Fukuoka-shi, Japan
Fukuoka-shi, Japan

Time filter

Source Type

The purpose of the present study was to determine whether teriparatide and monthly minodronic acid would have an additive effect on cancellous bone mass in ovariectomized rats. Seven-week-old female Sprague-Dawley rats were randomized into five groups of 10 animals each, including a sham-operation. +. vehicle group, an ovariectomy (OVX). +. vehicle group, an OVX. +. minodronic acid (6. μg/kg. s.c., every 4. weeks) group, an OVX. +. teriparatide (20. μg/kg. s.c., daily) group, and an OVX. +. minodronic acid. +. teriparatide group. After the 12-week experimental period, static and dynamic histomorphometric analyses were performed on the cancellous bone of the tibial proximal metaphysis. OVX decreased the bone volume per total volume (BV/TV) and the trabecular number (Tb.N) and increased the trabecular separation (Tb.Sp) as a result of increased bone remodeling. Minodronic acid prevented the OVX-induced decreases in BV/TV, while teriparatide increased the BV/TV and trabecular width (Tb.Wi) beyond the values of the sham controls. Minodronic acid prevented, but teriparatide only mitigated, the OVX-induced decrease in Tb.N, although both drugs similarly prevented the OVX-induced increase in Tb.Sp. A combination of teriparatide and minodronic acid further increased the BV/TV and Tb.N and decreased the Tb.Sp as a result of the suppression of bone remodeling, compared with teriparatide alone. These results suggest the differential effect of teriparatide and monthly minodronic acid on cancellous bone structure and the additive effect of the two drugs on cancellous bone mass in OVX rats. © 2014 Elsevier Inc.


News Article | November 10, 2016
Site: www.eurekalert.org

MINNEAPOLIS - A new study suggests probable scientific misconduct in at least some of 33 bone health trials published in various medical journals. The study used statistical methods to detect scientific misconduct or research fraud and calls into question the validity of a body of research work led mainly by one researcher in Japan. The study is published in the November 9, 2016, online issue of Neurology®, the medical journal of the American Academy of Neurology. "Our use of statistical methods to examine the integrity of the data in 33 randomized controlled trials raises serious concerns about the reported results in those trials," said study author Mark J. Bolland, MBChB, PhD, of the University of Auckland in New Zealand. Bolland and his team analyzed the 33 studies, three of which were published in Neurology and retracted this summer after the author, Yoshihiro Sato, MD, of Mitate Hospital in Tagawa, Japan, admitted to scientific misconduct. Sato accepted full responsibility, admitting fabrication of the fraudulent Neurology papers, which reported on the effects of therapies to reduce hip fractures both after stroke and in Parkinson's disease patients. Sato stated that none of the coauthors participated in any misconduct and were named as authors on an honorary basis only. Sato requested retraction of the three studies. For the analysis of the 33 trials, 26 of which Sato was lead author, Bolland's team conducted a rigorous review and found reported results that differed markedly from what could be expected statistically; further, the results were remarkably positive. The characteristics of the groups of people chosen to participate in the trials were much more similar than would have happened by chance. The trials reported large reductions in hip fractures, no matter what treatment was used, that were much greater than those reported in similar trials from other research groups. Overall in the 33 trials, the people receiving the therapy were 78 percent less likely to break a hip than the control group, while several meta-analyses of other trials found either no benefit of the treatments or a benefit of less than 40 percent. Bolland's team also found multiple examples of inconsistencies between and within trials, errors in reported data, misleading text, duplicated data and text as well as uncertainties about ethical oversight. "The researchers were remarkably productive, conducting 33 randomized controlled trials within 15 years, the outcomes of each being remarkably positive," said Bolland. "Our analysis suggests that the results of at least some of these trials are not reliable. In addition, results from these trials were not consistent with results found in similar studies by other researchers." "This statistical analysis demonstrates probable scientific misconduct on a large scale," said Robert A. Gross, MD, PhD, of Rochester, N.Y., Editor-in-Chief of Neurology and Fellow of the American Academy of Neurology, who wrote a corresponding editorial. "Fraud in an individual paper may be difficult to detect. One cannot conclude that any one study in the analysis is, or is not, fraudulent. As part of our due process, we have notified other editors of journals that published papers by Sato and colleagues, communicated with Sato's institution, and published retractions of the three papers and a letter published in Neurology." The analysis was supported by the Health Research Council of New Zealand and the Health and Social Care Directorate of the Scottish Government. The American Academy of Neurology is the world's largest association of neurologists and neuroscience professionals, with 30,000 members. The AAN is dedicated to promoting the highest quality patient-centered neurologic care. A neurologist is a doctor with specialized training in diagnosing, treating and managing disorders of the brain and nervous system such as Alzheimer's disease, stroke, migraine, multiple sclerosis, concussion, Parkinson's disease and epilepsy. For more information about the American Academy of Neurology, visit http://www. or find us on Facebook, Twitter, LinkedIn and YouTube.


