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Summary A randomized placebo-controlled trial was conducted to examine the effect of daily oral 1 mg minodronate on vertebral fractures in 704 postmenopausal women with established osteoporosis for 24 months. Minodronate treatment reduced vertebral fractures by 59% without serious adverse events. Minodronate is a safe and effective bisphosphonate for osteoporosis treatment. Introduction Minodronate increases bone mineral density (BMD) in postmenopausal osteoporotic patients. However, its efficacy in reducing osteoporotic fractures has not been tested. Methods To examine anti-fracture efficacy and safety of daily oral minodronate in postmenopausal women with established osteoporosis, a randomized, double-blind, placebo-controlled trial was conducted in 704 postmenopausal women (55 to 80 years) with one to five vertebral fractures and low BMD. Subjects were randomly assigned to receive daily oral 1 mg minodronate (n = 359) or placebo (n = 345) for 24 months, with daily supplements of 600 mg calcium and 200 IU vitamin D3. Results Daily 1 mg minodronate for 24 months reduced the risk of vertebral fractures by 59% (95% CI, 36.6–73.3%). Furthermore, when fractures during the first 6 months were eliminated, the risk of vertebral fractures from 6 to 24 months was reduced by 74% in minodronate-treated group. Minodronate treatment also reduced height loss. Bone turnover markers were suppressed by about 50% after 6 months of minodronate treatment and remained suppressed thereafter. The overall safety profile including gastrointestinal safety was similar between the two groups. Conclusions Daily oral minodronate is safe, well-tolerated, and is effective in reducing vertebral fracture risk in postmenopausal women with established osteoporosis.

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.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.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.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.

The mechanism whereby liposomal entrapment enhances the hypocalcemic effect of calcitonin (CT) was evaluated in the rat. Phosphatidylcholine (PC) and PC plus cholesterol (PCC) preparations of large multilammelar vesicles (MLV) and small unilammelar vesicles (SUV) were used to entrap human calcitonin (hCT). The effect of each of these preparations was assessed by measuring plasma calcium after their parenteral administration. Changes in calcium were compared with plasma concentrations of liposomal hCT (L-hCT) and free hCT (F-CT). The plasma form of hCT was also evaluated by gel filtration chromatography. Most of the liposomal preparations had a greater hypocalcemic effect than unencapsulated hCT. Following I.V. administration, the MLV-hCT preparations had the greatest hypocalcemic effect. Thus, to enhance the hypocalcemic effect of hCT, large vesicular size is important for I.V. administration and the absence of cholesterol in the liposome is important for I.M. administration. In general, the greatest hypocalcemic effect was achieved by those liposomal preparations that resulted in the most sustained increase of L-hCT and F-hCT in plasma. Thus, liposomal entrapment enhances the hypocalcemic effect of hCT by prolonging the presence of the peptide in the peripheral circulation.

Using a dual photon absorptiometer Dualomex HC-1 based on the scinticamera system utilizing153Gd, bone density of the lumbar vertebrae was measured to set up normative values for each group in both sexes along with fracture threshold.

Objective To compare the efficacy and safety of dienogest (DNG) with intranasal buserelin acetate (BA) in patients with endometriosis. Design Phase III, randomized, double-blind, multicenter, controlled trial. Setting Twenty-four study centers in Japan. Patient(s) Two hundred seventy-one patients with endometriosis. Intervention(s) Dienogest (2 mg/day, orally) or BA (900 μg/day, intranasally) for 24 weeks. Main Outcome Measure(s) The pre- to posttreatment changes in the scores of five subjective symptoms during nonmenstruation (lower abdominal pain, lumbago, defecation pain, dyspareunia, and pain on internal examination) and two objective findings (induration in the pouch of Douglas and limited uterine mobility). Result(s) Dienogest reduced the scores of all symptoms and findings at the end of treatment, and the mean changes in the scores of all symptoms and findings except induration in the pouch of Douglas were comparable to those obtained with BA. Compared with BA, DNG was associated with irregular genital bleeding more frequently and with fewer hot flushes. The reduction in bone mineral density (BMD) during DNG treatment was significantly lower than that during BA treatment. Conclusion(s) DNG is as effective as intranasal BA in alleviating endometriosis, and causes less BMD loss.

