was altered in two of these five patients.

Discordant normal ranges for proximal femur bone density in Australia.

The aim of the study was to investigate the reference ranges currently in use for femoral neck bone mineral density (BMD) in Australia. Representative scans were obtained of the proximal femur from 78 dual-energy X-ray absorptiometry centers across Australia. Femoral neck BMD was standardized using published conversion equations and corresponding T-scores calculated using an Australian reference range (ARR) and using the NHANES-III reference range (NH3RR). Reported T-scores (TR) from the DXA centers were compared with T-scores derived from the NH3RR (TNH) and from the ARR (TA). Examination of the regression lines comparing TR with TNH, and TR with TA, demonstrated that the reference ranges used by centers with Lunar, and some of the Norland and Hologic instruments, differed only slightly from both the NH3RR and the ARR. A number of centers, however, with Norland or Hologic scanners, were using reference ranges which differed from both the NH3RR and ARR. The reference ranges used with these latter Hologic or Norland scanners could result in T-score differences of up to I standard deviation in the clinically relevant T-score range. The NH3RR was compared with the ARR using a set of BMD values covering the clinical range. There was close agreement between TNH and corresponding TA, confirming close agreement between the NH3RR and ARR. There are thus clinically important differences in the reference ranges currently used within Australia for interpretation of femoral neck BMD. For consistency, and in view of its validation, the NH3RR is recommended as the most appropriate Caucasian normal range in Australia. The ARR for femoral neck BMD does not differ significantly from the NH3RR and is also acceptable. Problems relating to the use of discordant BMD reference ranges potentially may exist in other countries.

Future methods in the assessment of bone mass and structure.

There have been major advances in the diagnosis of osteoporosis over the last few decades not only in the definitions that are now used but also in the technology that is available. The future will see further development of the techniques currently in common clinical use, such us dual energy X-ray absorptiometry and quantitative ultrasound. In addition new techniques for assessing bone structure, including MRI and fractal analysis of X-rays, may add significantly to our understanding of the pathophysiology of osteoporosis and to the prediction of fracture risk.

Fluorine-18 FDG dual-head gamma camera coincidence imaging of radiation pneumonitis.

A 69-year-old man with inoperable stage I squamous cell carcinoma of the lung underwent a radical course of radiotherapy combined with platinum-based chemotherapy. Fluorine-18 fluorodeoxyglucose (FDG) imaging with a dual-head coincidence gamma camera system (Co-PET) diagnosed radiation pneumonitis 1 month after completion of radiotherapy, when the clinical and radiographic signs were atypical and more suggestive of carcinomatous lymphangitis. Treatment with oral steroids was begun based on FDG scan findings, with prompt clinical benefit as would be expected for radiation pneumonitis.

Potential roles for quantitative ultrasound in the management of osteoporosis.

OBJECTIVE: To assess the validity of four models for the role of quantitative ultrasound (QUS) in the management of osteoporosis. DESIGN: Cross-sectional survey and review of literature. SETTINGS: Nuclear medicine departments of three teaching hospitals in Sydney. SUBJECTS: 1000 women aged 22 to 88 years (mean, 59 years) referred for assessment of osteoporotic fracture risk. MAIN OUTCOME MEASURES: BMD categories as defined by dual-energy x-ray absorptiometry (DEXA) of the lumbar spine and proximal femur, and QUS category as defined by calcaneal ultrasound stiffness; prevalence of DEXA-defined osteoporosis in the different QUS categories. RESULTS: In women with QUS Achilles stiffness < or = 70 the prevalence of axial osteoporosis was 51%, whereas in the group with stiffness > 70 the prevalence of axial osteoporosis was 8%. In women 65 years and over the corresponding values were 59% and 17%. CONCLUSIONS: Of the four possible models for QUS, the use of QUS for the estimation of BMD, or in a "standalone" model, can not be recommended at the current time. The model of QUS as a "prescreening" modality may be acceptable assuming adequate education of clinicians and patients of its limitations, particularly the risk of false negatives. The model of QUS as one factor in a composite risk factor assessment of patients is promising but more data are required.

Temperature dependency of quantitative ultrasound.

