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(18)F-fluoride positron emission tomography ((18)F-PET) allows the assessment of regional bone formation and could have a role in the diagnosis of adynamic bone disease (ABD) in patients with chronic kidney disease (CKD). The purpose of this study was to examine bone formation at multiple sites of the skeleton in hemodialysis patients (CKD5D) and assess the correlation with bone biopsy. Seven CKD5D patients with suspected ABD and 12 osteoporotic postmenopausal women underwent an (18)F-PET scan, and bone plasma clearance, K i, was measured at ten skeletal regions of interest (ROI). Fifteen subjects had a transiliac bone biopsy following double tetracycline labeling. Two CKD5D patients had ABD confirmed by biopsy. There was significant heterogeneity in K i between skeletal sites, ranging from 0.008 at the forearm to 0.028 mL/min/mL at the spine in the CKD5D group. There were no significant differences in K i between the two study groups or between the two subjects with ABD and the other CKD5D subjects at any skeletal ROI. Five biopsies from the CKD5D patients had single tetracycline labels only, including the two with ABD. Using an imputed value of 0.3 μm/day for mineral apposition rate (MAR) for biopsies with single labels, no significant correlations were observed between lumbar spine K i corrected for BMAD (K i/BMAD) and bone formation rate (BFR/BS), or MAR. When biopsies with single labels were excluded, a significant correlation was observed between K i/BMAD and MAR (r = 0.81, p = 0.008) but not BFR/BS. Further studies are required to establish the sensitivity of (18)F-PET as a diagnostic tool for identifying CKD patients with ABD.

The evaluation of the osseous ankle and foot pathology often poses a clinical and diagnostic challenge because of the complex anatomy and structural biomechanics of the region. Further investigation involves a multimodality imaging approach. Although both structural and functional imaging techniques have their strengths, namely, the high specificity of the former and superior sensitivity of the latter, they also have a number of limitations when used in isolation. These include the inability to determine the functional significance of pathological anatomical abnormalities or to further characterize or localize abnormal metabolic activity. The development of integrated single-photon emission computed tomography/computed tomography systems has aimed to overcome the limitations of separate anatomical and functional imaging techniques. This may be of particular value in ankle and foot assessments, in which multiple joints may be affected by different pathologies. This review article aims to highlight the role of both structural and functional imaging techniques, with particular emphasis on the incremental value of single-photon emission computed tomography/computed tomography in evaluation of this complex anatomical region.

Nuclear medicine has entered a new era of multimodality imaging. Dedicated multislice single-photon emission computed tomography/computed tomography (SPECT/CT) cameras are relatively new additions to the diagnostic armamentarium in nuclear medicine. The integration of SPECT and CT provides precise anatomical localization and may enable characterization of abnormalities identified on planar or SPECT imaging by providing structural information by CT. The evidence in support of SPECT/CT is rapidly amounting but still relatively limited. To date, studies have suggested improved diagnostic confidence and specificity in the diagnosis of bone pathology. The combination of functional information and anatomical localization has the potential to influence medical practice with newer imaging algorithms. This review presents the current evidence and potential indications of SPECT/CT bone imaging in the assessment of benign and malignant conditions.

A common cause of morbidity and mortality in diabetic patients are foot infection/complications often leading to amputation of lower extremities. Various radiological and radionuclide techniques are available for the assessment of diabetic patients with bone or soft tissue infections. However, there are several advantages and limitations. The major limitation of all these techniques is their inability to accurately differentiate osteomyelitis from charcot's/neuropathic joints. Radiologically, magnetic resonance imaging (MRI) is the technique of choice and a radiolobeled white cell scan is a useful nuclear medicine technique in the evaluation of diabetic patients with suspected foot infection. In this review we discuss the efficacy of radiological and radionuclide techniques in the assessment of diabetic foot infection.