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.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.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).These results suggest that this method would serve as a convenient and less invasive method of rCBF measurement in the clinical setting.

Based on preclinical evidence in animal models, the present study examined the clinical efficacy and safety of recombinant human fibroblast growth factor-2 (rhFGF-2) to accelerate bone repair in a dose-escalation prospective trial. One of three dosages (200, 400 or 800 microg) of rhFGF-2 in a biodegradable gelatin hydrogel was injected during surgery into the osteotomy site of 59 knee osteoarthritis patients undergoing high tibial osteotomy, and 57 of them were monitored for 16 weeks. The rhFGF-2 dose dependently increased the percentage of patients with radiographic bone union, and decreased the average time needed for such union. The percentages of patients with an absence of pain and full-weight bearing were also greater in the higher dosage groups than in the low dosage group, especially in the clinically critical periods 6, 8, and 10 weeks. Neither blood chemistries nor clinical adverse events were associated with the rhFGF-2 dosages. We therefore conclude that the rhFGF-2 in gelatin hydrogel dose dependently accelerated radiographic bone union of a surgical osteotomy with a safety profile at least at the dosages used, suggesting the clinical efficacy of this agent for bone repair.

Previous study has shown that the vitamin K2 analog menaquinone-7 (MK-7) induces expression of the osteoblast-specific genes osteocalcin, osteoprotegerin, receptor activator of NFkappaB, and its ligand. Since MK-7 may also regulate osteoblast cell function, we examined the expression of osteoblast genes regulated by MK-7 administration. Differences between gene expression in control and MK-7-administered MC3T3E1 cells were analyzed using the suppression subtractive hybridization method. After 24 h of MK-7 administration, genes upregulated by MK-7 included tenascin C and BMP2. Genes downregulated by MK-7 administration included biglycan and butyrophilin. Real-time PCR showed a marked increase in tenascin C. When the protein level was examined using Western blot analysis, tenascin C was higher in MK-7-administered cells than in control cells. These results indicated that MK-7 affected the cellular function of osteoblastic MC3T3E1 cells. Considering BMP2 mRNA expression was higher in MK-7-administered cells than in control cells, the effect of MK-7 administration on the signal transduction system was examined. Western blot analysis showed that cells administered MK-7 displayed a higher phosphorylated Smad1 level than control cells. Because MC3T3E1 cells have a nuclear binding receptor for MK-7, this result might indicate an indirect effect of MK-7 through BMP2 production.

In this article, an outline of dual energy X-ray absorptiometry (DXA), quantitative ultrasound (QUS), and radiogram, and their characteristics, problems, and assessment of osteoporosis in the elderly were reviewed. It is well known that both DXA and QUS are available to risk assessment of fractures. However, because lumbar bone mineral density (BMD) is overestimated in the elderly complicated with fracture, deformity, and osteosclerotic change in the lumbar vertebra (e), some cases are unsuitable to measurement of BMD with lumbar DXA. To define vertebral fracture, visual semiquantitative and morphometric methods are used. In addition, differential diagnosis of osteoporotic vertebral fractures is necessary. Thus, to establish an exact diagnosis of osteoporosis in the elderly, it is important to understand some problems associated with the elderly.

With coming of aged society, male patients with osteoporosis are increasing, and it is important to prevent and treat them. In male osteoporosis, secondary osteoporosis is relatively common as an etiology, and therefore it is necessary to exclude secondary causes, when it will be diagnosed. In female a rapid decrease of bone mineral density (BMD) is observed after menopause, while in male such changes are not. Japanese Society of Bone and Mineral Research proposed diagnostic criteria of male osteoporosis, which 70% of young adult mean (YAM) of hip BMD was used as cut-off value for osteoporosis.

