Bridging analysis of the efficacy and safety of bazedoxifene in Japanese and global populations of postmenopausal women with osteoporosis.

This study examined whether the global clinical data for bazedoxifene could be extrapolated to a Japanese population by evaluating the results of a phase 2 study in postmenopausal Japanese women with osteoporosis as compared to those of a pivotal, phase 3 study. The efficacy of bazedoxifene 20 and 40 mg versus placebo on lumbar spine bone mineral density (BMD), bone turnover markers, lipid profile, incidence of fractures, and safety parameters was compared between the Japanese phase 2 study (N = 429) and the global phase 3 study (N = 7,492) during a 2-year period. In the primary population for assessment of bridging, differences in the mean percent change from baseline in lumbar spine BMD at 2 years relative to placebo were greater for women treated with bazedoxifene 20 and 40 mg in the phase 2 study than in the phase 3 study. BMD changes in the bazedoxifene groups were confirmed to be similar between the phase 2 study population and a subset of the phase 3 study population with similar baseline characteristics. The effects of bazedoxifene on incidence of fractures, bone turnover markers, and lipid metabolism were similar between studies. There were no major differences in safety parameters between studies. The greater improvement in lumbar spine BMD and similar results in bone turnover markers, fracture incidence, and safety profile observed with bazedoxifene in the phase 2 study compared with the phase 3 study confirmed the feasibility of extrapolating the global clinical data to a Japanese population.

Once-Weekly Injection of Low-Dose Teriparatide (28.2 µg) Reduced the Risk of Vertebral Fracture in Patients with Primary Osteoporosis.

We conducted a randomized, double-blind trial to assess the effect of 28.2 µg teriparatide versus placebo (1.4 µg teriparatide) on reduction of the incidence of vertebral fractures. Individuals enrolled in this study included patients with primary osteoporosis with one to five vertebral fractures and capable of self-supported walking. Attention was focused on incident vertebral fractures, change in bone mineral density (BMD) of the lumbar spine, and safety. A total of 316 subjects participated in the study, which lasted up to 131 weeks. Incident vertebral fractures occurred in 3.3% of subjects in the 28.2 µg teriparatide-treated group and 12.6% of subjects in the placebo group during the 78-weeks study period. Kaplan-Meier estimates of risk after 78 weeks were 7.5 and 22.2 % in the teriparatide and placebo groups, respectively, with a relative risk reduction of 66.4% by teriparatide (P = 0.008). Lumbar BMD in the 28.2 µg teriparatide group increased significantly by 4.4 ± 4.7 % at 78 weeks, which was significantly higher than the corresponding data in the placebo group (P = 0.001). Adverse events were observed in 86.7% of individuals in the teriparatide group and 86.1% of those in the placebo group. In conclusion, weekly injection of a low-dose of teriparatide (28.2 µg) reduced the risk of incident vertebral fractures and increased lumbar BMD.

Consensus of official position of IOF/ISCD FRAX initiatives in Asia-Pacific region.

The fracture risk assessment tool (FRAX(®)) has been developed for the identification of individuals with high risk of fracture in whom treatment to prevent fractures would be appropriate. FRAX models are not yet available for all countries or ethnicities, but surrogate models can be used within regions with similar fracture risk. The International Society for Clinical Densitometry (ISCD) and International Osteoporosis Foundation (IOF) are nonprofit multidisciplinary international professional organizations. Their visions are to advance the awareness, education, prevention, and treatment of osteoporosis. In November 2010, the IOF/ISCD FRAX initiative was held in Bucharest, bringing together international experts to review and create evidence-based official positions guiding clinicians for the practical use of FRAX. A consensus meeting of the Asia-Pacific (AP) Panel of the ISCD recently reviewed the most current Official Positions of the Joint Official Positions of ISCD and IOF on FRAX in view of the different population characteristics and health standards in the AP regions. The reviewed position statements included not only the key spectrum of positions but also unique concerns in AP regions.

The Official Positions of the International Society for Clinical Densitometry: Indications of Use and Reporting of DXA for Body Composition.