Bone scintigraphy is ideally suited for the investigation of benign bone disease as it functions at a physiological level. It is freely available and has whole-body capability and high-contrast resolution. When coupled with single-photon emission computed tomography/computed tomography (SPECT/CT), it can be utilized to provide precise anatomical localization, attenuation correction, and therefore better lesion localization. A considerable volume of data has accumulated on the role of bone scintigraphy in trauma and its complications, overuse injuries, vascular disease of bone, metabolic bone diseases, and a variety of other disorders. This article is an overview of the established applications and signposts of potential future applications with the increasing prevalence of SPECT/CT devices and technical advances in attenuation correction, collimator modeling, and resolution recovery software.

The role of positron emission tomography (PET) in the evaluation and management of skeletal disorders is increasing. A number of reports are available in both benign and malignant disease with a variety of tracers. The bone agent 18F-fluoride can be used to evaluate bone metastases both qualitatively and, for a number of focal and systemic skeletal disorders, quantitatively. 18-Fluorodeoxyglucose is used as a tumor agent in both primary and metastatic bone and bone marrow malignancies; its use has also been described in the evaluation of infection within the skeleton. A possible role for the use of the hypoxia selective tracer 18F-fluoromisonidazole in skeletal infection also exists. This article summarizes the current role of PET in the skeleton with regard to these tracers and diseases.

Patients with a wide variety of rheumatological conditions can be usefully investigated by nuclear medicine techniques and particularly by bone scintigraphy. This aspect of nuclear medicine work is increasing and the trend can be expected to continue. The principal conditions that can be imaged are sports medicine injuries, osteomyelitis, avascular necrosis, reflex sympathetic dystrophy syndrome, enthesopathies and bio-mechanical stress lesions, inflammatory arthropathies, metabolic bone disease and miscellaneous bone conditions such as costo-chondritis. Single photon emission tomography (SPECT) has provided new indications for bone scintigraphy such as the evaluation of spondylolysis and facet syndrome in the spine and of meniscal tears and ligamental lesions.

The isotope bone scan continues to be the most widely performed nuclear medicine investigation in the UK. The detection of skeletal metastases remains the most common clinical indication. However, the use of the bone scan is changing as it becomes subject to cost pressures, competing imaging modalities, and altering clinical indications. Overall, fewer studies are being performed for investigation of skeletal metastases, but this decrease in numbers has been compensated by increasing use in benign orthopaedic conditions. Advances such as correlative imaging and single photon emission computer tomography have increased its value and provided new clinical roles. Quantitation has still not achieved widespread usage, although it continues to be helpful to investigate sacroiliitis. Bone positron emission tomography imaging is now possible, although definite clinical roles have yet to be identified. Bone densitometry using dual x-ray absorptiometry is rapidly increasing in availability and usage throughout the UK, and this can be expected to continue to increase over the next few years.

Patients with a wide variety of orthopaedic disorders can be usefully investigated by nuclear medicine techniques, mostly by bone scintigraphy. Overall this area of nuclear medicine activity is increasing which is a trend that can be expected to continue. The principal conditions that are imaged are fractures and their sequelae, sports medicine injuries and osteomyelitis. However, there are many other orthopaedic problems that are appropriately investigated including biomechanical stress lesions, enthesopathies, avascular necrosis, some bone tumours, arthritidies, metabolic bone disease and nonaccidental injury. Single photon emission computed tomography (SPECT) has provided new indications for bone scintigraphy such as spondylolysis and facet syndrome in the lumbar spine, and meniscal tears in the knee. A role for positron emission tomography (PET) in orthopaedic nuclear medicine has yet to be identified but applications can be expected.

Five cases are presented in which lesions in the ribs were first detected on bone scanning. In all cases routine radiology was normal and the bone scans were of value in obtaining either the correct diagnosis or defining the extent of disease.

Certain easily recognisable features are commonly seen in the bone scans of patients with metabolic bone disorders. Seven such features have been numerically graded by three independent observers in the scans of 100 patients with metabolic bone disease and of 50 control subjects. The total score for each patient is defined as the metabolic index. The mean metabolic index for each group of patients with metabolic bone disease is significantly greater than that for the control group (P less than 0.001).