Quantitative ultrasound (QUS) parameters are temperature dependent. We examined the effect of temperature on QUS using Lunar Achilles+ and Hologic Sahara units. In vivo studies were performed in a cadaveric foot and in 5 volunteers. QUS scans were performed in the cadaveric foot, using both machines, at temperatures ranging from 15 to 40 degrees C. To assess the effect of change in water bath temperature in the Achilles+, independently of foot temperature, 5 volunteers were studied at water temperatures ranging from 10 to 42 degrees C. In the cadaveric foot there were strong negative correlations between temperature and speed of sound (SOS) but a moderately positive correlation between temperature and broadband ultrasound attenuation (BUA). Stiffness and the Quantitative Ultrasound Index (QUI) in the cadaveric foot showed strong negative correlations with temperature, reflecting their high dependence on SOS. In the 5 volunteers, in whom foot temperature was assumed to be constant, there was a small change in Stiffness in the Achilles+, with variation in water temperature. In conclusion, while there are opposite effects of temperature on SOS and BUA in vivo, there is still a significant effect of temperature variation on Stiffness and the QUI. This may have clinical significance in particular subjects. The precision of QUS may be affected by temperature variation of the environment or of the patient's limb. Instruments utilizing a water bath may be able partly to compensate for changes in environmental temperature, but standardization of water bath temperature is crucial to maximize precision.

Interpretation of bone mineral density measurement and its change.

Bone mineral density (BMD), an important measurable predictor of osteoporotic fractures, is used as a surrogate definition of osteoporosis, and often as an end point in clinical trials. However, BMD is measured with random error and random fluctuation within individuals. This study addresses two specific questions: Given an observed level of BMD for an individual, what is the individual's likely "true" level? To what extent does an observed BMD change reflect a real change? A Bayesian model was formulated to address these questions, using data from the Dubbo Osteoporosis Epidemiology Study, past clinical trials, and a short-term reliability study in individuals ages 60 yr and older. Measurements of lumbar spine and femoral neck BMD by dual X-ray absorptiometry are highly reliable, with coefficients of reliability ranging from 0.90 to 0.99. Consequently, for an individual, there is good agreement between observed and "true" BMD values. However, the 90% confidence interval for the true level in elderly people and those with low measured BMD values is particularly wide. Using the cutoff of 2.5 standard deviations below the young normal mean as a definition of osteoporosis, the rates of false positives and false negatives can be as high as 20% among individuals ages 80 yr and older. In a typical clinical trial with an overall average increase in BMD of 2%, for a subject whose baseline femoral neck BMD is 0.80 g/cm(2), no conclusion of significant change could be drawn until an observed increase of at least 5.5% or an observed decrease of at least 7.5%. If two measurements were taken at baseline and follow-up, the true change could be detected with an observed increase of 3.5% or an observed decrease of 5%. On the other hand, there needs to be an observed increase of 6.2 and 8.5% before one can be 90% certain that a true increase of 2 and 5%, respectively, has occurred in an individual. This analysis suggests that the diagnosis of osteoporosis based on a single measurement of BMD and point estimates of changes in BMD may be inappropriate and unreliable. We propose that the current practice of informing individuals who have BMD measurements about their actual T- and Z-scores be replaced with a system of reporting in which their osteoporosis probability risk category is conveyed. Also, assessment of change in an individual should take into account the overall change in a population.

Quantitative heel ultrasound as a predictor for osteoporosis.

OBJECTIVE: To determine the diagnostic value of quantitative ultrasound (QUS) to predict bone mineral density (BMD) categories as defined by dual-energy x-ray absorptiometry. DESIGN: Cross-sectional survey. SETTING: Rheumatology department of a tertiary care hospital (Royal North Shore Hospital, Sydney, NSW), 1997-1998. SUBJECTS: 326 healthy women aged 45-80 years who had volunteered for a twin study. Our study included both members of non-identical twin pairs but only one randomly selected member of identical twin pairs. MAIN OUTCOME MEASURES: BMD categories as defined by dual-energy x-ray absorptiometry of lumbar spine and left hip, and QUS of calcaneus; sensitivity, specificity and likelihood ratios (LRs) of QUS parameters to diagnose osteoporosis as defined by BMD. RESULTS: The sensitivity of QUS to diagnose BMD osteoporosis varied between 9% and 47%, depending on the QUS parameter. The specificity of QUS was high (88%-100%). If all QUS parameters were normal, osteoporosis was unlikely (LR, 0-0.2). One QUS parameter, broadband ultrasound attenuation (BUA), was highly predictive of osteoporosis by BMD when in the osteoporotic range (LR, infinity), but had low sensitivity (9%). QUS results in the osteoporotic range for other parameters and all QUS results in the osteopenic range were less predictive (LR, 1.0-5.2) of osteoporotic BMD. CONCLUSION: These results suggest that, for most of those tested for osteoporosis by QUS in the community, uncertainty remains about expected BMD.