The technique of body composition by dual-energy X-ray absorptiometry (DXA) has been used for several years in the research environment. Its ability to accurately and precisely measure lean, fat, and mineral composition in various body compartments has been well validated. Furthermore, the technique is widely available to clinical patients on existing DXA instruments throughout the world through the use of specific software packages and scanning algorithms. There have been few clear statements regarding the clinical indications for body composition measurement in patients outside the research setting. This is in part because of the lack of specific documented interventions that would be affected by body composition test results, beyond usual clinical advice. We have examined a few of the most common, specific scenarios (HIV therapy, sarcopenia, bariatric surgery, obesity) and proposed indications for body composition assessment. We have also discussed contraindications to body composition testing.

Design of a pragmatic approach to evaluate the effectiveness of concurrent treatment for the prevention of osteoporotic fractures: rationale, aims and organization of a Japanese Osteoporosis Intervention Trial (JOINT) initiated by the Research Group of Adequate Treatment of Osteoporosis (A-TOP).

The aim of osteoporosis treatment is to prevent future fractures. Although concurrent treatment has been used very frequently for osteoporosis in clinical practice, there are no data on accurate and verified effectiveness of concurrent treatment for fracture prevention in patients with osteoporosis. To clarify the clinical usefulness of concurrent treatment, the Japan Osteoporosis Society has authorized the establishment of the A-TOP (Adequate Treatment of Osteoporosis) research group. The objective of this research is to establish a design for a clinical trial to prove whether concurrent treatment using both alfacalcidol (1-alpha-hydroxycholecalciferol) and alendronate is more effective as compared to treatment using alendronate alone in terms of fracture prevention. The present study was named JOINT (Japanese Osteoporosis Intervention Trial) and is based on a method using national, prospective, randomized, open-labeled, blinded endpoints focusing on postmenopausal osteoporosis with a high risk for fracture. The patients were mainly selected by practitioners and allocated randomly by a central registration system into two groups, of which one received 5 mg/day of alendronate alone, and the other received 1 µg/day of 1-alpha-hydroxycholecalciferol (alfacalcidol) in addition to the alendronate. The endpoints focused primarily on fracture prevention, and the patients' quality of life (QOL) and change in body height, as well as adherence and the adverse events of the treatments were evaluated secondarily. To obtain sufficient statistical power in the events during a 2-year observation period, the patients who are expected to have higher risk were selected to participate in this study, and it was decided that the final plan would involve 890 patients per group (two-sided alpha = 0.05, power = 0.8). Data collection began in November 2003. Correspondence regarding the registration of the investigator and the progress of the study was conducted through a web system from the Public Health Research Foundation to practitioners.

International Society for Clinical Densitometry official positions: Asia-Pacific Region consensus.

The International Society for Clinical Densitometry (lSCD) is a nonprofit multidisciplinary international professional organization. The ISCD mission is to advance excellence in the assessment of skeletal health. To achieve this mission, the ISCD has conducted a number of Position Development Conferences over the past 10yr, bringing together international experts to review and create evidence-based position statements guiding clinicians involved in the area. The Asia-Pacific (AP) Panel of the ISCD was formed to give regional input to the ISCD from the AP Region and to oversee ISCD education and certification programs in the region. An AP Panel consensus meeting recently reviewed the most current Official Positions of the ISCD in view of the different population characteristics and health standards in the region. The reviewed position statements included those for bone testing by central and peripheral devices but did not include ISCD Official Positions on Vertebral Fracture Assessment or pediatric bone mineral density.

Peripheral dual-energy X-ray absorptiometry in the management of osteoporosis: the 2007 ISCD Official Positions.

