Relationship between risk factors for impaired bone health and HR-pQCT in young adults with type 1 diabetes.

Objective: In type 1 diabetes, risk factors associated with impaired bone health contribute to increased risk of fracture. The aim of this study was to (1): compare the high-resolution peripheral quantitative computed tomography (HR-pQCT) parameters of young adults with type 1 diabetes with those of healthy controls (2), identify sex differences, and (3) evaluate the association between diabetes and bone health risk factors, with HR-pQCT. Methods: This is a cross-sectional study in young Canadian adults with childhood onset type 1 diabetes. Z-scores were generated for HR-pQCT parameters using a large healthy control database. Diet, physical activity, BMI, hemoglobin A1C (A1C) and bone health measures were evaluated, and associations were analyzed using multivariate regression analysis. Results: Eighty-eight participants (age 21 ± 2.2 years; 40 males, 48 females, diabetes duration 13.9 ± 3.4 years) with type 1 diabetes were studied. Low trabecular thickness and elevated cortical geometry parameters were found suggesting impaired bone quality. There were no sex differences. Significant associations were found: Vitamin D (25(OH)D) with trabecular parameters with possible synergy with A1C, parathyroid hormone with cortical parameters, BMI with cortical bone and failure load, and diabetes duration with trabecular area. Conclusions: Our data suggests impairment of bone health as assessed by HR-pQCT in young adults with type 1 diabetes. Modifiable risk factors were associated with trabecular and cortical parameters. These findings imply that correction of vitamin D deficiency, prevention and treatment of secondary hyperparathyroidism, and optimization of metabolic control may reduce incident fractures.

Variation in external beam treatment plan quality: An inter-institutional study of planners and planning systems.

PURPOSE: This study quantifies variation in radiation treatment plan quality for plans generated by a population of treatment planners given very specific plan objectives. METHODS AND MATERIALS: A "Plan Quality Metric" (PQM) with 14 submetrics, each with a unique value function, was defined for a prostate treatment plan, serving as specific goals of a hypothetical "virtual physician." The exact PQM logic was distributed to a population of treatment planners (to remove ambiguity of plan goals or plan assessment methodology) as was a predefined computed tomographic image set and anatomic structure set (to remove anatomy delineation as a variable). Treatment planners used their clinical treatment planning system (TPS) to generate their best plan based on the specified goals and submitted their results for analysis. RESULTS: One hundred forty datasets were received and 125 plans accepted and analyzed. There was wide variability in treatment plan quality (defined as the ability of the planners and plans to meet the specified goals) quantified by the PQM. Despite the variability, the resulting PQM distributions showed no statistically significant difference between TPS employed, modality (intensity modulated radiation therapy versus arc), or education and certification status of the planner. The PQM results showed negligible correlation to number of beam angles, total monitor units, years of experience of the planner, or planner confidence. CONCLUSIONS: The ability of the treatment planners to meet the specified plan objectives (as quantified by the PQM) exhibited no statistical dependence on technologic parameters (TPS, modality, plan complexity), nor was the plan quality statistically different based on planner demographics (years of experience, confidence, certification, and education). Therefore, the wide variation in plan quality could be attributed to a general "planner skill" category that would lend itself to processes of continual improvement where best practices could be derived and disseminated to improve the mean quality and minimize the variation in any population of treatment planners.

Novel acyl coenzyme A (CoA): diacylglycerol acyltransferase-1 inhibitors: synthesis and biological activities of diacylethylenediamine derivatives.

A series of diacylethylenediamine derivatives were synthesized and evaluated for their inhibitory activity against DGAT-1 and pharmacokinetic profile to discover new small molecule DGAT-1 inhibitors. Among the compounds, N-[2-({[1-phenyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]carbonyl}amino)ethyl]-6-(2,2,2-trifluoroethoxy)pyridine-3-carboxamide 3x showed potent inhibitory activity and excellent PK profile. Oral administration of 3x to mice with dietary-induced obesity resulted in reduced body weight gain and white adipose tissue weight.

