Consensus Statement on Vitamin D Status Assessment and Supplementation: Whys, Whens, and Hows.

The 6th International Conference, "Controversies in Vitamin D," was convened to discuss controversial topics, such as vitamin D metabolism, assessment, actions, and supplementation. Novel insights into vitamin D mechanisms of action suggest links with conditions that do not depend only on reduced solar exposure or diet intake and that can be detected with distinctive noncanonical vitamin D metabolites. Optimal 25-hydroxyvitamin D (25(OH)D) levels remain debated. Varying recommendations from different societies arise from evaluating different clinical or public health approaches. The lack of assay standardization also poses challenges in interpreting data from available studies, hindering rational data pooling and meta-analyses. Beyond the well-known skeletal features, interest in vitamin D's extraskeletal effects has led to clinical trials on cancer, cardiovascular risk, respiratory effects, autoimmune diseases, diabetes, and mortality. The initial negative results are likely due to enrollment of vitamin D-replete individuals. Subsequent post hoc analyses have suggested, nevertheless, potential benefits in reducing cancer incidence, autoimmune diseases, cardiovascular events, and diabetes. Oral administration of vitamin D is the preferred route. Parenteral administration is reserved for specific clinical situations. Cholecalciferol is favored due to safety and minimal monitoring requirements. Calcifediol may be used in certain conditions, while calcitriol should be limited to specific disorders in which the active metabolite is not readily produced in vivo. Further studies are needed to investigate vitamin D effects in relation to the different recommended 25(OH)D levels and the efficacy of the different supplementary formulations in achieving biochemical and clinical outcomes within the multifaced skeletal and extraskeletal potential effects of vitamin D.

Dual-energy X-ray Absorptiometry Trends Among US Medicare Beneficiaries: 2005-2019.

INTRODUCTION: Bone density measured using dual-energy X-ray absorptiometry (DXA) volume, performance site and interpreters have changed in the US since 2005. The purpose of this report is to provide updated trends in DXA counts, rates, place of service and interpreter specialty for the Medicare fee-for-service population. METHODS: The 100 % Medicare Physician/Supplier Procedure Summary Limited Data Set between 2005-2019 was used. DXA counts and annual rates per 10,000 Medicare beneficiaries were calculated. Annual distributions of scan performance location, provider type and interpreter specialty were described. Place of service trends (significance assigned at p < 0.05) of the mean annual share of DXA utilization were identified using linear regression. RESULTS: Annual DXA use per 10,000 beneficiaries peaked in 2008 at 832, declined to 656 in 2015 then increased (p < 0.001) by 38 per year to 807 in 2019. From 2005 to 2019 DXA performance in office settings declined from 70.7 % to 47.2 %. Concurrently, outpatient hospital (OH) DXA increased from 28.6 % to 51.7 %. In 2005, 43.5 % of DXAs were interpreted by radiologists. This increased (p < 0.001) in the office and OH, averaging 0.3 and 2.0 percentage points per year respectively, reaching 73.5 % in 2019. Interpretation by most non-radiologist specialties declined (p < 0.001). CONCLUSIONS: From 2005-2019, total DXA use among Medicare beneficiaries declined reaching a nadir in 2015 then returned to 2005 levels by 2019. Office DXA declined since 2005 with 51.7 % of all scans now occurring in an OH setting. The proportion of DXAs interpreted by radiologists increased over time, reaching 73.5 % in 2019.

Intraoperative physician assessment of bone: correlation to bone mineral density.

