Previous fracture and subsequent fracture risk: a meta-analysis to update FRAX.

A large international meta-analysis using primary data from 64 cohorts has quantified the increased risk of fracture associated with a previous history of fracture for future use in FRAX. INTRODUCTION: The aim of this study was to quantify the fracture risk associated with a prior fracture on an international basis and to explore the relationship of this risk with age, sex, time since baseline and bone mineral density (BMD). METHODS: We studied 665,971 men and 1,438,535 women from 64 cohorts in 32 countries followed for a total of 19.5 million person-years. The effect of a prior history of fracture on the risk of any clinical fracture, any osteoporotic fracture, major osteoporotic fracture, and hip fracture alone was examined using an extended Poisson model in each cohort. Covariates examined were age, sex, BMD, and duration of follow-up. The results of the different studies were merged by using the weighted ß-coefficients. RESULTS: A previous fracture history, compared with individuals without a prior fracture, was associated with a significantly increased risk of any clinical fracture (hazard ratio, HR = 1.88; 95% CI = 1.72-2.07). The risk ratio was similar for the outcome of osteoporotic fracture (HR = 1.87; 95% CI = 1.69-2.07), major osteoporotic fracture (HR = 1.83; 95% CI = 1.63-2.06), or for hip fracture (HR = 1.82; 95% CI = 1.62-2.06). There was no significant difference in risk ratio between men and women. Subsequent fracture risk was marginally downward adjusted when account was taken of BMD. Low BMD explained a minority of the risk for any clinical fracture (14%), osteoporotic fracture (17%), and for hip fracture (33%). The risk ratio for all fracture outcomes related to prior fracture decreased significantly with adjustment for age and time since baseline examination. CONCLUSION: A previous history of fracture confers an increased risk of fracture of substantial importance beyond that explained by BMD. The effect is similar in men and women. Its quantitation on an international basis permits the more accurate use of this risk factor in case finding strategies.

Update of the fracture risk prediction tool FRAX: a systematic review of potential cohorts and analysis plan.

We describe the collection of cohorts together with the analysis plan for an update of the fracture risk prediction tool FRAX with respect to current and novel risk factors. The resource comprises 2,138,428 participants with a follow-up of approximately 20 million person-years and 116,117 documented incident major osteoporotic fractures. INTRODUCTION: The availability of the fracture risk assessment tool FRAX® has substantially enhanced the targeting of treatment to those at high risk of fracture with FRAX now incorporated into more than 100 clinical osteoporosis guidelines worldwide. The aim of this study is to determine whether the current algorithms can be further optimised with respect to current and novel risk factors. METHODS: A computerised literature search was performed in PubMed from inception until May 17, 2019, to identify eligible cohorts for updating the FRAX coefficients. Additionally, we searched the abstracts of conference proceedings of the American Society for Bone and Mineral Research, European Calcified Tissue Society and World Congress of Osteoporosis. Prospective cohort studies with data on baseline clinical risk factors and incident fractures were eligible. RESULTS: Of the 836 records retrieved, 53 were selected for full-text assessment after screening on title and abstract. Twelve cohorts were deemed eligible and of these, 4 novel cohorts were identified. These cohorts, together with 60 previously identified cohorts, will provide the resource for constructing an updated version of FRAX comprising 2,138,428 participants with a follow-up of approximately 20 million person-years and 116,117 documented incident major osteoporotic fractures. For each known and candidate risk factor, multivariate hazard functions for hip fracture, major osteoporotic fracture and death will be tested using extended Poisson regression. Sex- and/or ethnicity-specific differences in the weights of the risk factors will be investigated. After meta-analyses of the cohort-specific beta coefficients for each risk factor, models comprising 10-year probability of hip and major osteoporotic fracture, with or without femoral neck bone mineral density, will be computed. CONCLUSIONS: These assembled cohorts and described models will provide the framework for an updated FRAX tool enabling enhanced assessment of fracture risk (PROSPERO (CRD42021227266)).

Peri-operative complications of sphenopalatine artery ligation: a 10-year series from two secondary care centres.