Can porous tantalum be used to achieve ankle and subtalar arthrodesis?: a pilot study.

UNLABELLED: A structural graft often is needed to fill gaps during reconstructive procedures of the ankle and hindfoot. Autograft, the current gold standard, is limited in availability and configuration and is associated with donor-site morbidity in as much as 48%, whereas the alternative allograft carries risks of disease transmission and collapse. Trabecular metal (tantalum), with a healing rate similar to that of autograft, high stability, and no donor-site morbidity, has been used in surgery of the hip, knee, and spine. However, its use has not been documented in foot and ankle surgery. We retrospectively reviewed nine patients with complex foot and ankle arthrodeses using a tantalum spacer. Minimum followup was 1.9 years (average, 2 years; range, 1.9-2.4 years). Bone ingrowth into the tantalum was analyzed with micro-CT in three of the nine patients. All arthrodeses were fused clinically and radiographically at the 1- and 2 year followups and no complications occurred. The American Orthopaedic Foot and Ankle Society score increased from 32 to 74. The micro-CT showed bony trabeculae growing onto the tantalum. Our data suggest tantalum may be used as a structural graft option for ankle and subtalar arthrodesis. All nine of our patients achieved fusion and had no complications. Using tantalum obviated the need for harvesting of the iliac spine. LEVEL OF EVIDENCE: Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

Adaptations of trabecular bone to low magnitude vibrations result in more uniform stress and strain under load.

Extremely low magnitude mechanical stimuli (<10 microstrain) induced at high frequencies are anabolic to trabecular bone. Here, we used finite element (FE) modeling to investigate the mechanical implications of a one year mechanical intervention. Adult female sheep stood with their hindlimbs either on a vibrating plate (30 Hz, 0.3 g) for 20 min/d, 5 d/wk or on an inactive plate. Microcomputed tomography data of 1 cm bone cubes extracted from the medial femoral condyles were transformed into FE meshes. Simulated compressive loads applied to the trabecular meshes in the three orthogonal directions indicated that the low level mechanical intervention significantly increased the apparent trabecular tissue stiffness of the femoral condyle in the longitudinal (+17%, p<0.02), anterior-posterior (+29%, p<0.01), and medial-lateral (+37%, p<0.01) direction, thus reducing apparent strain magnitudes for a given applied load. For a given apparent input strain (or stress), the resultant stresses and strains within trabeculae were more uniformly distributed in the off-axis loading directions in cubes of mechanically loaded sheep. These data suggest that trabecular bone responds to low level mechanical loads with intricate adaptations beyond a simple reduction in apparent strain magnitude, producing a structure that is stiffer and less prone to fracture for a given load.

Combining high-resolution micro-computed tomography with material composition to define the quality of bone tissue.

Atraumatic fractures of the skeleton in osteoporotic patients are directly related to a deterioration of bone strength. However, the failure of the bone tissue to withstand functional load bearing cannot be explained as a simple decrease in bone mineral density (quantity); strength is also significantly dependent upon bone quality. While a formal definition of bone quality is somewhat elusive, at the very least, it incorporates architectural, physical, and biologic factors that are critical to bone strength. Such factors include bone morphology (ie, trabecular connectivity, cross-sectional geometry, longitudinal curvature); the tissue's material properties (eg, stiffness, strength); its chemical composition and architecture (eg, ratio of calcium to other components of the organic and/or inorganic phase, collagen orientation, porosity, permeability); and the viability of the tissue (eg, responsivity of the bone cell population). Combining high-resolution structural indices of bone, as determined by micro-computed tomography; material properties determined by nanoindentation; and the chemical make-up of bone, as determined by infrared spectroscopy, helps to provide critical information toward a more comprehensive assessment of the interdependence of bone quality, quantity, and fracture risk.