Epidemiological study of osteoporosis

An epidemiological investigation of osteoporosis was carried out in a community in which fishing is the primary industry, and correlations were investigated between the bone mass and various risk factors for osteoporosis and biochemical findings. In 852, who could be examined directly, of the 3541 males and females aged 40 years or above living in Nansei Town, Watarai District, Mie Prefecture, the age, sex, height, body weight, years after menopause, married or unmarried, area of residence, daily activity, and intakes of milk, fish, and alcohol were studied by direct oral inquiry, and the serum calcium, inorganic phosphorus, alkaline phosphatase, and total protein were measured. The subjects were divided into a decreased bone mass group who showed grade I or more advanced loss in bone mass and a normal bone mass group who showed no or only slight loss in bone mass on the basis of microdensitometry (MD). Eighty-two subjects (9.6%) were classified as the decreased bone mass group. Items that showed a close correlation with sigma GS/D, which is an index of bone density, were age, years after menopause, serum alkaline phosphatase level, height, and body weight in females, age and serum alkaline phosphatase level in males. In the decreased bone mass group, 79 of the 82 subjects were females. Significant differences were observed between the decreased bone mass group and the normal bone mass group in age, years after menopause, serum alkaline phosphatase level, height, and body weight. From these results, a high age, being a female, low height, and a low body weight were found to be factors correlated with osteoporosis. Also, the bone mass was correlated with the serum alkaline phosphatase level and years after menopause.     

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.     

Phyto-oestrogen excretion and rate of bone loss in postmenopausal women

OBJECTIVE: The hypothesis was tested that the rate of postmenopausal bone loss is inversely associated with long-term urinary excretion of phyto-oestrogens, as a marker of habitual dietary intake. DESIGN: Secondary analysis of a 10-year follow-up study (1979 1989) among postmenopausal women in the Netherlands. SUBJECTS: From the original population of 154 women, 32 women were selected with an annual rate of radial bone loss of < or = 0.5% over the first 5 years of the study and 35 women with a rate of > or = 2.5% per year. METHODS: The isoflavonoids genistein, daidzein and equol, and the lignan enterolactone were determined by gas chromatography mass spectrometry in aggregate samples from annually collected urine samples. Cortical bone density of the radius had previously been measured annually by single-photon absorptiometry. RESULTS: Excretion of isoflavonoids did not differ between both groups, although in multivariate analysis equol excretion was weakly positively associated with rate of bone loss in the 5 years after the menopause. Enterolactone excretion was significantly higher in the group with high rate of bone loss. This positive association remained in multivariate linear regression analysis after adjustment for age, years since menopause, body mass index and intake of calcium, vegetable protein and dietary fibre. CONCLUSIONS: Enterolactone excretion is likely to be an indicator of consumption of grains and legumes; it is not clear whether the observed positive association with rate of bone loss is a causal one. Our results do not support a preventive effect of low, unsupplemented dietary intake of phyto-oestrogens on postmenopausal cortical bone loss. However, no conclusions can be drawn about effects of higher doses of phyto-oestrogens.     

Effect of menopause on femoral and vertebral bone loss

The aim of this study was to investigate the effect of menopause on bone loss in the proximal femur and the lumbar spine. The rates of change in bone mineral density (BMD) were measured longitudinally by dual X-ray absorptiometry (DXA) at the femoral neck (FN), Ward's triangle (WT), and trochanter (TR) together with the lumbar spine in 81 healthy postmenopausal women (45-65 years of age) who had passed a natural menopause, 6 months to 12 years before. A significant correlation between the rate of change and interval since menopause was evidenced. The best fit of the data was a binomial function of interval since menopause at the spine, FN, and WT and a simple linear regression at TR level. At each skeletal site, the rate of bone loss (mean +/- SD) was significantly different (p<0.05) and twice as high in women who were between 6 months and 2 years postmenopausal at enrollment (FN, -1.82 +/- 1.1%; WT, -2.43 +/- 1.7%; TR, -1.12 +/- 1.7%) than in those who were beyond 5 years of menopause (FN, -0.48 +/- 0.8%; WT, -0.68 +/- 2.1% TR, 0.41 +/- 1.2%). A poor correlation (r = 0.39 - 0.42, p<0.001) was found between the rate of vertebral and that of femoral postmenopausal bone loss. This study demonstrates that menopause is associated with a rapid and transient bone loss in BMD of the proximal femur, which declines with time after 3 years. These data suggest that therapy should be initiated as early as possible after menopause to prevent bone loss.     

