Teruki Sone

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.

Apparent diffusion coefficient values in peripheral and transition zones of the prostate: comparison between normal and malignant prostatic tissues and correlation with histologic grade.

To investigate the utility of apparent diffusion coefficient (ADC) values for discriminating tumor in patients with prostate cancer from normal prostatic tissues in healthy adult men, and to identify correlations between ADC and histologic grade of prostate cancer.

Randomized Teriparatide [Human Parathyroid Hormone (PTH) 1–34] Once-Weekly Efficacy Research (TOWER) Trial for Examining the Reduction in New Vertebral Fractures in Subjects with Primary Osteoporosis and High Fracture Risk

CONTEXT Weekly teriparatide injection at a dose of 56.5 μg has been shown to increase bone mineral density. OBJECTIVE A phase 3 study was conducted to determine the efficacy of once-weekly teriparatide injection for reducing the incidence of vertebral fractures in patients with osteoporosis. DESIGN AND SETTING In this randomized, multicenter, double-blind, placebo-controlled trial conducted in Japan, the incidence of morphological vertebral fractures by radiographs was assessed. PATIENTS Subjects were 578 Japanese patients between the ages of 65 and 95 yr who had prevalent vertebral fracture. INTERVENTION Subjects were randomly assigned to receive once-weekly s.c. injections of teriparatide (56.5 μg) or placebo for 72 wk. MAIN OUTCOME MEASURE The primary endpoint was the incidence of new vertebral fracture. RESULTS Once-weekly injections of teriparatide reduced the risk of new vertebral fracture with a cumulative incidence of 3.1% in the teriparatide group, compared with 14.5% in the placebo group (P < 0.01), and a relative risk of 0.20 (95% confidence interval, 0.09 to 0.45). At 72 wk, teriparatide administration increased bone mineral density by 6.4, 3.0, and 2.3% at the lumbar spine, the total hip, and the femoral neck, respectively, compared with the placebo (P < 0.01). Adverse events (AE) and the dropout rates by AE were more frequently experienced in the teriparatide group, but AE were generally mild and tolerable. CONCLUSION Weekly s.c. administration of teriparatide at a dose of 56.5 μg may provide another option of anabolic treatments in patients with osteoporosis at higher fracture risk.

Prostate Cancer: Relationships between Postbiopsy Hemorrhage and Tumor Detectability at MR Diagnosis

PURPOSE To retrospectively evaluate the influence of postbiopsy hemorrhage on the accuracy of tumor detection at T2-weighted magnetic resonance (MR) imaging, dynamic contrast material-enhanced MR imaging, and diffusion-weighted (DW) MR imaging of prostate cancer, with histologic findings as the reference standard. MATERIALS AND METHODS The institutional review board approved this study and waived the requirement for informed consent. Forty male patients aged 62-84 years (mean age, 71 years) who had prostate cancer underwent MR imaging of the prostate gland after ultrasonographically (US) guided systematic 12-core-specimen biopsy. The mean time between biopsy and MR imaging was 24 days (range, 6-54 days). T1-weighted, T2-weighted, dynamic contrast-enhanced, and DW imaging examinations were performed at 1.5 T. The prostate was divided, according to the biopsy sites, into eight regions on the MR images. Three reviewers in consensus evaluated each region for hemorrhage and prostate cancer. Statistical evaluations were performed with Mann-Whitney U, Ryan, and Spearman rank correlation tests. RESULTS Intraglandular hemorrhage was observed in 38 (95%) patients and significantly more often in the peripheral zone (PZ) than in the transition zone (TZ) (P < .001). Degree of hemorrhage did not correlate significantly (P = .536) with time between biopsy and MR imaging. The sensitivity, specificity, and accuracy of combined T2-weighted, dynamic contrast-enhanced, and DW imaging in the diagnosis of prostate cancer were 69%, 85%, and 78%, respectively. Sensitivity and specificity were lower for the TZ than for the PZ. Degree of hemorrhage was significantly lower in regions of positive biopsy findings than in regions of negative biopsy findings (P = .001) and correlated negatively with tumor size (P = .043). CONCLUSION Interpretation of combined T2-weighted, dynamic contrast-enhanced, and DW MR image findings can yield reasonable diagnostic accuracy in both the PZ (80% [191 of 240 regions]) and the TZ (74% [59 of 80 regions]).

A new active vitamin D3 analog, eldecalcitol, prevents the risk of osteoporotic fractures--a randomized, active comparator, double-blind study.