Peripheral assessment of bone density using photon absorptiometry techniques has been available for over 40 yr. The initial use of radio-isotopes as the photon source has been replaced by the use of X-ray technology. A wide variety of models of single- or dual-energy X-ray measurement tools have been made available for purchase, although not all are still commercially available. The Official Positions of the International Society for Clinical Densitometry (ISCD) have been developed following a systematic review of the literature by an ISCD task force and a subsequent Position Development Conference. These cover the technological diversity among peripheral dual-energy X-ray absorptiometry (pDXA) devices; define whether pDXA can be used for fracture risk assessment and/or to diagnose osteoporosis; examine whether pDXA can be used to initiate treatment and/or monitor treatment; provide recommendations for pDXA reporting; and review quality assurance and quality control necessary for effective use of pDXA.

[Prevention of osteoporosis by foods and dietary supplements. Milk basic protein (MBP) increases bone mineral density in young adult women and perimenopausal women].

Milk has beneficial effects on bone health than other food sources. Recent in vitro and in vivo studies have shown that milk whey protein, especially its basic protein fraction (milk basic protein: MBP), contains components capable of promoting bone formation and inhibiting bone resorption. We tried to examine the effect of MBP on bone mineral density (BMD) and markers of bone metabolism in healthy young adult women and perimenopausal women. In the healthy young women study, we found that MBP increased BMD, by promoting bone formation and inhibiting bone resorption. In the healthy perimenopausal women study, we also found that MBP increased BMD, primarily by inhibiting bone resorption, while maintaining bone formation. Thus, bone remodeling balances become positive that leads to maintenance or increase of bone formation. MBP supplementation could be effective for bone health in a wide range of generation especially those who hate to drink milk.

[Examination about utility of a Streptococcus pneumoniae capsular antigen swiftness search kit urine in a pneumonia patient].

We investigated the usefullness of Binax NOW urine antigen test, an immunochromatographic assay that binds any soluble Streptococcus pneumoniae antigen (C polysaccharide) for the diagnosis of penumoniae form September 2003 to March 2005. We used 372 samples form the patinets with pneumoniae diagnosed for blood or sputum cultuter or gram-stained sputum smear. Out of 24 culture positive specimens, Binax NOW urine antigen test, showed positive in 18 (75%) specimens. The sensitivity of sputum and blood culture was 71.7% and 83.3%, respectively. Binax NOW urine antigen test was seemed false positives in 55 samples, false negatives in 6 samples. The specificity of Binax NOW urine antigen test was evaluated 84.1%. Overall agreement among tests was 83.6%. When compared to culture, false negative urine antigen may be the result of colonizing S. pneumoniae in sputum or pneumonia caused by an agent other than S. pneumoniae. CRP values for cases were both urine antigen and culture were positive ranged from 40 mg/dl to 10 mg/dl while urine antigen and culture negative cases were predominantly less than 10 mg/dl. Positive blood and pleural fluid culture cases were consistently associated with strongly positive urine antigen tests. Non-agreement between urine antigen, culture, and microscopy may be the result of specimen quality, labile nature of S. pneumoniae and antimicrobial therapy.

Changes in the organisms of resistant peritonitis in patients on continuous ambulatory peritoneal dialysis.

Peritonitis is one of the most serious complications of continuous ambulatory peritoneal dialysis (CAPD). Approximately 20% of peritonitis infections have been reported to be resistant to initial therapy, either failing to resolve with appropriate antibiotics or relapsing within 2 weeks of antibiotic discontinuation. To investigate the current situation with regard to resistant peritonitis, we retrospectively examined the incidence and the organisms of resistant peritonitis in our unit over a period of 9 years. From January 1, 1994, to January 1, 2003, we introduced 325 patients onto CAPD. At January 1, 2003, we followed up 172 patients who were receiving CAPD in our unit. During 1994-1996, 12 cases of peritonitis and 3 cases of resistant peritonitis (25%) occurred among our patients. Microbiologic examination revealed that the organisms involved in peritonitis were alpha-streptococcus (17%), coagulase-negative staphylococcus [CNS (17%)], and methicillin-sensitive Staphylococcus aureus [MSSA (17%)]. The organisms of resistant peritonitis were methicillin-resistant S. aureus [MRSA (67%)] and methicillin-resistant CNS (33%). During 1997-1999, 39 cases of peritonitis and 13 cases of resistant peritonitis (33%) occurred among our patients. The most frequently cultured organisms in peritonitis were CNS (26%), Candida species (13%), and alpha-streptococcus (10%). The organisms of resistant peritonitis were methicillin-resistant CNS (46%) and Candida species (38%). In the most recent 3-year period (2000-2002), our patients experienced 57 cases of peritonitis and 24 cases of resistant peritonitis (42%). The organisms of peritonitis were alpha-streptococcus (46%), CNS, MSSA, Escherichia coli, and Candida species (38%). However, the organisms of resistant peritonitis were methicillin-resistant CNS (13%), Candida species (21%), Pseudomonas aeruginosa (13%), Serratia (13%), Citrobacter (13%), and Corynebacterium (13%). In the last several years, methicillin-resistant CNS has come to be main organism of resistant peritonitis. In addition, opportunistic infection has become a serious peritonitis problem. Given these data, we conclude that the incidence of resistant peritonitis is increasing and that the organisms of resistant peritonitis are changing.