A prospective study of bone loss in African-American and white women--a clinical research center study

Although bone loss occurs universally with age, the incidence of age-related osteoporotic fractures varies widely among ethnic groups. In the U.S., age-adjusted hip fracture incidence is 50% lower in African-American than in white women. Adult African-American women also have higher bone mass, but it is not known whether this difference is entirely due to higher peak bone mass or also results from slower rates of bone loss. Rates of bone loss were measured prospectively in 122 white and 121 African-American healthy, nonobese, pre- and postmenopausal women. Bone density was measured at 6-month intervals over a mean of 3-4 yr using single and dual photon absorptiometry of the forearm (cortical bone) and spine (trabecular bone). Similar rates of premenopausal bone loss were documented in both white and African-American women. However, in early menopause, bone loss was faster in the white women in the forearm (-2.4%/yr in whites vs. -1.2%/yr in African-Americans; P = 0.045), with a similar trend in the spine (-2.2%/yr in whites vs. -1.3/yr in African-Americans; P = 0.27). In women more than 5 yr postmenopause, the rates of bone loss did not differ by ethnic group. Our results indicate that the higher bone mass in African-American women is largely due to the attainment of a greater peak bone mass by early adulthood. However, slower rates of bone loss in the early postmenopausal period may also contribute to the higher bone density of older African-American women. Although bone loss occurs in both groups, there are ethnic differences in bone loss rates which indicate that data derived from white women cannot be simply extrapolated to nonwhite populations. Ethnic group-specific data on the determinants of bone homeostasis are needed.     

Lateral entorhinal, perirhinal, and amygdala-entorhinal transition projections to hippocampal CA1 and dentate gyrus in the rat: a current source density study

In the health management of bone, of most importance is how to spend the period until peak bone mass, that is appropriate self management for bone health. Therefore, we evaluated the effects of physical characteristics and dietary habits on the bone mineral density (BMD) of the second metacarpal bone (sigma GS/D: BMD) by the digital image processing method (DIP) in 197 healthy adolescent girls (Japanese students at a junior high school, aged 12-15 y), an important period of physical and bone growth. Concerning the physical characteristics of the subjects according to age group, body height in each age group was higher than the standard values for Japanese according to age, but body weights in the 14-year-old and 15-year-old groups were significantly lower than the standard values for Japanese. Compared with the standard BMD values for Japanese according to age, BMD in the subjects was high in the 12-year-old, 13-year-old and 14-year-old groups but low in the 15-year-old group (-7.3%). Concerning the nutritional state, energy, calcium (Ca), and iron intakes were insufficient in every age group. BMD relative to the standard BMD value for Japanese (standard value was regarded as 0%) was evaluated according to the ingestion frequency of Ca-rich foods. The relative BMD value (%) increased with the ingestion frequency of Ca-rich foods. These results suggest that maintenance of an appropriate physique and adequate intake of nutrients such as Ca are important for bone growth during adolescence. Active promotion of educational guidance mainly on the effects of diet on bone health in adolescents in necessary.     

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.     