BACKGROUND Eldecalcitol is an analog of 1,25-dihydroxyvitamin D(3) that improves bone mineral density; however, the effect of eldecalcitol on the risk of fractures is unclear. The objective of this study is to examine whether eldecalcitol is superior to alfacalcidol in preventing osteoporotic fractures. This trial is registered with ClinicalTrials.gov, number NCT00144456. METHODS AND RESULTS This 3 year randomized, double-blind, active comparator, superiority trial tested the efficacy of daily oral 0.75 μg eldecalcitol versus 1.0 μg alfacalcidol for prevention of osteoporotic fractures. 1054 osteoporotic patients 46 to 92 years old were randomly assigned 1:1 to receive eldecalcitol (n=528) or alfacalcidol (n=526). Patients were stratified by study site and serum 25-hydroxyvitamin D level. Patients with low serum 25-hydroxyvitamin D levels (<50 nmol/L) were supplemented with 400 IU/day vitamin D(3). Primary end point was incident vertebral fractures. Secondary end points included any non-vertebral fractures and change in bone mineral density and bone turnover markers. Compared with the alfacalcidol group, the incidence of vertebral fractures was lower in eldecalcitol group after 36 months of treatment (13.4 vs. 17.5%; hazard ratio, 0.74; predefined 90% confidence interval [CI], 0.56-0.97). Eldecalcitol reduced turnover markers and increased bone mineral density more strongly than alfacalcidol. Eldecalcitol reduced the incidence of three major non-vertebral fractures, which was due to a marked reduction in wrist fractures by a post-hoc analysis (1.1 vs. 3.6%; hazard ratio, 0.29; 95% CI, 0.11-0.77). Among the adverse events, the incidence of increase in serum and urinary calcium was higher in the eldecalcitol group, without any difference in glomerular filtration rate between the two groups. CONCLUSIONS Eldecalcitol is more efficacious than alfacalcidol in preventing vertebral and wrist fractures in osteoporotic patients with vitamin D sufficiency, with a safety profile similar to alfacalcidol.

Gd-EOB-DTPA-enhanced MR imaging: Evaluation of hepatic enhancement effects in normal and cirrhotic livers

OBJECTIVE The purpose of this study was to assess differences in enhancement effects of liver parenchyma between normal and cirrhotic livers on contrast-enhanced MR imaging (CE-MRI) obtained with Gd-EOB-DTPA. METHODS A total of 99 patients with cirrhotic liver (n=58; Child-Pugh class A, n=30; B, n=22; C, n=6) and normal liver (n=41) underwent Gd-EOB-DTPA-enhanced MR imaging. CE images were obtained before contrast injection, in the arterial phase (AP) at 25s or modified scan delay, in the portal phase (PP) at 70s, in the equilibrium phase (EP) at 3 min, and in the hepatobiliary phase (HP) at 3 times (10, 15 and 20 min). Signal intensity of the liver in all phases was defined using region-of-interest measurements for relative enhancement (RE) calculation. RESULTS In normal-liver and Child-Pugh class A and B patients, mean RE of liver parenchyma increased significantly (P<0.03-0.001) with time until 20-min HP. Conversely, mean RE for Child-Pugh class C patients did not show any increasing tendency after PP. Mean RE of liver parenchyma at EP and HP (10-, 15- and 20-min) was highest in normal liver, followed by Child-Pugh class A, B and C cirrhosis (P<0.02-0.001). CONCLUSION Hepatic parenchymal enhancement on CE-MR images obtained using Gd-EOB-DTPA is affected by the severity of cirrhosis.

Dynamic contrast-enhanced magnetic resonance imaging of abdominal solid organ and major vessel: comparison of enhancement effect between Gd-EOB-DTPA and Gd-DTPA.

To evaluate the differences in enhancement of the abdominal solid organ and the major vessel on dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI) obtained with gadolinium ethoxybenzyldiethylenetriamine pentaacetic acid (Gd‐EOB‐DTPA: EOB) and gadolinium diethylenetriamine pentaacetic acid (Gd‐DTPA) in the same patients.

Effects of endurance exercise on three-dimensional trabecular bone microarchitecture in young growing rats

Appropriate endurance exercise is capable of increasing bone mass and strength in both animals and humans. We examined the skeletal changes induced by treadmill running exercise in young growing rats with a particular emphasis on three-dimensional trabecular bone microarchitecture. Fourteen male Wistar rats were divided into sedentary (CON; n = 7) and exercised (RUN; n = 7) groups at the age of 4 weeks. The rats in the RUN group performed the treadmill running exercise of 30 m/min for 60 min, 5 times a week. After 10 weeks of exercise, bone mineral density (BMD), cortical geometry, diaphyseal breaking force, and trabecular bone microarchitecture in the femur were measured. Three-dimensional trabecular bone microarchitecture was evaluated at the distal femoral metaphysis using microcomputed tomography. The running exercise significantly increased BMD, bone volume, bone volume fraction, trabecular thickness, and trabecular number, whereas trabecular bone pattern factor, the parameter associated with decreased trabecular connectivity, was significantly lower in the RUN group than the CON group. On the other hand, no significant difference in the degree of anisotropy and structure model index was observed between the two groups. At the femoral diaphysis, running exercise significantly increased cortical bone area, width, and maximum load without affecting bending stress, implying that the material properties of bone had not changed in the exercised rats. These results suggest that the increase in bone strength induced by endurance exercise is mediated by changes in trabecular bone microarchitecture as well as density and cortical geometry.