This study evaluated the intraoperative physician assessment (IPA) of bone status at time of total knee arthroplasty. IPA was highly correlated with distal femur and overall bone mineral density. When IPA identifies poor bone status, formal bone health assessment is indicated. PURPOSE: Intuitively, intraoperative physician assessment (IPA) would be an excellent measure of bone status gained through haptic feedback during bone preparation. However, no studies have evaluated the orthopedic surgeon's ability to do so. This study's purpose, in patients undergoing total knee arthroplasty (TKA), was to relate IPA with (1) the lowest bone mineral density (BMD) T-score at routine clinical sites; and (2) with distal femur BMD. METHODS: Seventy patients undergoing TKA by 3 surgeons received pre-operative DXA. Intraoperatively, bone quality was assessed on a 5-point scale (1 excellent to 5 poor) based on tactile feedback to preparation. Demographic data, DXA results, and IPA score between surgeons were compared by factorial ANOVA. Lowest T-score and distal femur BMD were associated with IPA using Spearman's correlation. RESULTS: The mean (SD) age and BMI were 65.8 (7.6) years and 31.4 (5.1) kg/m2, respectively. Patient demographic data, BMD, and IPA (mean [SD] = 2.74 [1.2]) did not differ between surgeons. IPA correlated with the lowest T-score (R = 0.511) and distal femur BMD (R = 0.603-0.661). Based on the lowest T-score, no osteoporotic patients had an IPA above average, and none with normal BMD was classified as having poor bone. CONCLUSIONS: IPA is highly correlated with local (distal femur) and overall BMD. This study supports the International Society for Clinical Densitometry position that surgeon concern regarding bone quality should lead to bone health assessment. As IPA is comparable between surgeons, it is logical this can be widely applied by experienced orthopedic surgeons. Future studies evaluating IPA at other anatomic sites are indicated.

Bone Texture Assessment on Lateral VFAs Using the Texture Research Investigational Platform (TRIP) and its Fracture Discrimination Ability.

Texture Research Imaging Platform applies trabecular bone score (TBS) measurement principles to images acquired with multiple modalities to assess bone texture at various skeletal sites. This study aimed to assess the bone texture score in dual-energy X-ray absorptiometry-acquired lateral vertebral fracture assessment (VFA) images (BTSVFA), evaluate its reproducibility, and vertebral fracture discrimination ability. Subjects included 178 VF cases and 178 non-VF controls, 136 women and 42 men in each group, age 55-92 years, from two research centers. Cases and controls were matched for age (±5 years), body mass index (±5 kg/m2) and TBS. All participants underwent dual-energy X-ray absorptiometry TBS assessment from standard posterior-anterior lumbar spine scans and BTSVFA assessment. VF presence was determined using VFA images applying the Genant's method. BTSVFA was lower among fractured women compared to non-fractured (0.626 ± 0.109 vs 0.675 ± 0.099, p < 0.01), but not among men. In a binary logistic regression adjusted for study center and sex, for each SD lower BTSVFA, there was a 40% increase (OR 1.40, 95% CI (1.13-1.74)) in the risk of having a prevalent VF; area under the curve (95% CI) 0.616 (0.557-0.675). Inter-assessor and inter-centers ICCs for BTSVFA measurements were very good; 0.96 (0.64-0.99) and 0.98 (0.95-0.99), respectively. The BTSVFA precision (coefficient of variation) was 2.42%. This feasibility study demonstrates the potential to assess trabecular bone texture in lateral VFA images with good reproducibility. BTSVFA can discriminate between fractured and non-fractured women independent of their age, body mass index and TBS. In conclusion, BTSVFA, a potential trabecular texture assessment that excludes the posterior elements, may have value in fracture prediction or as a novel approach to be further investigated in spine surgery planning.

Best Practice Guidelines for Assessment and Management of Osteoporosis in Adult Patients Undergoing Elective Spinal Reconstruction.

