Vertebral bone marrow glucose uptake is inversely associated with bone marrow fat in diabetic and healthy pigs: [18F]FDG-PET and MRI study

ObjectivesDiabetes induces osteoporosis and during osteoporosis, vertebral bone marrow (VBM) adipose tissue amount increases. The association between this adiposity and bone marrow metabolism is unclear. Here, we compared VBM glucose metabolism and fat content in healthy and diabetic pigs, in vivo, using positron emission tomography (PET), in-phase and out-of-phase magnetic resonance imaging and magnetic resonance proton spectroscopy (¹H MR spectroscopy).Materials/methodsEleven pigs (n = 11) were used. The intervention group had five diabetic and the control group had six healthy pigs. To measure metabolism, PET-imaging with [¹⁸F]fluoro-deoxy-glucose ([¹⁸F]FDG) intravenous tracer was used. 1.5-T MRI with ¹H spectroscopy, in-phase and out-of-phase imaging and chemical TAG analysis of the VBM were performed.ResultsWe found a significant inverse correlation between VBM glucose uptake (GU) and VBM fat content (R = − 0.800, p < 0.01) and TAG concentration assay (R = − 0.846, p < 0.05). There was a trend, although non-significant, of a linear correlation between VBM ¹H MR spectroscopy and TAG concentration (R = 0.661) and ¹H MR spectroscopy and in-phase and out-of-phase MR imaging (R = 0.635).ConclusionsVBM glucose metabolism coupled with VBM fat content may impact diabetic induced osteoporosis.     

A systematic framework to classify physical activity research for individuals with spina bifida

BackgroundIdentifying the types of research conducted in the area of physical activity (PA) for the spina bifida (SB) population is important in order to move research forward to increase PA behaviors and improve health. The Behavioral Epidemiological Framework is a one way to systematically classify PA and SB literature by organizing research into one of five phases: phase 1 research links behaviors to health, phase 2 includes research focused on developing methods for measuring behavior, phase 3 research identifies factors that influence behavior, phase 4 research evaluates interventions to change the behavior, and phase 5 studies translates research into practice.ObjectiveTo systematically classify PA research for individuals with SB by using the Behavioral Epidemiologic Framework and to identify where the research has focused.MethodAn audit of the literature was conducted using search engines and keywords related to PA and SB. Inter-rater reliability was established between the research team coding articles based on established inclusion criteria. Finally, literature was categorized into one of the five phases.ResultsSeventy-seven articles met the inclusion criteria and were categorized. Forty three percent of the articles were categorized in phase 1, 21% in phase 2, 32% in phase 3, 4% in phase 4, and zero in phase 5.ConclusionThe majority of articles are in phase 1, indicating that PA and SB research is still in early stages of development. Future research needs to move beyond phase 1 to examine factors that affect PA behaviors and ways to increase PA behaviors in the SB population.     

Vertebral bone quality score predicts fragility fractures independently of bone mineral density

BackgroundCurrent evidence suggests that dual-energy x-ray absorptiometry (DXA) scans, the conventional method defining osteoporosis, is underutilized and, when used, may underestimate patient risk for skeletal fragility. It has recently been suggested that other imaging modalities may better estimate bone quality, such as the magnetic resonance imaging (MRI)-based vertebral bone quality (VBQ) score which also may assess vertebral compression fracture risk in patients with spine metastases.PurposeTo evaluate whether VBQ score is predictive of fragility fractures in a population with pre-existing low bone density and at high-risk for fracture.Study Design/SettingRetrospective single-center cohort.Patient SamplePatients followed at a metabolic bone clinic for osteopenia and/or osteoporosis.Outcome MeasuresRadiographically-documented new-onset fragility fracture.MethodsPatients with a DXA and MRI scans at the time of consultation and ≥2-year follow-up were included. Details were gathered about patient demographics, health history, current medication use, and serological studies of kidney function and bone turnover. For each patient, VBQ score was calculated using T1-weighted lumbar MRI images. Univariable and multivariable analyses were used to identify the independent predictors of a new fragility fracture. To support the construct validity of VBQ, patient VBQ scores were compared to those in a cohort of 45 healthy adults.ResultsSeventy-two (39.1%) study participants suffered fragility fractures, the occurrence of which was associated with higher VBQ score (3.50 vs. 3.01; p<.001), chronic glucocorticoid use (30.6% vs. 15.2%; p=.014), and a history of prior fragility fracture (36.1% vs. 21.4%; p=.030). Mean VBQ score across all patients in the study cohort was significantly higher than the mean VBQ score in the healthy controls (p<.001). In multivariable analysis, new-onset fracture was independently associated with history of prior fracture (OR=6.94; 95% confidence interval [2.48–19.40]; p<.001), higher VBQ score (OR=2.40 per point; [1.30–4.44]; p=.003), higher body mass index (OR=1.09 per kg/m²; [1.01–1.17]; p=.03), and chronic glucocorticoid use (OR=2.89; [1.03–8.17]; p=0.043). Notably, DXA bone mineral density (BMD) was not found to be significantly predictive of new-onset fractures in the multivariable analysis (p=.081).ConclusionsHere we demonstrate the novel, MRI-derived VBQ score is both an independent predictor of fragility fracture in at-risk patients and a superior predictor of fracture risk than DXA-measured BMD. Given the frequency with which MRIs are obtained by patients undergoing spine surgery consultation, we believe the VBQ score could be a valuable tool for estimating bone quality in order to optimize the management of these patients.     

