Detection of Aortic Calcification during Vertebral Fracture Assessment (VFA) Compared to Digital Radiography

Background: Cardiovascular disease is the most common cause of mortality among post-menopausal women. Our objective was to determine whether or not lateral spine images obtained on a bone densitometer to detect prevalent vertebral fracture can also accurately detect radiographic abdominal aortic calcification (AAC), an important risk factor for cardiovascular disease independent of clinical risk factors. Methodology/Principal Findings: One hundred seventy four postmenopausal women had bone densitometry, lateral spine densitometry imaging (called vertebral fracture assessment, or VFA), and lateral spine digital radiographs. Radiographs and VFA images were scored for AAC using a previously validated 24 point scale and a simplified, new 8 point scale (AAC-8). One hundred fifty six (90%) of the VFA images were evaluable for AAC. The non-parametric intraclass correlation coefficient between VFA and radiographic 24 point and AAC-8 readings, respectively, were 0.80 (95% C.I. 0.68–0.87) and 0.76 (95% C.I. 0.65–0.84). Areas under receiver operating characteristics (ROC) curves for VFA to detect those with a radiographic 24-point AAC score ≥5 were 0.86 (95% C.I. 0.77–0.94) using the 24 point scale and 0.84 (95% C.I. 0.76–0.92) using the AAC-8 scale. Conclusion/Significance: VFA imaging intended to detect prevalent vertebral fracture can also detect radiographic AAC, an important cardiovascular disease risk factor. Since bone densitometry is recommended for all women age 65 and older, VFA imaging at the time of bone densitometry offers an opportunity to assess this risk factor in the post-menopausal female population at very little incremental time and expense

Long-Term Velaglucerase Alfa Treatment in Children with Gaucher Disease Type 1 Naïve to Enzyme Replacement Therapy or Previously Treated with Imiglucerase

Background Gaucher Disease type 1 (GD1) often manifests in childhood. Early treatment with enzyme replacement therapy (ERT) may prevent disease complications. We report the assessment of velaglucerase alfa ERT in pediatric GD1 patients who participated in a long-term extension study (HGT-GCB-044, ClinicalTrials.gov Identifier NCT00635427). Methods Safety and efficacy were evaluated in pediatric patients receiving velaglucerase alfa 30–60 U/kg by intravenous infusion every other week. In addition to key hematological and visceral efficacy assessments, exploratory assessments conducted specifically in pediatric patients included evaluation of height, bone age, bone marrow burden, and Tanner stage of puberty. Results The study included 24 pediatric patients. Fifteen patients were naïve to ERT on entry into the preceding trials TKT032 (12-month trial) or HGT-GCB-039 (9-month trial): in the preceding trials, ten of these 15 patients received velaglucerase alfa and five patients received imiglucerase ERT. Nine patients in the study were previously treated with imiglucerase for \u3e 30 months and were switched to velaglucerase alfa in the preceding trial TKT034 (12-month trial). Cumulative ERT exposure in the clinical studies ranged from 2.0 to 5.8 years. Three serious adverse events, including a fatal convulsion, were reported; none were deemed related to velaglucerase alfa. One patient tested positive for anti-velaglucerase alfa antibodies. An efficacy assessment at 24 months showed that velaglucerase alfa had positive effects on primary hematological and visceral parameters in treatment-naïve patients, which were maintained with longer-term treatment. Disease parameters were stable in patients switched from long-term imiglucerase ERT. Exploratory results may suggest benefits of early treatment to enable normal growth in pediatric patients. Conclusion The safety profile and clinical response seen in pediatric patients are consistent with results reported in adults

The OsteoQuant: An Isotope-Based CT Scanner for Precise Measurement of Bone Density