In this multicenter, randomized, double-blind controlled trial, the efficacy and safety of once-weekly dosing with 17.5 mg risedronate was compared with once-daily dosing with 2.5 mg risedronate in Japanese patients with involutional osteoporosis. A total of 496 patients were randomized to receive either once-weekly (n = 249) or once-daily (n = 247) treatment. All patients were supplemented with 200 mg/day calcium. Following 48 weeks of treatment, the mean (+/-SD) percent changes, from baseline, in the bone mineral density of the lumbar spine (L2-L4 BMD) in the once-weekly and once-daily treatment groups were 5.36 +/- 4.27% and 5.87 +/- 4.47%, respectively. The difference between the groups was -0.5% (95% confidence interval: -1.35% to 0.35%), demonstrating that the effect on BMD of once-weekly treatment was not inferior to that of once-daily treatment. The time-course reductions in biochemical markers of bone resorption (urinary N- and C-telopeptide of type I collagen) and bone formation (bone-specific alkaline phosphatase) were similar for the two dosing regimens. There were no differences in the incidence of new vertebral fractures or the worsening of existing fractures between the once-weekly (2.2%) and once-daily (2.7%) dosing regimens. No significant differences were observed between the two dosing regimens in the incidence or the type of adverse events. However, 10.1% of the patients in the once-daily group withdrew due to adverse events as compared to 5.2% in the once-weekly group. Moreover, drug-related adverse events, including upper gastrointestinal disorders and abnormal changes in laboratory parameters, tended to be less in the once-weekly dosing regimen than in the once-daily dosing regimen. In conclusion, once-weekly oral dosing with 17.5 mg risedronate was well tolerated in Japanese osteoporotic patients, and showed equivalent efficacy to once-daily oral dosing with 2.5 mg risedronate. This once-weekly regimen is expected to provide a more convenient therapeutic option as an alternative to daily dosing and to enhance patient compliance in long-term therapy for osteoporosis.

Bone strength is determined by bone mineral density and bone quality. Bone quality can be assessed by only bone turnover markers. Nutrients that reduce bone resorption markers are calcium and isoflavone, nutrients that increase bone formation markers are vitamin C, vitamin D and vitamin K. These nutrients affect bone turnover and, as a result, improve bone density. These nutrients might contribute to prevent the incidence of osteoporosis when they are taken from adolescence.

The diagnosis of Osteoporosis on WHO Technical Report of Prevention and Management of Osteoporosis in 2003, in addition to present status in Japan, has been reviewed. Since Technical Report of Assessment of Fracture Risk and Its Application to Screening for Postmenopausal Osteoporosis was published by WHO in 1994, the field of osteoporosis has progressed remarkably. In particular, in regard to methods of measuring bone mass or density, diagnosis, assessment of fracture risk, and assessment of osteoporosis, this Technical Report describes evidences, confirmed from current many data, and provides informations available to osteoporosis practice. This Report also shows future direction and issues of osteoporosis which should be resolved.

Osteoporosis occurs more common in women than that in men. In addition, there exist the sex differences in bone indexes such as bone mineral density (BMD), bone mineral content, and bone area or width, and in the decreased pattern of BMD associated with aging. Therefore, it is necessary to use a cut-off value of BMD of not women but men, as diagnostic criteria for male osteoporosis. In this article, from a point of view of sex difference, diagnosis and treatment of osteoporosis will be reviewed.

In this paper, bone mass measurement and its evaluation have been reviewed. The bone lesions in renal osteodystrophy are classified into high- and low turnover, and the decreased rate of bone mineral density (BMD) might be different in osteitis fibrosa and adynamic bone disease. Secondary hyperparathyroid patients showed lower BMD values in mainly composed of the cortical bone than those in mainly composed of the trabecular bone.

In this paper, the assessment of radiographic vertebral fracture (prevalent fracture and incident fracture) in the diagnosis of osteoporosis and the therapeutical assessment by bone mineral density measurements are reviewed.

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.

NIH Consensus Development Panel states that bone strength primarily reflects the integration of bone density and bone quality. In addition, it is reported that bone quality refers to architecture, turnover, damage accumulation, and mineralization. Increased bone turnover is an independent risk of fracture of low bone mineral density. Increased bone turnover of urinary CTX, free DPD and free PYD, or decreased turnover of serum ICTP leads to increased relative risk of fractures in the femoral neck or spine/non-spine. Reduction of 50-70% in bone metabolic markers with therapy reduces fracture risk by 40-44%.