BACKGROUND: There is currently limited evidence regarding the potential complications of sphenopalatine artery ligation. The post-operative outcomes at two secondary care centres over a 10-year period were reviewed. METHODS: A retrospective review was undertaken of patients undergoing emergency and elective sphenopalatine artery ligation between January 2011 and January 2021. Their demographics, peri-operative care and post-operative outcomes were recorded. The median follow-up time was 54 days (range, 0-2657 days). RESULTS: Ninety-one patients were included. Four patients (4.4 per cent) had a septal perforation at post-operative review. Nineteen patients (20.9 per cent) had post-operative bleeding that extended their in-patient stay, with five patients (5.5 per cent) requiring revision surgery. Pre-operative non-dissolvable nasal packing was used a median of 1 time (range, 0-8 times). CONCLUSION: Further research on outcomes of sphenopalatine artery ligation is needed. Pre-operative non-dissolvable nasal packing, concurrent septal surgical procedures, surgical techniques, and co-morbidities such as hypertension represent potential confounding factors that could not be further assessed in this small, retrospective study.

Ex vivo normothermic perfusion of isolated segmental porcine bowel: a novel functional model of the small intestine.

BACKGROUND: There is an unmet need for suitable ex vivo large animal models in experimental gastroenterology and intestinal transplantation. This study details a reliable and effective technique for ex vivo normothermic perfusion (EVNP) of segmental porcine small intestine. METHODS: Segments of small intestine, 1.5-3.0 m in length, were retrieved from terminally anaesthetized pigs. After a period of cold ischaemia, EVNP was performed for 2 h at 37°C with a mean pressure of 80 mmHg using oxygenated autologous blood diluted with Ringer's solution. The duration of EVNP was extended to 4 h for a second set of experiments in which two segments of proximal to mid-ileum (1.5-3.0 m) were retrieved from each animal and reperfused with whole blood (control) or leucocyte-depleted blood to examine the impact of leucocyte depletion on reperfusion injury. RESULTS: After a mean cold ischaemia time of 5 h and 20 min, EVNP was performed in an initial group of four pigs. In the second set of experiments, five pigs were used in each group. In all experiments bowel segments were well perfused and exhibited peristalsis during EVNP. Venous glucose levels significantly increased following luminal glucose stimulation (mean(s.e.m.) basal level 1.8(0.6) mmol/l versus peak 15.5(5.8) mmol/l; P < 0.001) and glucagon-like peptide 1 (GLP-1) levels increased in all experiments, demonstrating intact absorptive and secretory intestinal functions. There were no significant differences between control and leucocyte-depleted animals regarding blood flow, venous glucose, GLP-1 levels or histopathology at the end of 4 h of EVNP. CONCLUSIONS: This novel model is suitable for the investigation of gastrointestinal physiology, pathology and ischaemia reperfusion injury, along with evaluation of potential therapeutic interventions.

Establishment of normative biometric data for body composition based on computed tomography in a North American cohort.

BACKGROUND & AIMS: Accurate and reproducible biomarkers are required to allow a more personalized approach to patient care. Body composition is one such biomarker affecting outcomes in a range of surgical and oncological conditions. The aim of this study is to determine the age and sex specific distribution of body composition data, based on information gathered from computed tomography (CT). METHODS: This prospective study used healthy subjects from the medical records linkage of the Rochester Epidemiology Project, based in Minnesota, USA. Each patient had a CT scan without intravenous contrast performed between 1999 and 2001. Quantification was performed using previously validated semi-automated in-house developed software for body composition analysis. Subcutaneous adipose tissue area, visceral adipose tissue area, intermuscular adipose tissue area and skeletal muscle area were measured and indexed to subject height. Generalized Additive Models for Location, Scale and Shape were used to assess the location, scale, and shape of each variable across age, stratified by sex. Z-scores specific to sex were assessed for each of the parameters analyzed. Age-specific z-scores were calculated using the formula: Z = (Index Variable - µ)/σ or Z = (√ (Index Variable) - µ)/σ. RESULTS: There were 692 subjects enrolled in the study. The fitted model equation was offered for each variable with values presented for µ and σ. Modelling with penalized splines was performed for VAT index, IMAT index and total adipose tissue index. Scatterplots of each variable were produced with lines of Z-scores as a visual representation. CONCLUSION: This study offers comparative data to allow comparison amongst multiple populations. This will form an important reference for future research and clinical practice.

Biomechanical Computed Tomography analysis (BCT) for clinical assessment of osteoporosis.