STUDY DESIGN: Expert consensus study. OBJECTIVE: This expert panel was created to establish best practice guidelines to identify and treat patients with poor bone health prior to elective spinal reconstruction. SUMMARY OF BACKGROUND DATA: Currently, no guidelines exist for the management of osteoporosis and osteopenia in patients undergoing spinal reconstructive surgery. Untreated osteoporosis in spine reconstruction surgery is associated with higher complications and worse outcomes. METHODS: A multidisciplinary panel with 18 experts was assembled including orthopedic and neurological surgeons, endocrinologists, and rheumatologists. Surveys and discussions regarding the current literature were held according to Delphi method until a final set of guidelines was created with over 70% consensus. RESULTS: Panelists agreed that bone health should be considered in every patient prior to elective spinal reconstruction. All patients above 65 and those under 65 with particular risk factors (chronic glucocorticoid use, high fracture risk or previous fracture, limited mobility, and eight other key factors) should have a formal bone health evaluation prior to undergoing surgery. DXA scans of the hip are preferable due to their wide availability. Opportunistic CT Hounsfield Units of the vertebrae can be useful in identifying poor bone health. In the absence of contraindications, anabolic agents are considered first line therapy due to their bone building properties as compared with antiresorptive medications. Medications should be administered preoperatively for at least 2 months and postoperatively for minimum 8 months. CONCLUSION: Based on the consensus of a multidisciplinary panel of experts, we propose best practice guidelines for assessment and treatment of poor bone health prior to elective spinal reconstructive surgery. Patients above age 65 and those with particular risk factors under 65 should undergo formal bone health evaluation. We also established guidelines on perioperative optimization, utility of various diagnostic modalities, and the optimal medical management of bone health in this population.Level of Evidence: 5.

Preoperative bone health assessment and optimization in spine surgery.

OBJECTIVE: The purpose of this investigation was to characterize the bone health in preoperative spine surgery patients. This information will provide a framework to understand the needs and methods for providing bone health optimization in elective spine surgery patients. METHODS: A retrospective study of 104 patients undergoing bone health optimization was performed. Patients were selected based on risk factors identified by the surgeon and suspected compromised bone health. Evaluation included history and examination, laboratory investigations, and bone mineral density (BMD) at 3 sites (femoral neck, lumbar spine, and radius). Patients' bone status was classified using WHO criteria and expanded criteria recommended by the National Osteoporosis Foundation (NOF). The 10-year Fracture Risk Assessment Tool (FRAX) scores of the hip and major osteoporotic fracture (MOF) were calculated with and without femoral neck BMD, with spine BMD, and with the trabecular bone score (TBS). Antiresorptive and anabolic agents were provided in accordance with meeting NOF criteria for treatment of osteoporosis. RESULTS: The mean patient age was 69.0 years, and 81% of patients were female. The mean historical height loss was 5.6 cm, and 54% of patients had a history of fracture. Secondary osteoporosis due to chronic renal failure, inflammatory arthritis, diabetes, and steroid use was common (51%). The mean 25-hydroxy vitamin D was 42.4 ng/ml and was normal in 81% of patients, with only 4 patients being deficient. The mean T-scores were -2.09 (SD 0.71) of the femoral neck, -0.54 (1.71) of the lumbar spine, and -1.65 (1.38) of the distal radius. These were significantly different. The 10-year FRAX MOF score was 20.7%, and that for hip fracture was 6.9% using the femoral neck BMD and was not significantly different without the use of BMD. The FRAX risk-adjusted score using the lumbar spine BMD and TBS was significantly lower than that for the hip. Osteoporosis was present in 32.1% according to WHO criteria compared with 81.6% according to NOF criteria. Antiresorptive medications were recommended in 31 patients and anabolic medications in 44 patients. CONCLUSIONS: Surgeons can reliably identify patients with poor bone health by using simple criteria, including historical height loss, history of fracture, comorbidities associated with osteoporosis, analysis of available imaging, and calculation of FRAX score without BMD. High-risk patients should have BMD testing and bone health assessment. In patients with osteoporosis, a comprehensive preoperative bone health assessment is recommended and, if warranted, pharmacological treatment should be started.

Impact of spine-hip discordance on fracture risk assessment and treatment qualification in Canada: the Manitoba BMD registry.