In this article, the diagnosis and medical checkup of osteoporosis are reviewed. Osteoporosis is defined by bone histomorphometry, radiography, morphometry of vertebral body, and semiquantitative assessment of vertebral deformity. Diagnostic criteria of osteoporosis in Japanese Society for Bone and Mineral Research is composed of fragility fracture and low bone mass. The aim of osteoporosis checkup is to detect subjects with low bone mass using measurement of bone mineral density.

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.

To demonstrate the clinical benefit of risedronate at 2.5 mg daily in the treatment of involutional osteoporosis, the effect of risedronate on incidence of vertebral fracture was compared with that of etidronate. A total of 547 patients with one to four vertebral fractures were randomized to receive either treatment with 2.5 mg/day of risedronate or intermittent treatment (treatment of 2 weeks and off period of 10 weeks) with 200 mg/day of etidronate for 96 weeks in a double-masked fashion. All patients received 200 mg calcium supplement daily. Lateral and anteroposterior thoracic and lumbar spine radiographs were obtained at baseline and at 24, 48, 72, and 96 weeks. Cumulative incidence rates of patients who had at least one new or worsening vertebral fracture during the 96-week period were 12.3% for risedronate and 14.2% for etidronate, and it was verified that the fracture prevention effect of risedronate was not inferior to that of etidronate. The incidence rates of fracture during the initial 24-week period were 8.8% for risedronate and 6.0% for etidronate, but the cumulative incidence rate of fracture from 24 to 96 weeks was lower in the risedronate group (3.9%) as compared to the etidronate group (8.7%). Height loss was significantly less in the risedronate group (-0.28 cm) than in the etidronate group (-0.70 cm) after 96 weeks. Decreases in bone resorption markers including urinary total deoxypyridinoline and NTX were significantly greater in the risedronate group than in the etidronate group throughout the treatment period. An improvement of patient QOL was observed in both groups. No significant difference in the incidence of adverse events was observed between the two treatments. Daily oral risedronate (2.5 mg) was shown to provide an effective therapy for involutional osteoporosis in Japanese patients with good tolerability.

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.

Vertebral fractures are the most common complication associated with osteoporosis. The definition of prevalent or incident vertebral fractures is important in epidemiological evaluation and in clinical trials of osteoporosis treatment. There have been few reports regarding the morphometric cutoff criteria for incident fractures in Asians, and only a few reports of their occurrence in Caucasians. The aim of this study was to establish a definition for incident fractures in Japanese women. A total of 279 women, aged 64.8 +/- 9.9 (mean +/- SD) years, were recruited, and repeated thoracolumbar spinal radiographs were performed at a mean of 1.45 +/- 0.44 years after the baseline film. Vertebral fractures were graded from 0 to 3 in both baseline and follow-up films using a semiquantitative assessment by the consensus of three readers. Incident fractures were defined as an increase of grade, except grade 3, and a vertebral body height of less than 12 mm on the baseline film. As morphometric criteria, both absolute height reduction (AHr) and the percent height ratio (PHr) were calculated. Prevalent fractures were observed in 207 vertebrae (6.2%) and 85 cases (30.5%), and incident fractures in 42 vertebrae (1.3%) and 29 cases (10.4%). As morphometric criteria for incident fracture, both a PHror =15% and an AHror =3 mm oror =4 mm indicated sensitivity of 49.17% and 50.83% and specificity of 99.92% and 99.90%, respectively. In conclusion, the morphometric criteria of incident fracture combined with a semiquantitative assessment will provide useful information in the study of clinical osteoporosis, especially for international comparisons.

Risedronate (RSD) containing nitrogen, the third generation of bisphosphonate, has a powerful antiresorptive activity, without a stronger inhibition of mineralization. RSD is available for the treatment of osteoporosis. In Japanese the effective dose is 2.5 mg given orally daily, while in Caucasians it is 5 mg. This difference of dose suggests that RSD may be absorbed more efficiently in Japanese than in Caucasians. RSD administered orally at 2.5 mg per day for 48 weeks induced a 5% increase of bone mineral density in the lumbar spines in osteoporotic women. RSD, 5 mg daily, decreases vertebral and non-vertebral, especially hip fractures in elderly osteoporotic women. Thus, RSD is an important agent for the treatment of osteoporosis.

