Bartter''s syndrome, supraventricular tachycardia, mitral valve prolapse, and asthma: a therapeutic challenge

The aim of this study was to evaluate the influence of age on bone mineral density (BMD) of teh lumbar spine for health Chinese men. In 430 healthy Chinese men (ages 20-92 years) living on Taiwan, BMD at the level of the 2nd to 4th lumbar vertebraes (L2-L4) was determined with a commercial dual-energy X-ray absorptiometer (DXA). Our study found that the peak BMD value of lumbar spines of healthy Chinese men was 1.056 +/- 0.127 g/cm2 which occurs from age 20 to 29. The results show that a linear correlation between the age and BMD of lumbar vertebraes for healthy Chinese is notable. Only slight decreases of BMD values in the different age groups are found. In comparison with the normal data of white men and Asian men from Japan and Korea, the mean BMD values of lumbar spines of Chinese men seem to be lower than those of the white, Japanese, and Korean men of the same ages. Our findings indicate that the influence of age and ethnicity may exist in the BMD values for healthy Chinese males.     

Investigation of bone mineral distribution in Japanese using dual-energy X-ray absorptiometry

To investigate bone mineral distribution in humans, the authors conducted a cross-sectional survey of, and performed bone-density measurements on, 1,310 healthy Japanese ranging in age 5 to 85 years. Eight hundred fifty-eight of the subjects were female, and 452 were male. Arm, leg, and spine bone mineral content (BMC) and bone mineral density (BMD) were assessed by dual-energy X-ray absorptiometry (DXA), and the subjects were divided into 5-year age groups. BMD showed increases with skeletal growth until reaching a peak at 15 to 19 years in females, and 25 to 29 for males. For both sexes the fastest growth to maturity in terms of bone mass values was in the late 20s. Females, though, had higher arm, leg, and spine remodeling rates than males. In premenopausal women no changes in arm, leg or spine BMC and BMD were observed. Postmenopausal women showed an overall reduction in bone mass, most noticeably in the spine. After menopause, women had about 10 years of accelerated loss (1.46%/year). Vertebral BMD values were similar for men and women (1.10 +/- 0.20g/cm2 for males vs. 1.09 +/- 0.14g/cm2 for females, p > 0.05). BMC values were significantly higher in males, and males at all times had a higher arm and leg BMD. There were no significant value differences in either sex for left and right leg BMC and BMD; however, from the age of 15, right arm values were significantly higher likely due to right handedness. For both sexes the order of BMC and BMD was leg, spine, and arm.     

Osteoporotic fracture rate, bone mineral density, and bone metabolism in Taiwan

Taiwanese people have spinal bone mineral density (BMD) values similar to those of Caucasians, whereas their hip BMD values are 10% to 15% lower. In 1992, the prevalence of vertebral fractures, diagnosed according to the -3 SD morphometric criteria, was 18% for women and 12% for men older than 65 years in the major cities of Taiwan. Despite this high prevalence of vertebral fractures, the incidence of hip fractures in the elderly of both sexes was only 203 per 100,000 in 1996, which was lower than in Caucasians and similar to that in mainland Chinese. Hip and vertebral fractures are both associated with lower BMD values. The risk factors for low BMD in Taiwan include a lighter body weight and aging in both sexes, and menopause for women. An increased bone turnover rate is associated with a lower BMD in both men and postmenopausal women, although the rate seems to increase in women but decrease in men with aging. In Taipei City, daily calcium intake is relatively low (mean intake +/- SD; 640 +/- 240 mg), but the vitamin D stores seem to be generally adequate for middle-aged and elderly women. There was a significant association between a higher daily calcium intake and a higher BMD/lower bone turnover rate for women in this age group. Vitamin D receptor allelic polymorphism was not an important factor in low BMD and rapid bone turnover.     

