Inter-rater variability and repeatability in the assessment of the Tanner-Whitehouse classification of hand radiographs for the estimation of bone age.

OBJECTIVE: To determine which bones and which grades had the highest inter-rater variability when employing the Tanner-Whitehouse (T-W) method. MATERIALS AND METHODS: Twenty-four radiologists were recruited and trained in the T-W classification of skeletal development. The consistency and skill of the radiologists in determining bone development status were assessed using 20 pediatric hand radiographs of children aged 1 to 18 years old. Four radiologists had a poor concordance rate and were excluded. The remaining 20 radiologists undertook a repeat reading of the radiographs, and their results were analyzed by comparing them with the mean assessment of two senior experts as the reference standard. Concordance rate, scoring, and Kendall's W were calculated to evaluate accuracy and consistency. RESULTS: Both the radius, ulna, and short finger (RUS) system (Kendall's W = 0.833) and the carpal (C) system (Kendall's W = 0.944) had excellent consistency, with the RUS system outperforming the C system in terms of scores. The repeatability analysis showed that the second rating test, performed after 2 months of further bone age assessment (BAA) practice, was more consistent and accurate than the first. The capitate had the lowest average concordance rate and scoring, as well as the lowest overall concordance rate for its D classification. Moreover, the G classifications of the seven carpal bones all had a concordance rate less than 0.6. The bones with lower Kendall's W were likewise those with lower scores and concordance rates. CONCLUSION: The D grade of the capitate showed the highest variation, and the use of the Tanner-Whitehouse 3rd edition (T-W3) to determine bone age (BA) was frequently inconsistent. A more comprehensive description with a focus on inaccuracy bones or ratings and a modification to the T-W3 approach would significantly advance BAA.

Assessment of bone densitometry using radiography with a step-wedge phantom: a pilot study of the forearm.

Background: Radiographic absorptiometry (RA) is one of the earliest methods of bone densitometry and has been used to measure the phalanges and metacarpals where soft tissue attenuation is minimal. The aim of this study was to determine whether the technique can be adapted to correct for soft tissue attenuation and measure areal bone mineral density (aBMD) in the forearm. Methods: A total of 51 patients referred for a clinical spine and hip dual-energy X-ray absorptiometry (DXA) examination and 8 young and middle-aged volunteers were recruited to this study. The first 29 participants (20 women, 9 men, aged 61±14 years) served as the training cohort, and the remaining 30 (20 women, 10 men, aged 55±16 years) comprised the validation cohort. All participants underwent a DXA scan of their non-dominant forearm, and a digital X-ray image of the same arm was acquired with a step phantom. Identical regions of interest (ROIs) in the radius and ulna at the one-third radius site were measured on the X-ray and DXA images, and a soft tissue ROI was measured on X-ray images between the radius and ulna. The X-ray measurements in the training cohort were expressed as equivalent step phantom thickness (Eq. SPT) and used to estimate forearm aBMD using a linear equation calibrated against the DXA scans. Estimates of forearm aBMD made from the digital X-ray images acquired in the validation cohort were compared with the results of the DXA scans. Results: Digital X-ray estimates of radius and ulna aBMD at the one-third radius site in the validation cohort showed a good correlation with GE-Lunar iDXA scanner measurements (r=0.795; P<0.001). The Bland-Altman plot had a mean bias of -0.002 g/cm2 and 95% limits of agreement of -0.185 to +0.181 g/cm2. Conclusions: Digital X-ray estimates of proximal forearm aBMD corrected for soft tissue attenuation correlated with DXA measurements with correlation coefficients comparable to those seen for other peripheral bone densitometry technologies.

Is Response Assessment of Breast Cancer Bone Metastases Better with Measurement of 18F-Fluoride Metabolic Flux Than with Measurement of 18F-Fluoride PET/CT SUV?

Our purpose was to establish whether noninvasive measurement of changes in 18F-fluoride metabolic flux to bone mineral (Ki) by PET/CT can provide incremental value in response assessment of bone metastases in breast cancer compared with SUVmax and SUVmeanMethods: Twelve breast cancer patients starting endocrine treatment for de novo or progressive bone metastases were included. Static 18F-fluoride PET/CT scans were acquired 60 min after injection, before and 8 wk after commencing treatment. Venous blood samples were taken at 55 and 85 min after injection to measure plasma 18F-fluoride activity concentrations, and Ki in individual bone metastases was calculated using a previously validated method. Percentage changes in Ki, SUVmax, and SUVmean were calculated from the same index lesions (≤5 lesions) from each patient. Clinical response up to 24 wk, assessed in consensus by 2 experienced oncologists masked to PET imaging findings, was used as a reference standard. Results: Of the 4 patients with clinically progressive disease (PD), mean Ki significantly increased (>25%) in all, SUVmax in 3, and SUVmean in 2. Of the 8 non-PD patients, Ki decreased or remained stable in 7, SUVmax in 5, and SUVmean in 6. A significant mean percentage increase from baseline for Ki, compared with SUVmax and SUVmean, occurred in the 4 patients with PD (89.7% vs. 41.8% and 43.5%, respectively; P < 0.001). Conclusion: After 8 wk of endocrine treatment for bone-predominant metastatic breast cancer, Ki more reliably differentiated PD from non-PD than did SUVmax and SUVmean, probably because measurement of SUV underestimates fluoride clearance by not considering changes in input function.