In 50,330 women undergoing bone mineral density (BMD) testing, adjusting FRAX® major osteoporotic fracture (MOF) probability for T-score differences between lumbar spine and femoral neck had a small impact on treatment qualification, with only 1.1% reclassified from below to above the 20% MOF intervention threshold. PURPOSE: Discordance between lumbar spine and femoral neck T-score measurements are frequently encountered in clinical practice. The FRAX tool accepts femoral neck BMD as an optional input but does not consider lumbar spine BMD, though adjustments based upon T-score difference have been proposed. This analysis was undertaken to examine change in treatment qualification using the lumbar spine T-score adjustment to FRAX assuming an intervention threshold of 20% MOF. METHODS: Women aged > 50 years with baseline FRAX MOF probability computed with femoral neck BMD of ≥ 20% but without previous high-risk fracture or high-risk medication use were identified in the province of Manitoba BMD registry. If lumbar spine T-score was lower than the femoral neck T-score, MOF probability was recalculated, and treatment qualification, reassessed. RESULTS: The study population consisted of 50,300 women (mean age 64.2 ± 8.6 years). During mean follow-up of 9.5 years, 4550 sustained incident MOF. The baseline mean T-score difference (femoral neck minus lumbar spine) was - 0.2 ± 1.1. Recalculated MOF probability using the T-score difference significantly improved overall net reclassification index for incident MOF prediction (+ 0.017, p < 0.001). A total of 561 (1.1%) of these women were reclassified from below to above 20% MOF probability based upon the T-score difference. No individuals with MOF probability less than 15% were reclassified to the higher risk category. Risk reclassification increased with lower lumbar spine T-score (15.6% reclassification for lumbar spine T-score of - 3.5 or lower, 4.0% of the study population) and larger T-score differences (9.7% reclassification for T-score difference of 2.5 or more, < 1% of the study population). CONCLUSIONS: Very few women showed risk reclassification based upon adjusting FRAX MOF probability for lumbar spine T-score. Reclassification occurred only in those with baseline MOF probability > 15%.

Osteoporosis treatment considerations based upon fracture history, fracture risk assessment, vertebral fracture assessment, and bone density in Canada.

Among 39,475 women, age 65 years and older, use of fracture history, major osteoporotic fracture (MOF) probability from FRAX®, vertebral fracture assessment (VFA), and bone mineral density (BMD) T-score stratified women into different levels of risk. The majority of women identified as being at high risk from fracture history, FRAX MOF-BMD > 20%, or vertebral fracture on VFA had a BMD T-score in the osteoporotic range. PURPOSE: To inform criteria for pharmacologic treatment in women age 65 years and older, we examined subgroups defined from fracture history, MOF calculated with BMD (MOF-BMD), VFA, and BMD T-score using the population-based Manitoba BMD Program registry. METHODS: The study population consisted of women age > 65 years was divided into mutually exclusive subgroups based upon fracture history, MOF-BMD ≥ 20%, vertebral fracture on VFA, and osteoporotic BMD T-score. Healthcare records were assessed for the presence of fracture diagnosis codes occurring after DXA assessment. For each subgroup, we estimated the proportion of individuals with BMD T-score in the osteoporotic range, predicted versus observed 10-year MOF probability, hazard ratio (HR) for MOF, and number needed to treat (NNT) for 3 years to prevent a fracture event. RESULTS: The study population consisted of 39,475 women (median age 72 years). The majority of women (76.8%) selected as being at high risk based on fracture history, MOF-BMD > 20%, or vertebral fracture on VFA had a BMD T-score in the osteoporotic range. During a median follow-up of 8 years, 5169 (13.1%) sustained one or more incident MOF. Fracture rates and HRs generally paralleled the FRAX prediction, except in women with a positive VFA where predicted risk based upon clinical risk factors prior to VFA underestimated the observed risk. NNT differed by the risk subgroup, and showed a gradient of decreasing NNT (consistent with greater benefit) in individuals with the highest fracture risk. CONCLUSIONS: Fracture history, fracture probability from FRAX, targeted vertebral fracture assessment (VFA), and BMD T-score can stratify older women into different levels of risk and treatment benefit. These results are expected to inform clinical practice guidelines in Canada.

Targeted vertebral fracture assessment for optimizing fracture prevention in Canada.