Type of physical activity, muscle strength, and pubertal stage as determinants of bone mineral density and bone area in adolescent boys

The present study was conducted to evaluate the influence of different types of weight-bearing physical activity, muscle strength, and puberty on bone mineral density (BMD, g/cm2) and bone area in adolescent boys. Three different groups were investigated. The first group consisted of 12 adolescent badminton players (age 17.0 +/- 0.8 years) training for 5.2 +/- 1.9 h/week. The second group consisted of 28 ice hockey players (age 16.9 +/- 0.3 years) training for 8.5 +/- 2.2 h/week. The third group consisted of 24 controls (age 16.8 +/- 0.3 years) training for 1.4 +/- 1.4h/week. The groups were matched for age, height, and pubertal stage. BMD, bone mineral content (BMC, g), and the bone area of the total body, lumbar spine, hip, femur and tibia diaphyses, distal femur, proximal tibia, and humerus were measured using dual-energy X-absorptiometry. When adjusting for the difference in body weight between the groups, the badminton players were found to have significantly higher BMD (p < 0.05) of the trochanter and distal femur compared with the ice hockey players despite a significantly lower weekly average training. The badminton players had higher BMD compared with the control with the control group at all weight-bearing BMD sites, except at the diaphyses of the femur and tibia and lumbar spine. The independent predictors of bone density were estimated by adjusting BMC for the bone area in a multivariate analysis among all subjects (n = 64). Accordingly, the bone density of all sites except the spine was significantly related to muscle strength and height, and the bone density of the total body, neck, trochanter, distal femur, and proximal tibia was significantly related to type of physical activity (beta = 0.09-0.33, p < 0.05). The bone area values at different sites were strongly related to muscle strength and height and less strongly related to the type of physical activity and pubertal stage. In conclusion, it seems that during late puberty in adolescent boys the type of weight-bearing physical activity is an important determinant of bone density, while the bone area is largely determined by parameters related to body size. The higher BMD at weight-bearing sites in badminton players compared with ice hockey players, despite significantly less average weekly training, indicates that physical activity including jumps in unusual directions has a great osteogenic potential.     

Screening for osteopenia and osteoporosis: do the accepted normal ranges lead to overdiagnosis?

Osteoporosis is a common disease which causes significant morbidity and mortality and in many cases may be preventable. In the absence of fragility fractures the accepted method of identifying those at high risk is based upon bone mineral density (BMD) measurements with defined cut-off points. To correctly delineate normal from abnormal, reliable reference ranges appropriate to the observed population are required. We have studied the age-dependent changes in mean BMD and standard deviation at the lumbar spine and femoral neck in a normal population extracted from 4280 women screened for osteopenia and compared our findings with the manufacturer's normal range (MNR). The recent World Health Organization criteria for the diagnosis of osteopenia and osteoporosis using the 'manufacturer's young normal' (MYN) values and our 'study young normal' (SYN) values have been applied. The study normal population (SNP) included 2068 women (mixed social class; mean age 53 years, range 30-79 years). The distribution of mean lumbar spine BMD with age in SNP was generally similar to the MNR. In contrast mean femoral neck bone density from SNP was significantly different from the MNR, ranging from 3% to 12% lower in each 5-year group analysed (p < 0.05). Comparison of standard deviations in spine BMD in SNP against the fixed MNR standard deviation showed a statistically significant increase commencing at 45 years of age. The magnitude of this increase appeared to rise with age and remained significant in the 75- to 79-year age group (p < 0.05). In contrast, standard deviation in femoral neck BMD in SNP appeared relatively constant with age except in the group of women at and around the time of the menopause. The SYN value for mean lumbar spine BMD was 0.994 g/cm2 (cf. MYN value 1.047, p < 0.0001) with a standard deviation of 0.122 g/cm2 (cf. MYN 0.11, p = 0.0005). Similarly our SYN value for femoral neck BMD was 0.787 (cf. MYN value 0.895, p < 0.0001) with a standard deviation of 0.109 (cf. MYN value 0.10, p = 0.0027). Using SYN values 36% (748) for the spine and 33% (675) for the hip of our normal population are classified as osteopenic or osteoporotic. Using MYN values increases the proportion of women classified as osteopenic or osteoporotic to 52% (1078) for the spine and 68% (1409) for the femur. If both sites of measurement are considered simultaneously SYN classifies 46% (952) as either osteopenic or osteoporotic at one or other site, which is increased to 73% (1513) when the MYN values are used. We observe that manufacturer's reference ranges may not be appropriate for the local population and may lead to an erroneously high diagnosis of osteopenia and osteoporosis, which would lead to unnecessary patient anxiety and perhaps errors regarding treatment.     

