Thyroglobulin flare response after radioiodine ablation in 2 patients with differentiated thyroid cancer.

Serum thyroglobulin (Tg) measurement facilitates monitoring differentiated thyroid cancer. We describe 2 patients with papillary thyroid cancer who developed dramatic transient serum Tg level elevations within 1 week of I radioiodine (RAI) ablation without cancer recurrence on follow-up. The first patient received recombinant human thyroid-stimulating hormone injections. The pre-injection Tg level was 3.8 µg/L and increased to 3060 µg/L 3 days post-RAI. In the second patient, the serum Tg level increased from 1.3 µg/L to 209.9 µg/L 7 days after RAI. This transient early serum Tg "flare response" could be misleading if interpreted as suggesting more extensive high-risk thyroid cancer.

Urinary Iodine Clearance following Iodinated Contrast Administration: A Comparison of Euthyroid and Postthyroidectomy Subjects.

Purpose. To compare iodine clearance following iodinated contrast administration in thyroidectomised thyroid cancer patients and euthyroid individuals. Methods. A convenience population (6 thyroidectomised thyroid cancer patients and 7 euthyroid controls) was drawn from patients referred for iodinated contrast-enhanced computed tomography (CT) studies. Subjects had sequential urine samples collected up to 6 months (50 samples from the thyroidectomised and 63 samples from the euthyroid groups). t-tests and generalised estimating equations (GEE) were used to test for group differences in urinary iodine creatinine ratios. Results. Groups had similar urinary iodine creatinine ratios at baseline, with a large increase 2 weeks following iodinated contrast (P = 0.005). Both groups had a return of urinary iodine creatinine ratios to baseline by 4 weeks, with no significant group differences overall or at any time point. Conclusions. Thyroidectomised patients did not have a significantly different urinary iodine clearance than euthyroid individuals following administration of iodinated contrast. Both had a return of urinary iodine creatinine ratios to baseline within 4 weeks.

Multimodality imaging of aortic dimensions: comparison of transthoracic echocardiography with multidetector row computed tomography.

BACKGROUND: With recent advances in multimodality cardiac imaging, a number of methods exist for the noninvasive assessment of aortic disease. Although multidetector row computed tomography (MDCT) remains the gold standard for aortic measurements, there are a number of limitations including radiation and contrast-induced nephropathy. Transthoracic echocardiography (TTE) is an alternative to MDCT for providing accurate anatomic assessment of aortic root and ascending aorta dimensions. OBJECTIVES AND METHODS: To determine the accuracy of two-dimensional (2D) TTE for determining aortic measurements in comparison to MDCT, a retrospective study of individuals with varying aortic root and ascending aorta dimensions was performed. RESULTS: There were 116 patients (77 males, mean age 49 ± 12 years) in total. The maximum aortic diameters by 2D TTE were 26.1 ± 4.3 mm (annulus), 32.4 ± 5.6 mm (sinuses), 30.1 ± 5.9 mm (sinotubular [ST] junction), and 33.4 ± 7.3 mm (ascending aorta). The maximum aortic diameters by MDCT were 30.1 ± 4.1 mm (annulus), 35.8 ± 5.8 mm (sinuses), 33.2 ± 5.9 mm (ST junction), and 37.4 ± 7.6 mm (ascending aorta). There was good to excellent correlation between 2D TTE and MDCT at all four levels of the aorta (annulus: r = 0.84; sinuses: r = 0.93; ST junction: r = 0.93; ascending aorta: r = 0.88). There was a consistent underestimation of aortic measurements obtained by 2D TTE when compared to MDCT. CONCLUSION: 2DTTE is a feasible, accurate, and reproducible method for the noninvasive assessment of thoracic aortic diameters as compared to MDCT.

Simplified system for absolute fracture risk assessment: clinical validation in Canadian women.

