Radiation dose and cataract surgery incidence in atomic bomb survivors, 1986-2005.

PURPOSE: To examine the incidence of clinically important cataracts in relation to lens radiation doses between 0 and approximately 3 Gy to address risks at relatively low brief doses. MATERIALS AND METHODS: Informed consent was obtained, and human subjects procedures were approved by the ethical committee at the Radiation Effects Research Foundation. Cataract surgery incidence was documented for 6066 atomic bomb survivors during 1986-2005. Sixteen risk factors for cataract, such as smoking, hypertension, and corticosteroid use, were not confounders of the radiation effect on the basis of Cox regression analysis. Radiation dose-response analyses were performed for cataract surgery incidence by using Poisson regression analysis, adjusting for demographic variables and diabetes mellitus, and results were expressed as the excess relative risk (ERR) and the excess absolute risk (EAR) (ie, measures of how much radiation multiplies [ERR] or adds to [EAR] the risk in the unexposed group). RESULTS: Of 6066 atomic bomb survivors, 1028 underwent a first cataract surgery during 1986-2005. The estimated threshold dose was 0.50 Gy (95% confidence interval [CI]: 0.10 Gy, 0.95 Gy) for the ERR model and 0.45 Gy (95% CI: 0.10 Gy, 1.05 Gy) for the EAR model. A linear-quadratic test for upward curvature did not show a significant quadratic effect for either the ERR or EAR model. The linear ERR model for a 70-year-old individual, exposed at age 20 years, showed a 0.32 (95% CI: 0.09, 0.53) [corrected] excess risk at 1 Gy. The ERR was highest for those who were young at exposure. CONCLUSION: These data indicate a radiation effect for vision-impairing cataracts at doses less than 1 Gy. The evidence suggests that dose standards for protection of the eye from brief radiation exposures should be 0.5 Gy or less.

Height loss starting in middle age predicts increased mortality in the elderly.

The purpose of this study was to determine the mortality risk among Japanese men and women with height loss starting in middle age, taking into account lifestyle and physical factors. A total of 2498 subjects (755 men and 1743 women) aged 47 to 91 years old underwent physical examinations during the period 1994 to 1995. Those individuals were followed for mortality status through 2003. Mortality risk was estimated using an age-stratified Cox proportional hazards model. In addition to sex, adjustment factors such as radiation dose, lifestyle, and physical factors measured at the baseline--including smoking status, alcohol intake, total cholesterol, blood pressure, and diagnosed diseases--were used for analysis of total mortality and mortality from each cause of death. There were a total of 302 all-cause deaths, 46 coronary heart disease and stroke deaths, 58 respiratory deaths including 45 pneumonia deaths, and 132 cancer deaths during the follow-up period. Participants were followed for 20,787 person-years after baseline. Prior history of vertebral deformity and hip fracture were not associated with mortality risk. However, more than 2 cm of height loss starting in middle age showed a significant association with all-cause mortality among the study participants (HR = 1.76, 95% CI 1.31 to 2.38, p = 0.0002), after adjustment was made for sex, attained age, atomic-bomb radiation exposure, and lifestyle and physical factors. Such height loss also was significantly associated with death due to coronary heart disease or stroke (HR = 3.35, 95% CI 1.63 to 6.86, p = 0.0010), as well as respiratory-disease death (HR = 2.52, 95% CI 1.25 to 5.22, p = 0.0130), but not cancer death. Continuous HL also was associated with all-cause mortality and CHD- or stroke-caused mortality. Association between height loss and mortality was still significant, even after excluding persons with vertebral deformity. Height loss of more than 2 cm starting in middle age was an independent risk factor for cardiovascular and respiratory-disease mortality among the elderly, even after adjusting for potential risk factors.

Vertebral fracture status and the World Health Organization risk factors for predicting osteoporotic fracture risk in Japan.

INTRODUCTION: Vertebral fractures are the most common osteoporotic fracture and the prevalence of vertebral fracture is commonly assessed in clinical practice in Japan. The objective of this study was to evaluate potential risk factors for osteoporotic fractures, including morphometric spine fracture status and the WHO risk factors for predicting 4-year fracture risk. METHODS: A population-based community cohort, the Adult Health Study, consisting of 2613 men and women with mean age of 65 enrolled in Hiroshima was followed prospectively for 4 years. The prevalence and incidence of spine fractures were identified from lateral and posterior-anterior spine radiographs using a semiquantitative method. Information on incident nonvertebral fragility fractures (hip, proximal humeral, and forearm) was collected at interviews by trained nurses and physicians during biennial health examinations. RESULTS: A model, including spine fracture status in addition to the WHO risk factors, appeared to provide greater prognostic information regarding future fracture risk (gradient of risk/standard deviation: GR/SD=2.73) than a model with the WHO risk factors alone (GR/SD=2.54). In univariate analyses, age, bone mineral density (BMD), prior clinical fracture, and spine fracture status had the highest gradient of risk. The presence of multiple prevalent spine or non-spine fractures significantly increased fracture risk, but, their contributions to the gradient of risk were similar to those when fracture status was categorized as a binary variable. A model considering those four risk factors yielded GR/SD=2.67, indicating that it could capture most of the predictive information provided by the model with spine fracture status plus the WHO risk factors. CONCLUSION: The use of age, BMD, prior clinical fracture and spine fracture predicted future fracture risk with greater simplicity and higher prognostic accuracy than consideration of the risk factors included in the WHO tool.