The influence of sternal marrow aspiration, iliac crest marrow aspiration, and iliac crest bone biopsy on bone scan appearances was examined. Eighteen patients were scanned a mean of 9.9 days after sternal marrow aspiration with a Salah needle (diameter 1.2 mm). Only one patient had an abnormality at the biopsy site. Bone scans obtained in 9 patients a mean of 10 days after iliac crest trephine marrow biopsy with a Jamshidi needle (diameter 3.5 mm) showed no abnormality at the biopsy site. In 18 patients with metabolic bone disease who had undergone iliac crest bone biopsy with an 8-mm needle, a scan abnormality due to the biopsy was usually present when the interval between the biopsy and the scan was 5 days to 2 months. Patients who were scanned within 3 days of iliac crest bone biopsy or more than 2 months after biopsy had normal scan appearance at the biopsy site.

99mTc diphosphonate bone scanning has proved to be a sensitive, though nonspecific, way of detecting a wide variety of metabolic bone disorders. Classic scan appearances of generalized increased tracer uptake throughout the skeleton are found in many types of metabolic bone disease, and whole-body retention measurements can be used to detect early forms of disease. Focal disease identified on bone scanning such as pseudofractures and brown tumors are clearly identified on the 99mTc diphosphonate bone scan, with isotope scan changes preceding radiological changes by up to 18 months. The use of whole-body retention measurements will further increase sensitivity of detection in patients with metabolic bone disease.

The bone scan is generally recognized to be an extremely powerful investigational tool in the evaluation of patients with skeletal disease. Currently 99mTc-methylene diphosphonate is the most widely used bone scanning agent, but recently several new diphosphonate compounds have been introduced which appear to have relatively higher skeletal affinity, leading to greater absolute uptake of tracer by bone. While the resulting improved contrast between bone and background soft-tissue may provide more pleasing scan images, it is not clear that increased bone uptake of tracer is equally desirable for identification of disease. Nevertheless, to date, no significant difference in lesion detection has been found in any comparative study of diphosphonate compounds. In this review the clinical studies evaluating diphosphonate bone scanning agents are summarized and the properties required of an ideal bone scanning agent in both benign and malignant disease discussed.

Radioisotopic bone scanning using technetium-99m labelled phosphate and diphosphonate compounds is a relatively new method of imaging the skeleton which has rapidly assumed major clinical importance. In this review of pathophysiology of bone uptake of radiopharmaceutical, the relative sensitivity of bone scan and radiograph, and the more important uses of bone scanning in clinical practice are described.

The limited role of bone scanning in the diagnosis of metabolic bone disease might be considerably improved by accurate quantification of skeletal uptake of the radiopharmaceutical. Using a standard shadow-shield whole-body monitor, we have measured whole-body retention (WBR) of Tc-99m HEDP up to 24 hr in 11 patients with renal osteodystrophy (mean WBR 88.6% at 24 hr); in ten patients with Paget's disease (mean 56.9%); in seven patients with osteomalacia (mean 40.7%); in five patients with primary hyperparathyroidism (mean 50.7%); in four patients with osteoporosis (mean 21.2%); and in 12 normals (mean 19.2%). The osteoporotic group could not be differentiated from the normal group, but the other groups were significantly different from the normal group at 24 hr (p less than 0.002), and each individual rest for the 24-hr WBR of Tc-99m HEDP in these groups lay outside our normal range. This test may, therefore, provide a sensitive means of detecting conditions with increased bone turnover. We obtained measurements of plasma activity of Tc-99m HEDP in these patients up to 24 hr, and 4-hr bone to soft-tissue ratios from bonescan images, but little additional information resulted.