Vertebral fracture assessment (VFA) provides incremental information in identifying women and men aged 70 years and older qualifying for anti-osteoporosis treatment compared with FRAX® major osteoporotic fracture (MOF) probability computed with bone mineral density (BMD). PURPOSE: This analysis was performed to inform appropriate use of VFA testing as part of Osteoporosis Canada's Guidelines Update, assuming vertebral fracture is an indication for pharmacotherapy in women and men. METHODS: Women and men aged 70 years and older without previous high-risk fracture (i.e., hip, spine, or multiple fractures) were identified in a BMD registry for the province of Manitoba, Canada. MOF probability with BMD was computed using the Canadian FRAX® tool. VFA was performed in those with a minimum BMD T-score of -1.5 or lower. RESULTS: The study population consisted of 7289 women (mean age 76.7 ± 5.6 years) and 1323 men (77.9 ± 5.8 years). More women than men qualified for VFA testing (48.7% vs 25.4%, respectively, p < 0.001). Among those undergoing VFA, a vertebral fracture was more commonly detected among men than women (22.9% vs 13.3%, p < 0.001), and vertebral fracture prevalence increased with lower BMD T-score (both p trend <0.001). The number needed to screen with VFA to detect a vertebral fracture was 8 for women and 4 for men. MOF probability was substantially lower in men than in women, and fewer men than women (3.3% vs 20.2%, p < 0.001) met a treatment threshold of MOF 20% or greater. In those with MOF probability <20%, VFA identified an incremental 5.4% of men and 3.4% of women for treatment based upon vertebral fracture. CONCLUSIONS: The number needed to screen to identify a previously unappreciated vertebral fracture is low and further improves with lower BMD T-score. VFA identified more men as qualifying for treatment than MOF probability. In women, treatment qualification was predominantly from MOF probability.

Non-invasive DXA-derived bone structure assessment of acromegaly patients: a cross-sectional study.

Introduction Impaired bone microarchitecture is involved in vertebral fracture (VF) development among acromegaly patients. Aim of the study Comparison of DXA-derived bone parameters, areal BMD (aBMD), trabecular bone score (TBS) and 3D-SHAPER parameters in acromegaly patients with healthy controls. Methods This cross-sectional study evaluated acromegaly patients and a control group of healthy subjects. In all subjects, a single measurement of pituitary axis hormone levels, bone turnover markers, aBMD, (total hip (TH) and lumbar spine (LS)), TBS and 3D-SHAPER of the proximal femur region was performed. All subjects underwent DXA assessment of VF using the semiquantitative approach. Results One hundred six patients with acromegaly (mean age 56.6 years, BMI 30.2 kg/m2) and 104 control subjects (mean age 54.06 years, 28.4 BMI kg/m2) were included. After adjustment for weight, LS aBMD, TBS and TH trabecular volumetric BMD (vBMD) remained lower (P = 0.0048, <0.0001 and <0.0001, respectively) while cortical thickness (Cth) at TH and neck remained thicker (P = 0.006) in acromegaly patients compared with controls. The best multivariate model (model 1) discriminating patients with and without acromegaly included TBS, TH trabecular vBMD and TH Cth parameters (all P < 0.05). Twenty-two VFs (13 acromegaly subjects) were recognized. In these subjects after adjustment for age, FN aBMD, TH cortical sBMD and TH cortical vBMD remained significantly associated with the prevalent VF (OR = 2.69 (1.07-6.78), 2.84 (1.24-6.51) and 2.38 (1.11-5.10) for neck aBMD, TH cortical sBMD and TH cortical vBMD respectively)). The AUCs were similar for each parameter in this model. Conclusions Acromegaly patients, regardless of VF presence, have lower trabecular bone quantitative parameters, but those with VFs had decreased cortical density.

Combination of DXA and BIS body composition measurements is highly correlated with physical function-an approach to improve muscle mass assessment.