Thalamic NMDA transmission in a genetic model of absence epilepsy in rats

OBJECTIVES: Whether menopause per se influences fat distribution independently of the effect of aging remains controversial. The lack of consistency in the menopause related changes in body fat distribution may be the result of differences in the methods for measuring fat distribution or in the characteristics of the women studied. The aim of this cross sectional study in obese women was to compare total body composition and regional fat and lean distribution, in premenopausal, perimenopausal and postmenopausal women. METHODS: Body composition was assessed by dual energy X-ray absorptiometry (DEXA) in premenopausal (n = 26), perimenopausal (n = 24) and postmenopausal (n = 73) obese women with no intercurrent diseases. RESULTS: It was shown that postmenopausal obese (n = 73) women had a higher proportion of total fat mass in the trunk and a lower proportion of total fat and lean mass in the femoral and leg regions than premenopausal women after adjustment for age and total fat mass. In the same analysis, perimenopausal women had a lower proportion of total fat in the leg and femoral regions and of total lean in the femoral region than premenopausal women; they had a regional body composition similar to that of postmenopausal women. CONCLUSION: The present data indicate that in obese women, post menopause and perimenopause are associated with differences in fat and lean distribution, independently of age and total fat.     

Effects of weight and body mass index on bone mineral density in men and women: the Framingham study

We evaluated the association of weight and bone mass in elderly male and female subjects of the Framingham osteoporosis study, a subset of the Framingham study cohort. By examining the differences in the correlations of weight with bone mass among men and women in weight-bearing and non-weight-bearing sites and weight change since early adulthood, we attempted to understand different ways in which weight or body mass index affects bone mass. During biennial examination 20 of the Framingham cohort (1988-1989), 693 women and 439 men (mean age 76 years) had proximal femur bone mineral density assessed by dualphoton absorptiometry (DPA) and radius bone mass assessed by single-photon absorptiometry. The majority of these subjects also had spine measurements by DPA. Subjects had been weighed repeatedly over 40 years. After adjusting for other factors affecting bone density, we found that both recent weight and body mass index explained a substantial proportion of the variance in bone mineral density for all sites in women (8.9-19.8% of total variance, all p < 0.01) and for only weight-bearing sites (femur and spine) in men (2.8-6.9% of total variance, all p < 0.01). For bone mineral density at the proximal radius, weight and body mass index accounted for < 1% of variance in men (p NS). Weight change since biennial examination 1 (1948-1951) was the strongest explanatory factor for bone mineral density among women at all sites, but weight change did not affect radius bone mineral density in men. The effect of weight and of weight change on bone mineral density was in general much less in men than in women. Our results suggest that the strong effect of weight on bone mineral density is due to load on weight-bearing bones sexes. The sex difference is unexplained but may be due to adipose tissue production of estrogen in women after menopause.     

Studies on the bone metabolisms in either after natural menopause or surgical menopause: implications of IGF-IGFBP system for postmenopausal osteoporosis

It is well established that accelerated bone loss occurs in association with estrogen deprivation as seen following the natural menopause and in premenopausal women undergoing surgical oophorectomy (i.e., surgical menopause). We have measured serum levels of bone biochemical markers after both natural menopause and surgical menopause. Circulating levels of insulin-like growth factor-I (IGF-I), which is considered to be the local regulator of osteoblast activity and one of its binding protein, insulin-like growth factor binding protein-4 (IGFBP-4) which binds to IGF-I and suppress its biological activity, were also measured. Bone mineral density measured by dual energy X-ray absorptiometry was decreased more rapidly after surgical menopause. A concomitantly higher rate of bone turnover as assessed by bone biochemical markers was observed after surgical menopause, and thus the levels of procollagen type I C-peptide, pyridinoline and deoxypyridinoline were increased. The serum levels of IGF-I were significantly reduced after natural menopause compared with that after surgical menopause. The levels of IGF-I were correlated with bone mineral density after natural menopause (r = 0.62, p < 0.001), but no significant correlation was observed between these two variables after surgical menopause. The binding activity of IGFBP-4 was significantly greater after surgical menopause than after natural menopause. A stronger inverse correlation existed between the binding activity of IGFBP-4 and bone mineral density after surgical menopause (r = -0.90, p < 0.001) compared to that after natural menopause (r = -0.29, p < 0.05). The simplest explanation is that whereas the loss of bone depends upon the decreased level of IGF-I after natural menopause, after surgical menopause it depends upon the increased level of IGFBP-4.     