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/m2, 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/m2 (−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. [ABSTRACT FROM AUTHOR]

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 anin vivocross-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 ranger= 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/cm2 for the femoral neck to 0.060 g/cm2 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. [ABSTRACT FROM AUTHOR]

The menopause has a large effect on bone density, and hormone replacement therapy (HRT) has been shown to be an effective treatment for preventing postmenopausal bone loss. The aim of this study was to compare the effects of HRT use on speed of sound (SOS) measurements at the radius, tibia, phalanx, and metatarsal with bone mineral density (BMD) measurements of the lumbar spine and proximal femur. The study population consisted of 278 healthy premenopausal women, 194 healthy postmenopausal women, and 126 healthy postmenopausal women currently receiving HRT for one or more years. SOS measurements were taken at the radius, tibia, phalanx, and metatarsal using the Sunlight Omnisense, and BMD measurements at the lumbar spine and proximal femur using Hologic QDR-4500 densitometers. Z-scores were calculated using the postmenopausal control group. Z-score differences between the postmenopausal controls and HRT group, for the entire group and with the HRT group subdivided into three groups based on duration of HRT usage, were calculated. Significant postmenopausal bone loss was found for all SOS and BMD measurements. A positive effect of HRT usage was found for all SOS measurement sites and lumbar spine BMD, although only the radius and tibia SOS and lumbar spine BMD reached statistical significance. The Z-score differences between the two groups were 0.44, 0.37, 0.15, and 0.26 for the radius, tibia, phalanx, and metatarsal SOS respectively, and 0.28, 0.00, and -0.03 for the lumbar spine, femoral neck, and total hip BMD respectively. A clear effect of the duration of HRT use was seen for the radius measurements, the differences being less marked elsewhere. In conclusion, these results demonstrate a positive effect of HRT on SOS measurements at the radius and tibia and BMD measurements of the lumbar spine. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine whether calcaneal quantitative ultrasound can discriminate between women with and those without fragility fracture at (1) the wrist or (2) at sites other than the spine, hip, or forearm, as well as axial DXA measurements of BMD can. The study population consisted of 342 postmenopausal Caucasian women who were placed into one of three groups: (1) healthy women with no clinical risk factors for osteoporosis (n = 240); (2) women with a history of atraumatic fracture at the wrist (n = 50); (3) women with a history of atraumatic fracture at a skeletal site other than the spine, hip, or wrist (n = 52). Subjects had DXA measurements of the lumbar spine (LS), femoral neck (FN), and total hip (THIP), and calcaneal broadband ultrasound attenuation (BUA) and speed of sound (SOS) measurements on the Hologic Sahara (s) and Osteometer DTUone (d). Z-scores were calculated using the mean and SD obtained from the healthy postmenopausal group. All the BMD and QUS variables were significantly reduced in women reporting a fracture of the wrist or at a site other than the spine, hip, or forearm. When the group of women with a history of wrist fracture were compared with the postmenopausal controls, age-adjusted logistic regression yielded odds ratios associated with a 1 SD decrease, that were significant for both BMD and QUS, averaging 2.2. The AUC values ranged from 0.65 for FN BMD to 0.75 for BUAd. BMD and QUS measurements were also significantly reduced in women reporting a skeletal fracture at a site other than the spine, hip, or wrist, and odds ratios for BMD and QUS were significant, averaging 1.7. BMD and QUS showed similar fracture discriminatory abilities that were not significantly different from one another. In conclusion, calcaneal QUS can discriminate between women with and those without fracture at the wrist or at sites other than the spine, hip, or forearm as well as axial DXA measurements of BMD can. [ABSTRACT FROM AUTHOR]

