Akemi Morita

Biochemical markers of bone turnover predict bone loss in perimenopausal women but not in postmenopausal women-the Japanese Population-based Osteoporosis (JPOS) Cohort Study

IntroductionThe predictive value of biochemical markers of bone turnover for subsequent change in bone density in a population sample of healthy women with a wide range of ages has not been fully established.MethodsWe followed 1,283 women aged 15–79 years at baseline selected randomly from the inhabitants of three areas in Japan for 6 years, and examined 1,130 subjects with no disease or administration of drugs affecting bone metabolism. The annual change in bone density at the spine, total hip, and distal one third of the radius was determined during the follow-up period by dual x-ray absorptiometry and was compared among the groups using different levels of biochemical markers at baseline, including serum osteocalcin (OC) and bone-specific alkaline phosphatase (bone ALP), free and total (tDPD) forms of immunoreactive deoxypyridinoline, and type I collagen crosslinked C-terminal telopeptide (CTX) in urine.ResultsPremenopausal women aged 45 years or older with elevated levels of OC, bone ALP, CTX, or tDPD showed significantly greater bone loss at most skeletal sites during the follow-up period than those with lower levels, after adjustment for the effects of age, height, weight, dietary calcium intake, regular exercise, and current smoking. The greatest coefficient of determination of the model was observed in the association between CTX and bone loss at the hip during the first 3 years of follow-up (42.8%). These subjects were pooled with perimenopausal women at baseline, and those who still menstruated at follow-up in this pooled group showed significant but more modest associations, whereas those who entered menopause during the follow-up period showed clear associations. However, early postmenopausal women with less than 5 or 10 years since menopause showed an association that was limited mostly to the distal radius, and other postmenopausal groups had virtually no association.ConclusionBiochemical markers of bone turnover may predict bone loss in women undergoing menopausal transition but may not predict bone loss in postmenopausal women.

Age-Specific Values and Cutoff Levels for the Diagnosis of Osteoporosis in Quantitative Ultrasound Measurements at the Calcaneus with SAHARA in Healthy Japanese Women: Japanese Population-Based Osteoporosis (JPOS) Study

To establish the reference values of the quantitative ultrasound (QUS) indices in healthy Japanese women and to propose a diagnostic criterion for osteoporosis by means of the QUS indices, 659 healthy women aged 20-79 years recruited from a larger cohort study (JPOS study), were examined for bone mass measurements by QUS at the calcaneus (SAHARA, Hologic Inc., USA) and by dual-energy X-ray absorptiometry at the spine, hip, and distal forearm. We presented 10-year age-specific mean values and T-scores of the QUS indices. The pattern of decrease in the T-score appeared to be linear in the QUS indices and total hip BMD but not in BMD at the spine. The T-score of the QUS of indices of the subjects in their 70s were significantly higher than that of BMD at the spine. The prevalence rates of osteoporosis in the subjects aged 50 and older diagnosed by QUS (8.7% for SOS, 10.7% for BUA) were similar to that diagnosed by total hip BMD (11.5%) and significantly lower than that by the spine BMD (36.1%) when the WHO criteria were applied. We performed receiver-operating characteristic analysis to set a cutoff level of the QUS indices for the diagnosis of osteoporosis to accurately identify the subjects diagnosed by either the spine or total hip BMD. The highest likelihood ratios for SOS and BUA were obtained at the cutoff levels of 1,517.7 m/sec (T-score: -1.58) with the sensitivity of 0.65 and the specificity of 0.65 and 59.5 dB/MHz (T-score: -1.52) with 0.66 and 0.69, respectively. The diagnostic accuracy of QUS indices for osteoporosis was not superior to that of age. However, the QUS indices showed a significant contribution to forming the diagnosis of osteoporosis independently of age and body size in multivariate diagnostic models developed by the logistic regression analysis. Therefore, the cutoff values presented in this study may be used as a tentative criterion until the cutoff levels for the QUS indices are set according to the fracture risk.

Effects of pubertal development, height, weight, and grip strength on the bone mineral density of the lumbar spine and hip in peripubertal Japanese children: Kyoto kids increase density in the skeleton study (Kyoto KIDS study).

The effects of growth and pubertal development on the bone mineral density (BMD) of the lumbar spine and hip in peripubertal Japanese children were studied as a basis for evaluating the effects of modifiable factors on bone mass gain. The study comprised bone mass measurements in the lumbar spine (L2–4), femoral neck, and total hip using dual-energy X-ray absorptiometry as well as body size measurements and detailed interviews on medical history and pubertal status. The subjects were 404 first-grade students in three junior high schools (129 boys and 275 girls, mean age 12.8 ± 0.3 years) with no diseases or medication that would affect bone metabolism. BMD at each site showed an increasing trend with physical growth and sexual maturity. Significant positive correlations were observed between BMD at every skeletal site and height, weight, and grip strength in pre- and postpubertal boys and girls. In multiple regression analyses, pubertal development had a significant positive independent effect on BMD at every skeletal site in girls, but not in boys. Physical and pubertal development showed major effects on BMD, but the magnitude of these effects differed in boys and girls, even if they were of the same age. We conclude that confounding factors due to physical and pubertal development should be taken into consideration in different ways for boys and girls in investigations on the effects of environmental or behavioral factors on bone mass acquisition in peripubertal children.