Absolute 10-yr fracture risk based on multiple factors is the preferred method for risk assessment. A simplified risk assessment system from sex, age, DXA, and two clinical risk factors (CRFs)--prior fracture and systemic corticosteroid (CS) use--has been used in Canada since 2005. This study was undertaken to evaluate this system in the Canadian female population. A total of 16,205 women > or =50 yr of age at the time of baseline BMD (1998-2002) were identified in a database containing all clinical DXA test results for the Province of Manitoba, Canada. Basal 10-yr fracture risk from age and minimum T-score (lumbar spine, femur neck, trochanter, total hip) was categorized as low (<10%), moderate (10-20%), or high (>20%). Health service records since 1987 were assessed for prior fracture codes (N = 5224), recent major CS use (N = 616), and fracture codes after BMD testing (mean, 3.1 yr of follow-up) for the hip, vertebrae, forearm, or humerus (designated osteoporotic, N = 757). Fracture risk predicted from age and minimum T-score alone showed a significant gradient in observed fracture rates (low 5.1 [95% CI, 4.1-6.4], moderate 11.5 [95% CI, 10.1-13.0], high 25.4 [95% CI, 23.2-27.9] per 1000 person-years; p-for-trend <0.0001). There was an incremental increase in incident fracture rates from a prior fracture (13.9 [95% CI, 11.3-16.4] per 1000 person-years) or major CS use (11.2 [95% CI, 4.1-18.2] per 1000 person-years). This simplified fracture risk assessment system provides an assessment of fracture risk that is consistent with observed fracture rates.

10-year probability of recurrent fractures following wrist and other osteoporotic fractures in a large clinical cohort: an analysis from the Manitoba Bone Density Program.

BACKGROUND: Wrist fractures are the most prevalent type of fracture occurring in postmenopausal women. We sought to contrast the probability of recurrent osteoporotic fractures after a primary wrist fracture with other important primary fracture sites. METHODS: A historical cohort study comprising 21,432 women 45 years or older referred for bone mineral density (BMD) testing. Longitudinal health service records were assessed for the presence of fracture codes before and after BMD testing (359,737 person-years of observation). RESULTS: A total of 2652 women (12.4%) experienced a primary fracture (wrist, vertebra, humerus, hip) prior to BMD testing, of which wrist fractures were the largest single group (1225 [46.2%]). The adjusted hazard ratio (HR) for recurrent osteoporotic fracture following a primary wrist fracture (HR, 1.58; 95% confidence interval [CI], 1.29-1.93) was lower than for other primary fractures (HR, 2.66; 95% CI, 2.30-3.08). Primary wrist fractures were not significantly associated with subsequent hip fractures (adjusted HR, 1.29; 95% CI, 0.88-1.89), whereas other primary fracture sites were individually and collectively significant predictors of future hip fractures (HR, 1.72; 95% CI, 1.31-2.26). The 10-year probability of any recurrent fracture after a primary wrist fracture was 14.2% (95% CI, 11.9%-16.5%), which was significantly less than for other primary fractures (spine, 25.7%; hip, 24.9%; humerus, 23.7%; P < .001 for all comparisons vs wrist) but greater than in those without prior fractures (10.8%; P < .001). The relationship between BMD and fracture risk was much stronger after a primary wrist fracture (HR, 2.20 per standard deviation; 95% CI, 1.70-2.80) than after other primary osteoporotic fractures (HR, 1.21; 95% CI, 1.05-1.40), reflecting the dominance of the other fracture information over BMD. CONCLUSIONS: Wrist fractures are the most common of the clinical osteoporotic fractures in patients referred for BMD testing. However, the risk of recurrent fractures in the 10 years following a wrist fracture is substantially lower than that following other osteoporotic fractures, although it remains significantly higher than for those who have yet to experience a fracture.

Validation of ten-year fracture risk prediction: a clinical cohort study from the Manitoba Bone Density Program.