Iwamoto J.,Keio University | Sato Y.,Mitate Hospital
Therapeutics and Clinical Risk Management | Year: 2014

An open-label randomized controlled trial was conducted to clarify the effect of eldecalcitol (ED) on body balance and muscle power in postmenopausal osteoporotic women treated with bisphosphonates. A total of 106 postmenopausal women with osteoporosis (mean age 70.8 years) were randomly divided into two groups (n=53 in each group): a bisphosphonate group (control group) and a bisphosphonate plus ED group (ED group). Biochemical markers, unipedal standing time (body balance), and five-repetition chair-rising time (muscle power) were evaluated. The duration of the study was 6 months. Ninety-six women who completed the trial were included in the subsequent analyses. At baseline, the age, body mass index, bone mass indices, bone turnover markers, unipedal standing time, and chair-rising time did not differ significantly between the two groups. During the 6-month treatment period, bone turnover markers decreased significantly from the baseline values similarly in the two groups. Although no significant improvement in the unipedal standing time was seen in the ED group, compared with the control group, the chair-rising time decreased significantly in the ED group compared with the control group. The present study showed that ED improved the chair-rising time in terms of muscle power in postmenopausal osteoporotic women treated with bisphosphonates. © 2014 Iwamoto and Sato. This work is published by Dove Medical Press Limited.


Iwamoto J.,Keio University | Sato Y.,Mitate Hospital
Expert Opinion on Pharmacotherapy | Year: 2013

Introduction: The effect of the anti-osteoporosis medicine, menatetrenone (vitamin K2; menaquinone-4) on the skeleton remains a matter of controversy. The objective of the present review study was to evaluate the effect of menatetrenone on the skeleton of postmenopausal women, men and glucocorticoid-treated patients. Methods: PubMed was used to search the literature for randomized controlled trials (RCTs), meta-analyses and systematic reviews. Thirteen RCTs, one meta-analysis and one systematic review were available for analysis. Results: Except for one large Japanese RCT (Phase IV trial: Osteoporotic Fracture (OF) study, n = 4378), RCTs with small sample size showed non-significant or modest effect on bone mineral density (BMD) in postmenopausal women and patients treated with glucocorticoid, positive effect on hip geometry in postmenopausal women and efficacy against fractures (mainly vertebral fractures) in postmenopausal women with osteoporosis. A post hoc analysis of the OF study showed that the incidence of vertebral fractures decreased in postmenopausal women with at least five vertebral fractures. A meta-analysis study, but not a systematic review study, showed efficacy against vertebral and non-vertebral fractures mainly in postmenopausal women with osteoporosis. There was no available evidence for men with osteoporosis. Conclusion: The present review of the literature revealed some evidence of a positive effect of menatetrenone on the skeleton of postmenopausal women and in patients treated with glucocorticoid. Expert opinion: Menatetrenone is considered to be a second-line medicine for postmenopausal osteoporotic women with an increased risk for vertebral fractures. © 2013 Informa UK, Ltd.


