Hideaki Ishibashi

Bio: Hideaki Ishibashi is an academic researcher from University of Tokyo. The author has contributed to research in topics: Population & Osteoarthritis. The author has an hindex of 18, co-authored 31 publications receiving 1851 citations.

Prevalence of knee osteoarthritis, lumbar spondylosis, and osteoporosis in Japanese men and women: the research on osteoarthritis/osteoporosis against disability study.

Abstract: Musculoskeletal diseases, especially osteoarthritis (OA) and osteoporosis (OP), impair activities of daily life (ADL) and quality of life (QOL) in the elderly. Although preventive strategies for these diseases are urgently required in an aging society, epidemiological data on these diseases are scant. To clarify the prevalence of knee osteoarthritis (KOA), lumbar spondylosis (LS), and osteoporosis (OP) in Japan, and estimate the number of people with these diseases, we started a large-scale population-based cohort study entitled research on osteoarthritis/osteoporosis against disability (ROAD) in 2005. This study involved the collection of clinical information from three cohorts composed of participants located in urban, mountainous, and coastal areas. KOA and LS were radiographically defined as a grade of ≥2 by the Kellgren–Lawrence scale; OP was defined by the criteria of the Japanese Society for Bone and Mineral Research. The 3,040 participants in total were divided into six groups based on their age: ≤39, 40–49, 50–59, 60–69, 70–79, and ≥80 years. The prevalence of KOA in the age groups ≤39, 40–49, 50–59, 60–69, 70–79, and ≥80 years 0, 9.1, 24.3, 35.2, 48.2, and 51.6%, respectively, in men, and the prevalence in women of the same age groups was 3.2, 11.4, 30.3, 57.1, 71.9, and 80.7%, respectively. With respect to the age groups, the prevalence of LS was 14.3, 45.5, 72.9, 74.6, 85.3, and 90.1% in men, and 9.7, 28.6, 41.7, 55.4, 75.1, and 78.2% in women, respectively. Data of the prevalence of OP at the lumbar spine and femoral neck were also obtained. The estimated number of patients with KOA, LS, and L2–L4 and femoral neck OP in Japan was approximately 25, 38, 6.4, and 11 million, respectively. In summary, we estimated the prevalence of OA and OP, and the number of people affected with these diseases in Japan. The ROAD study will elucidate epidemiological evidence concerning determinants of bone and joint disease.

Factors associated with mortality following hip fracture in Japan.

Abstract: Various factors have been reported to increase the risk of death following hip fracture. However, our review of the literature indicates that previous studies were generally performed based on a rough classification of comorbidities. In this study, comorbidities were classified in detail, and the risk of death following hip fracture was investigated. Four hundred and eighty patients with hip fracture were enrolled. The patients' comorbidities and walking ability before injury were investigated using their own or their family's reports or their medical history, and the residences where the subjects were taken after discharge were recorded. Subsequently, the patients or their family were interviewed about whether they were alive or dead on January 1, 2002, by mail or telephone. A survival curve was drawn based on the Kaplan-Meier method. Cox proportional hazards regression models were used to determine the risk factors for death. An expected mortality rate for the Japanese population from 1991 to 2002 was obtained from a life table published by the Ministry of Health, Labour, and Welfare and compared to our observed mortality. The 1-year survival rate following hip fracture was 88.5%, which was a little lower than the expected survival rate. In subsequent years, the survival rate was lower than the expected survival rate. Being male and/or having a trochanteric fracture were risk factors for death. Patients who walked with a walker or other support or were nonambulatory before injury had an increased risk of death. Among the comorbidities, dementia, diabetes mellitus, and a history of gastrectomy or colonectomy were risk factors for death. Among the complications, pneumonia during hospitalization was a risk factor for death.

Regulation by PGE2 of the production of interleukin-6, macrophage colony stimulating factor, and vascular endothelial growth factor in human synovial fibroblasts

Abstract: 1. We examined the effects of endogenous prostaglandin E(2) (PGE(2)) on the production of interleukin-6 (IL-6), macrophage colony stimulating factor (M-CSF), and vascular endothelial growth factor (VEGF) by interleukin-1beta (IL-1beta)-stimulated human synovial fibroblasts. 2. NS-398 (1 microM), a cyclo-oxygenase-2 (COX-2) inhibitor, inhibited IL-6 and VEGF production (35+/-4% and 26+/-2%, respectively) but enhanced M-CSF production (38+/-4%) by IL-1beta (1 ng ml(-1)) in synovial fibroblasts isolated from patients with osteoarthritis (OA) and rheumatoid arthritis (RA). Exogenous PGE(2) completely abolished the effects of NS-398 on the production of each mediator by OA fibroblasts stimulated with IL-1beta. 3. 8-Bromo cyclic AMP and dibutyryl cyclic AMP, cyclic AMP analogues, mimicked the effects of PGE(2) on IL-6, M-CSF, and VEGF production by OA fibroblasts. 4. The EP(2) selective receptor agonist ONO-AE1-259 (2 nM) and the EP(4) selective receptor agonist ONO-AE1-329 (2 or 20 nM), but not the EP(1) selective receptor agonist ONO-DI-004 (1 microM) and the EP(3) selective receptor agonist ONO-AE-248 (1 microM), replaced the effects of PGE(2) on IL-6, M-CSF, and VEGF production by OA and RA fibroblasts stimulated with IL-1beta in the presence of NS-398. 5. Both OA and RA fibroblasts expressed mRNA encoding EP(2) and EP(4) but not EP(1) receptors. In addition, up-regulation of EP(2) and EP(4) receptor mRNAs was observed at 3 h after IL-1beta treatment. 6. These results suggest that endogenous PGE(2) regulates the production of IL-6, M-CSF, and VEGF by IL-1beta-stimulated human synovial fibroblasts through the activation of EP(2) and EP(4) receptors with increase in cyclic AMP.