Spinal and femoral bone mass accumulation during normal adolescence: comparison with female patients with sexual precocity and with hypogonadism

Since the attainment of higher bone mineral density (BMD) is a crucial strategy in preventing age-related bone loss and consequent fracture, we determined when bone mass of the lumbar spine (L2-L4) (g/cm2) and femoral neck (g/cm2) reaches its peak in healthy Japanese subjects and examined the influence of early exposure to estrogen and estrogen deficiency on BMD. We also determined the volumetric BMD, termed bone mineral apparent density (BMAD), of the lumbar spine and femoral neck. Using dual-energy x-ray absorptiometry (DXA) (Hologic QDR-1000), we measured BMD of both the lumbar spine and the femoral neck in 31 healthy children aged 2-11 yr, 269 children (138 males and 131 females) aged 13-19 yr, 12 men and 12 women aged 20-34 yr as adult controls, 11 patients with female central sexual precocity, and 3 patients with female primary hypogonadism. Because the densitometric data obtained from DXA are strongly influenced by the size of the bone in growing subjects, the volumetric BMAD (g/cm3) of the vertebral cube (L2-L4) and femoral neck were determined: BMAD (g/cm3) = BMD (g/cm2)/square root of scanned area (cm2) for the lumbar spine and by BMAD = BMD/width for the femoral neck. The BMD, both lumbar spine and femoral neck, nearly reached its peak at age 14.5-15 yr in girls and 16.5-17 yr in boys when compared with adult normal values. The difference in this age between sexes is identical to the difference in age at sexual maturation. BMD in patients with sexual precocity was high compared to age-matched controls, whereas patients with primary hypogonadism showed lower lumbar apparent BMD, and the increase in lumbar BMAD (g/cm3) was noted after the progression of puberty in healthy children, probably suggesting the importance of sex steroids in the increase of BMD and lumbar BMAD in both sexes. The girls with earlier menarche showed higher lumbar BMD at age 18 and 19 yr. For the femoral BMAD, there was no significant relationship between this value and age in girls. We conclude that peak bone mass is mainly achieved by late adolescence in Japanese as in Caucasians and that pubertal progression and probably estrogen itself play a crucial role in accumulation of bone mass in females.     

Bone density, bone turnover, and hormone levels in men over age 75

BACKGROUND: Osteoporosis is a substantial problem in older men, with 25% of all hip fractures occurring in men. The mechanisms of bone loss in older men are unknown, but elevated parathyroid hormone (PTH) and diminished testosterone (T) levels are postulated as contributing factors. METHODS: We measured bone mineral density (BMD), sex hormones, bone turnover markers, and calcium regulating hormones in a group of community-living men over the age of 75. RESULTS: Thirty-five men (mean age 79; range 75-88 years) without disease or medication known to affect bone metabolism participated in the study. Whole body BMD was 1.21+/-.15 g/cm2; lumbar spine BMD (L1-L4) was 1.10+/-.15 g/cm2; femoral neck BMD was .77+/-.14 g/cm2; and trochanteric region was .71+/-.13 g/cm2. The femoral neck and trochanteric region values were more than 1 SD below the mean for adult men (age 25-33 years) in 28/35 and 15/35 men, respectively. Deoxypyridinoline levels were above the normal range for premenopausal women in 23% of the men; N-telopeptide and C-telopeptide demonstrated a wide scatter, but the values remained in the normal range. T levels were found to be below normal range for adult men in 12 of 32 (38%) subjects and the PTH levels above the normal range in 8 of 35 (23%) subjects. Bone resorption markers correlated inversely with BMD of the whole body, femur, and spine (r=-.22 to -.48). There was an inverse correlation between total T and spine BMD which became insignificant after correcting for body mass index (BMI). In addition, there was no correlation between free or bioavailable testosterone and BMD. 1,25-(OH)2D levels correlated inversely with BMD at the femur and whole body, but no association was found with PTH or 25 OH-D. CONCLUSIONS: Men over 75 years of age had a wide range of BMD but frequently had low values at femoral sites. T levels were below the normal range in 38% of men, and PTH levels were elevated in 23% of men. There was an inverse correlation between total T and spine BMD which may have been dependent on the common effect of BMI. Bone mineral density was inversely related to markers of bone resorption.     