Quantitative PET Imaging Using (18)F Sodium Fluoride in the Assessment of Metabolic Bone Diseases and the Monitoring of Their Response to Therapy.

Studies of bone remodeling using bone biopsy and biochemical markers of bone turnover measured in serum and urine are important for investigating how new treatments for osteoporosis affect bone metabolism. Positron emission tomography with (18)F sodium fluoride ((18)F NaF PET) for studying bone metabolism complements these conventional methods. Unlike biochemical markers, which measure the integrated response to treatment across the whole skeleton, (18)F NaF PET can distinguish changes occurring at sites of clinically important osteoporotic fractures. Future studies using (18)F NaF PET may illuminate current clinical problems, such as the possible association between long-term treatment with bisphosphonates and atypical fractures of the femur.

The assessment of regional skeletal metabolism: studies of osteoporosis treatments using quantitative radionuclide imaging.

Studies of bone remodeling using bone biopsy and biochemical markers of bone turnover play an important role in research studies to investigate the effect of new osteoporosis treatments on bone quality. Quantitative radionuclide imaging using either positron emission tomography with fluorine-18 sodium fluoride or gamma camera studies with technetium-99m methylene diphosphonate provides a novel tool for studying bone metabolism that complements conventional methods, such as bone turnover markers (BTMs). Unlike BTMs, which measure the integrated response to treatment across the whole skeleton, radionuclide imaging can distinguish the changes occurring at sites of particular clinical interest, such as the spine or proximal femur. Radionuclide imaging can be used to measure either bone uptake or (if done in conjunction with blood sampling) bone plasma clearance. Although the latter is more complicated to perform, unlike bone uptake, it provides a measurement that is specific to the bone metabolic activity at the measurement site. Treatment with risedronate was found to cause a decrease in bone plasma clearance, whereas treatment with the bone anabolic agent teriparatide caused an increase. Studies of teriparatide are of particular interest because the treatment has different effects at different sites in the skeleton, with a substantially greater response in the flat bone of the skull and cortical bone in the femur compared with the lumbar spine. Future studies should include investigations of osteonecrosis of the jaw and atypical fractures of the femur to examine the associated regional changes in bone metabolism and to throw light on the underlying pathologies.

Clinical evaluation of a phalangeal bone mineral density assessment system.

Because osteoporosis is common and usually managed in primary care, there is a requirement for cheap and convenient methods of measuring bone mineral density (BMD). AccuDEXA (Lone Oak Medical Technologies, Doylestown, PA) is a tabletop dual-energy X-ray absorptiometry (DXA) device that performs BMD measurements of the hand in the middle phalanges of the third finger. The aims of this study were to (1) evaluate the use of AccuDEXA in UK women; (2) investigate the concordance between AccuDEXA T-scores and DXA T-scores for central (spine and hip) sites; (3) investigate the comparative response of AccuDEXA measurements to clinical risk factors for osteoporosis. Measurements of phalangeal and central BMD were performed in 620 women referred by their family doctors for bone densitometry (group 1) and 159 healthy female volunteers (group 2). For 65 women in group 2, aged 39 yr or younger, the mean Z-scores for AccuDEXA and the central sites calculated from US reference ranges were consistent with the expected value of 0, whereas for the 62 group 2 women, aged 50 yr or older, the mean Z-scores for AccuDEXA and the central sites were in the range 0.4-0.7 and were statistically significantly different from 0. In both group 1 and group 2, the AccuDEXA T-scores in older and younger women were systematically higher than those in the central sites by up to 1 unit. Of the 157 women aged 50 yr or older, with osteoporosis, based on their central DXA results, only 34 (22%) had an AccuDEXA T-score less than or equal to -2.5, whereas 76 (48%) had osteopenia and 47 (30%) were normal based on their AccuDEXA T-scores. When assessed by the effect of clinical risk factors on Z-scores, both AccuDEXA and central BMD were affected to a similar extent. We conclude that the conventional World Health Organisation T-score criteria for the diagnosis of osteoporosis should not be applied to AccuDEXA measurements in UK women. Clinical risk factors for low BMD were found to affect AccuDEXA measurements to a similar extent as central BMD measurements. AccuDEXA measurements could, therefore, provide an alternative method for identifying individuals with low bone mass, provided care is taken in interpreting T-scores, perhaps, through the use of device-specific thresholds.

Assessment of regional changes in skeletal metabolism following 3 and 18 months of teriparatide treatment.