Effects of the Cdx-2 Polymorphism of the Vitamin D Receptor Gene and Lifestyle Factors on Bone Mineral Density in a Representative Sample of Japanese Women: The Japanese Population-based Osteoporosis (JPOS) Study

Using a large-scale representative sample of the Japanese female population, we examined the effects of a single nucleotide polymorphism within a binding site of Cdx-2 in the promoter region of the vitamin D receptor gene on bone mineral density (BMD), and the interactions between this polymorphism and lifestyle factors on BMD. Fifty women were randomly selected from each of the 5-year age-stratified populations (15–79 years) in each of three chosen municipalities as a part of the Japanese Population-based Osteoporosis Study. BMD at the lumbar spine, hip, and distal forearm was measured using dual-energy X-ray absorptiometry at baseline and again in a follow-up study conducted 3 years later. Information on lifestyle factors was collected in a questionnaire and followed up in interviews. The G-to-A polymorphism within the Cdx-2 binding site was determined by a TaqMan allelic discrimination assay. At baseline, 1,340 women were analyzed. The baseline BMD in the ultradistal forearm in premenopausal women with the GG genotype was significantly lower than in those with other genotypes. There was no association between the Cdx-2 genotype and the change in BMD at any of the skeletal sites. We found significant associations between daily milk consumption and baseline BMD at some skeletal sites but only in subjects with the GG genotype. In conclusion, the Cdx-2 polymorphism alone did not have a substantial effect on BMD in Japanese women. However, this polymorphism might have some effect in women with low calcium intake.

Association of Natural Killer Cell Activity with Serum IgE

Association of natural killer (NK) cell activity (NKCA) or NK cell subsets with total IgE or antigen-specific IgE in serum were studied among 66 healthy non-allergic males. NKCA was determined by using 61Cr release assay and NK subsets were counted usings surface antigens (CD16, CD57) in peripheral blood mononuclear cells. NKCA was associated mainly with the frequency of a CD16+,CD57- subset. When the subjects were classified into three groups according to total IgE values in serum (grade 0: IgE < 10 IU/ml; grade 1: IgE 10-400 IU/ml; grade 2: IgE > 400 IU/ml), one-way analysis of variance of NKCA showed that the grades of total IgE were significantly associated with increasing NKCA. In addition, NKCA in the grade 0 group was significantly lower than that in the grade 2 group and than a mixture of grade 1 group and grade 2 group. A similar finding was not observed between NKCA and RAST for specific IgE against mites. Therefore, NKCA may be related to total IgE level in serum.

Ultrasound bone densitometry of the calcaneus, determined with Sahara, in healthy Japanese adolescents: Japanese Population-based Osteoporosis (JPOS) Study

To establish the reference values for quantitative ultrasound (QUS) indices (speed of sound [SOS]), and broadband ultrasonic attenuation [BUA]) in healthy Japanese adolescents, and to evaluate the effects of age and body size on QUS in comparison with their effects on bone mineral density (BMD), 632 healthy adolescents aged 12 through 17 years recruited from a larger cohort study (Japanese Population-based Osteoporosis [JPOS] Study), were examined in terms of bone mass measurements by QUS at the calcaneus (Sahara; Hologic) and by dual-energy X-ray absorptiometry at the distal one-third radius and ultradistal forearm. We present sex- and age-specific mean values of the QUS and BMD indices. BMD increased significantly up to 17 years of age in males and up to 16 years in females. However, the age-related change in the QUS indices in males was not as clear as that seen for BMD and no age-related change in the QUS indices was observed in females. Significant positive correlation coefficients between BMD and body size were observed in both sexes even after adjusting for the effect of age. SOS showed no correlation with body size and BUA showed a positive but weak correlation with body size in both sexes. Thus, the relationships of age and body size to BMD and QUS were different from each other, even though the QUS indices had significant positive correlations with BMD, allowing for the effect of age.

The effect of aging on the mineral status of female SAMP1 and SAMR1

The effect of aging on the status of macrominerals and trace elements in tissues was studied using two strains (SAMP1 and SAMR1) of senescence accelerated mouse. Two-month-old, 6-mo-old, and 10-mo-old female SAMP1 and SAMR1 mice were fed a commercial diet. Iron, zinc, copper, calcium, magnesium, phosphorus, sulfur, sodium, and potassium concentrations in blood, liver, kidney, brain, and tibia of the mice were determined. The copper concentration in the brain was significantly increased with age in SAMP1 and SAMR1. In addition, the brain copper levels in SAMP1 were significantly higher than that in SAMR1 at respective ages. The calcium concentration in the kidney was significantly increased with age, but the copper and phosphorus concentrations significantly decreased with age in SAMP1 and SAMR1. In the liver of SAMR1, all minerals measured in this study except for sodium and potassium were significantly decreased with age. In addition, all mineral concentrations in the liver of 2-mo-old mice in SAMR1 except for copper and sodium were markedly higher than those in SAMP1 of the same age. These results suggest that the genetic factor is related to the age-associated mineral changes in tissues.

A cross-sectional population-based study on senile dementia in a rural city.

All residents aged 65 or over in a rural city (n=5340) were studied with a self-administered questionnaire on psychiatric symptoms, physical health status, medical history, and environmental factors. After the screening, the clinical diagnosis of senile dementia was made by psychiatrists. The overall prevalence was 4.0% among responders staying at home (201/4969). The prevalence increased with age for both males and females and tended to be higher for females than males. The multilogistic analysis of the above variables showed that in the cerebrovascular type, stroke and inactive physical status might be risk factors for both gender groups. For the Alzheimer’s type, age and inactive physical status might be risk factors. For overall dementia, age, stroke, and inactive physical status might be risk factors.