The surgeon general of the USA defines osteoporosis as "a skeletal disorder characterized by compromised bone strength, predisposing to an increased risk of fracture." Measuring bone strength, Biomechanical Computed Tomography analysis (BCT), namely, finite element analysis of a patient's clinical-resolution computed tomography (CT) scan, is now available in the USA as a Medicare screening benefit for osteoporosis diagnostic testing. Helping to address under-diagnosis of osteoporosis, BCT can be applied "opportunistically" to most existing CT scans that include the spine or hip regions and were previously obtained for an unrelated medical indication. For the BCT test, no modifications are required to standard clinical CT imaging protocols. The analysis provides measurements of bone strength as well as a dual-energy X-ray absorptiometry (DXA)-equivalent bone mineral density (BMD) T-score at the hip and a volumetric BMD of trabecular bone at the spine. Based on both the bone strength and BMD measurements, a physician can identify osteoporosis and assess fracture risk (high, increased, not increased), without needing confirmation by DXA. To help introduce BCT to clinicians and health care professionals, we describe in this review the currently available clinical implementation of the test (VirtuOst), its application for managing patients, and the underlying supporting evidence; we also discuss its main limitations and how its results can be interpreted clinically. Together, this body of evidence supports BCT as an accurate and convenient diagnostic test for osteoporosis in both sexes, particularly when used opportunistically for patients already with CT. Biomechanical Computed Tomography analysis (BCT) uses a patient's CT scan to measure both bone strength and bone mineral density at the hip or spine. Performing at least as well as DXA for both diagnosing osteoporosis and assessing fracture risk, BCT is particularly well-suited to "opportunistic" use for the patient without a recent DXA who is undergoing or has previously undergone CT testing (including hip or spine regions) for an unrelated medical condition.

Hip load capacity and yield load in men and women of all ages.

Quantitative computed tomography (QCT) based finite element (FE) models can compute subject-specific proximal femoral strengths, or fracture loads, that are associated with hip fracture risk. These fracture loads are more strongly associated with measured fracture loads than are DXA and QCT measures and are predictive of hip fracture independently of DXA bone mineral density (BMD). However, interpreting FE-computed fracture loads of younger subjects for the purpose of evaluating hip fracture risk in old age is challenging due to limited reference data. The goal of this study was to address this issue by providing reference data for male and female adult subjects of all ages. QCT-based FE models of the left proximal femur of 216 women and 181 men, age 27 to 90 years, from a cohort of Rochester, MN residents were used to compute proximal femoral load capacities, i.e. the maximum loads that can be supported, in single-limb stance and posterolateral fall loading (Stance_LC and Fall_LC, respectively) [US Patent No. 9,245,069] and yield load under fall loading (Fall_yield). To relate these measures to information about hip fracture, the CT scanner and calibration phantom were cross-calibrated with those from our previous prospective study of hip fracture in older fracture and control subjects, the Age Gene/Environment Susceptibility (AGES) Reykjavik cohort. We then plotted Stance_LC, Fall_LC and Fall_yield versus age for the two cohorts on the same graphs. Thus, proximal femoral strengths in individuals above 70 years of age can be assessed through direct comparison with the FE data from the AGES cohort which were analyzed using identical methods. To evaluate younger individuals, reductions in Stance_LC, Fall_LC and Fall_yield from the time of evaluation to age 70 years can be cautiously estimated from the average yearly cross-sectional decreases found in this study (108 N, 19.4 N and 14.4 N, respectively, in men and 120 N, 19.4 N and 21.6 N, respectively, in women), and the projected fracture loads can be compared with data from the AGES cohort. Although we did not set specific thresholds for identifying individuals at risk of hip fracture, these data provide some guidance and may be used to help establish diagnostic criteria in future. Additionally, given that these data were nearly entirely from Caucasian subjects, future research involving subjects of other races/ethnicities is necessary.

Parapharyngeal abscess secondary to lymphovenous malformation.

BACKGROUND: Deep neck space abscesses are an uncommon but life-threatening emergency presentation to the ENT surgeon because of potential acute airway compromise. OBJECTIVE: This paper presents a novel case of a palatine tonsillar, low-flow, lymphovenous malformation pre-disposing to multifocal deep neck space collections and resultant acute airway compromise.