Sato Y.,Mitate Hospital | Iwamoto J.,Keio University | Honda Y.,Mitate Hospital
Journal of Stroke and Cerebrovascular Diseases | Year: 2011

Although vitamin D supplementation has been suggested to reduce the risk of falling in ambulatory or institutionalized elderly persons, no study has examined whether it reduces the frequency of falling in immobilized stroke patients who have immobilization-induced hypercalcemia reflecting increased bone resorption leading to inhibited renal synthesis of 1, 25-dihydroxyvitamin D (1, 25-[OH]2D). Bisphosphonate is known to reduce immobilization-induced hypercalcemia by inhibiting bone resorption of calcium. This study compared the efficacy of 2 drugs in reducing the risk of falling in patients with long-standing stroke. Eighty-two elderly patients with poststroke hemiparesis were followed for 1 year. The patients were randomly assigned to one of 2 groups; 41 patients received alendronate 35 mg once weekly, and 41 patients received alphacalcidiol 1 μg daily. The number of falls per person and incidence of hip fracture in the 2 groups were compared. At baseline, all patients had a low serum 1, 25-[OH]2D level. Alphacalcidol therapy enhanced immobilization-induced hypercalcemia by increasing intestinal calcium absorption, leading to a reduction of serum 1, 25-[OH]2D level, while alendronate therapy enhanced 1, 25-[OH]2D production by decreasing hypercalcemia. Alendronate treatment accounted for a 55% reduction in falls (95% confidence interval [CI] = 25-72%; P = .0021). During the 1-year study period, hip fracture occurred in 1 of 41 subjects in the alphacalcidol group and in no subjects in the alendronate group. Bone mineral density was increased by 3.2% in the alendronate group and decreased by 0.1% in the alphacalcidol group (P < .0001). Alendronate therapy increased serum 1, 25-[OH]2D levels by improving immobilization-induced hypercalcemia, which may lead to decreased falling and subsequent hip fractures. © 2011 by National Stroke Association.


Sato Y.,Mitate Hospital | Iwamoto J.,Keio University | Honda Y.,Mitate Hospital
Journal of Neurology, Neurosurgery and Psychiatry | Year: 2011

Background: Incidence of a fracture, particularly in the hip joint, is high in Parkinson's disease (PD), owing to the immobilisation-induced bone resorption and vitamin D deficiency with reduced bone mineral density (BMD). The authors previously demonstrated the lowered incidence of hip fractures in PD by daily administration of risedronate and vitamin D. Methods: This randomised, double-blind, placebo-controlled study was conducted to determine the efficacy of 17.5 mg once-weekly risedronate in the prevention of hip fracture in women with PD. Patients were randomly assigned to 17.5 mg risedronate once a week (n=136) or a placebo (n=136) combined with daily 1000 IU of ergocalciferol. Incidence of hip fractures was compared between the two groups during the 2-year follow-up. Results: Hip fractures occurred in 15 patients in the placebo group and 3 patients in the risedronate group. The RR for hip fractures in the risedronate group as compared with the placebo group was 0.20 (95% CI 0.06 to 0.66). In the risedronate group, serum calcium levels decreased during the follow-up, while the levels in the placebo group increased. BMD increased by 3.4% in the risedronate group and decreased by 3.2% in the placebo group (p<0.01). Conclusions: Treatment with once-weekly risedronate and ergocalciferol prevents hip fractures in older women with PD.