Association of bone mineral density with vitamin D receptor gene polymorphism--changes in radial bone mineral density with long-term follow-up: longitudinal study

Recent studies have shown that genetic effects on bone mineral density (BMD) and bone turnover are related to vitamin D receptor (VDR) gene polymorphism. However, discordant studies have been published and it is still not clear whether VDR genotypes influence bone mass accretion and/or postmenopausal bone loss. To assess allelic influence of the VDR gene on BMD, we determined changes in 1/6-radial-BMD by several repeat measurements in the same subjects for about ten years and analyzed VDR polymorphism of BsmI restriction enzyme in 53 normal healthy Japanese women (age: 50.3 +/- 4.7 years, mean +/- SD). Twenty-seven (age: 53.2 +/- 4.7 years) of the subjects were post-menopausal (POST group). Among these 53 subjects, the distribution of bb, Bb and BB genotypes was 64.2%, 34% and 1.9%, respectively. The genotype frequencies in this study were very similar to those in previous reports concerning other Japanese women. There was no difference between the b group (women with bb genotype) and B group (women with BB or Bb genotype) in age, body weight, height, body mass index (BMI), years since menopause, serum osteocalcin and serum alkaline phosphatase values. In the POST group, BMD of the B group at menopause was lower than that of the b group (p < 0.05). About ten years after menopause, BMD did not differ significantly between these groups because the decrease in BMD in the b group was larger than that in the B group. Regarding changes in BMD in the POST group for four years after menopause, BMD of the b group was significantly decreased compared with the B group (p < 0.01). Our findings suggest that the differences in BMD by VDR genotype were larger among pre- and pri-menopausal women and seemed to decrease with years after menopause. It is suggested that there are other factors influencing BMD and postmenopausal bone loss in elderly women.     

Is there a means for cost reduction in intensive care fluid therapy without a loss of quality?

The objective of this study was to examine the value of NTx, a urinary cross-linked N-telopeptides of type I collagen, as a marker of bone resorption. We assessed changes in pre- and postmenopausal bone resorption by evaluating the correlation of NTx with L2-4 bone mineral density (BMD) in a total of 1100 Japanese women, aged 19-80 years [272 premenopausal (45.2 +/- 6.2 years) and 828 postmenopausal (59.5 +/- 6.2 years)]. Postmenopausal women were divided into three groups based on the range of BMD (normal, osteopenic, and osteoporotic). Within each group, subjects were further segregated according to years since menopause (YSM). NTx values were then evaluated for each group. Our results showed that BMD was significantly decreased (P < 0.05) and NTx was significantly increased (P < 0.01) after menopause in age-matched analysis. Consistent with a previous report, NTx was inversely correlated with BMD for the entire cohort of study subjects (r = -0.299), although NTx correlated better with premenopausal than postmenopausal BMD (r = -0.240 versus r = -0.086). This may have been due to the fact that elevated values of NTx were exhibited over the entire range of BMD present in the postmenopausal women, suggesting that NTx might respond faster to the estrogen withdrawal than BMD. In all postmenopausal women, regardless of the range of BMD, the increase in NTx reached a peak within 5 YSM. After 11 YSM, however, NTx remained elevated in the osteoporotic group but it decreased in the osteopenic group, and showed no significant change in the group of postmenopausal women with normal BMD. These findings suggest that bone resorption is dramatically increased within 5 years after menopause but remains increased only in osteoporotic women.     

Determinants of peak bone mass in Chinese women aged 21-40 years. III. Physical activity and bone mineral density