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.     

Traversing the menopause: changes in energy expenditure and body composition

The menopause transition is associated with several physiological changes that may impact women's health outcome. Among the changes associated with the loss of ovarian function is an increased risk of metabolic and cardiovascular disease. The present review focuses on changes in energy expenditure, body composition and body fat distribution during the postmenopausal transition. Previous work indicates that the most important component of total daily expenditure, resting metabolic rate, may be reduced by the menopause, independently of the effects of the normal aging process. This effect is mainly attributable to a decrease in fat-free mass. The energy expenditure associated with physical activity is the most variable component of total daily energy expenditure. However, small changes in this component may have a substantial impact on body composition. Longitudinal data from our laboratory indicate that the menopause transition also leads to significant decreases in physical activity energy expenditure. The changes in body composition that accompany the menopause transition have been studied by several groups and, although some studies suggested increases in body mass index or total body fat mass with the menopause, currently available cross-sectional data preclude a firm conclusion. Nevertheless, results from our longitudinal study showed significant increases in fat mass with the menopause. The accumulation of abdominal fat, which may be a better correlate of the comorbidities associated with obesity, has also been shown to be accelerated by the menopause transition. In this regard, it has been shown that treatment with hormone replacement therapy prevents the increase in the rate of abdominal adipose tissue accumulation that was noted with the menopause. Thus, it appears that the loss of ovarian function induces a reduction in resting metabolic rate, physical activity energy expenditure, fat-free mass, and an increase in fat mass and abdominal adipose tissue accumulation. These modifications probably contribute to the increased risk of cardiovascular disease of postmenopausal women.     

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.     

Pulmonary scintigraphy at the bedside in intensive care patients with suspected pulmonary embolism

We report the results of a longitudinal study aimed at better defining concomitant changes of both bone mineral density (BMD) and of four independent markers of bone turnover (serum osteocalcin, serum alkaline phosphatase activity, fasting urinary hydroxyproline/creatinine and calcium/creatinine ratio) following natural menopause. The results obtained indicate that, within a relatively short period of time since cessation of gonadal function, conventional markers of bone turnover behave differently. In fact, while the mean values of hydroxyproline/creatinine ratio (felt to be a marker of bone resorption) rise immediately at the first control (19.7 +/- 11.7 months), the bone formation markers gradually increase and, as far as serum osteocalcin levels are concerned, this increment appears to be long-lasting. As a result of these changes, a negative skeletal balance follows, which is documented by the prolonged reduction of bone mineral density during the entire observation period. Mean +/- SD % measured yearly bone loss was -2.83 +/- 2.6. There was a highly significant correlation between initial and final BMD values (r = 0.908, p < 0.001; r2 = 82.5) and a weak inverse correlation (r = -0.298, p < 0.046) between initial serum alkaline phosphatase values and % yearly bone loss. In conclusion, measurement of the biological indices of bone remodelling following natural menopause indicate that the increase in osteogenesis is delayed compared to that of bone resorption; furthermore, in the immediate postmenopausal period, the actual bone mass should be considered the best predictor of future bone mass. The inverse correlation found between % yearly bone loss and serum alkaline phosphatase values seems to emphasize the importance of increased bone turnover as an independent predictor of bone loss.     