Impact of degenerative spinal diseases on bone mineral density of the lumbar spine in elderly women

Abstract: Degenerative diseases of lumbar spine commonly noted in elderly people may affect their lumbar spine bone mineral density (BMD). The aim of this study is to determine whether the degree of degenerative spinal diseases is correlated with lumbar spine and femoral neck BMD. This study included 630 women age 60 years or over (mean age 73.3 ± 6.9 years) visiting the Osteoporosis Outpatient Clinic at the Tokyo Metropolitan Geriatric Medical Center. Subjects underwent anteroposterior and lateral X-rays of the lumbar spine. The score of degenerative spinal diseases for each subject was calculated according to the scores for the Kellgren-Lawrence method, osteophyte formation, bone sclerosis, disk space narrowing, and spondylolisthesis involving L1-L2 through L4-L5 interspaces. Moreover, the number of vertebral fractures at L2 through L4 was recorded. The BMD of the second to fourth lumbar spine from anteroposterior projections and femoral neck were measured using an Expert-5000 (GE Lunar, Madison, WI USA). Most subjects had degenerative diseases of the lumbar spine. Scores for the Kellgren-Lawrence method, osteophyte formation, bone sclerosis, disk space narrowing, and spondylolisthesis were positively correlated with lumbar spine BMD, while they were not correlated with femoral neck BMD. Multiple regression analysis indicated that the scores for osteophyte formation, bone sclerosis, and disk space narrowing were independently correlated with lumbar spine BMD. Thus, in this study, the scores for degenerative spinal diseases were correlated with lumbar spine BMD, while they were not correlated with femoral neck BMD. This discrepancy indicates that degenerative spinal diseases are associated with increased lumbar spine BMD measurements. Femoral neck BMD therefore may be more appropriate than lumbar spine BMD in evaluating osteoporosis in elderly women.

The global burden of hip and knee osteoarthritis: estimates from the Global Burden of Disease 2010 study

Abstract: Objective To estimate the global burden of hip and knee osteoarthritis (OA) as part of the Global Burden of Disease 2010 study and to explore how the burden of hip and knee OA compares with other conditions. Methods Systematic reviews were conducted to source age-specific and sex-specific epidemiological data for hip and knee OA prevalence, incidence and mortality risk. The prevalence and incidence of symptomatic, radiographic and self-reported hip or knee OA were included. Three levels of severity were defined to derive disability weights (DWs) and severity distribution (proportion with mild, moderate and severe OA). The prevalence by country and region was multiplied by the severity distribution and the appropriate disability weight to calculate years of life lived with disability (YLDs). As there are no deaths directly attributed to OA, YLDs equate disability-adjusted life years (DALYs). Results Globally, of the 291 conditions, hip and knee OA was ranked as the 11th highest contributor to global disability and 38th highest in DALYs. The global age-standardised prevalence of knee OA was 3.8% (95% uncertainty interval (UI) 3.6% to 4.1%) and hip OA was 0.85% (95% UI 0.74% to 1.02%), with no discernible change from 1990 to 2010. Prevalence was higher in females than males. YLDs for hip and knee OA increased from 10.5 million in 1990 (0.42% of total DALYs) to 17.1 million in 2010 (0.69% of total DALYs). Conclusions Hip and knee OA is one of the leading causes of global disability. Methodological issues within this study make it highly likely that the real burden of OA has been underestimated. With the aging and increasing obesity of the world9s population, health professions need to prepare for a large increase in the demand for health services to treat hip and knee OA.

Meta-analysis: Excess Mortality After Hip Fracture Among Older Women and Men

Abstract: Interest is increasing in quantifying the magnitude and duration of excess mortality after hip fractures for use in cost-effectiveness analyses of strategies for hip fracture prevention (1-3). Although an increased risk for death after hip fracture is well established in both women and men, it is unclear whether this excess mortality persists over time (4). Although almost all studies have reported an increased risk for death in the first 3 to 6 months after injury, results from long-term (5- to 10-year) follow-up have been conflicting, with some studies finding persistent excess mortality and others finding none (5-8). These conflicting results have several potential causes, including differences in control populations, difficulties in comparing crude and adjusted mortality statistics, and differences in model covariates (4-6, 9-16). At longer follow-up, the number of patients at risk and therefore the number of events (deaths) provide limited statistical power (17). An additional source of variability occurs in time-to-event (survival) analyses when the mortality risk is not constant over time and follow-up varies across the cohorts (17, 18). Because of these factors, reported hazard estimates are varied and have wide CIs, limiting any inferences physicians or public health policymakers can make. Further drawbacks include limited sample size, low frequency of observations, lack of stratification by sex, and reporting relative rather than absolute risks (17, 19, 20). We summarize longitudinal evidence about the magnitude and duration of excess mortality after hip fracture in older men and women.