The aim of this study was to evaluate the diagnostic potential of whole-body MRI (WB-MRI) for the detection of bone marrow and extramedullary involvement in patients with non-Hodgkin's lymphoma. WB-MRI, which was performed on 34 patients, consisted of the recording of T1-weighted spin-echo images and a fast STIR sequence covering the entire skeleton. The WB-MRI findings for bone marrow and extramedullary involvement were compared with those from (67)Ga and bone scintigraphies and bone marrow biopsy results. Two MRI specialists reviewed the WB-MRI results and two expert radiologists in the field of nuclear medicine reviewed the bone and (67)Ga scintigraphy findings. Bone marrow and extramedullary involvement of non-Hodgkin's lymphoma were confirmed by follow-up radiographs and CT and/or a histological biopsy. The detection rate of WB-MRI was high. More bone marrow involvement was detected by biopsy, and more lesions were detected by scintigraphies. In total, 89 lesions were detected by WB-MRI, whereas 15 were found by biopsy, 5 by (67)Ga scintigraphy, and 14 by bone scintigraphy. WB-MRI could also detect more extramedullary lesions than (67)Ga scintigraphy; i.e., 72 lesions were detected by WB-MRI, whereas 54 were discovered by (67)Ga scintigraphy. WB-MRI is useful for evaluating the involvement of bone marrow and extramedullary lesions throughout the skeleton in patients with non-Hodgkin's lymphoma.

Cleidocranial dysplasia is a congenital systemic bone disorder characterized by delayed ossification of skull, aplastic or hypoplastic clavicle, delayed deciduous dentition, and hereditary characteristics.A 14-year old girl came to our clinic because of many unerupted permanent teeth. She was diagnosed to he cleidocranial dysplasia based on the above characteristics.Further examinations concerning bone metabolism revealed low serum calcitonin level, high levels of bone metabolic markers for absorption, and low lumbar spinal bone mineral density. These findings suggested abnormal bone metabolism in this patient.

The aim of the present study was to assess the performance of pre-biopsy T2-weighted MR imaging using multishot echo-planar imaging (EPI) sequence for visualization of prostate cancer and to compare image quality with that of fast spin-echo (FSE) sequence. Thirty-nine patients with suspected prostate cancer and one healthy male volunteer were examined on a 1.5-T MR scanner equipped with a pelvic phased-array coil. Axial MR images were obtained using multishot EPI sequence with a multishot number of 16 and FSE sequence without fat suppression. Paired EPI and FSE images were independently evaluated by three radiologists. Furthermore, signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were compared between EPI and FSE images of 12 pathologically proven lesions of prostate cancer. Delineation of the periprostatic venous plexus, prostate zonal anatomy, and seminal vesicle on EPI was graded to be superior/inferior to FSE in 15.8/0, 14.6/0, and 21.5/4.3% of cases, respectively. On the other hand, delineation of the neurovascular bundle was superior/inferior to FSE in 2.6/13.2% of cases. The SNR and CNR of prostate cancer on EPI were significantly higher than those on FSE (7.99 +/- 2.51 vs 3.36 +/- 0.58, p0.0001, and 5.51 +/- 2.02 vs 2.21 +/- 0.79, p0.0001, respectively). In conclusion, multishot EPI has higher quality of contrast resolution for imaging of prostate cancer compared with FSE and would have the potential usefulness in the detection of prostate cancer, although these results obtained with a phased-array coil cannot be extrapolated to examinations performed with an endorectal coil.