The potential effect on hip fracture incidence of mass screening for osteoporosis.

With ageing of the Australian population, treatment of osteoporosis-related hip fractures will impose an increasing burden on the healthcare system. Based on current age-adjusted hip fracture incidence and population projections for New South Wales, we estimated a 90% increase in hip fractures by the year 2021. Contributing significantly to this increase will be the number of men reaching the high risk age group for osteoporotic hip fractures. A suggested solution--screening and appropriate therapy for individuals at high risk of osteoporosis--may have only a modest impact. Our calculations show that, even with optimistic screening and therapy compliance rates, hip fractures could still increase by over 50%. Other approaches need to be further explored.

Quantitative diagnostic methods in osteoporosis: a review.

During the last two decades there have been major advances in the understanding of pathophysiology and in the diagnosis of osteoporosis. There are now, in addition to standard radiographs, a number of different diagnostic modalities available to doctors for the quantitative assessment of bone mass. These methodologies are having an increasingly important role, not only in the clinical diagnosis, but also in the monitoring of patients with osteoporosis. As the population ages there will be an increasing demand for these services, and radiologists need to be aware of the strength and limitations of the different modalities available.

Femoral neck axis length, height loss and risk of hip fracture in males and females.

Hip axis length (HAL) has been proposed as an independent predictor of hip fracture risk in Caucasian females. Femoral neck axis length (FNAL) is a similar measure of femoral geometry but does not include acetabular structures. The aim of this study was to examine the association between hip geometry, using FNAL, and hip fractures in elderly males and females in relation to other anthropometric data. The study group comprised 123 females (23 hip fracture patients and 100 age-matched controls) and 137 males (13 hip fracture patients, 65 age-matched controls and 59 current-height-matched controls). All subjects had femoral neck bone mineral density measured by dual-energy X-ray absorptiometry. From these scans, FNAL was measured as the linear distance from the base of the greater trochanter to the apex of the femoral head. FNAL was correlated significantly with current height (r = 0.47 and r = 0.56 for females and males respectively; p < 0.0001) and peak height (r = 0.45 and r = 0.57 for females and males respectively; p < 0.0001) in both sexes. In females, FNAL in the fracture patients (91.5 +/- 5.4 mm, mean +/- SD) was not significantly different from FNAL in controls (89.7 +/- 5.4 mm; p = 0.2). Fracture patients had the same current height as controls and a trend towards a greater peak height (163 +/- 6 cm vs 160 +/- cm; p = 0.09). After adjusting FNAL for current or peak height there was no difference in FNAL between fracture patients and controls. In males, FNAL in the fracture patients (103.9 +/- 3.9 mm) was not significantly different from that of age-matched controls (103.4 +/- 6.3 mm; p = 0.79). Fracture patients had a significantly lower current height (168 +/- 6 cm) than the age-matched controls (174 +/- 6 cm; p = 0.0008) but had the same peak height. When adjusted for peak height there were no significant differences between height of hip fracture patients (102.0 +/- 4.9 cm), age-matched controls (102.1 +/- 5.1 cm) and current-height-matched controls (102.6 +/- 5.3 cm). Fracture patients had a significantly greater height loss (peak height minus current height) than either control group. In logistic regression analyses peak height in females and height loss in males but not FNAL were independent predictors of hip fracture. The greater height, FNAL and presumably HAL in males versus females is not associated with increased hip fracture risk. However, in this study of elderly males and females, peak height (females) and height loss (males) were independent risk factors for hip fracture. Moreover, FNAL appears to have limited utility in the prediction of hip fracture risk and any role of HAL in the prediction of hip fracture does not relate to its major component of femoral neck length.