RATIONALE: Fluid volume estimates may help predict functional status and thereby improve sarcopenia diagnosis. MAIN RESULT: Bioimpedance-derived fluid volume, combined with DXA, improves identification of jump power over traditional measures. SIGNIFICANCE: DXA-measured lean mass should be corrected for fluid distribution in older populations; this may be a surrogate of muscle quality. PURPOSE: Sarcopenia, the age-related loss of muscle mass and function, negatively impacts functional status, quality of life, and mortality. We aimed to determine if bioimpedance spectroscopy (BIS)-derived estimates of body water compartments can be used in conjunction with dual-energy X-ray absorptiometry (DXA) measures to aid in the prediction of functional status and thereby, ultimately, improve the diagnosis of sarcopenia. METHODS: Participants (≥ 70 years) had physical and muscle function tests, DXA, and BIS performed. Using a BMI correction method, intracellular water (ICWc), extracellular water (ECWc), and ECWc to ICWc (E/Ic) ratio was estimated from standard BIS measures. Jump power was assessed using jump mechanography. RESULTS: The traditional measure used to diagnose sarcopenia, DXA-derived appendicular lean mass (ALM) corrected for height (ALM/ht2), was the least predictive measure explaining jump power variability (r2 = 0.31, p < 0.0001). The best measure for explaining jump power was a novel variable combining DXA ALM and BIS-derived E/Ic ratio (ALM/(E/Ic); r2 = 0.70, p < 0.0001). ALM/(E/Ic) and ICWc had the highest correlation with jump power and grip strength, specifically jump power (r = 0.84 and r = 0.80, respectively; p < 0.0001). CONCLUSIONS: The creation of a novel variable (ALM/(E/Ic)) improved the ability of DXA to predict jump power in an older population. ALM/(E/Ic) substantially outperformed traditional lean mass measures of sarcopenia and could well be an improved diagnostic approach to predict functional status. DXA-measured ALM should be corrected for fluid distribution, i.e., ALM/(E/Ic); this correction may be considered a surrogate of muscle quality.

Stop the war on DXA!

Dual-energy X-ray absorptiometry (DXA) is a versatile technology that is widely used in clinical practice in the management of osteoporosis and other skeletal diseases. It is a safe and inexpensive procedure that measures bone mineral density (BMD) to diagnose osteoporosis, assess fracture risk, and monitor osteoporosis treatment. However, DXA has been subjected to recurring claims that it is overutilized, too expensive, and not helpful in patient management. In recent years, there has been a decline in the number of office-based DXA facilities, a reduction in BMD tests performed, and fewer women being diagnosed and treated for osteoporosis, despite aging of the population with more people at risk for fractures. Here, we identify some of the challenges to DXA, which in the aggregate amount to a disturbing war on DXA and, as a result, a threat to good patient care. We suggest potential strategies to restore DXA to its proper role in osteoporosis management.

Toward Clarity in Clinical Vitamin D Status Assessment: 25(OH)D Assay Standardization.

Widespread variation in 25-hydroxyvitamin D (25(OH)D) assays continues to compromise efforts to develop clinical and public health guidelines regarding vitamin D status. The Vitamin D Standardization Program helps alleviate this problem. Reference measurement procedures and standard reference materials have been developed to allow current, prospective, and retrospective standardization of 25(OH)D results. Despite advances in 25(OH)D measurement, substantial variability in clinical laboratory 25(OH)D measurement persists. Existing guidelines have not used standardized data and, as a result, it seems unlikely that consensus regarding definitions of vitamin D deficiency, inadequacy, sufficiency, and excess will soon be reached. Until evidence-based consensus is reached, a reasonable clinical approach is advocated.

Childhood socioeconomic status and adult femoral neck bone strength: findings from the Midlife in the United States Study.

PURPOSE: Bone acquisition in childhood impacts adult bone mass, and can be influenced by childhood socioeconomic conditions. Socioeconomic status is also associated with body weight which affects the load that bone is exposed to in a fall. We hypothesized that socioeconomic advantage in childhood is associated with greater bone strength relative to load in adulthood. METHODS: Hip dual x-ray absorptiometry scans from 722 participants in the Midlife in the United States Study were used to measure femoral neck size and bone mineral density, and combined with body weight and height to create composite indices of femoral neck strength relative to load in different failure modes: compression, bending, and impact. A childhood socioeconomic advantage score was created for the same participants from parental education, self-rated financial status relative to others, and not being on welfare. Multiple linear regression was used to determine the association of childhood socioeconomic advantage with femoral neck composite strength indices, stratified by gender and race (white/non-white), and adjusted for study site, age, menopause status in women, education, and current financial advantage. RESULTS: Childhood socioeconomic advantage was independently associated with higher indices of all three composite strength indices in white men (adjusted standardized effect sizes, 0.19 to 0.27, all p values<0.01), but not in the other three race/gender groups. Additional adjustment for adult obesity, physical activity in different life stages, smoking, and heavy drinking over the life-course significantly attenuated the associations in white men. CONCLUSIONS: Socioeconomic disadvantage in childhood is associated with lower hip strength relative to load in white men, and these influences are dampened by healthy lifestyle choices.