[Epidemiological study of Arbekacin-resistant, methicillin resistant Staphylococcus aureus in Saitama Medical School Hospital].

Arbekacin-resistant, methicillin-resistant Staphylococcus aureus was frequently isolated in Saitama Medical School Hospital during 1996 and 1998. The minimum inhibitory concentration for ABK was 8 micrograms/ml in 14 strains, 16 micrograms/ml in 6 strains, and 32 micrograms/ml in 2 strains. The maximum isolation rate of these resistant strains in one month was 8%. Use of ABK in the hospital did not increase during the same period. The infection control team (ICT) of the hospital recognized the increase of resistant strains and started intervention for the hospital staff. The ICT instructed the staff of each ward to follow standard precautions for the prevention of nosocomial infections and the risk of ABK-resistant MRSA was explained repeatedly. Thereafter, the isolation rate decreased to 3%. An epidemiological study was done using 22 strains of ABK-resistant MRSA that were isolated in this period. The strains originated from different patients and from 10 different wards, which were designated as wards A to J. Eight strains were isolated from surgical ward A, followed by the other wards (ward B: 3, C: 2, D: 2, E: 2, F: 1, G: 1, H: 1, I: 1, J: 1). The specimens from which ABK-resistant MRSA were isolated were as follows,: sputum: 4, wound: 4, decubitus ulcer: 4, urine: 2, pus: 2, blood :1, central venous catheter: 1, drainage tube: 1, tracheal aspirate: 1, skin: 1, stool: 1. Several investigations were done using these strains. Sensitivity tests for ABK, VCM, MINO, LVFX, FOM, IPM were performed by the standard method of the Japan Society for Chemotherapy. Coagulase types were determined. Production of toxic shock syndrome toxin-1 (TSST-1), enterotoxin, and beta-lactamase was assayed. Pulse-field gel electrophoresis (PFGE) using Sma I was also done and differences were compared. Seven of the 8 strains from ward A showed the same drug sensitivity profile and biological phenotype. Two of the 3 strains from ward B and 2 strains from ward C were also identical by these methods. Six of the 8 strains from ward A were also identical by PFGE. These 6 isolates showed the same drug sensitivity pattern, same coagulase type, and same production of TSST-1 and enterotoxin. Two other strains from ward B, one strain from ward F, and one from ward I also showed the same PFGE pattern, drug sensitivity profile, and toxin profile as the 6 strains from ward A. Our data show that the same strains were transmitted around the hospital during the study period, although serious nosocomial infections due to ABK-resistant MRSA were avoided. Thus, intervention by the ICT in each ward was effective. ABK-resistant MRSA should be recognized as an important hospital pathogen and should be surveyed consistently.

[The future of SERM (selective estrogen receptor modulator)].

Selective estrogen receptor modulator (SERM) is a kind of drug that has agonistic and antagonistic effects of estrogen in different tissues. MORE study has shown that raloxyfene reduces osteoporotic vertebral fractures and serum cholesterol levels in postmenopausal women, while it does not stimulate the endometrium and decreases the breast cancer occurrence. There are more to be investigated like developing newer SERMs, a combination therapy with estrogen or the elucidation of mechanisms of estrogen effects.