Previous studies on the relation between moderate physical activity and bone mass have observed conflicting results. Many of these studies have not dissociated the role of physical activity by age groups and in relation to the period of peak bone mass formation. Our cross-sectional analysis of the baseline data of a longitudinal study of 273 women aged 21-40 attempted to evaluate the role of moderate physical activity on bone mass around the period of peak bone mass attainment. The analyses were carried out separately for the two age groups--21-30 and 31-40--and had also taken into account the effects of age, dietary calcium intake, and lean body mass on bone mineral density (BMD). The total metabolic equivalent values (MET) of leisure time physical activity was based on the MET values for each activity and the reported time spent on each activity in the past year. The results indicated that among the younger group of women, high level of leisure time physical activity was associated with higher bone mass at both the spine and the hip. Additive effects of physical activity and dietary calcium intake on the spine and the hip BMD were observed. Together with age and lean body mass, physical activity and dietary calcium intake accounted for 19% of the variances of bone mineral at the spine and 9-11% at the hip. Among women aged 31-40, presumably after the peak bone mass formation, lean body mass as well as fat mass have independent strong association with BMD. Physical activity was not associated with bone mass in this age group.     

Effect of vitamin D receptor gene polymorphism and lifestyle on bone mineral density and bone mineral density decrement rate

The effects of genetic and environmental factors on bone mineral density (BMD) were investigated in 108 healthy Japanese women. Of the 108 subjects, BMD (from the second to forth lumbar vertebrae) was measured in 1992 in 103, in 1993 in 100, and in both years in 95 by dual energy X-ray absorptiometry. Vitamin D receptor (VDR) gene polymorphism in intron 8 was used as a genetic marker. Information on menstruation, health status, lifestyle, quantities of nutrient intake and frequencies of food intake was obtained by questionnaire. The frequency of allele B (825bp), whose polymerase chain reaction (PCR) products cannot be cut with BsmI, was 0.259 and the frequency of allele b (650bp), whose PCR products can be cut with BsmI, was 0.741. The subjects in our study obeyed the Hardy-Weinberg law. While the frequency of allele B was 0.448 in European whites as reported by Morrison et al, it was 0.259 in our Japanese subjects, suggesting a racial difference. Z score values (average value 0, standard deviation 1) increased in the order BB, Bb and bb. This result indicates that allele B is associated with the lower BMD in Japanese, as in European whites. The BMD decrement rate increased in the order bb, Bb and BB, indicating that VDR gene polymorphism may be a regulatory factor for losing BMD. Most of lifestyle variables, calcium intake and vitamin D intake were not correlated with BMD, but the food frequency score (which was defined as values weighted in each of three food categories obtained by factor analysis) was significantly correlated with BMD. Multiple regression analysis showed significant influences of years after menopause, the food frequency score and VDR genotype on BMD. VDR genotype and years after menopause influenced the BMD decrement rate significantly in multiple regression analysis. Neither a relationship between BMD and calcium intake nor between BMD and vitamin D intake by VDR genotype was found. These results suggest that the VDR gene is a genetic factor in BMD and the BMD decrement rate in Japanese.     

Femoral and spinal bone mineral density in Japanese osteoporotics with hip fracture

In the present study, bone mineral density (BMD) of femoral neck and lumbar spine was compared between 38 Japanese female patients with hip fracture (age 63-89 years, mean +/- SD 76 +/- 7 years) and 162 age-matched female controls (age 62-90 years, mean +/- SD 75 +/- 7 years). BMD was measured in the femoral neck and lumbar spine (L2-4) using dual-photon absorptiometry (Norland model 2600). BMD values of femoral neck as well as lumbar spine were significantly lower in patients with hip fracture than in controls (0.504 +/- 0.097 v 0.597 +/- 0.101, p < 0.01, for femoral neck; 0.661 +/- 0.146 v 0.720 +/- 0.128, p < 0.05, for lumbar spine). Patients with hip fracture and controls were stratified according to their BMD levels at two measuring sites, and the ratio of the number of patients and controls at each BMD level was calculated as an indicator of fracture rate. This ratio showed an exponential increase as the femoral neck BMD declined, but only a gradual increase as the lumbar spine BMD declined. Specificity-sensitivity analysis revealed that BMD values of 0.59 and 0.54 g/cm2 at the femoral neck provided a specificity of 52% and 68% with a sensitivity of 90% and 75%, respectively. These findings suggest that Japanese patients with hip fracture are more osteoporotic than age-matched controls and that the selective measurement of femoral neck would be useful for predicting the risk of hip fracture.     