Objective: We attempted to design and construct a computed tomography scanner with an in vivo precision of better than 0.5% for trabecular bone density of the radius. Materials and Methods: A number of considerations involving physical limitations, stability of the system, and cost led to the development of the Osteo-Quant, an isotope-based computed tomography scanner working on the trans-late-rotate principle. With 16 detectors providing a total of 128 projections and 256 data points per projection, the measurement time for one cross section is typically 90 s. Optimal for bone measurements in arms and legs, 125I was chosen as the photon source. The detectors are photomultipliers with Na1(TI) crystals employed in the counting mode. Usually, six to ten slices are measured at a given site, 2 mm apart from each other, and bone density is calculated for trabecular, subcompact, and compact bone. For repeat measurements, the evaluation sites are carefully matched, and the same volume of bone is analyzed at each measurement occasion. Results: The long-term precision of the scanner, measured with a water cylinder, is 0.03%. This error includes the performance of the scanner hardware, calibration of the photon count rates, and reconstruction process. In vivo precision is influenced by additional factors such as slice positioning, patient cooperation, and bone contour detection. At the distal end of the tibia, trabecular bone density can be measured with a precision of 0.1%. The error for trabecular bone density in the radius is 0.3%. Conclusion: The OsteoQuant surpasses the design goals and represents an ideal instrument to assess small changes in bone density over time

A Study of the Long-Term Precision of Dual-Energy X-Ray Absorptiometry Bone Densitometers and Implications for the Validity of the Least-Significant-Change Calculation

Introduction Short-term precision is often quoted and used as the most important performance parameter of a dual-energy X-ray absorptiometry (DXA) scanner; however, long-term precision has a more profound impact on patient monitoring. Long-term precision refers to the combination of in-vivo precision errors and long-term equipment stability. Methods To monitor long-term equipment stability, a phantom was designed with four inserts ranging in bone-mineral density from 0.5 to 3.3 g/cm2. This phantom was used to monitor the equipment stability of four modern fan-beam densitometers, two each from Hologic and GE/Lunar, over a 4-year period. Manufacturer-recommended quality assurance (QA) procedures were performed, and the scanners stayed within manufacturer-specified tolerances throughout the study. Results and conclusion During the 4-year period, the Hologic scanners were observed to cause clinically insignificant BMD shifts (maximum of 0.34%), whereas the GE/Lunar scanners revealed BMD shifts that were clinically significant (1.5% and 2.1%). As a result, using least-significant-change (LSC) calculations based only on short-term in-vivo precision studies for monitoring patients is not valid for the two GE/Lunar densitometers due to the poorer long-term stability they exhibited

Image-Based Strength Assessment of Bone

A patient\u27s bone status is commonly assessed by radiologic methods. Although the desired information concentrates on the probability of future fractures, the radiologic density is widely used as a surrogate for bone strength. There have been attempts to develop new parameters that have a closer relationship with bone strength, but the investigators tend to use a linear relationship between measured density and their strength-related parameter. We briefly discuss the background of mechanical deformation as it relates to bone and point out some of the basic principles involved in the assessment of strength. We then show that the relevant connection between strength and density makes use of the elastic modulus, which relates to density in a power law with an exponent of close to 2. We suggest modifications of some of the widely used strength-related parameter expressions that follow the theory more closely and will, thus, have the potential to better reflect the patient\u27s bone status

Correction of Scatter in Computed Tomography Images of Bone

A cylindrical aluminum/Plexiglas phantom representing trabecular bone surrounded by various amounts of cortical bone was constructed. Measurements of this phantom using a computed tomography scanner with a 125I photon source demonstrated errors of 0% to 28% in the density of trabecular bone. Two contributing factors are identified: scatter and exponential edge-gradient effect. A simple first-order correction is developed to correct for the scatter-induced error. Relative to the exponential edge-gradient effect, which contributes up to 3.4% error over the range of cortical thicknesses measured, the correction procedure reduces the scatter-induced error to a level of -0.66% to +0.61%. The consistency of the optimized correction parameters with the physical model as well as the effect of scatter measured by the same phantom on a GE 8800 scanner are shown