Skeletal health in long-duration astronauts: nature, assessment, and management recommendations from the NASA Bone Summit.

Concern about the risk of bone loss in astronauts as a result of prolonged exposure to microgravity prompted the National Aeronautics and Space Administration to convene a Bone Summit with a panel of experts at the Johnson Space Center to review the medical data and research evidence from astronauts who have had prolonged exposure to spaceflight. Data were reviewed from 35 astronauts who had served on spaceflight missions lasting between 120 and 180 days with attention focused on astronauts who (1) were repeat fliers on long-duration missions, (2) were users of an advanced resistive exercise device (ARED), (3) were scanned by quantitative computed tomography (QCT) at the hip, (4) had hip bone strength estimated by finite element modeling, or (5) had lost >10% of areal bone mineral density (aBMD) at the hip or lumbar spine as measured by dual-energy X-ray absorptiometry (DXA). Because of the limitations of DXA in describing the effects of spaceflight on bone strength, the panel recommended that the U.S. space program use QCT and finite element modeling to further study the unique effects of spaceflight (and recovery) on bone health in order to better inform clinical decisions.

Socioeconomic status over the life-course and adult bone mineral density: the Midlife in the U.S. Study.

PURPOSE: Adult bone mass depends on acquisition in childhood and decline in adulthood, and may be influenced by socioeconomic conditions over the entire life course. METHODS: We examined associations of bone mineral density (BMD) in adulthood with life course socioeconomic status in 729 participants in the Midlife in the United States Biomarker Project, adjusting for age, menopausal transition stage, race, gender, body weight, smoking, physical activity in several life stages, and research site. Primary predictors were a) childhood socioeconomic advantage score (including parental education, self-rated financial status relative to others, not being on welfare), b) adult education level (no college vs. some college vs. college graduate), and c) adult current financial advantage score (including family-adjusted poverty to income ratio, self-assessed current financial situation, having enough money to meet needs, ease in paying bills). RESULTS: Mean age was 56.9 (range 34-85) years. After adjustment for covariates, childhood socioeconomic advantage and adult education level were positively associated with lumbar spine BMD: 0.27 standard deviations (SD) higher at 90th compared to 10th percentile of childhood advantage score (P=0.009), and 0.24 SD higher in college graduates compared to participants without college education (P=0.01). Adult current financial advantage was not associated with lumbar spine BMD. None of the three socioeconomic indicators was significantly associated with femoral neck BMD. CONCLUSIONS: Childhood socioeconomic advantage and adult education level were associated with higher adult lumbar spine BMD. Current financial advantage was not associated with BMD. Childhood socioeconomic factors may influence acquisition of lumbar BMD.

Simultaneous screening for osteoporosis at CT colonography: bone mineral density assessment using MDCT attenuation techniques compared with the DXA reference standard.

