Eldecalcitol is superior to alfacalcidol in maintaining bone mineral density in glucocorticoid-induced osteoporosis patients (e-GLORIA).

INTRODUCTION: Eldecalcitol increases bone mineral density (BMD) and reduces vertebral fracture in patients with primary osteoporosis. However, the effect of eldecalcitol on BMD and fracture in glucocorticoid-induced osteoporosis (GIO) patients is unknown. This study was undertaken to compare the effect of eldecalcitol on BMD and fracture with that of alfacalcidol in GIO patients. MATERIALS AND METHODS: A randomized, open-label, parallel group study was conducted to identify the effectiveness and safety of monotherapy with 0.75 µg eldecalcitol compared with 1.0 µg alfacalcidol in GIO patients. RESULTS: Lumbar spine BMD increased with eldecalcitol, but decreased with alfacalcidol at 12 and 24 months (between group difference 1.29%, p < 0.01, and 1.10%, p < 0.05, respectively). Total hip and femoral neck BMD were maintained until 24 months by eldecalcitol, but decreased by alfacalcidol (between group difference 0.97%, p < 0.05 and 1.22%, p < 0.05, respectively). Both bone formation and resorption markers were more strongly suppressed by eldecalcitol than by alfacalcidol. Eldecalcitol showed better effect on BMD than alfacalcidol in patients with no prevalent fracture and BMD > 70% of the young adult mean, and with ≤ 3 months of previous glucocorticoid treatment. No significant difference in the incidence of vertebral fracture was found, and the incidence of adverse events was similar between the two groups. CONCLUSIONS: Eldecalcitol was more effective than alfacalcidol in maintaining BMD in GIO patients. Because eldecalcitol was effective in patients with no or short-term previous glucocorticoid treatment, as well as those without prevalent fracture or low BMD, eldecalcitol can be a good candidate for primary prevention of GIO. CLINICAL TRIAL REGISTRATION NUMBER: UMIN000011700.

The effects of once-weekly teriparatide on hip geometry assessed by hip structural analysis in postmenopausal osteoporotic women with high fracture risk.

Weekly administration of teriparatide has been shown to reduce the risk of vertebral and non-vertebral fractures in patients with osteoporosis at higher fracture risk in Japan. However, its efficacy for hip fracture has not been established. To gain insight into the effect of weekly teriparatide on the hip, hip structural analysis (HSA) based on dual-energy X-ray absorptiometry (DXA) was performed using the data of 209 postmenopausal osteoporotic women who had participated in the original randomized, multicenter, double-blind, placebo-controlled trial assessing the effects of once-weekly 56.5 µg teriparatide for 72 weeks. The DXA scans, obtained at baseline, 48 weeks and 72 weeks, were analyzed to extract bone mineral density (BMD) and cross-sectional geometrical indices at the narrowest point on the neck (NN), the intertrochanteric region (IT), and the proximal shaft. Compared with placebo after 72 weeks, the teriparatide group showed significantly higher BMD, average cortical thickness, bone cross-sectional area, and section modulus, and lower buckling ratio at both the NN and IT regions. No significant expansion of periosteal diameter was observed at these regions. There were no significant differences in BMD and HSA indices at the shaft region. The results indicate that overall structural strength in the proximal femur increased compared to placebo, suggesting that once-weekly teriparatide effectively reverses changes in hip geometry and strength with aging.

Hip structural analysis: a comparison of DXA with CT in postmenopausal Japanese women.

Geometry of the proximal femur is one determinant of fracture risk, and can be analyzed by a simple method using dual-energy X-ray absorptiometry (DXA). The aim of the present study was to investigate the accuracy of hip structural analysis (HSA) using clinical data in postmenopausal Japanese women. A total of 184 postmenopausal women aged 51-88 years (mean, 70.5 ± 8.7 years) who underwent artificial joint replacement surgery for osteoarthrosis of the hip or knee joint were included. Computed tomography (CT) data from preoperative assessment were utilized for analysis of proximal femoral geometry (CT-HSA) using QCTPro Software (Mindways Software Inc., Austin, TX) and compared with HSA results based on DXA (DXA-HSA). The results of femoral geometry were further compared with a CT-based finite-element method (CT/FEM). There was moderate to high correlation between DXA-HSA and CT-HSA (r=0.60-0.90, p<0.001), except for the buckling ratio in the intertrochanteric region. Moreover, the correlation of HSA with CT/FEM was similar between DXA-HSA and CT-HSA. The present results suggest that the geometry of proximal femoral cross sections can be reasonably well characterized using DXA.