[Daily practice using the guidelines for prevention and treatment of osteoporosis. Association between height loss and QOL in the elderly].

Medical care of osteoporosis aims at preventing bone fractures and thereby maintaining and improving the quality of life (QOL). It was observed in some studies that height loss and vertebral fracture had an independent, significant impact on QOL in the elderly. It had been believed thus far that the phenomenon of height loss was attributable mainly to incurred spinal fracture and that it had no clinical value other than as a sign of osteoporosis, but some studies revealed that height loss was also a factor affecting QOL independently of vertebral fracture.

Effect of angiotensin converting enzyme inhibitor and benzodiazepine intake on bone loss in older Japanese.

We investigated the effects of several frequently described medication regimens on annual percentage change in bone mineral density (BMD). A longitudinal cohort study (a retrospective analysis) was conducted. Subjects in the Adult Health Study (a prospective cohort study begun in 1958) have been followed through biennial medical examinations in Hiroshima, Japan. Participants were 2,111 subjects (67% women; aged 47-95 years) who were undergoing biennial health examinations from 1994 to 2000. The subjects were examined for the effect of certain drugs on bone mineral change during baseline and one follow-up (4 year later) measurements. Mean annual percentage change in BMD at the femoral neck was -0.38% for men, and -1.14% for women. After adjustment for sex, age, change of weight, alcohol consumption, and smoking status, annual percentage change in BMD decreased by 0.61% among individuals taking angiotensin converting enzyme (ACE) inhibitors continuously in comparison with individuals who had not taken them (p = 0.002): also decreased 0.40% among individuals taking benzodiazepines (BZDs) continuously (p = 0.034). Our results suggest that careful consideration should be given to the use of ACE inhibitors and BZDs in a cohort of Japanese elderly.

Serum uric acid concentration as a risk factor for cardiovascular mortality: a longterm cohort study of atomic bomb survivors.

OBJECTIVE: To elucidate the association of serum uric acid concentration with cardiovascular mortality risk. METHODS: Serum uric acid level measured from 1966 through 1970 in 10,615 Japanese individuals from a cohort of atomic bomb survivors was analyzed for association with subsequent cardiovascular and all-cause mortality until 1999 using the Cox proportional hazard model. RESULTS: During an average followup of 24.9 years, 5225 deaths occurred, of which 1984 were ascribed to cardiovascular disease. In men, after adjustment for age, elevated serum uric acid level was associated with both cardiovascular and all-cause mortality. After additional adjustment for potential cardiovascular disease risk factors including body mass index, smoking status, alcohol consumption, systolic blood pressure, cholesterol level, and histories of hypertension, diabetes and cardiovascular disease, elevated serum uric acid level in men was associated with all-cause mortality but not with cardiovascular mortality. In women, even after these adjustments, elevated serum uric acid level was significantly associated with cardiovascular and all-cause mortality. CONCLUSION: Increased serum uric acid level is a significant and independent risk factor for cardiovascular mortality in women and for all-cause mortality in both men and women.

Prevalence of atherosclerosis in relation to atomic bomb radiation exposure: an RERF Adult Health Study.

PURPOSE: To determine whether exposure to atomic bomb radiation altered the prevalence of asymptomatic atherosclerosis. MATERIAL AND METHODS: In a cross-sectional analysis, we examined aortic arch calcification by plain chest radiography and common carotid artery intima-media thickness (IMT) by ultrasonography among 1804 survivors of the atomic bombing in Hiroshima. We evaluated the association between atherosclerotic changes and radiation exposure, while adjusting for potentially confounding factors. RESULTS: Multivariate logistic regression analysis showed that aortic arch calcification was significantly associated with radiation exposure (p < 0.05). The odds ratio at 1 Gy was 1.30 (95% confidence interval [CI]: 1.05 - 1.53) for men and 1.31 (95% CI: 1.13 - 1.51) for women. Carotid artery IMT did not vary significantly with radiation dose (p = 0.18). CONCLUSION: Radiation dose contributed to the prevalence of aortic atherosclerosis but not carotid artery atherosclerosis in atomic bomb survivors.

Self-reported number of remaining teeth is associated with bone mineral density of the femoral neck, but not of the spine, in Japanese men and women.