Sato Y.,Mitate Hospital | Iwamoto J.,Keio University | Honda Y.,Mitate Hospital
Parkinsonism and Related Disorders | Year: 2011

A high incidence of fractures, particularly of the hip, represents an important problem in patients with Parkinson's disease (PD), who are prone to falls and have osteoporosis. We previously showed that 25-hydroxyvitamin D (25-OHD) deficiency due to sunlight deprivation with compensatory hyperparathyroidism causes reduced bone mineral density (BMD) in elderly patients with PD. The present study was undertaken to address the possibility that sunlight exposure may maintain BMD and reduce the incidence of hip fracture in elderly patients with PD. In a prospective study, PD patients were assigned to regular sunlight exposure (n = 162) or usual lifestyle (n = 162), and followed for 2 years. BMD of the second metacarpal bone was measured using a computed X-ray densitometer. Incidence of hip fracture in the two patient groups during the 2 year follow-up period was assessed. At baseline, patients of both groups showed vitamin D deficiency due to sunlight deprivation with compensatory hyperparathyroidism. The exposed group patients were exposed to sunlight (3231. min/year). BMD increased by 3.8% in the sunlight-exposed group and decreased by 2.6% in the usual lifestyle group (p< .0001). Serum 25-OHD level increased from 27. nmol/L to 52. nmol/L in the sunlight-exposed group. Eleven patients sustained hip fracture in the normal lifestyle group, and 3 fractures occurred among the sunlight-exposed group (p = .03; odds ratio. = 2.4). Sunlight exposure can increase the BMD of vitamin D deficient bone by increasing 25-OHD concentration and leads to the prevention of hip fracture. © 2010 Elsevier Ltd.


Sato Y.,Mitate Hospital
Journal of musculoskeletal & neuronal interactions | Year: 2013

Minodronate is a nitrogen-containing bisphosphonate that is commercially available for the treatment of osteoporosis in Japan. Preclinical studies demonstrated that minodronate is at least 10 times more potent than alendronate in inhibiting bone resorption in vivo. A high incidence of fractures, particularly of the hip, represents an important problem in Alzheimer disease (AD) patients who are prone to falls and may have osteoporosis. A total of 256 elderly patients with AD were assigned to daily treatment with 1.0 mg of minodronate or a daily treatment with risedronate combined with daily 1000 IU ergocalciferol and 1200 mg elemental calcium, and followed up for 12 months. At baseline, patients of both groups showed low 25-hydroxyvitamin D with compensatory hyperparathyroidism. Non-vertebral fractures occurred in 5 patients in the minodronate group and 7 patients in the risedronate group (5 hip fractures; one fracture each at the distal forearm and pelvis). There was no difference in risk of hip fracture between the two groups (p=.70; odds ratio=0.8). The study medications were well tolerated with relatively few adverse events and were equivalent in reducing the risk of a fracture in elderly patients with AD.


News Article | November 11, 2016
Site: www.sciencedaily.com

A new study suggests probable scientific misconduct in at least some of 33 bone health trials published in various medical journals. The study used statistical methods to detect scientific misconduct or research fraud and calls into question the validity of a body of research work led mainly by one researcher in Japan. The study is published in the November 9, 2016, online issue of Neurology®, the medical journal of the American Academy of Neurology. "Our use of statistical methods to examine the integrity of the data in 33 randomized controlled trials raises serious concerns about the reported results in those trials," said study author Mark J. Bolland, MBChB, PhD, of the University of Auckland in New Zealand. Bolland and his team analyzed the 33 studies, three of which were published in Neurology and retracted this summer after the author, Yoshihiro Sato, MD, of Mitate Hospital in Tagawa, Japan, admitted to scientific misconduct. Sato accepted full responsibility, admitting fabrication of the fraudulent Neurology papers, which reported on the effects of therapies to reduce hip fractures both after stroke and in Parkinson's disease patients. Sato stated that none of the coauthors participated in any misconduct and were named as authors on an honorary basis only. Sato requested retraction of the three studies. For the analysis of the 33 trials, 26 of which Sato was lead author, Bolland's team conducted a rigorous review and found reported results that differed markedly from what could be expected statistically; further, the results were remarkably positive. The characteristics of the groups of people chosen to participate in the trials were much more similar than would have happened by chance. The trials reported large reductions in hip fractures, no matter what treatment was used, that were much greater than those reported in similar trials from other research groups. Overall in the 33 trials, the people receiving the therapy were 78 percent less likely to break a hip than the control group, while several meta-analyses of other trials found either no benefit of the treatments or a benefit of less than 40 percent. Bolland's team also found multiple examples of inconsistencies between and within trials, errors in reported data, misleading text, duplicated data and text as well as uncertainties about ethical oversight. "The researchers were remarkably productive, conducting 33 randomized controlled trials within 15 years, the outcomes of each being remarkably positive," said Bolland. "Our analysis suggests that the results of at least some of these trials are not reliable. In addition, results from these trials were not consistent with results found in similar studies by other researchers." "This statistical analysis demonstrates probable scientific misconduct on a large scale," said Robert A. Gross, MD, PhD, of Rochester, N.Y., Editor-in-Chief of Neurology and Fellow of the American Academy of Neurology, who wrote a corresponding editorial. "Fraud in an individual paper may be difficult to detect. One cannot conclude that any one study in the analysis is, or is not, fraudulent. As part of our due process, we have notified other editors of journals that published papers by Sato and colleagues, communicated with Sato's institution, and published retractions of the three papers and a letter published in Neurology." The analysis was supported by the Health Research Council of New Zealand and the Health and Social Care Directorate of the Scottish Government.