Diagnostic criteria for primary osteoporosis: year 2012 revision.

In 1995, the Japanese Society for Bone and Mineral Metabolism (now the Japanese Society for Bone and Mineral Research) established the Osteoporosis Diagnostic Criteria Review Committee. Following discussion held at the 13th scientific meeting of the Society in 1996, the Committee, with the consensus of its members, proposed diagnostic criteria for primary osteoporosis. The Committee revised those criteria in 1998 and again in 2000. The Japanese Society for Bone and Mineral Research and Japan Osteoporosis Society Joint Review Committee for the Revision of the Diagnostic Criteria for Primary Osteoporosis aimed at obtaining international consistency and made a revised edition based on the new findings in 2012.

[Assessment of the exposure dose value displayed on operator console in a computed tomography system deciding exposure dose from positioning image].

The aim of this study was to assess the exposure dose value (DLP) displayed on the operator console in a computed tomography system with automatic exposure control (CT-AEC) which decides the exposure dose from a positioning image. We measured exposure dose with two kinds of CT systems and evaluated the error of the displayed DLP value on the operator console against the measured DLP value. The assessment was performed in three sites: head and neck, upper chest, and lower abdomen. As a result, the errors of displayed value with CT-AEC against the error without CT-AEC in system A (4.09%) were significantly different on two assessment sites (head and neck: -4.02%, upper chest: 6.60%). There is no significant difference on the third assessment site (lower abdomen: 0.06%). On the other hand, those values in system B (8.38%) were almost similar with no significant differences (head and neck: -1.12%, upper chest: -1.85%, lower abdomen: -0.64%). The results show that there were significant differences noted between the errors of displayed value with CT-AEC and without CT-AEC in system A for the head and neck and the upper chest. In conclusion, displayed value with CT-AEC and without CT-AEC were about the same error. However, the possibility that the error depended on a model and the examination site of CT was shown.

[Study of the additional filter in transcatheter hepatic arterial embolization].

It is well known that Interventional Radiology (IVR) is useful. However, the patient dose in IVR is increasing because of the prolongation of fluoroscopic time and the increase in the number of radiographies in recent years. We studied the adequacy of the additional filter for the decrease of the skin surface dose in patients with hepatocellular carcinoma of transcatheter arterial embolization (TAE). In 20 patients (15 men and 5 women, average age: 66.9 and 72.0 years old) who had undergone TAE, we estimated the skin surface dose from the records of their exposure condition (tube voltage, tube current, time, and field size of image intensifier) and the results of the phantom experiment with 2 kinds of additional filter. The estimated skin surface dose of the patient was 1.75 ± 0.84 with the additional filter of 1.5 mm thickness of aluminum (1.5 mmAl), 1.46 ± 0.67 Gy with 0.03 mm thickness tantalum (0.03 mmTa) and 1.17 ± 0.55 Gy with 0.06 mm thickness of tantalum (0.06 mmTa). Against a skin surface dose of 1.5 mmAl, the dose reduction of 16.7% was shown in 0.03 mmTa and 33.2% in 0.06 mmTa. With a DSA phantom of iodine density 0.5 and 1.0 and 2.0 mgI/ml, DSA images were acquisitioned at tube voltage 70, 80 and 90 kV to compare the detectability of contrast media in 0.06 mmTa with 1.5 mmAl. To evaluate the detectability of contrast media in 0.06 mmTa in 1.5 mmAl, receiver operating characteristic (ROC) analysis was performed with the pixel value of the phantom image. The area under the ROC curve in a 1.5 mmAl filter and the 0.06 mmTa filter provided with each contrast media density and each tube voltage was approximately a constant value. It was suggested that there was no differences in the detectability of contrast media in both additional filters. In conclusion, the skin surface dose of the patient was able to be reduced 33.2% without decreasing contrast media detectability by changing the additional filter from 1.5 mmAl to 0.06 mmTa. It was most suitable in TAE in our hospital to choose 0.06 mmTa as an additional filter.

[Method of calculating patient skin surface dose in transcatheter arterial embolization].