Dysphagia in Parkinson's Disease Improves with Vocal Augmentation.

While voice-related disorders in Parkinson's disease (PD) are commonly discussed in the literature, dysphagia in PD is less widely published. Vocal fold augmentation, including injection laryngoplasty (IL), is a well-established treatment for glottal insufficiency (Cates et al. in Otolaryngol Head Neck Surg 155(3):454-457, 2016). This study aimed to observe the effects of IL in PD patients with vocal bowing, with or without therapy, on glottic closure and patient-reported dysphagia outcomes. The study design was based on retrospectively collected database and cohort-case series. PD patients selected for retrospective review over a 2-year period were referred and evaluated in the Voice, Swallowing, and Airway multidisciplinary clinic by speech language pathologist and laryngologist, and were undergoing IL. Charts were reviewed for age, gender, Body Mass Index (BMI), onset of PD, and Movement Disorders Society-Unified Parkinson's Disease Rating Scale Part 3 (MDS-UPDRS) scoring. We compared pre/postoperatively (> 1 < 3 months) using validated patient-reported outcome tools: Reflux Symptom Index (RSI), Glottal Function Index (GFI), Eating Assessment Tool-10 (EAT), and stroboscopic examinations. The study included 14 patients undergoing 22 IL or 1.6 IL/patient: mean age 70 years (63-80), 100% male, and BMI 25.9 ± 4.3 (mean ± SD). MDS-UPDRS scoring 33 ± 20 (moderate severity), with time between PD diagnosis and IL 8 ± 10 years. All patients had pre- and post-stroboscopic examinations; however, only 4:14 underwent formal swallowing evaluation. Overall, 14 IL patients improved on patient-reported measures (ΔRSI = 4; ΔGFI = 3; ΔEAT = 4). Based on the findings of the study, we conclude that PD is a progressive neurodegenerative condition with dysphagia. The presented pilot data suggest that IL may be considered as a beneficial adjunct for PD patients with glottal insufficiency. LEVEL OF EVIDENCE: 4.

Diagnostic and therapeutic utility of indigenous technique of pleuroscopy in undiagnosed cases of exudative pleural effusions

Background and aims: In developing countries, there is a shortage of resources and skilled manpower and a large num-ber of patients. To overcome these problems, an indigenous technique of pleuroscopy has been developed in our institute. In this technique, medical thoracoscopy is done by using a set of patented conduits and a fibre-optic bronchoscope. In this study, we describe our experience with this technique of pleu-roscopy in undiagnosed cases of exudative pleural effusion. Methods: 156 undiagnosed cases of exudative pleural effu-sion were conducted over a period of two and half years. Indigenous technique of pleuroscopy, permitted thorough exploration of the pleural space, permitting multiple biopsies to clinch the diagnosis. Results: The appearance of pleura showed as inflamed/red-dened pleura in 29 (18.6%) cases, thin transparent adhesions in 31 (19.9%), thin transparent loculations in 26 (16.7%) , thick loculations in 12 (7.7%) , hard pleural surface in 11 (7%), large nodules/masses in 13 (8.4%), small milliary seedlings or sago grain appearance in 18 (11.5%), scattered masses or nodules in 13 (8.4%) and broncho-pleural fistula in 3 (1.9%) cases. Histopathological analysis showed chronic inflammation in 40.8% (58), Tubercular lesions in 25.4 % (36) of patients. There were three cases each of Primary Aspergillosis and malig-nant mesothelioma, and the rest 26.9% (42) were malignant metastasis in the pleura. The diagnostic yield of pleuroscopy pleural biopsy was 91% (142). Follow-up chest x-rays after six months showed significant reduction in residual pleural thickening (RPT).Conclusion: TheIndigenous Pleuroscopy technique is an efficient procedure and has good diagnostic and therapeutic yield for undiagnosed exudative pleural effusions. It also reduces morbidity, complications, disease progression, and has a significant role in reduction of RPT

The impact of the new National Bone Health Alliance (NBHA) diagnostic criteria on the prevalence of osteoporosis in the United States: supplementary presentation.