Efficacy of extended adjuvant therapy with aromatase inhibitors in early breast cancer among common clinicopathologically-defined subgroups: A systematic review and meta-analysis

BackgroundRandomized controlled trials (RCTs) have shown improvements in breast cancer outcomes from extending treatment with aromatase inhibitors (AIs) beyond the initial 5 years after diagnosis. Consistency of this effect in common clinicopathologically defined subgroups was not been reported systematically.MethodsWe identified RCTs comparing extended AIs to placebo or no treatment using a systematic search of MEDLINE and a review of abstracts from key conferences between 2013 and 2016. Hazard ratios (HRs) and 95% confidence intervals (CI) for disease-free survival (DFS) were included in a meta-analysis using generic inverse variance and random effects modelling. Pre-specified subgroups included: age (<60 ± 5 years versus ≥60 ± 5 years), tumor size (>2 cm versus ≤2 cm), nodal status (positive versus negative), hormone receptor status (double versus single receptor expression) and receipt of adjuvant chemotherapy (yes versus no).ResultsSeven trials comprising 16,349 patients were analyzed. Overall, the effect of extended AIs was similar in all subgroups. Non-significantly greater effect sizes were seen in patients with larger tumors (HR for DFS 0.77 versus 0.88, p for difference = 0.44), nodal involvement (HR = 0.72 versus 0.83, p for difference = 0.22), double hormone receptor expression (HR = 0.68 versus 1.01, p for difference = 0.31) and receipt of adjuvant chemotherapy (HR = 0.71 versus 0.80, p for difference = 0.51).ConclusionsExtended treatment with AIs is associated with similar relative improvements in DFS in all subgroups analyzed. The combination of greater effect size and higher absolute risk of recurrence in node positive and larger tumors will likely translate to higher absolute benefits from extended AIs in these groups.     

Low Prevalence of Clinically Apparent Cardiac Amyloidosis Among Carriers of Transthyretin V122I Variant in a Large Electronic Medical Record

BackgroundTransthyretin (TTR) gene mutations are the most common cause of hereditary amyloidosis. Valine replaced by isoleucine in position 122 (V122I) variant is common, particularly in the black population. Carriers of V122I have increased risk for developing cardiac amyloidosis. Despite a relatively high prevalence, the penetrance of V122I is not firmly established. This study sought to determine the prevalence of clinically apparent cardiac amyloidosis among carriers of the TTR V122I variant.MethodsBioVU, a Vanderbilt University resource linking DNA samples and pre-existing genetic data to de-identified electronic medical records was used to identify TTR V122I mutation carriers. Automated billing code queries (International Classification of Diseases, 9th revision codes), problem list searches, and manual chart reviews were used to identify subjects with clinically diagnosed cardiac amyloidosis.ResultsAmong 28,429 subjects with available genotype data, 129 were V122I carriers. Carriers had a median age of 42 years (interquartile range 16-64). Noncarriers had a median age of 62 years, (interquartile range 41-77). The carrier rate was 3.7% in blacks and 0.02% in whites. Overall, the prevalence of clinically apparent cardiac amyloidosis was 0.8% in carriers and 0.04% in noncarriers (P = .05). Above age 60, the prevalence of cardiac amyloidosis was 2.6% in carriers and 0.06% in noncarriers (P = .03).ConclusionCarriers of the TTR V122I variant are at a higher risk for development of cardiac amyloidosis, particularly at age>60 years. However, clinically apparent cardiac amyloidosis in this population was uncommon. These results support that the penetrance of TTR V122I is age dependent and suggest it may be significantly lower than previously reported.