The usefulness of interventional radiology (IVR) in clinical practice is well known. However, patient dose in IVR has recently been increased as a result of the prolongation of fluoroscopic time and the increased number of radiographies. We studied a simple method of calculating skin surface dose in patients who underwent transcatheter arterial embolization (TAE) for the treatment of hepatocellular carcinoma by obtaining the value of a dose area product meter attached to the digital subtraction angiography system. In 20 subjects (15 men and 5 women, aged an average of 68.2+/-7.3 years, respectively) who underwent TAE, exposure conditions (tube voltage, tube current, time, and size of image intensifier) in a time series and last value indicated on the dose area product meter were recorded. A dosimetric phantom was placed at a position the same as that of the patient for TAE, the surface dose (SD) of the phantom was measured under various exposure conditions, and SD per unit mAs (SD/mAs) was obtained. Then the skin surface dose in each subject was estimated from the values of the exposure condition and SD/mAs. A high correlation was observed between the last value (x) on the dose area product meter and the estimated skin surface dose (y) (r=0.933), and the following regression equation was derived: y=0.005x-0.589. The skin surface dose calculated using the regression equation was compared with that obtained by the method recommended by the Japan Association on Radiological Protection in Medicine (JARPM), considering the value estimated from the value of exposure conditions with SD/mAs as the gold standard. The results indicated that the error in the method using the regression equation was significantly lower than that of the JARPM method (18.3+/-14.0% and 75.5+/-66.0%, respectively, p<0.01). In conclusion, the skin surface dose in TAE could be monitored with high precision using the value of the dose area product meter by obtaining the regression formula between the value of the dose area product meter and the skin surface dose estimated with the phantom values.

[Study on the accuracy of regional cerebral blood flow measurement using N-isopropyl-p-[123I]iodoamphetamine: effects of differences in venous sampling site and static imaging direction in one-point venous sampling method based on the causality model].

PURPOSE: We have previously reported the method of regional cerebral blood flow measurement using N-isopropyl-p-[123I]iodoamphetamine, in which the input function into brain was estimated from one-point venous blood sampling value based on the method of causality analysis between input and output functions. In the present study, we examined the effects of differences in blood sampling site and direction of static image collection on the accuracy of estimating input function using this method. METHODS: The subjects consisted of 50 patients of right forearm venous sampling and 50 patients of left forearm venous sampling. As the static imaging directions, the following four combinations were compared 10 all four directions, 2) anterior and posterior directions, 3) right and left directions, and 4) an anterior direction. The accuracy of measurement was evaluated by comparing the estimated and directly measured value of input/output function (Caoct/Cvoct), and by the error indices and the correlation coefficients between the estimated and directly measured value. RESULT: In both groups of venous sampling, there was no significant difference between the estimated and directly measured value of Caoct/Cvoct. The error indices and correlation coefficient showed no significant difference between the right and left venous sampling groups. Similarly, no significant influence on Caoct/Cvoct value was observed by the difference of static imaging direction. Finally, the rCBF values calculated using these estimations were not significantly different from those by continuous arterial sampling method. CONCLUSIONS: These results indicate that both the difference in venous sampling site and the static imaging direction have little effect on the accuracy in our new method of rCBF measurement, and suggest its clinical versatility.

Side-to-side differences in cortical bone mineral density of tibiae in young male athletes.

The importance of physical activity in the development and maintenance of bone mineral density (BMD) is widely accepted. However, the effects on cortical BMD have not been clarified in detail. The present study examined bilateral asymmetries in cortical BMD of the tibia using peripheral quantitative computed tomography. Subjects comprised 37 young male athletes and 57 controls (age range, 18-28 years). BMD and geometrical indices were determined in bilateral tibiae. Cortical and trabecular BMD were calculated at the diaphysis and distal metaphysis, respectively. Cortical width, periosteal cross-sectional area, and cross-sectional moment of inertia were calculated using tomographic data of the tibial diaphysis. In athletes, the non-dominant leg showed greater cortical BMD than the dominant leg (mean difference, 5.42%; P < 0.0001). Cortical width and moment of inertia were also greater in the non-dominant leg. Periosteal area displayed no significant difference between legs. The control group exhibited similar results except for cortical BMD. No differences in trabecular BMD were noted between legs in either athletes or controls. These results implies the existence of mechanisms for the mechanical adaptation of cortical BMD. Dominant leg is used for mobility or manipulation whereas the non-dominant leg contributes to support the actions of the dominant leg. Loading differences in bilateral legs in young athletes might affect the remodeling rate leading to the side-to-side differences in cortical BMD.

Measurement of regional cerebral blood flow with 123I-IMP using one-point venous blood sampling and causality analysis: evaluation by comparison with conventional continuous arterial blood sampling.