: This study evaluated the clinical utility of a new multisite ultrasound device capable of measuring speed of sound (SOS) at the phalanx, radius, tibia and metatarsal. The in vitro and in vivo short- and long-term precision were evaluated, reference data were collected for 409 healthy white women (236 premenopausal and 173 postmenopausal), and age and menopause related changes were calculated using linear regression. Fracture discrimination was evaluated using 109 women with vertebral fractures and the age-adjusted odds ratios calculated for each standard deviation decrease in SOS measurement. Correlations between SOS measurements and spine and femur bone mineral density (BMD) were calculated. T-score equivalence with BMD was also investigated together with the prevalence of osteoporosis as defined by the WHO criteria. The in vivo short-term precision standardized in T-score units ranged from 0.14 to 0.33 and long-term standardized precision was 0.35–0.65. Postmenopausal age-related bone loss expressed as the annual change in T-score ranged from 0.040 to 0.089 for SOS and 0.053 to 0.066 for BMD, whilst menopause-related annual loss ranged from 0.036 to 0.094 for SOS and 0.050 to 0.074 for BMD. Correlations between the different SOS sites ranged from r= 0.24 to 0.55, and between SOS and BMD from r= 0.12 to 0.47. The odds ratio (and 95% confidence intervals) for fracture per 1 SD decrease in SOS were 2.0 (1.22 to 3.23) for the phalanx; 1.5 (1.01 to 2.24) for the metatarsal; 1.4 (1.03 to 1.99) for the radius and 1.2 (0.87 to 1.66) for the tibia. Odds ratios for BMD in the same population ranged from 2.6 to 4.8 (1.70 to 8.29). The prevalence of osteoporosis as defined by T= <–2.5 in the age range 60–69 ranged from 7.1% to 20.6% for SOS and 6.4% to 12.1% for BMD. In conclusion, this study demonstrated that multisite ultrasound has adequate precision for investigating skeletal status, is capable of differentiating between pre- and postmenopausal women and women with vertebral fractures, has a T-score equivalence similar to that of dual-energy X-ray absorptiometry (DXA), and appears to be a promising new technique for evaluating skeletal status at clinically relevant sites. [ABSTRACT FROM AUTHOR]

: The widespread availability of quantitative ultrasound (QUS) and X-ray absorptiometry densitometers raises the question of whether a combination of QUS and bone mineral density (BMD) measurements could provide a clinically useful method of enhancing the prediction of fracture risk. The aim of this study was to examine whether a combination of axial BMD and calcaneal QUS measurements can enhance fracture discrimination compared with either method alone. The study population consisted of 154 postmenopausal women with a history of atraumatic fracture at the spine, hip or forearm and 221 healthy postmenopausal women with no clinical risk factors for osteoporosis. Subjects had dual-energy X-ray absorptiometry (DXA) measurements of the lumbar spine (LS), femoral neck (FN) and total hip (THIP) and calcaneal broadband ultrasound attenuation (BUA) and speed of sound (SOS) measurements on the Hologic Sahara (SAH) and Osteometer DTUone (DTU). Z-scores were calculated using the mean and SD obtained from the healthy postmenopausal group. Logistic regression analysis yielded odds ratios for BMD measurements at the LS, FN and THIP of 2.2, 2.2 and 2.3, respectively. The odds ratios obtained for QUS measurements ranged from 2.5 for DTU BUA to 3.3 for SAH SOS. While these odds ratios for QUS measurements were higher than those obtained for BMD measurements, the differences were not statistically significant. When the odds ratios for QUS were adjusted for BMD at the spine and hip, the odds ratios remained significant in all cases indicating that QUS and BMD variables contribute independently to fracture discrimination. When the BMD-adjusted odds ratios were compared with those for QUS alone, they were slightly lower but not significantly so. When the QUS measurements were adjusted for THIP BMD, the odds ratios for QUS tended to be lower than when adjusted for LS and FN BMD. The Z-scores for each of the QUS measurement variables were combined with spine or hip Z-scores. Logistic regression analysis of the QUS and BMD combined Z-scores yielded slightly higher odds ratios of approximately 3.1 (compared with 2.9 obtained for QUS alone) and increases in the area under the curve of approximately 2%. However, these increases were not clinically significant. In conclusion, the combination of axial BMD and calcaneal QUS measurements did not significantly improve fracture discrimination compared with either method alone. [ABSTRACT FROM AUTHOR]