Recent studies suggest that a small number of remaining teeth may be associated with low skeletal bone mineral density (BMD) in postmenopausal women. Estrogen deficiency after menopause is considered potential cause relating to tooth loss accompanied by low skeletal BMD in women. Since estrogen plays a dominant role in regulating the male skeleton, it is likely that a small number of remaining teeth also may be associated with low skeletal BMD in men. However, it remains uncertain whether tooth loss is associated with low skeletal BMD in both men and women. We investigated the association between self-reported number of remaining teeth and BMD of the spine and the femoral neck in a cohort of 1914 Japanese subjects aged 48-95 years who were recruited from the Adult Health Study conducted by the Radiation Effects Research Foundation (RERF). BMD of the spine and the femoral neck was measured by dual energy X-ray absorptiometry (DXA). Tooth count was self-reported in response to a simple question to subjects about the number of remaining teeth they had at the time of the survey. Multiple regression analysis adjusted for age, weight, height, smoking, estrogen use, and years since menopause revealed a significant association between number of remaining teeth and BMD of the femoral neck in both men and women; however, no association was found between number of remaining teeth and BMD of the spine in both sexes. Retention of four teeth was significantly associated with a 0.004 g/cm2 increase in femoral neck BMD in men (P<0.05), which was similar to that observed in women (P<0.01). Our results suggest the presence of common causes, except age and body weight, relating to tooth loss accompanied by low BMD of the femoral neck in both men and women.

Fracture prediction from bone mineral density in Japanese men and women.

UNLABELLED: In a cohort of 2356 Japanese elderly, after adjusting for age and prevalent vertebral fracture, baseline BMD predicted the risk of spine and hip fracture with similar RR to that obtained from previous reports in whites. The RR per SD decrease in BMD for fracture declined with age. INTRODUCTION: Low bone mineral density (BMD) is one of the most important predictors of a future fracture. However, we are not aware of any reports among Japanese in Japan. MATERIALS AND METHODS: We examined the association of BMD with risk of fracture of the spine or hip among a cohort of 2356 men and women aged 47-95 years, who were followed up by biennial health examinations. Follow-up averaged 4 years after baseline measurements of BMD that were taken with the use of DXA. Vertebral fracture was assessed using semiquantitative methods, and the diagnosis of hip fracture was based on medical records. Poisson and Cox regression analysis were used. RESULTS: The incidence was twice as high in women as in men, after adjusting for age. After adjusting for baseline BMD and prevalent vertebral fracture, however, the gender difference was no longer significant. Age, baseline BMD of spine and femoral neck, and prior vertebral fracture predicted vertebral fracture and hip fracture. Loss of absolute BMD of the femoral neck predicted spine fracture, after adjusting for baseline BMD; rates of change in percent BMD, weight, height, body mass index, and age at menopause did not. The predictive value of baseline BMD for vertebral fracture risk was similar in men and women. The relative risk (RR) for vertebral fracture and hip fracture per SD decrease in BMD declined with age, after adjustment for prevalent vertebral fractures. CONCLUSIONS: Baseline BMD, loss of femoral neck BMD, and prior vertebral fracture predict the risk of spine and hip fracture in Japanese with similar RR to that obtained from previous reports in whites. The RR per SD decrease in BMD for fracture declined with age, suggesting that factors other than BMD might play a greater role in the elderly.

Association between dementia and midlife risk factors: the Radiation Effects Research Foundation Adult Health Study.

OBJECTIVES: To investigate the association between midlife risk factors and the development of vascular dementia (VaD) or Alzheimer's disease (AD) 25 to 30 years later. DESIGN: A prevalence study within a longitudinal cohort study. SETTING: Subjects in the Adult Health Study (a prospective cohort study begun in 1958) have been followed through biennial medical examinations in Hiroshima, Japan. PARTICIPANTS: One thousand seven hundred seventy-four subjects in Hiroshima, Japan born before September 1932 (1,660 with no dementia, 114 with dementia (51 with AD, and 38 with VaD) diagnosed from 1992 to 1997 according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria). MEASUREMENTS: The subjects were examined for effect on dementia of sex, age, education, atomic bomb radiation dose, and midlife factors associated with risk (smoking, alcohol intake, physical activity, dietary habits, systolic blood pressure (SBP), body mass index, and history of diabetes mellitus) that had been evaluated in 1965-1970. RESULTS: VaD prevalence increased significantly with age, higher SBP, and lower milk intake. The odds ratios of VaD for age (in 5-year increments), SBP (10 mmHg increments), and milk intake (almost daily/less than four times a week) were 1.29, 1.33, and 0.35, respectively. The risk factors for VaD were compatible with the risk factors for stroke in this study population. AD prevalence increased significantly with age and lower education. Other midlife factors and radiation dose did not show any significant association with VaD or AD. CONCLUSION: Increased SBP and low milk intake in midlife were associated with VaD detected 25 to 30 years later. Early behavioral control of the risk factors for vascular disease might reduce the risk of dementia.