OBJECTIVE: Arterial input function represents the delivery of intravascular tracer to the brain. The optimal setting of this function is essential for measuring regional cerebral blood flow (rCBF) based on the microsphere model using N-isopropyl-4-[123I]iodoamphetamine (123I-IMP), in which the arterial 123I-IMP concentration (integral value) during the initial 5 min is usually applied. We developed a novel method in which the arterial 123I-IMP concentration is estimated from that in venous blood samples. METHODS: Brain perfusion SPECT with 123I-IMP was performed in 110 patients with disorders of the central nervous system. A causality analysis determined the relationship between various SPECT parameters and the ratio of the octanol-extracted arterial radioactivity concentration during the first 5 min (Caoct) to the octanol-extracted venous radioactivity concentration at 27 min after an intravenous injection of 123I-IMP (Cvoct). The Caoct/Cvoct value was estimated using various SPECT parameters and compared with the directly measured value. RESULTS: The measured and estimated values of Caoct/ Cvoct (r = 0.856, n = 50) closely correlated when the following 7 parameters were included in the regression formula: radioactivity concentration in venous blood sampled at 27 min (Cv), Cvoct, Cvoct/Cv, and 4 parameters related to cerebral tissue accumulation that were measured using a four-head gamma camera 5 and 28 min after 123I-IMP injection. Furthermore, the rCBF values obtained using the input function estimated by this method also closely correlated with the rCBF values measured using the continuous arterial blood sampling (r = 0.912, n = 180). CONCLUSION: These results suggest that this method would serve as a convenient and less invasive method of rCBF measurement in the clinical setting.

Therapeutic effects of alendronate 35 mg once weekly and 5 mg once daily in Japanese patients with osteoporosis: a double-blind, randomized study.

The efficacy and safety of treatment with oral alendronate (ALN) 35 mg once weekly for 52 weeks were compared with those of ALN 5 mg once daily in a double-blind, randomized, multicenter study of Japanese patients with involutional osteoporosis. The primary efficacy end point was the percent change from baseline in the lumbar spine (L1-L4) bone mineral density (BMD) after 52 weeks of treatment. In this study, 328 patients were randomized to ALN 5 mg once daily (160 patients) or ALN 35 mg once weekly (168 patients). The adjusted mean percent change from baseline in lumbar spine (L1-L4) BMD after 52 weeks of treatment was 5.8% and 6.4% in the once-daily group and the once-weekly group, respectively (both P < 0.001). The 95% confidence interval for the difference in spine BMD change between the two treatment groups was -0.31% to 1.48%, indicating that the two regimens were therapeutically equivalent, since the confidence interval fell entirely within the predefined equivalence criterion (+/-1.5%). The time course of the spine BMD increase was also similar for both regimens. Regarding total hip BMD, mean changes from baseline at 52 weeks were 2.8% and 3.0% in the once-daily group and the once-weekly group, respectively. In addition, the bone markers (urinary deoxypyridinoline, urinary type-I collagen N-telopeptides, and serum bone-specific alkaline phosphatase) were reduced to a similar level by either treatment throughout the treatment period. The tolerability and safety profiles were also similar between the treatment groups. Taken together, we conclude that the efficacy and safety of the ALN 35-mg once-weekly regimen are therapeutically equivalent to those of the ALN 5-mg once-daily regimen.

Comparison of vertebral morphometry in the lumbar vertebrae by T1-weighted sagittal MRI and radiograph.

PURPOSE: In this study, we investigated the usefulness of T1-weighted sagittal MR images at the lumbar vertebrae in the vertebral morphometry, in comparison with lateral radiographs. SUBJECTS AND METHODS: The subjects were 42 men (mean age: 53.0 years) and 41 women (mean age: 57.9 years). Both MRI and radiography of the lumbar spine were performed within 1 month. The vertebral body heights and their ratios were measured by the semi-automatic measuring system. The frequency of a vertebral fracture and the absolute value of vertebral body height in both morphometry were compared. RESULTS: Based on the criteria for prevalent vertebral fracture using vertebral height ratios, the vertebrae were classified into four groups. Group 1 was defined as the vertebrae without fracture (n=347 vertebrae). Groups 2-4 were defined as the vertebrae with fracture; Group 2 by both MRI and X-ray morphometry (n=17), Group 3 by MRI morphometry alone (n=17), and Group 4 by X-ray morphometry alone (n=4). The rate of prevalent vertebral fracture diagnosed by MRI morphometry (8.8%) was higher than that by X-ray morphometry (5.5%). In Group 1, the values of anterior and posterior vertebral height obtained by MRI morphometry were greater than those obtained by X-ray morphometry. On the other hand, the values of central vertebral height obtained by MRI morphometry were smaller than those obtained by X-ray morphometry. CONCLUSION: Severe biconcave deformity of vertebra can be detected by both MRI and X-ray morphometry, although mild biconcave deformity can be detected only by MRI morphometry.