News Article | November 10, 2016
Site: www.biosciencetechnology.com

A new study suggests probable scientific misconduct in at least some of 33 bone health trials published in various medical journals. The study used statistical methods to detect scientific misconduct or research fraud and calls into question the validity of a body of research work led mainly by one researcher in Japan. The study is published in the November 9, 2016, online issue of Neurology, the medical journal of the American Academy of Neurology. "Our use of statistical methods to examine the integrity of the data in 33 randomized controlled trials raises serious concerns about the reported results in those trials," said study author Mark J. Bolland, MBChB, Ph.D., of the University of Auckland in New Zealand. Bolland and his team analyzed the 33 studies, three of which were published in Neurology and retracted this summer after the author, Yoshihiro Sato, M.D., of Mitate Hospital in Tagawa, Japan, admitted to scientific misconduct. Sato accepted full responsibility, admitting fabrication of the fraudulent Neurology papers, which reported on the effects of therapies to reduce hip fractures both after stroke and in Parkinson's disease patients. Sato stated that none of the coauthors participated in any misconduct and were named as authors on an honorary basis only. Sato requested retraction of the three studies. For the analysis of the 33 trials, 26 of which Sato was lead author, Bolland's team conducted a rigorous review and found reported results that differed markedly from what could be expected statistically; further, the results were remarkably positive. The characteristics of the groups of people chosen to participate in the trials were much more similar than would have happened by chance. The trials reported large reductions in hip fractures, no matter what treatment was used, that were much greater than those reported in similar trials from other research groups. Overall in the 33 trials, the people receiving the therapy were 78 percent less likely to break a hip than the control group, while several meta-analyses of other trials found either no benefit of the treatments or a benefit of less than 40 percent. Bolland's team also found multiple examples of inconsistencies between and within trials, errors in reported data, misleading text, duplicated data and text as well as uncertainties about ethical oversight. "The researchers were remarkably productive, conducting 33 randomized controlled trials within 15 years, the outcomes of each being remarkably positive," said Bolland. "Our analysis suggests that the results of at least some of these trials are not reliable. In addition, results from these trials were not consistent with results found in similar studies by other researchers." "This statistical analysis demonstrates probable scientific misconduct on a large scale," said Robert A. Gross, M.D., Ph.D., of Rochester, N.Y., Editor-in-Chief of Neurology and Fellow of the American Academy of Neurology, who wrote a corresponding editorial. "Fraud in an individual paper may be difficult to detect. One cannot conclude that any one study in the analysis is, or is not, fraudulent. As part of our due process, we have notified other editors of journals that published papers by Sato and colleagues, communicated with Sato's institution, and published retractions of the three papers and a letter published in Neurology."

Loading Mitate Hospital collaborators
Loading Mitate Hospital collaborators