Moderate exercise during growth in prepubertal boys: changes in bone mass, size, volumetric density, and bone strength: a controlled prospective study

Cross-sectional studies of elite athletes suggest that growth is an opportune time for exercise to increase areal bone mineral density (BMD). However, as the exercise undertaken by athletes is beyond the reach of most individuals, these studies provide little basis for making recommendations regarding the role of exercise in musculoskeletal health in the community. To determine whether moderate exercise increases bone mass, size, areal, and volumetric BMD, two socioeconomically equivalent schools were randomly allocated to be the source of an exercise group or controls. Twenty boys (mean age 10.4 years, range 8.4-11.8) allocated to 8 months of 30-minute sessions of weight-bearing physical education lessons three times weekly were compared with 20 controls matched for age, standing and sitting height, weight, and baseline areal BMD. Areal BMD, measured using dual-energy X-ray absorptiometry, increased in both groups at all sites, except at the head and arms. The increase in areal BMD in the exercise group was twice that in controls; lumbar spine (0.61 +/- 0.11 vs. 0.26 +/- 0.09%/month), legs (0.76 +/- 0.07 vs. 0.34 +/- 0.08%/month), and total body (0.32 +/- 0.04 vs. 0.17 +/- 0.06%/month) (all p < 0.05). In the exercise group, femoral midshaft cortical thickness increased by 0.97 +/- 0. 32%/month due to a 0.93 +/- 0.33%/month decrease in endocortical (medullary) diameter (both p < 0.05). There was no periosteal expansion so that volumetric BMD increased by 1.14 +/- 0.33%/month, (p < 0.05). Cortical thickness and volumetric BMD did not change in controls. Femoral midshaft section modulus increased by 2.34 +/- 2. 35 cm3 in the exercise group, and 3.04 +/- 1.14 cm3 in controls (p < 0.05). The growing skeleton is sensitive to exercise. Moderate and readily accessible weight-bearing exercise undertaken before puberty may increase femoral volumetric BMD by increasing cortical thickness. Although endocortical apposition may be a less effective means of increasing bone strength than periosteal apposition, both mechanisms will result in higher cortical thickness that is likely to offset bone fragility conferred by menopause-related and age-related endocortical bone resorption.     

Urinary excretion of free and acetylated polyamines in hepatocellular carcinoma

Bone mineral density (BMD), and associated biochemical and endocrine markers were compared in a group of runners with menstrual dysfunction (IR, n=13), and a group of performance matched eumenorrheic runners (R, n=15). All subjects claimed to have normal eating habits. Body height and weight, body mass index, and amount of body fat were similar. The IR group consisted of 5 presently oligomenorrheic (O) and 8 presently amenorrheic (A) runners. The BMD values of the athletes were additionally compared with corresponding values in a reference group (C) of healthy age matched controls (n=54). BMD values were significantly lower in IR compared with R on all measuring sites: Total body (-9%, p=0.03), femoral neck (-11%, p=0.01), lumbar spine (-12%, p=0.001), lower leg (-6.5%, p=0.03) and arms (-7%, p=0.01). In addition, IR athletes had lower total body (-5%, p=0.01), and lumbar spine BMD (-10%, p=0.001) than C. No differences were observed in serum IGF-1, SHBG, testosterone and cortisol, or in the biochemical marker of bone formation (osteocalcin) and bone resorption (1 CTP). Values of serum E2, FSH and LH were low in IR and normal in R. TSH was in the normal range in both groups, but f-T4 was significantly lower in IR than in R. The athletes were furthermore grouped according to past and present menstrual dysfunction severity. At all measuring sites, with the exception of the lower leg, increasing menstrual dysfunction severity was linearly associated with declining BMD values (p<0.05). In conclusion, even highly conditioned cortical bone tissue seems to be negatively related to menstrual disorders, which may serve to explain the high incidence of stress fractures in athletes with menstrual disorders. Single measurements of biochemical markers of bone resorption and formation may not reflect the current bone status.     