We evaluated the prevalence of osteoporosis using the osteoporosis diagnostic criteria developed by the National Bone Health Alliance (NBHA), which includes qualified fractures, FRAX score in addition to BMD. The expanded definition increases the prevalence compared to BMD alone definitions; however, it may better identify those at elevated fracture risk. Recently an NBHA working Group published a paper in OI with recommendations for expanding the criteria that would constitute an osteoporosis diagnosis in postmenopausal women and in men over age 50 for use in the US - Siris et al., Osteoporosis International 25(%): 1439-1443, 2014. The recommendations have now been endorsed by NOF, ASBMR and a number of professional medical groups and appear in the NOF Clinician's Guide. The new diagnostic criteria continue to include a T-score by DXA of spine or hip that is less than or equal to -2.5, but alternatively also include a hip fracture with or without BMD testing or a vertebral, pelvis, proximal humerus and in some cases a distal forearm fracture in a person with low bone mass, or a FRAX score that meets or exceeds the NOF Guide osteoporosis treatment cut point.

Patient-Centered Network of Learning Health Systems: Developing a resource for clinical translational research.

INTRODUCTION: The Learning Health System Network clinical data research network includes academic medical centers, health-care systems, public health departments, and health plans, and is designed to facilitate outcomes research, pragmatic trials, comparative effectiveness research, and evaluation of population health interventions. METHODS: The Learning Health System Network is 1 of 13 clinical data research networks assembled to create, in partnership with 20 patient-powered research networks, a National Patient-Centered Clinical Research Network. RESULTS AND CONCLUSIONS: Herein, we describe the Learning Health System Network as an emerging resource for translational research, providing details on the governance and organizational structure of the network, the key milestones of the current funding period, and challenges and opportunities for collaborative science leveraging the network.

The comparability of HR-pQCT bone measurements is improved by scanning anatomically standardized regions.

We investigated the sensitivity of distal bone density, structure, and strength measurements by high-resolution peripheral quantitative computed tomography (HR-pQCT) to variability in limb length. Our results demonstrate that HR-pQCT should be performed at a standard %-of-total-limb-length to avoid substantial measurement bias in population study comparisons and the evaluation of individual skeletal status in a clinical context. INTRODUCTION: High-resolution peripheral quantitative computed tomography (HR-pQCT) measures of bone do not account for anatomic variability in bone length: a 1-cm volume is acquired at a fixed offset from an anatomic landmark. Our goal was to evaluate HR-pQCT measurement variability introduced by imaging fixed vs. proportional volumes and to propose a standard protocol for relative anatomic positioning. METHODS: Double-length (2-cm) scans were acquired in 30 adults. We compared measurements from 1-cm sub-volumes located at the default fixed offset, and the average %-of-length offset. The average position corresponded to 4.0% ± 1.1 mm for radius, and 7.2% ± 2.2 mm for tibia. We calculated the RMS difference in bone parameters and T-scores to determine the measurement variability related to differences in limb length. We used anthropometric ratios to estimate the mean limb length for published HR-pQCT reference data, and then calculated mean %-of-length offsets. RESULTS: Variability between fixed vs. relative scan positions was highest in the radius, and for cortical bone in general (RMS difference Ct.Th = 19.5%), while individuals had T-score differentials as high as +3.0 SD (radius Ct.BMD). We estimated that average scan position for published HR-pQCT reference data corresponded to 4.0% at the radius, and 7.3% at tibia. CONCLUSION: Variability in limb length introduces significant bias to HR-pQCT measures, confounding cross-sectional analyses and limiting the clinical application for individual assessment of skeletal status. We propose to standardize scan positioning using 4.0 and 7.3% of total bone length for the distal radius and tibia, respectively.

Operator variability in scan positioning is a major component of HR-pQCT precision error and is reduced by standardized training.