Cellular and molecular mechanisms of action of bisphosphonates

Abstract: BACKGROUND Bisphosphonates currently are the most important class of antiresorptive agents used in the treatment of metabolic bone diseases, including tumor-associated osteolysis and hypercalcemia, Paget's disease, and osteoporosis. These compounds have high affinity for calcium and therefore target to bone mineral, where they appear to be internalized selectively by bone-resorbing osteoclasts and inhibit osteoclast function. METHODS This article reviews the pharmacology of bisphosphonates and the relation between the chemical structure of bisphosphonates and antiresorptive potency, and describes recent new discoveries of their molecular mechanisms of action in osteoclasts. RESULTS Bisphosphonates can be grouped into two pharmacologic classes with distinct molecular mechanisms of action. Nitrogen-containing bisphosphonates (the most potent class) act by inhibiting the mevalonate pathway in osteoclasts, thereby preventing prenylation of small GTPase signaling proteins required for osteoclast function. Bisphosphonates that lack a nitrogen in the chemical structure do not inhibit protein prenylation and have a different mode of action that may involve the formation of cytotoxic metabolites in osteoclasts or inhibition of protein tyrosine phosphatases. CONCLUSIONS Bisphosphonates are highly effective inhibitors of bone resorption that selectively affect osteoclasts. After more than 30 years of clinical use, their molecular mechanisms of action are only just becoming clear. Cancer 2000;88:2961–78. © 2000 American Cancer Society.

Prevalence of knee osteoarthritis, lumbar spondylosis, and osteoporosis in Japanese men and women: the research on osteoarthritis/osteoporosis against disability study.

Abstract: Musculoskeletal diseases, especially osteoarthritis (OA) and osteoporosis (OP), impair activities of daily life (ADL) and quality of life (QOL) in the elderly. Although preventive strategies for these diseases are urgently required in an aging society, epidemiological data on these diseases are scant. To clarify the prevalence of knee osteoarthritis (KOA), lumbar spondylosis (LS), and osteoporosis (OP) in Japan, and estimate the number of people with these diseases, we started a large-scale population-based cohort study entitled research on osteoarthritis/osteoporosis against disability (ROAD) in 2005. This study involved the collection of clinical information from three cohorts composed of participants located in urban, mountainous, and coastal areas. KOA and LS were radiographically defined as a grade of ≥2 by the Kellgren–Lawrence scale; OP was defined by the criteria of the Japanese Society for Bone and Mineral Research. The 3,040 participants in total were divided into six groups based on their age: ≤39, 40–49, 50–59, 60–69, 70–79, and ≥80 years. The prevalence of KOA in the age groups ≤39, 40–49, 50–59, 60–69, 70–79, and ≥80 years 0, 9.1, 24.3, 35.2, 48.2, and 51.6%, respectively, in men, and the prevalence in women of the same age groups was 3.2, 11.4, 30.3, 57.1, 71.9, and 80.7%, respectively. With respect to the age groups, the prevalence of LS was 14.3, 45.5, 72.9, 74.6, 85.3, and 90.1% in men, and 9.7, 28.6, 41.7, 55.4, 75.1, and 78.2% in women, respectively. Data of the prevalence of OP at the lumbar spine and femoral neck were also obtained. The estimated number of patients with KOA, LS, and L2–L4 and femoral neck OP in Japan was approximately 25, 38, 6.4, and 11 million, respectively. In summary, we estimated the prevalence of OA and OP, and the number of people affected with these diseases in Japan. The ROAD study will elucidate epidemiological evidence concerning determinants of bone and joint disease.

Mechanisms of diabetes mellitus-induced bone fragility

Abstract: The risk of fragility fractures is increased in patients with either type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM). Although BMD is decreased in T1DM, BMD in T2DM is often normal or even slightly elevated compared with an age-matched control population. However, in both T1DM and T2DM, bone turnover is decreased and the bone material properties and microstructure of bone are altered; the latter particularly so when microvascular complications are present. The pathophysiological mechanisms underlying bone fragility in diabetes mellitus are complex, and include hyperglycaemia, oxidative stress and the accumulation of advanced glycation endproducts that compromise collagen properties, increase marrow adiposity, release inflammatory factors and adipokines from visceral fat, and potentially alter the function of osteocytes. Additional factors including treatment-induced hypoglycaemia, certain antidiabetic medications with a direct effect on bone and mineral metabolism (such as thiazolidinediones), as well as an increased propensity for falls, all contribute to the increased fracture risk in patients with diabetes mellitus.