[Fractal analysis of trabecular architecture: with special reference to slice thickness and pixel size of the image].

Many analyses of bone microarchitecture using three-dimensional images of micro CT (microCT) have been reported recently. However, as extirpated bone is the subject of measurement on microCT, various kinds of information are not available clinically. Our aim is to evaluate usefulness of fractal dimension as an index of bone strength different from bone mineral density in in-vivo, to which microCT could not be applied. In this fundamental study, the relation between pixel size and the slice thickness of images was examined when fractal analysis was applied to clinical images. We examined 40 lumbar spine specimens extirpated from 16 male cadavers (30-88 years; mean age, 60.8 years). Three-dimensional images of the trabeculae of 150 slices were obtained by a microCT system under the following conditions: matrix size, 512 x 512; slice thickness, 23.2 em; and pixel size, 18.6 em. Based on images of 150 slices, images of four different matrix sizes and nine different slice thicknesses were made using public domain software (NIH Image). The threshold value for image binarization, and the relation between pixel size and the slice thickness of an image used for two-dimensional and three-dimensional fractal analyses were studied. In addition, the box counting method was used for fractal analysis. One hundred forty-five in box counting was most suitable as the threshold value for image binarization on the 256 gray levels. The correlation coefficients between two-dimensional fractal dimensions of processed images and three-dimensional fractal dimensions of original images were more than 0.9 for pixel sizes < or =148.8 microm at a slice thickness of 1 mm, and < or =74.4 microm at one of 2 mm. In terms of the relation between the three-dimensional fractal dimension of processed images and three-dimensional fractal dimension of original images, when pixel size was less than 74.4 microm, a correlation coefficient of more than 0.9 was obtained even for the maximal slice thickness (1.74 mm) examined in this study.

Fractal analysis of bone architecture at distal radius.

Bone strength depends on bone quality (architecture, turnover, damage accumulation, and mineralization) as well as bone mass. In this study, human bone architecture was analyzed using fractal image analysis, and the clinical relevance of this method was evaluated. The subjects were 12 healthy female controls and 16 female patients suspected of having osteoporosis (age range, 22-70 years; mean age, 49.1 years). High-resolution CT images of the distal radius were acquired and analyzed using a peripheral quantitative computed tomography (pQCT) system. On the same day, bone mineral densities of the lumbar spine (L-BMD), proximal femur (F-BMD), and distal radius (R-BMD) were measured by dual-energy X-ray absorptiometry (DXA). We examined the correlation between the fractal dimension and six bone mass indices. Subjects diagnosed with osteopenia or osteoporosis were divided into two groups (with and without vertebral fracture), and we compared measured values between these two groups. The fractal dimension correlated most closely with L-BMD (r=0.744). The coefficient of correlation between the fractal dimension and L-BMD was very similar to the coefficient of correlation between L-BMD and F-BMD (r=0.783) and the coefficient of correlation between L-BMD and R-BMD (r=0.742). The fractal dimension was the only measured value that differed significantly between both the osteopenic and the osteoporotic subjects with and without vertebral fracture. The present results suggest that the fractal dimension of the distal radius can be reliably used as a bone strength index that reflects bone architecture as well as bone mass.

Effects of genetic and nutritional factors on bone mineral density in young adults.

To estimate the genetic and dietary factors influencing bone mineral density (BMD) in young adults, a total of 53 healthy volunteers (HV) (age 20.89+/-1.34), from whom informed consent was obtained, answered a questionnaire on dietary factors and had DNA from peripheral blood mononuclear cells analyzed for single nucleotide polymorphisms (SNPs) for vitamin (Vit) D receptor (VDR), estrogen receptor alpha (ERalpha), interleukin 1 receptor antagonist (IL1RA), and apolipoprotein E (ApoE) genes. Daily intakes of Vit C, fiber, soybean and related foods, and green and yellow vegetables showed a correlation with % BMD. In addition, Vit B2 as well as Vit C, and vegetables were identified as important factors for BMD by Stepwise regression analysis. Among the SNPs analyzed, the B+ type of the VDR gene tended to be associated with a lower BMD, and pp type of the ER gene digested by the PvuII enzyme in females indicated a significantly lower BMD than that in males. In addition, these SNPs were also identified by factor analysis to be associated with BMD. These results suggested that a complex array of genetic factors, such as two or more SNPs or SNPs and gender, may be important to BMD.