INTRODUCTION: Absolute 10-year fracture risk is the preferred method for fracture risk assessment. The validity of applying published fracture rates from one population to another population is uncertain. METHODS: 20,579 women age 47.5 years or older at the time of baseline femoral neck bone mineral density (BMD) were identified in a database containing all clinical DXA results for the Province of Manitoba, Canada. Individual 10-year fracture risk was predicted from age-only and age plus femoral neck T-score using published 10-year fracture risk for Swedish women. Health service records were assessed for the presence of non-trauma 'osteoporotic' fracture codes (hip, clinical spine, wrist, humerus) subsequent to BMD testing (86,447 person-y follow up, 1173 patients with osteoporotic fractures). Fracture rates were derived for subgroups stratified by age (5-year strata) and estimated risk (5% strata). 10-year fracture rates were computed directly by the Kaplan-Meier method (10-year continuous data) and by the actuarial method (two 5-year periods with adjustments for aging, death and expected BMD loss). RESULTS: Direct and actuarial methods gave nearly identical point estimates, but the latter were more precise. There was a strong linear correlation between predicted and observed fracture rates based upon age-only (r = 0.95) and age plus BMD (r = 0.99). For age strata 50 to 75, and for estimated risk strata from 0-5% to 20-25%, the confidence intervals overlapped the line of identity. For women age >77.5 or estimated risk >25%, observed exceeded estimated fracture rates. This is explained by healthy selection bias whereby elderly women referred for BMD testing have lower mortality than expected, hence more years at risk for fracture. Corrected for survival bias, women age >77.5 had observed fracture rates no different than predicted. CONCLUSION: Swedish 10-year fracture risk data are generally applicable to the Canadian female population referred for clinical BMD testing, though fracture rates were underestimated in the oldest and highest risk subgroups due to healthy selection bias.

Effect of total hip bone area on osteoporosis diagnosis and fractures.

DXA is affected by skeletal size, with smaller bones giving lower areal BMD despite equal material density. Whether this size effect confounds the use of BMD as a diagnostic and fracture risk assessment tool is unclear. We identified 16,205 women of white ethnicity >or=50 yr of age undergoing baseline hip assessment with DXA (1998-2002) from a population-based database that contains all clinical DXA test results for the Province of Manitoba, Canada. Total hip measurements were categorized according to quartile in total hip bone area (Q1 = smallest, Q4 = largest). Longitudinal health service records were assessed for the presence of nontraumatic osteoporotic fracture codes during a mean of 3.2 yr of follow-up after BMD testing (757 osteoporotic fractures, 186 hip fractures). Total hip bone area strongly affected osteoporosis diagnosis with much higher rates in Q1 (14.4%) than Q4 (8.9%). However, incident fracture rates were constant across all area quartiles, and prevalent fractures were paradoxically fewer in smaller area quartiles (p < 0.001 for trend). Age was a potential confounder that correlated positively with area (r = 0.12, p < 0.0001). When age was not included in a Cox regression model, Q1 seemed to have a lower rate of incident osteoporotic fractures (HR = 0.80, 95% CI = 0.66-0.98, reference Q4) and hip fractures (HR = 0.63, 95% CI = 0.43-0.94) for a given level of BMD. In age-adjusted regression models, total hip BMD was strongly predictive of incident osteoporotic fractures (HR per SD = 1.83, 95% CI = 1.68-1.99) and hip fractures (HR per SD = 2.80, 95% CI = 2.33-3.35), but there was no independent effect of bone area (categorical or continuous). Nested matched subgroup analysis and ROC analysis confirmed that bone area had no appreciable effect on incident fractures. We conclude that total hip areal BMD categorizes a substantially higher fraction of women with smaller bone area as being osteoporotic despite younger age. Incident fracture rates correlate equally well with BMD across all bone area quartiles when adjusted for age.

Low bone mineral density and fracture burden in postmenopausal women.

BACKGROUND: The study objectives were to determine fracture rates in relation to bone mineral density at various central skeletal sites, using the World Health Organization definition for osteoporosis (T-score -2.5 or less), and to contrast fracture patterns among women 50 to 64 years of age with those among women 65 years of age and older. METHODS: Historical cohort study with a mean observation period of 3.2 (standard deviation [SD] 1.5) years. The study group (16,505 women 50 years of age or older) was drawn from the Manitoba Bone Density Program database, which includes all bone mineral density results for Manitoba. Baseline density measurements for the lumbar spine and hip were performed with dual-energy x-ray absorptiometry. Outcomes included the percentage of osteoporotic fractures and the rates of fracture and excess fracture (per 1000 person-years) among postmenopausal women with osteopenia and osteoporosis relative to those with normal bone mineral density (according to the classification of the World Health Organization). RESULTS: The mean age was 65 (SD 9) years, and the mean T-scores for all sites fell within the osteopenic category. There were 765 incident fractures (fracture rate 14.5 [95% confidence interval, CI, 13.5-15.6 [per 1000 person-years). Fracture rates were significantly higher among women 65 years of age or older than among women 50-64 years of age (21.6 [95% CI 19.7-23.4] v. 8.6 [95% CI 7.5-9.7] per 1000 person-years, p < 0.001). Although fracture rates were significantly higher among women with osteoporotic T-scores, most fractures occurred in women with nonosteoporotic values (min-max: 59.7%-67.8%). INTERPRETATION: In this study, most of the postmenopausal women with osteoporotic fractures had nonosteoporotic bone mineral density values. This finding highlights the importance of considering key clinical risk factors that operate independently of bone mineral density (such as age) when assessing fracture risk.