[Comparison of a rapid antigen test and cultures for diagnosis of meningitis in children].

Fourteen pediatric patients diagnosed as bacterial meningitis between August 1997 and April 2002 were enrolled in this study. Both rapid antigen detection test, Slidex Meningite 5 Kit (Biomerieux) and culture were performed using cerebrospinal fluids (CSF). H. influenzae was isolated from 11 samples and was the most frequently isolated bacteria, followed by S. pneumoniae from 4 samples and enteric bacteriae from 2 samples. Five out of six samples with positive result by culture were also positive by the rapid antigen test. Gram-negative rod was identified in smear specimens of CSF from all these 5 samples. Significance of the rapid antigen test should be recognized under drug resistance of those bacteriae are increasing.

Effects of bazedoxifene on bone mineral density, bone turnover, and safety in postmenopausal Japanese women with osteoporosis.

This randomized, double-blind, placebo-controlled, dose-response late phase 2 study evaluated the efficacy and safety of bazedoxifene in postmenopausal Japanese women 85 years of age or younger with osteoporosis. Eligible subjects received daily treatment with oral doses of bazedoxifene 20 or 40 mg or placebo for 2 years. Efficacy assessments included bone mineral density (BMD) at the lumbar spine and other skeletal sites, bone turnover marker levels, lipid parameters, and incidence of new fractures. Of 429 randomized subjects, 387 were evaluable for efficacy, and 423 were included in the safety analyses (mean age, 64 years). At 2 years, the mean percent changes from baseline in lumbar spine BMD were significantly greater with bazedoxifene 20 and 40 mg (2.43% and 2.74%, respectively) than with placebo (-0.65%, p < .001 for both). Both bazedoxifene doses significantly improved BMD at the total hip, femoral neck, and greater trochanter compared with placebo (p < .001 for all). Decreases in bone turnover markers were observed with bazedoxifene 20 and 40 mg as early as 12 weeks (p < .05 for all) and were sustained throughout the study. Total and low-density lipoprotein cholesterol levels were significantly decreased from baseline with both bazedoxifene doses compared with placebo (p < .05 for all). Incidences of new vertebral and nonvertebral fractures were similar among the bazedoxifene and placebo groups. Overall, the incidence of adverse events with bazedoxifene 20 and 40 mg was similar to that with placebo. Bazedoxifene significantly improved BMD, reduced bone turnover, and was well tolerated in postmenopausal Japanese women with osteoporosis.

Short-term menatetrenone therapy increases gamma-carboxylation of osteocalcin with a moderate increase of bone turnover in postmenopausal osteoporosis: a randomized prospective study.

The effect of vitamin K(2) (menatetrenone) on bone turnover was investigated in postmenopausal patients with osteoporosis. A 6-month open-label, randomized prospective study was conducted in 109 patients. The control group (n = 53) received calcium aspartate (133.8 mg of elemental calcium daily), while the menatetrenone group (n = 56) received 45 mg of menatetrenone daily for 6 months. Serum and urinary levels of bone turnover markers were monitored. The serum level of undercarboxylated osteocalcin (uc-OC) was significantly lower (P < 0.001) in the menatetrenone group than in the control group (at 1 month), while there was a higher level of osteocalcin containing gamma-carboxylated glutamic acid (Gla-OC) in the menatetrenone group than the control group (P = 0.018). Significant differences of uc-OC and Gla-OC between the two groups were observed from 1 month onward. In addition, a higher level of intact osteocalcin was found in the menatetrenone group compared with the control group after 6 months (P = 0.006). Assessment of bone resorption markers showed that menatetrenone therapy was associated with significantly higher urinary N-telopeptide of type I collagen (NTX) excretion compared with the control group after 6 months, while there was no significant difference of urinary deoxypyridinoline excretion between the two groups. In conclusion, one month of menatetrenone therapy enhanced the secretion and gamma-carboxylation of osteocalcin, while urinary NTX excretion was increased after 6 months of treatment. Further investigations are required to determine whether the effects of menatetrenone on bone turnover are associated with fracture prevention.