Aspirin therapy for cardiovascular disease

Bone densitometry has become a major tool for osteoporosis risk assessment. The traditional dual-energy X-ray absorptiometry (DXA) methods are able to evaluate the bone mineral content (BMC; mg/cm) and the areal density (BMD; mg/cm2), but only quantitative computed tomography (QCT) has the potential to measure the true volumetric bone density in the sense of mass per unit volume (mg/cm3). Peripheral QCT (pQCT) measurements were carried out at the nondominant radius using a Stratec XCT 960 (Unitrem, Roma) in 241 postmenopausal and 29 premenopausal women. The sites of evaluation were both the ultradistal and the proximal radius. The technique used has a coefficient of variation of 2% and it allows separation of the bone section into trabecular and cortical bone on the basis of density threshold. Bone mass of radius, hip and spine was also evaluated by DXA procedures. The bone density data obtained by pQCT were significantly correlated with all DXA measurements. The correlation coefficients between their respective BMD values ranged from 0.48 to 0.75, but for the BMC values of the radius the correlation coefficients ranged from 0.82 to 0.93. The BMD values measured by DXA, but not by pQCT, were positively related with patient heights. All pQCT density measurements, including those obtained at the proximal radius and containing exclusively cortical bone, where negatively related with age and years since menopause. A partial volume effect, which is increasingly relevant the thinner are the bone cortices, might explain that. However, by applying increasing density thresholds, cortical bone density seems to decrease with age as a consequence of a gradual density diminution from the inner part of the bone cortex outwards. Trabecular bone density decreases with aging, but its overall mass does not change as a consequence of an age-related enlargement of trabecular area. Thus, the proportion of trabecular bone over total bone rises, and this might be relevant for our understanding of the age-related changes in bone turnover and rate of bone loss.     

Increased bone resorbing activity of peripheral monocyte culture supernatants in elderly women

Accelerated bone loss occurs in the years after menopause, and is an ongoing phenomenon in elderly women. The role of cytokines in bone loss after estrogen deficiency has been shown in ovariectomized rat and mice models. In humans, the involvement of bone resorbing cytokines is now well established. In the early years after menopause, monocyte activation leads to increased cytokine production. We have previously shown that the bone resorbing activity (BRA) of peripheral blood monocyte culture supernatants from postmenopausal women is higher than in premenopausal (Pre-M) women. This increased activity was related to interleukin (IL)-1, IL-6, and tumor necrosis factor-alpha levels. We here investigate whether monocyte activation still occurs in older women and whether this relates to bone resorption. We studied 19 healthy Pre-M, and 24 early (E-Post-M, menopause < 10 yr) and 24 late (L-Post-M, menopause > 10 yr) postmenopausal women. Peripheral blood monocytes were cultured for 48 h with 20% autologous plasma. BRA of monocyte supernatants (expressed as the ratio of monocyte supernatant over control bones supernatant) was assessed using fetal long-bone resorbing assays. Bone resorption was determined by urinary total pyridinoline excretion. BRA was significantly increased in E-Post-M and L-Post-M, compared with Pre-M subjects (1.20 +/- 0.10 and 1.15 +/- 0.20 vs. 0.73 +/- 0.10, respectively, both P < 0.05). Moreover, BRA of bones cultured with the supernatant of Pre-M was lower than BRA of control bones. BRA was significantly correlated with levels of IL-1, IL-6, and tumor necrosis factor-alpha in supernatant. Supernatant IL-1 levels were increased in E-Post-M, compared with Pre-M women (506 +/- 180 vs. 122 +/- 30, P < 0.05). Similarly, pyridinoline levels were increased in E-Post-M and L-Post-M, compared with Pre-M subjects (8.8 +/- 1 and 10.5 +/- 0.9 vs. 5.8 +/- 0.5, respectively, both P < 0.05). BRA was significantly correlated to pyridinoline levels. These data indicate the presence of monocyte activation in L-Post-M, which may be responsible for the increased bone resorption and bone loss observed in this elderly population.     

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.     

Bone mass and ageing

Bone can be divided into two kinds of tissue, cortical and trabecular bone. The skeleton comprises approximately 80% cortical bone, mainly in peripheral bones, and 20% trabecular bone, mainly in the axial skeleton. Bone density increases with skeletal growth to a peak in late adolescence or early adulthood. Bone loss subsequently occurs with ageing in both sexes, and in females accelerated loss occurs at the menopause. The risk of osteoporotic fracture in later life is the result of peak bone mass achieved at skeletal maturity and subsequent age-related and postmenopausal bone loss. Peak bone mass is largely genetically determined but is also influenced by environmental factors such as dietary calcium and physical activity. Bone loss with ageing occurs at different rates and different times in different skeletal sites. Femoral neck bone loss probably occurs in a linear fashion throughout life from early adulthood but may be accelerated at the menopause. Spinal bone loss may commence before the menopause but is rapidly increased in the immediate postmenopausal years. Bone strength is directly related to bone density, but the loading force is also relevant to risk of fracture.     