Single-site vs multisite bone density measurement for fracture prediction.

BACKGROUND: Bone density measurement with dual-energy x-ray absorptiometry is widely used for fracture risk assessment. Discordance between measurement sites is common, but it is unclear how this affects fracture prediction. METHODS: We performed a historical cohort study among 16 505 women 50 years or older at the time of baseline dual-energy x-ray absorptiometry of the spine and hip (mean +/- SD observation period, 3.2 +/- 1.5 years). The study population was drawn from a database that contains all clinical dual-energy x-ray absorptiometry test results for the province of Manitoba, Canada. Each subject's longitudinal health service record was assessed for the presence of fracture codes after bone density testing. The likelihood ratio test was used to assess the improvement in fracture prediction from Cox proportional hazards models using bone density covariates from a single site or from combined sites. RESULTS: Age-adjusted hazard ratios (HRs) per standard deviation for osteoporotic fracture ranged from 1.61 (95% confidence interval [CI], 1.39-1.87) for the lumbar spine to 1.85 (95% CI, 1.70-2.01) for the total hip, with intermediate values for the femur neck (HR, 1.76 [95% CI, 1.62-1.92]) and trochanter (HR, 1.77 [95% CI, 1.63-1.92]). For fracture prediction, use of the minimum bone density measurement was no better than use of a hip measurement alone. When the total hip measurement was included in a fracture prediction model for the overall population, none of the other measurements added substantial information. The spine was the most useful site for the prediction of spine fractures alone. CONCLUSIONS: Proximal femur bone density measurements consistently outperformed lumbar spine measurements for global fracture prediction. In this cohort, the total hip was the best site for overall fracture assessment.

Exclusion of focal vertebral artifacts from spine bone densitometry and fracture prediction: a comparison of expert physicians, three computer algorithms, and the minimum vertebra.

UNLABELLED: Expert physicians and automated methods for the exclusion of vertebral levels in DXA scans containing focal artifacts were compared. All methods of vertebral exclusion led to a small improvement in fracture prediction. Computer algorithms performed at least as well as physicians. INTRODUCTION: Lumbar spine DXA is often confounded by focal artifacts. Clinical rules and automated methods for vertebral exclusion have been proposed, but their concordance, effect on diagnosis, and fracture prediction is unknown. MATERIALS AND METHODS: We analyzed clinical DXA scans of the lumbar spine (20,478 women and 1534 men) performed from 1998 to 2002 (Province of Manitoba, Canada). Longitudinal health service records were assessed for the presence of nontrauma fracture codes after BMD testing. The effect of vertebral exclusions by expert physicians and several automated methods on diagnosis and prediction of incident fractures was compared. RESULTS: Vertebral exclusions were reported by physicians in over one quarter of the scans (31% of women and 29% of men). All methods of vertebral exclusion significantly decreased the mean spine T-score and increased the proportion of women designated as osteoporotic. kappa values and ROC area under the curve (AUC) for physician-computer agreement in the identification of abnormal scans indicated fair to moderate agreement in both women and men. Compared with no vertebral exclusions, a small increase in the hazard ratio and AUC for spine fracture and osteoporotic fracture prediction was seen after physician and computer exclusions. Compared with physician exclusions, AUC for prediction of osteoporotic fractures in men increased significantly with one computer algorithm (p = 0.004). The minimum vertebral T-score enhanced fracture prediction compared with no exclusions but approximately doubled the prevalence of osteoporotic categorization. CONCLUSIONS: We observed fair to moderate agreement between the physician and computer methods for vertebral level exclusion. All methods of vertebral exclusion led to a small improvement in fracture prediction using the lumbar spine measurement. The automated algorithms performed at least as well as physicians when fractures were used as the endpoint.