Epidemiology of osteoporosis: incidence, prevalence, and prognosis

Though the exact and cumulative incidence of osteoporosis has not been examined, using the criteria that osteoporosis is defined by a decrease of bone mineral density (BMD) below 70% from young adult mean (YAM), the prevalence of osteoporosis among the Japanese women can be estimated as to be more than either 30% (by spinal BMD) or 37% (by femoral BMD) in 60's, 37% or 64% in 70's, and 42% or 90% in 80's, respectively. The total number of osteoporosis among the women with age 50 and over can be also estimated as to be either about 5 million (by spinal BMD) or 8.5 million (by forearm BMD). National survey shows that the ratio of people receiving treatment for osteoporosis is 34.5 per 1,000 among the elderly with age 65 and over. In addition, both functional transition and survival rate of discharged patients with osteoporotic hip fracture are discussed as prognosis of osteoporosis.     

Responses of trabecular and cortical bone turnover and bone mass and strength to bisphosphonate YH529 in ovariohysterectomized beagles with calcium restriction

Thirty-six beagles, 18 months of age, underwent ovariohysterectomy (OHX) or a sham operation. Sham-operated animals were given a diet with standard calcium (1.4%) (group 1, n = 6) or a restricted calcium diet (0.14%) (group 2, n = 6). The OHX animals were given the restricted calcium diet and YH529 orally with respective daily doses of 0, 0.02, 0.1, and 0.5 mg/kg of body weight (groups 3-6, n = 6 each) for 12 months. At the end of this period, the lumbar bone mineral densities (BMDs) in groups 2 and 3 and the load values for group 3 were significantly smaller than those for group 1. The midfemur BMD did not differ among the groups. The urinary deoxypyridinoline (U-Dpy) and bone formation rates (BFR/BS, BFR/BV) in groups 2 and 3 and the osteonal BFR/BS and trabecular osteoclast number (Oc.N/BS) in group 3 were significantly larger than the respective values for group 1. However, these parameters did not significantly differ between groups 2 and 3. The serum osteocalcin (OC) level, wall thickness (W.Th), and mineral apposition rate values for group 3 were significantly larger than those for group 2. In group 2, the trabecular activation frequency (Ac.F) increased by 3.11 times, and the percent values of the number of labeled osteons (L-Ot.N/T-Ot.N, %) in the tibia by 3.28 times over those for group 1. In group 3, the Ac.F increased by 3.20 times and the number of labeled osteons by 3.77 times over those for group 1. In groups 4-6, the U-Dpy and Oc.N/BS values were smaller, but their OC levels did not significantly differ from the level for group 3. The lumbar BMD, the load, and W.Th were dose-dependently significantly larger than those for group 3. The Ac.F values were significantly smaller, and the respective value in groups 4-6 was 67.9, 25.5, and 10.2% of that in group 3. The BMDs of the midfemur in groups 4-6 were significantly larger than those in group 3, but the ultimate load values did not significantly differ. The L-Ot.N/T-Ot.N values were also significantly smaller, and the respective value in groups 4-6 was 82.0, 48.5, and 55.2% of that in group 3. The tibial endocortical and periosteal BFR/BSs did not differ significantly. These data demonstrate that the effects of OHX on bone mass and turnover were small in the beagles fed a restricted calcium diet. YH529 maintained the mass and strength of the lumbar bone by reducing the bone resorption. The cortical bone appeared to be less sensitive to the agent than the trabecular bone in this animal model.     

Development of mass, density, and estimated mechanical characteristics of bones in Caucasian females

Three hundred and thirty healthy Finnish girls and premenopausal women, aged 7-47 years, were examined to evaluate the natural development of bone mineral mass and density from early childhood to menopause. Bone mineral content (BMC,g) and areal density (BMD, g/cm2) were measured from the spine (L2-L4), femoral neck, trochanter region of the femur, and distal radius using dual-energy X-ray absorptiometry (DXA). In addition, the bone mineral apparent density (BMAD, g/cm3) was assessed from the above described skeletal sites, and the mechanical competence of the femoral neck was estimated. Special attention was paid to the timing of the peak values of these bone parameters as well as to the evidence of premenopausal bone loss. The BMC, BMD, and BMAD of the spine, femoral neck, and trochanter region of the femur achieved peak values around the age of 20, and the bone loss seemed to start soon thereafter. In contrast, the bone mass of the distal radius slightly increased between the ages of 20 and 47. In the femoral neck, the estimated bending strength achieved its peak value around the age of 20 and showed a slight decrease during the following decades. The highest body weight and neck-length adjusted strength values of the femoral neck were, however, found in early childhood, with the values decreasing linearly thereafter. In conclusion, this study supports previous findings of rapid bone mineral accumulation in late adolescence, and occurrence of the peak bone mass and density around the age of 20. Premenopausal bone loss seems to occur in the proximal femur and lumbar spine. Our observations of femur strength development imply that from childhood to menopause the mechanical strength of the femoral neck is well adjusted to the biomechanical loading requirements of the body.     