The purpose of this study was to evaluate the utility of lumbar spine attenuation measurement for bone mineral density (BMD) assessment at screening computed tomographic colonography (CTC) using central dual-energy X-ray absorptiometry (DXA) as the reference standard. Two-hundred and fifty-two adults (240 women and 12 men; mean age 58.9 years) underwent CTC screening and central DXA BMD measurement within 2 months (mean interval 25.0 days). The lowest DXA T-score between the spine and hip served as the reference standard, with low BMD defined per World Health Organization as osteoporosis (DXA T-score ≤ -2.5) or osteopenia (DXA T-score between -1.0 and -2.4). Both phantomless quantitative computed tomography (QCT) and simple nonangled region-of-interest (ROI) multi-detector CT (MDCT) attenuation measurements were applied to the T(12) -L(5) levels. The ability to predict osteoporosis and low BMD (osteoporosis or osteopenia) by DXA was assessed. A BMD cut-off of 90 mg/mL at phantomless QCT yielded 100% sensitivity for osteoporosis (29 of 29) and a specificity of 63.8% (143 of 224); 87.2% (96 of 110) below this threshold had low BMD and 49.6% (69 of 139) above this threshold had normal BMD at DXA. At L(1) , a trabecular ROI attenuation cut-off of 160 HU was 100% sensitive for osteoporosis (29 of 29), with a specificity of 46.4% (104 of 224); 83.9% (125 of 149) below this threshold had low BMD and 57.5% (59/103) above had normal BMD at DXA. ROI performance was similar at all individual T(12) -L(5) levels. At ROC analysis, AUC for osteoporosis was 0.888 for phantomless QCT [95% confidence interval (CI) 0.780-0.946] and ranged from 0.825 to 0.853 using trabecular ROIs at single lumbar levels (0.864; 95% CI 0.752-0.930 at multivariate analysis). Supine-prone reproducibility was better with the simple ROI method compared with QCT. It is concluded that both phantomless QCT and simple ROI attenuation measurements of the lumbar spine are effective for BMD screening at CTC with high sensitivity for osteoporosis, as defined by the DXA T-score.

Current status of clinical 25-hydroxyvitamin D measurement: an assessment of between-laboratory agreement.

BACKGROUND: Historically, methodological differences and lack of standardization led to between-laboratory variability in 25(OH)D results. Recent observations raised concern about persisting variability. This quality assurance exercise investigated 25(OH)D result comparability between laboratories. METHODS: Serum pools (n=25) were prepared to contain endogenous 25(OH)D(2) and 25(OH)D(3) at 25(OH)D concentrations from ~12 to 150 nmol/l (5-60 ng/ml). Aliquots were sent to 8 laboratories utilizing various 25(OH)D assay methods including high performance liquid chromatography with ultraviolet detection (LC-UV), LC with tandem mass spectroscopy detection (LC-MS/MS) or an automated immunoassay (Diasorin Liaison). The LC-UV results were selected as a referent to which all others were compared using linear regression and Bland-Altman analysis. RESULTS: Good correlation (R(2)=0.87 to 0.97) was observed for all laboratories. Modest systematic bias was observed for some laboratories ranging from a positive mean bias of 10.5 nmol/l (4.2 ng/ml) to a negative mean bias of 3.5 nmol/l (1.4 ng/ml). For the laboratory with the greatest bias, 22/25 results were numerically higher (mean +15.7%) than LC-UV results. For Liaison, the primary error was likely random, whereas the major LC-MS/MS assay error source was biases likely due to calibration issues. CONCLUSIONS: Modest inter-laboratory variability persists in serum 25(OH)D measurement. The National Institute of Standards and Technology 25(OH)D Standard Reference and calibration materials will further improve between-laboratory agreement for chromatography-based assays.

Vertebral Fracture Assessment: the 2007 ISCD Official Positions.

Vertebral fracture assessment (VFA) is an established, low radiation method for detection of prevalent vertebral fractures. Vertebral fractures are usually not recognized clinically at the time of their occurrence, but their presence indicates a substantial risk for subsequent fractures independent of bone mineral density. Significant evidence supporting VFA use for many post-menopausal women and older men has accumulated since the last ISCD Official Position Statement on VFA was published. The International Society for Clinical Densitometry considered the following issues at the 2007 Position Development Conference: (1) What are appropriate indications for Vertebral Fracture Assessment; (2) What is the most appropriate method of vertebral fracture detection with VFA; (3) What is the sensitivity and specificity for detection of vertebral fractures with this method; (4) When should additional spine imaging be performed following a VFA; and (5) What are the reporting obligations for those interpreting VFA images?