Bisphosphonate risedronate prevents bone loss in women with artificial menopause due to chemotherapy of breast cancer: a double-blind, placebo-controlled study

PURPOSE: To determine the effectiveness and safety of the bisphosphonate risedronate in preventing bone loss in young women with breast cancer and early menopause induced by chemotherapy who are at major risk for the development of postmenopausal osteoporosis. PATIENTS AND METHODS: Fifty-three white women, aged 36 to 55 years, with breast cancer and artificially induced menopause were stratified according to prior tamoxifen use. Thirty-six patients received tamoxifen (20 mg/d). Within each stratum, patients were randomly assigned to receive risedronate (n = 27) or placebo (n = 26). Treatment consisted of eight cycles oral risedronate 30 mg/d or placebo daily for 2 weeks followed by 10 weeks of no drug (12 weeks per cycle). Patients were monitored for a third year without treatment. RESULTS: Main outcomes of the study were changes in lumbar spine and proximal femur (femoral neck, trochanter, and Ward's triangle) bone mineral density (BMD), and biochemical markers of bone turnover. In contrast to a significant decrease of BMD at the lumbar spine and hip in the placebo group, there was an increase in BMD in the risedronate group. On treatment withdrawal, bone loss ensued, which suggests that treatment needs to be continuous to maintain a protective effect on bone mass. At 2 years, the mean difference (+/- SEM) between groups was 2.5% +/- 1.2%, (95% confidence interval [CI], 0.2 to 4.9) at the lumbar spine (P = .041) and 2.6% +/- 1.1%, (95% CI, 0.3 to 4.8) at the femoral neck (P = .029). Similar results were observed at the hip trochanter. Results by stratum indicate a beneficial, although partial, effect of tamoxifen in reducing bone loss. Risedronate was well tolerated and showed a good safety profile, with no evidence of laboratory abnormalities. CONCLUSION: Risedronate appears to be a safe treatment that prevents both trabecular and cortical bone loss in women with menopause induced by chemotherapy for breast cancer.     

Timing of menopause, reproductive years, and bone mineral density: a cross-sectional study of postmenopausal Japanese women

Age at menopause has been found to be associated positively with bone mineral density, and age at menarche has been found to be associated negatively with bone mineral density. However, there have been few studies on the relations of timing of menopause and length of the reproductive period with bone mineral density. The purpose of this study was to examine the relations of timing of menopause and reproductive years (calculated as age at menopause minus age at menarche) with mineral density of the second metacarpal bone in postmenopausal Japanese women. The study population consisted of 1,035 naturally menopausal women aged 40-70 years who were screened in 1996-1997. Using computed x-ray densitometry, the authors measured bone mineral density by analyzing radiographic films of the right second metacarpal bone. Using the women with early menopause (age < 49 years) as the reference group and adjusting for age, subjects with late menopause were at decreased risk for low bone mineral density (odds ratio (OR) = 0.69, 95% confidence interval (CI) 0.49-0.97). After adjustment for additional covariates (grip strength, physical activity, body mass index, smoking, and calcium intake), the association was unchanged (OR = 0.70, 95% CI 0.50-0.99). Postmenopausal women with more reproductive years (> or = 40 years) were at decreased risk for low bone mineral density compared with those with fewer reproductive years, after adjustment for age (OR = 0.73, 95% CI 0.40-1.30) and potentially confounding factors (OR = 0.76, 95% CI 0.41-1.37); the p-value for trend was not statistically significant. In multiple linear regression analysis, early menopause and fewer reproductive years were independent predictors of low bone mineral density. In this study, postmenopausal Japanese women who had a late menopause and more reproductive years were at decreased risk for low bone mineral density, and may therefore be less prone to osteoporosis.