[Standardizing the diagnosis of acute ischemic stroke--the concept of an institutional manual and its clinical impact].

UNLABELLED: In the management of acute ischemic stroke, a diagnostic procedure is critically important. However, till date, no guideline or consensus regarding a standard diagnosis procedure has been established. We hereby report an institutional manual for the consistent diagnosis of acute ischemic stroke. METHODS: The institutional manual was based on the National Institute of Neurological Disorders and Stroke III classification; however, the criteria for each stroke subtype were clearly defined using a rating system that included the representative observations specific to each subtype. The present manual was prepared in order to clearly define the characteristics of the stroke subtypes, which are often ambiguous in the clinical settings, and to design a diagnostic procedure within the institute with more emphasis on standardization rather than achieving complete accuracy. Several characteristic points were considered while doing this: lacunar infarctions should be clearly differentiated from other small infarctions, subtypes of "suspicious cardioembolism," "atherothrombotic infarction (embolic mechanism)," and "infarction due to arterial dissection" should be determined separately in order to identify the causal mechanism to the extent possible. For a final diagnosis, the patients were examined 3 time points during: at admission, during the subacute stage (day 4-7), and at discharge or more than 2 weeks after the onset of stroke. The current version of the manual has been used since 2006 after a transitional phase from 2004 to 2005. Retrospective comparisons on stroke diagnoses and clinical outcomes were performed between the periods during which the present manual was used and those during which it was not. RESULTS: The present manual was retrospectively applied for diagnosing 311 consecutive ischemic stroke patients who were admitted to our institute within 7 days after the onset in 2003; in the case of 85 patients (29%), the diagnosis was different from that made in 2003. Of all the lacunar infections reported in 2003, 17 were diagnosed as other conditions when the manual was used. Similarly, 45% of the cases of atherothrombotic infarction (thrombotic mechanism) and 24% of those of cardiac embolism in 2003 were diagnosed differently when the present manual was applied. The mean modified Rankin scale at discharge was 2.63 +/- 0.07 (mean +/- standard error of the mean) in patients in 2002 and 2003 (n=491), which was significantly different from 2.32 +/- 0.06 in patients in 2006 through March of 2008 (n=903; p=0.01). CONCLUSION: The present manual appears to be helpful to improve the uniformity of the diagnoses and the clinical results. It may also assist residents and their mentors in the educational field. The manual will require periodical evaluation and version upgrade in order to maintain its efficacy.

A double-blinded head-to-head trial of minodronate and alendronate in women with postmenopausal osteoporosis.

INTRODUCTION: In a randomized, active-controlled, double-blinded, multicenter study, the efficacy and safety of minodronate were examined and compared to that of alendronate. METHODS: A total of 270 postmenopausal osteoporotic women >or=45 years of age were randomized into the minodronate group (n=135) or alendronate group (n=135). Each subject received 1 mg minodronate or 5 mg alendronate once a day for 12 months. RESULTS: Both treatment groups showed similar changes in BMD after 12 months. After 1 year of treatment, the lumbar spine BMD increased by 5.86% and 6.29% in the minodronate and alendronate groups, respectively, and the total hip BMD increased by 3.47% and 3.27%, respectively. Bone turnover markers were rapidly reduced within 1 month in both treatment groups. Urine DPD was significantly lower in the minodronate group than in the alendronate group at 6 months, and urine NTX was significantly lower in the minodronate group than in the alendronate group at 1 and 9 months. Both completion rates for the 12-month study and the overall incidence of clinical adverse events, including gastrointestinal events, were similar between the two groups. CONCLUSIONS: The effects on lumbar and hip BMD and the safety profile of minodronate are comparable to those of alendronate. Minodronate is a promising new potent bisphosphonate for the treatment of osteoporosis.