To determine the clinical recommended dosage regimen of risedronate for the treatment of involutional osteoporosis in Japanese patients, dose-response relationships for the efficacy and safety of this drug were investigated using a multi-center, randomized, double-blind, parallel group comparative design with four dose levels of risedronate (placebo, 1 mg, 2.5 mg and 5 mg per day). A total of 211 patients diagnosed with involutional osteoporosis according to the criteria proposed by the Japanese Society for Bone and Mineral Research were randomized and received one of the four doses once daily for 36 weeks. All patients were supplemented with 200 mg of calcium daily in the form of calcium lactate. The primary efficacy endpoint was the percent change in bone mineral density of the lumbar spine (L2-L4 BMD) determined by dual-energy X-ray absorptiometry (DXA) from baseline to the time of final evaluation. Changes in biochemical markers of bone turnover and safety profile were also compared. Percent changes in L2-L4 BMD at final evaluation in the placebo, and 1-, 2.5-, and 5-mg risedronate groups were 0.79+/-5.30, 2.71+/-4.93, 5.29+/-3.96, and 5.15+/-4.25% (mean+/-SD), respectively. A linear dose-response relationship was obtained up to a dose of 2.5 mg, whereas no further increase in BMD was observed at 5 mg. The decrease in bone turnover markers, including N-terminal osteocalcin, phosphorus, and urinary deoxypyridinoline, also showed a linear dose-response relationship up to a dose of 2.5 mg. Alkaline phosphatase level decreased linearly up to a dose of 5 mg. Risedronate was well tolerated in this 36-week study with 1- to 5-mg doses. Neither the overall incidence of adverse events nor the percentage of patients without problem in overall safety assessment differed significantly among the dose groups including the placebo group. Based on these results, a once-daily dose of 2.5 mg of risedronate, which is half that used in Caucasians, is recommended for the treatment of involutional osteoporosis in Japanese patients.

1 Department of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan 2 Department of Orthopedic Surgery, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan 3 Department of Obstetrics and Gynecology, Tokyo Women’s Medical University, Tokyo, Japan 4 Department of Orthopedic Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan 5 Department of Obstetrics and Gynecology, Yokohama City University Medical School, Yokohama, Japan 6Research Institute and Practice for Involutional Diseases, Nagano, Japan 7 Department of Nuclear Medicine, Kawasaki Medical School, Kurashiki, Japan 8 Endocrinology Section, Tokyo Metropolitan Geriatric Hospital, Tokyo Japan 9 Department of Geriatric Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan 10 R & D Department, Mitsubishi Kagaku BCL, Tokyo, Japan

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 procoIlagen 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.

To prevent osteoporosis, which is expected to increase in incidence in this rapidly aging society, in recent years bone mineral density (BMD) has frequently been measured as a predisposition index. However, these measurements are made on different sites with different apparatus, and the results are independently studied by different institutions. In our present investigation, to establish the standard radius BMD as determined by dual-energy X-ray absorptiometry (DXA), we carried out a general population survey in 29 municipalities and prefectures on 11,252 locally residing females aged 15 to 83 years (mean, 35.61 +/- 12.85 years). Their YAM (young adult mean) BMD was estimated at 0.664 +/- 0.054 g/cm2, which was almost the same as the figure given in the 1996 version of the diagnostic criteria for primary osteoporosis. We further studied the relationships of BMD to age and physical factors known to be influential to BMD. It was found that BMD was correlated negatively to age and positively to body mass index (BMI). The average values we obtained for age and physique groups appeared to have provided reliable indices for the primary prevention of osteoporosis.

In order to exclude the metabolically less-active cortical bone in the posterior portion of the lumbar spine, and to exclude the calcification of abdominal aorta which frepuently occurs in elderly persons, both of which are included in the conventional anteroposterior (AP) bone mineral determinations, clinical interest has been directed toward lateral scanning. In this paper, the performance and clinical application of lateral scanning with dual energy X-ray absorptiometry (DEXA) have been reviewed. The precision, estimated as the reproducibility of measurements, of lateral bone mineral density (BMD), is inferior to that of AP-BMD (N=5, C.V. 5.57% vs 1.80%). With lateral scanning, the distributions of bone mineral within the vertebral body was different. The highest BMD was observed in the posterior inferior portion (100%), followed by the posterior superior (89%), anterior inferior (77%), and anterior superior portions (65%). In lateral scans, BMD within the region of interest (ROI) containing the shell, composed of cortical bone, is higher than BMD within the ROI without the shell (N=28, 87.8±5.9% for shell (+) vs 81.5±10.3% for shell (−), p