Effectiveness of bone density measurement for predicting osteoporotic fractures in clinical practice.

CONTEXT: Bone density measurement with dual-energy x-ray absorptiometry is widely used for fracture risk assessment. It has not been established that published gradients of fracture risk from study populations can be directly applied to clinical populations. OBJECTIVE: The objective of the study was to assess osteoporotic fracture prediction with dual-energy x-ray absorptiometry in a large clinical cohort. DESIGN: This was a historical cohort study (mean observation period 3.2 +/- 1.5 yr). PATIENTS: The study population was drawn from the population-based database of the Manitoba Bone Density Program. Analyses were limited to women aged 50 yr or older at baseline (n = 16,505). MAIN OUTCOME MEASURE: Each subject's longitudinal health service record was assessed for the presence of nontrauma fracture codes (hip, spine, wrist, and humerus) after bone density testing. Age-adjusted hazard ratios for fracture were derived from Cox proportional hazards models. RESULTS: Site-specific and overall fracture rates were significantly associated with each site of bone density measurement (all P < 0.00001). The 95% confidence intervals overlapped those from a widely cited metaanalysis of fracture prediction from different sites. Although fracture prediction was not significantly different between the three hip measurement sites, each hip site was better than the lumbar spine for predicting overall fractures (nonoverlapping 95% confidence intervals). The manufacturer sd (equivalent to a unit change in T-score) resulted in a significantly smaller gradient of risk for the spine than when the population sd was used. CONCLUSIONS: Bone density measurements are effective for predicting fractures in clinical practice. However, hip measurements were superior to the spine in overall osteoporotic fracture prediction.

Number of osteoporotic sites and fracture risk assessment: a cohort study from the Manitoba Bone Density Program.

UNLABELLED: Site-discordance in BMD assessment is common and significantly affects patient categorization. Greater number of osteoporotic sites correlates with lower T scores at each index site. This largely explains the positive association between number of osteoporotic sites and fracture risk. INTRODUCTION: Site-discordance in BMD is common when used to classify patients based on a cut-off T score of -2.5. It is unclear whether fracture risk assessment is improved by considering BMD information from multiple sites. Our objective was to assess the contribution of number of osteoporotic sites to overall fracture risk. MATERIALS AND METHODS: The study population was drawn from the regionally based clinical database of the Manitoba Bone Density Program that includes all clinical DXA test results for the Province of Manitoba, Canada. Analyses were limited to 16,505 women>or=50 years of age at the time of baseline DXA of the spine (L1-L4) and hip (three sites). During follow-up (3.2+/-1.5 years), longitudinal health service records showed 765 women with at least one osteoporotic fracture code (hip, forearm, spine, or humerus). RESULTS: Of 5012 women classified as osteoporotic by at least one site (T score -2.5 or lower), almost one half (2370; 47%) were abnormal at only a single site. Among the 1856 women with an osteoporotic total hip measurement, mean total hip T scores decreased as the number of additional osteoporotic sites increased (-2.58, no other osteoporotic sites; -2.69, one other site; -2.87, two other sites; -3.17, three other sites; Spearman r=-0.44, p<0.0001). Age-adjusted fracture risk from a Cox proportional hazards model increased as the number of osteoporotic sites increased (p<0.0001), but number of osteoporotic sites was no longer an independent predictor after total hip BMD was included as a covariate (p=0.19). Covariate adjustment for other sites of BMD measurement attenuated, but did not eliminate, the effect of number of osteoporotic sites. CONCLUSIONS: Site-discordance is common and significantly affects patient categorization when different skeletal sites are used for diagnosis. Greater number of osteoporotic sites correlates with lower T scores at each index site. This largely explains the positive association between number of osteoporotic sites and fracture risk.