In this study, we determined that operator positioning precision contributes significant measurement error in high-resolution peripheral quantitative computed tomography (HR-pQCT). Moreover, we developed software to quantify intra- and inter-operator variability and demonstrated that standard positioning training (now available as a web-based application) can significantly reduce inter-operator variability. INTRODUCTION: HR-pQCT is increasingly used to assess bone quality, fracture risk, and anti-fracture interventions. The contribution of the operator has not been adequately accounted in measurement precision. Operators acquire a 2D projection ("scout view image") and define the region to be scanned by positioning a "reference line" on a standard anatomical landmark. In this study, we (i) evaluated the contribution of positioning variability to in vivo measurement precision, (ii) measured intra- and inter-operator positioning variability, and (iii) tested if custom training software led to superior reproducibility in new operators compared to experienced operators. METHODS: To evaluate the operator in vivo measurement precision, we compared precision errors calculated in 64 co-registered and non-co-registered scan-rescan images. To quantify operator variability, we developed software that simulates the positioning process of the scanner's software. Eight experienced operators positioned reference lines on scout view images designed to test intra- and inter-operator reproducibility. Finally, we developed modules for training and evaluation of reference line positioning. We enrolled six new operators to participate in a common training, followed by the same reproducibility experiments performed by the experienced group. RESULTS: In vivo precision errors were up to threefold greater (Tt.BMD and Ct.Th) when variability in scan positioning was included. The inter-operator precision errors were significantly greater than the short-term intra-operator precision (p < 0.001). New trained operators achieved comparable intra-operator reproducibility to experienced operators and lower inter-operator reproducibility (p < 0.001). Precision errors were significantly greater for the radius than for the tibia. CONCLUSION: Operator reference line positioning contributes significantly to in vivo measurement precision and is significantly greater for multi-operator datasets. Inter-operator variability can be significantly reduced using a systematic training platform, now available online ( http://webapps.radiology.ucsf.edu/refline/ ).

The impact of the new National Bone Health Alliance (NBHA) diagnostic criteria on the prevalence of osteoporosis in the USA.

We evaluated the prevalence of osteoporosis using the osteoporosis diagnostic criteria developed by the National Bone Health Alliance (NBHA), which includes qualified fractures, FRAX score in addition to bone mineral density (BMD). The expanded definition increases the prevalence compared to BMD alone definitions; however, it may better identify those at elevated fracture risk. PURPOSE: The purpose of this paper is to estimate the prevalence of osteoporosis in US adults ≥50 years using the NBHA osteoporosis diagnostic criteria. METHODS: Utilizing 2005-2008 data of the National Health and Nutrition Examination Survey (NHANES), we identified participants with osteoporosis with any one of the following: (1) femoral neck or lumbar spine T-score ≤ -2.5; (2) low trauma hip fracture irrespective of BMD or clinical vertebral, proximal humerus, pelvis, or distal forearm fracture with a T-score >-2.5 <-1.0; or (3) FRAX score at the National Osteoporosis Foundation intervention thresholds (≥3% for hip fracture or ≥20% for major osteoporotic fracture). We estimated the prevalence overall and by gender and age. RESULTS: Our sample included 1948 (54.3%) men and 1639 (45.7%) women. Approximately 12% were 80+ years and 21% were from racial/ethnic minority groups. We estimated that 16.0% (0.8) of men and 29.9% (1.0) of women 50+ years have osteoporosis. The prevalence increases with age to 46.3% in men and 77.1% in women 80+ years. The combination of FRAX score and fractures was the largest contributing factor defining osteoporosis in men (70-79, 88.1%; 80+, 80.1%), whereas T-score was the largest contributing factor in women (70-79, 49.2%; 80+, 43.5%). CONCLUSIONS: We found that 16% of men and 29.9% of women 50+ have osteoporosis based on the NBHA diagnostic criteria. Although the expanded definition increases the prevalence compared to BMD alone-based definitions, it may better identify those at elevated fracture risk in order to reduce the burden of fractures in older adults.

Technical note: Recommendations for a standard procedure to assess cortical bone at the tissue-level in vivo using impact microindentation.

Impact microindentation is a novel method for measuring the resistance of cortical bone to indentation in patients. Clinical use of a handheld impact microindentation technique is expanding, highlighting the need to standardize the measurement technique. Here, we describe a detailed standard operation procedure to improve the consistency and comparability of the measurements across centers.

Can vitamin D metabolite measurements facilitate a "treat-to-target" paradigm to guide vitamin D supplementation?