: Vertebral morphometry, the quantification of vertebral body shape, has proved a useful tool in the identification and evaluation of osteoporotic vertebral deformities in both epidemiologic surveys and clinical trials. Although conventionally it has been performed on lateral radiographs of the thoracolumbar spine (morphometric radiography, MRX), it may now be accomplished on morphometric X-ray absorptiometry (MXA) scans, acquired on dual-energy X-ray absorptiometry (DXA) machines. In this study the long-term precision of vertebral height measurement using MXA and MRX was directly compared. Initially 24 postmenopausal women were recruited (mean age 67 ± 5.8 years): 12 normal subjects (group 1) and 12 with osteoporosis and known vertebral deformities (group 2). Each subject attended for a baseline visit at which they had a MXA examination and lateral thoracic and lumbar radiographs. Twenty-one subjects then returned 1.7 ± 0.4 years later (10 subjects from group 1 and 11 from group 2) for a follow-up visit to repeat both the MXA scans and conventional radiographs. The baseline MXA scans and conventional radiographs were each analyzed quantitatively by two observers in a masked fashion, using a standard six-point method. The follow-up images were then analyzed by the same observers. The MRX observers were masked to the baseline analyses, while the MXA observers utilized the manufacturer’s ‘compare’ facility. On all scans and radiographs anterior (Ha), mid (Hm) and posterior (Hp) vertebral heights were measured and wedge (Ha/Hp) and mid-wedge (Hm/Hp) ratios calculated for each vertebral body, ideally from T4 to L4. MRX analyzed 129 of the 130 available vertebrae in group 1 at both visits and 141 of the 143 available in group 2, while MXA analyzed 124 vertebrae in group 1 at both visits and 127 in group 2. Intra- and inter-observer precision errors, particularly in terms of coefficient of variation (CV%), were larger for MXA than for MRX in both normal subjects and those with vertebral deformities. For example, intra-observer precision errors for vertebral height measurement were 0.62 mm (2.9%) for MXA compared with 0.63 mm (2.2%) for MRX in group 1 (normal) subjects and 0.82 mm (4.2%) for MXA compared with 0.85 mm (3.3%) for MRX for group 2 (osteoporosis and vertebral deformities) subjects. Both MXA and MRX inter-observer precision was clearly poorer than the intra-observer precision, a problem associated with any morphometric technique. This was particularly noticeable for MXA; for example, precision of vertebral height measurement in group 1 subjects was 0.62 mm (2.9%) for intra-observer compared with 0.99 mm (4.6%) for inter-observer analyses. MXA and MRX intra- and inter-observer precision was significantly poorer for subjects with vertebral deformities compared with those without, with the CV% for subjects with vertebral deformity approximately 50% greater than that of normal subjects. For example, MRX intra-observer precision for the mid-wedge ratio was 2.6% for group 1 subjects compared with 3.8% for group 2 subjects. The precision of vertebral height measurement on deformed vertebrae of group 2 subjects was poorer than that for normal vertebrae in the same subjects using both MXA and MRX, as a result of increased variability in point placement. For example, MXA intra-observer precision (RMS SD) for the wedge ratio precision was 0.037 (3.9%) for normal vertebrae compared with 0.060 (6.6%) for deformed vertebrae. We conclude that MXA precision was generally poorer than MRX, although both techniques were adversely affected by the presence of vertebral deformities and the use of more than one observer. Although precision errors for both techniques were substantially smaller than the 20–25% reduction in vertebral height frequently proposed to identify incident deformities, the poorer precision of MXA may lead to an increased risk of erroneous classification of vertebrae as normal or deformed. [ABSTRACT FROM AUTHOR]

: 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. [ABSTRACT FROM AUTHOR]

: 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. [ABSTRACT FROM AUTHOR]

: 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 ≤–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. [ABSTRACT FROM AUTHOR]

: 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. [ABSTRACT FROM AUTHOR]