Digital anomalies, microcephaly, and normal intelligence: new syndrome or Feingold syndrome?

To investigate risk factors for spinal fracture, we studied the relationship between the prevalence of asymptomatic spinal fracture and various morphological measures including spinal bone mineral density (BMD) in women. A total of 122 women ranging in age from 55 to 79 years were studied. The group consisted of 46 women aged 55-59 years (18 with fracture), 51 women aged 60-69 years (26 with fracture), and 26 women aged 70-79 years (14 with fracture). BMD of cortical and trabecular bone from L1 to L3 was measured using quantitative computed tomography (QCT). Run-length analysis was applied to evaluate the spinal trabecular textural features using CT images; the texture indices which represent the mean width of trabecular (the T-texture) and that of intertrabecular spaces (the I-texture) were obtained. Anthropometric factors including body weight and height, psoas muscle area, and vertebral bone volume were measured using CT images. Among the various factors, trabecular BMD in women aged 55-69 years showed the highest odds ratio for the presence of fracture per standard deviation (SD) decrease in bone density. However, in women aged 70-79 years, the highest odds ratio was observed for trabecular texture index but not for trabecular BMD. The I-texture in women aged 55-59 years, the muscle area in women aged 60-69 years, and cortical BMD and muscle area in women aged 70-79 years were also considered significantly related to the risk of fracture.     

Fos-immunoreactive responses in inferior colliculi of rats with experimental audiogenic seizure susceptibility

Quantitative ultrasound (QUS) is a simple, inexpensive and non-invasive measure of bone which has been used in research settings for the prediction of osteoporosis. This review summarizes the current status of the epidemiology of QUS analysis, including its relationship with bone mineral density (BMD), risk of osteoporotic fracture and risk factors for osteoporosis. Although only moderately correlated with BMD, QUS appears to be as strong a predictor of osteoporotic fracture as BMD and may predict fracture independent of BMD. Risk factors for low QUS, including age, menopause, body composition and physical inactivity, seem to parallel those of low BMD. More longitudinal research is needed to confirm the clinical utility of QUS and more experimental and population-based studies are needed to determine whether the etiology of low QUS values is different from that of low bone mass.     

Overexpression, purification and characterization of Dictyostelium calcineurin A

We examined the mechanical properties of bone in ovariectomized rats treated with tiludronate. 186 Sprague-Dawley (SD) rats, 6 months of age, were assigned to 13 groups and were maintained for 3-9 months after surgery. Ovariectomy (ovx) groups were given tiludronate orally at the respective doses of 0 (vehicle), 12.5 (low), 25 (medium), and 50 (high) mg/kg body weight daily for 3 months beginning 3 months after surgery. Rats were killed at 0 (start), 3, 6, and 9 months. Whereas bone mineral density (BMD) values of the midfemur did not increase after ovx, the values in the sham-operated groups increased age-dependently. Bending moment to failure of the femur in the sham group was larger than that of the ovx control group at 9 months. In the ovx control groups, the ultimate compressive load values of the third lumbar body were reduced compared with those in the sham groups at 3 months and thereafter. Although serum osteocalcin levels were decreased in the medium- and high-dose tiludronate groups, both serum PTH and 1,25(OH)2D levels were increased only in the high-dose group. Femoral BMD, mechanical properties, and the cortical bone area were increased by the high dose at 9 months. Lumbar ultimate compressive load and the circumscribing cortical shell area in the high-dose group were increased at 6 months and thereafter. The trabecular number values were maintained at 6 and 9 months by the high dose. These data demonstrate that tiludronate administration increased the mechanical properties of bone by preserving the age-dependent increases in the cortical bone mass and three-dimensional structure of trabecular bone. These effects seemed to be due to reduced bone turnover by the agent.