Teriparatide (TPTD) increases skeletal mass, bone turnover markers, and bone strength, but in vivo effects at individual skeletal sites have not been characterized. Quantitative radionuclide imaging studies reflect bone blood flow and osteoblast activity to assess regional changes in bone metabolism. Changes in bone plasma clearance using technetium-99m methylene diphosphonate ((99m)Tc-MDP) were quantified and correlated with changes in bone turnover markers in 10 postmenopausal women with osteoporosis. Subjects underwent bone scintigraphy at baseline and 3 and 18 months after initiating TPTD 20 microg/day subcutaneously. Subjects were injected with 600 MBq (99m)Tc-MDP, and whole-body bone scan images were acquired at 10 minutes and 1, 2, 3, and 4 hours. Multiple blood samples were taken between 5 minutes and 4 hours after treatment, and free (99m)Tc-MDP was measured using ultrafiltration. The Patlak plot method was used to evaluate whole-skeleton (99m)Tc-MDP plasma clearance (K(bone)) and derive regional bone clearance for the calvarium, mandible, spine, pelvis, and upper and lower extremities using gamma camera counts. Bone turnover markers were measured at baseline and 3, 12, and 18 months. Median increases from baseline in whole-skeleton K(bone) were 22.3% (p = .004) and 33.7% (p = .002) at 3 and 18 months, respectively. Regional K(bone) values were increased significantly in all six subregions at 3 months and in all subregions except the pelvis at 18 months. Bone markers were increased significantly from baseline at 3 and 18 months and correlated significantly with whole-skeleton K(bone). This is the first study showing a direct metabolic effect of TPTD at different skeletal sites in vivo, as measured by tracer kinetics.

Long-term precision of 18F-fluoride PET skeletal kinetic studies in the assessment of bone metabolism.

UNLABELLED: (18)F-Fluoride PET allows noninvasive evaluation of regional bone metabolism and has the potential to become a useful tool for assessing patients with metabolic bone disease and evaluating novel drugs being developed for these diseases. The main PET parameter of interest, termed K(i), reflects regional bone metabolism. The aim of this study was to compare the long-term precision of (18)F-fluoride PET with that of biochemical markers of bone turnover assessed over 6 mo. METHODS: Sixteen postmenopausal women with osteoporosis or significant osteopenia and a mean age of 64 y underwent (18)F-fluoride PET of the lumbar spine and measurements of biochemical markers of bone formation (bone-specific alkaline phosphatase and osteocalcin) and bone resorption (urinary deoxypyridinoline) at baseline and 6 mo later. Four different methods for analyzing the (18)F-fluoride PET data were compared: a 4k 3-compartmental model using nonlinear regression analysis (K(i-4k)), a 3k 3-compartmental model using nonlinear regression analysis (K(i-3k)), Patlak analysis (K(i-PAT)), and standardized uptake values. RESULTS: With the exception of a small but significant decrease in K(i-3k) at 6 mo, there were no significant differences between the baseline and 6-mo values for the PET parameters or biochemical markers. The long-term precision, expressed as the coefficient of variation (with 95% confidence interval in parentheses), was 12.2% (9%-19%), 13.8% (10%-22%), 14.4% (11%-22%), and 26.6% (19%-40%) for K(i-3k), K(i-PAT), mean standardized uptake value, and K(i-4k), respectively. For comparison, the precision of the biochemical markers was 10% (7%-15%), 18% (13%-27%), and 14% (10%-21%) for bone-specific alkaline phosphatase, osteocalcin, and urinary deoxypyridinoline, respectively. Intraclass correlation between the baseline and 6-mo values ranged from 0.44 for K(i-4k) to 0.85 for K(i-3k). No significant correlation was found between the repeated mean standardized uptake value measurements. CONCLUSION: The precision and intraclass correlation observed for K(i-3k) and K(i-PAT) was equivalent to that observed for biochemical markers. This study provided initial data on the long-term precision of (18)F-fluoride PET measured at the lumbar spine, which will aid in the accurate interpretation of changes in regional bone metabolism in response to treatment.

Atypical Paget's disease with quantitative assessment of tracer kinetics.

INTRODUCTION: Paget's disease of bone is characterized by alterations in skeletal metabolism, affecting a single or multiple bones. Paget's is usually confined to an individual bone and typically does not spread or extend across joints. A patient with an unusual pattern of disease is presented together with quantitative assessment of the tracer kinetics pre- and posttreatment. MATERIAL AND METHODS: A 75-year-old lady patient presented to her general practitioner in May 2002 with a history of lethargy. Clinical examination was unremarkable and further investigations such as blood tests (alkaline phosphatase levels), Tc-99m MDP bone scan, biopsy, and CT scan were carried out. RESULTS: Alkaline phosphatase levels were greater than 2000 IU/L (Normal: 31-116 IU/L). The Tc-99m MDP bone scan showed strikingly increased uptake in the central skeleton involving the thoracic vertebrae and the adjoining ribs. The bone biopsy was inconclusive. CT scan revealed symmetrical expansion of the ribs with bridging osteophytes across the ribs and spine. The patient was treated with risedronate and quantitative analysis of the pre- and posttherapy bone scans showed reduced plasma clearance in the pagetic bones. CONCLUSIONS: This case illustrates an unusual distribution of bone lesions in Paget's disease, which we think could be due to the result of degenerative disease leading to bridging and allowing direct extension of disease from one bone to another.