UNLABELLED: Substantial variability exists in the serum 25(OH)D increase observed in response to vitamin D supplementation. Measurement of circulating cholecalciferol and 24,25(OH)2D, as indicators of vitamin D absorption and degradation, respectively, account for approximately half of the variation in serum 25(OH)D observed following supplementation. INTRODUCTION: Vitamin D supplementation produces a variable response in serum 25(OH)D. This variability likely reflects, in part, differences in vitamin D absorption and/or degradation. Despite this variation in response, virtually all expert recommendations endorse a fixed vitamin D supplementation dose, an approach also used in most prospective studies. Such utilization of a single vitamin D dose does not assure attaining any pre-specified target 25(OH)D level, thereby compromising clinical care and prospective supplementation trials. This study begins addressing this weakness by exploring the feasibility of vitamin D metabolite measurements to predict serum 25(OH)D level attained following supplementation. METHODS: Ninety-one community-dwelling postmenopausal women with baseline 25(OH)D of 10-30 ng/mL received oral vitamin D3, 2300 or 2500 IU, daily for 4-6 months. Serum 25(OH)D, cholecalciferol (D3), and 24,25(OH)2D were measured before and at the end of supplementation to determine if metabolite concentrations allow prediction of the 25(OH)D level attained. RESULTS: From baseline and follow-up data, we derived a multiple linear regression model predicting posttreatment 25(OH)D as follows: final 25(OH)D = 8.3 + (1.05*initial 25(OH)D) - (7.7*initial 24,25(OH)2D) + (0.53*final D3) + (4.2*final 24,25(OH)2D). This model has an adjusted R(2) = 0.55, thus accounting for approximately half of the observed variance in the final 25(OH)D level. CONCLUSIONS: The contributions of circulating cholecalciferol and 24,25(OH)2D to this predictive model can be considered as indicators of intestinal absorption and clearance, respectively. This paradigm requires further study; it may allow efficient "treat-to-25(OH)D-target" strategies useful in optimizing prospective studies and clinical practice.

Novel anthropomorphic hip phantom corrects systemic interscanner differences in proximal femoral vBMD.

Quantitative computed tomography (QCT) is increasingly used in osteoporosis studies to assess volumetric bone mineral density (vBMD), bone quality and strength. However, QCT is confronted by technical issues in the clinical research setting, such as potentially confounding effects of body size on vBMD measurements and lack of standard approaches to scanner cross-calibration, which affects measurements of vBMD in multicenter settings. In this study, we addressed systematic inter-scanner differences and subject-dependent body size errors using a novel anthropomorphic hip phantom, containing a calibration hip to estimate correction equations, and a contralateral test hip to assess the quality of the correction. We scanned this phantom on four different scanners and we applied phantom-derived corrections to in vivo images of 16 postmenopausal women scanned on two scanners. From the phantom study, we found that vBMD decreased with increasing phantom size in three of four scanners and that inter-scanner variations increased with increasing phantom size. In the in vivo study, we observed that inter-scanner corrections reduced systematic inter-scanner mean vBMD differences but that the inter-scanner precision error was still larger than expected from known intra-scanner precision measurements. In conclusion, inter-scanner corrections and body size influence should be considered when measuring vBMD from QCT images.

Meta-analysis of peak wall stress in ruptured, symptomatic and intact abdominal aortic aneurysms.

BACKGROUND: Abdominal aortic aneurysm (AAA) is an important cause of sudden death; however, there are currently incomplete means to predict the risk of AAA rupture. AAA peak wall stress (PWS) can be estimated using finite element analysis (FEA) methods from computed tomography (CT) scans. The question is whether AAA PWS can predict AAA rupture. The aim of this systematic review was to compare PWS in patients with ruptured and intact AAA. METHODS: The MEDLINE database was searched on 25 May 2013. Case-control studies assessing PWS in asymptomatic intact, and acutely symptomatic or ruptured AAA from CT scans using FEA were included. Data were extracted independently. A random-effects model was used to calculate standard mean differences (SMDs) for PWS measurements. RESULTS: Nine studies assessing 348 individuals were identified and used in the meta-analysis. Results from 204 asymptomatic intact and 144 symptomatic or ruptured AAAs showed that PWS was significantly greater in the symptomatic/ ruptured AAAs compared with the asymptomatic intact AAAs (SMD 0·95, 95 per cent confidence interval 0·71 to 1·18; P < 0·001). The findings remained significant after adjustment for mean systolic blood pressure, standardized at 120 mmHg (SMD 0·68, 0·39 to 0·96; P < 0·001). Minimal heterogeneity between studies was noted (I(2) = 0 per cent). CONCLUSION: This study suggests that PWS is greater in symptomatic or ruptured AAA than in asymptomatic intact AAA.