Biochemical markers for the detection of bone metastasis in patients with prostate cancer : diagnostic efficacy and the effect of hormonal therapy

Abstract In the present study, we investigated the diagnostic effectiveness of biochemical markers of bone turnover for the detection of bone metastasis from prostate cancer and changes in the levels of these markers caused by hormonal therapy. Ninety-five patients with prostate cancer were divided into one of three groups: 26 patients with bone metastasis (BM(+)), 35 patients without bone metastasis on nonhormonal therapy (BM(−)HT(−)) and 34 patients without bone metastasis on hormonal therapy (BM(−)HT(+)). All patients in the BM(+) group had received hormonal therapy. Serum or urinary levels of the following biochemical markers of bone turnover were examined: bone-specific alkaline phosphatase (B-ALP), osteocalcin (OC), type I procollagen C-propeptide (PICP), type I collagen cross-linked C-telopeptide (ICTP), C-telopeptide fragment (CTx), N-telopeptide fragment (NTx), total pyridinoline (T-Pyr), total deoxypyridinoline (T-D-Pyr) and free deoxypyridinoline (F-D-Pyr). The BM(+) group showed significantly higher values than the BM(-)HT(-) group for B-ALP, PICP, NTx, CTx, T-Pyr, T-D-Pyr, and F-D-Pyr. Compared with the BM(−)HT(+) group, the BM(+) group showed significantly higher values for B-ALP, ICTP, NTx, T-Pyr and T-D-Pyr. The levels of B-ALP, NTx, CTx, T-D-Pyr and F-D-Pyr were significantly different between the BM(−)HT(−) and BM(−)HT(+) groups. All markers, except OC and CTx, significantly were correlated with the extent of bone metastasis on bone scintigraphy. Of all markers, receiver operating characteristic (ROC) analyses revealed B-ALP and F-D-Pyr to be the most sensitive and specific for differentiation between the BM(+) and BM(−)HT(−) groups with regard to bone formation and resorption, respectively. In contrast, B-ALP and ICTP were most sensitive and specific for differentiation between the BM(+) and BM(−)HT(+) groups. The results suggest that hormonal therapy greatly affects the efficacy of PICP, CTx and F-D-Pyr in the diagnosis of bone metastasis, whereas its effects on ICTP are small. Although bone metabolic markers would be useful in the diagnosis of bone metastasis from prostate cancer, the effects of hormonal therapy on bone metabolism should be kept in mind in their evaluation.

Urinary excretion of type I collagen crosslinked N-telopeptides in Healthy japanese adults: Age- and sex-related changes and reference limits

A new immunoassay for measuring urinary excretion of type I collagen crosslinked N-telopeptides (NTx) has been reported to be a specific and sensitive method for assessing bone resorption. We have studied factors affecting biological variations in urinary NTx excretion in a population of 452 healthy Japanese adults, comprising 238 men and 214 women, 20-79 years of age. Urinary NTx excretion increased significantly with age in women (> or = 25 years of age) (r = 0.55, p < 0.0001) and modestly correlated with lumbar bone mineral density (L-BMD) in both sexes (> or = 25 years of age) (r = 0.31, p < 0.0001 for men; r = 0.50, p < 0.0001 for women). Urinary NTx levels in women were significantly higher than in the corresponding male age groups after the fifth decade (p < 0.0001). None of the anthropometric variables (weight, height, and body mass index) showed a linear effect on the urinary NTx excretion independent of age and L-BMD. In women, menopause was reflected by a twofold increase in urinary NTx excretion, from a mean of 28-59 pmol bone collagen equivalents (BCE)/mumol creatinine, and this menopause-related increase persisted for the entire postmenopausal period. In postmenopausal women, the interindividual variations of urinary NTx excretion were much more marked than in men and in premenopausal women. Moreover, in the subgroups of pre- and postmenopausal women, urinary NTx excretion correlated with neither age nor L-BMD. These data show that the major biological factor that modifies urinary NTx level is menopause and suggest that the bone turnover rates in the elderly women are increased, on average, irrespective of bone mineral density.