Postmenopausal Bone Mineral Density Research Articles

Bone Mineral Density in the Reproductive-Age Woman: <I>Effects of Medications, Pregnancy, Lactation, and Exercise

Multiple factors affect the attainment and preservation of bone mass throughout the reproductive years of a woman’s life, although the immediate effects of these factors may not be apparent in younger women. Exercise, contraceptives, gonadotropin-releasing hormone agonists, hormonal breast cancer treatments, pregnancy, and lactation may all affect pre- and postmenopausal bone mineral density. Sedentary adolescent females should be counseled about appropriate exercise and its lifelong importance in bone health. Athletes should be carefully screened for components of the female athlete triad. When prescribing contraception, factors such as formulation, patient age, and menstrual history should be taken into consideration, as these factors can affect bone density. Clinical use of gonadotropin-releasing hormone agonists should remain limited because of significant bone loss associated with their use. Because premenopausal tamoxifen use and anomatase inhibitors affect fracture risk, patients should be carefully selected prior to the use of these drugs. Although pregnancy and lactation induce metabolic changes that may seem deleterious to bone, lasting effects are not generally apparent. This article presents a review of the factors currently implicated in the maintenance of bone health in premenopausal women.

Risk factors for low bone mineral density and the 6-year rate of bone loss among premenopausal and perimenopausal women.

Risk factors that are associated with lower bone mineral density (BMD) may not necessarily be associated with increased bone loss among premenopausal and perimenopausal women. We determined risk factors for lower premenopausal and perimenopausal BMD while simultaneously determining risk factors for increased 6-year rate of bone loss among women aged 24-50 years within a population-based prospective cohort study. BMD of the lumbar spine and femoral neck, reported as t scores, were measured five times within the 6-year study among 614 women who were between the ages of 24 and 44 in 1992/1993. Rates of bone loss were calculated from the repeated BMD measurements. Risk factors for lower BMD over time at the lumbar spine included history of any fracture ( P=0.005). The major risk factor for lower BMD over time at the femoral neck was family history of osteoporosis ( P<0.002). The major protective factor for greater BMD over time at both skeletal sites was additional body weight ( P<0.0001). Other protective factors for greater BMD over time at the femoral neck were modest alcohol consumption ( P=0.0002) and high-school sports participation ( P=0.002). Risk factors for greater bone loss at either skeletal site included postmenopausal status ( P<0.0001 at the lumbar spine; P=0.01 at the femoral neck), and the reporting of a reproductive cancer ( P<0.0001 at the lumbar spine; P=0.0008 at the femoral neck). Body weight was protective against bone loss at both skeletal sites ( P<0.0001). Baseline age, calcium intake, smoking, and current physical activity were not associated with BMD or bone loss. The understanding of the relative importance of risk factors for both low BMD and bone loss may assist in the identification of women at greater risk for subsequent low postmenopausal BMD.

Evaluation of bone mineral density of the peripheral skeleton in pre- and postmenopausal women with newly diagnosed endogenous Cushing's syndrome.

Cushing's syndrome (CS) is a well recognized cause of bone loss. Although many previous studies have shown decreased bone mineral density (BMD) in the lumbar spina and proximal femur of patients with endogenous CS, so far, the data estimating BMD in their peripheral skeleton are sparse. The aim of the present study was to evaluate BMD in the forearm and heel of women with newly diagnosed CS and to investigate its possible correlation with serum osteocalcin (BGP) and 24-hour urinary free cortisol levels (UFC). BMD in the forearm (distal and ultradistal area) of 29 (13 premenopausal and 16 postmenopausal) women with newly diagnosed CS (18 with pituitary adenoma, 10 with adrenal tumor and 1 with ectopic) was measured by dual x-ray absorptiometry (DEXA) and was compared with BMD of 29 age, body mass index (BMI)- and oestrogen status matched healthy controls. Furthermore, in 18 (9 premenopausal and 9 postmenopausal) of the above patients (14 with pituitary adenoma, 5 with adrenal tumor and 1 with ectopic) broadband ultrasound attenuation (BUA) by quantitative ultrasound (QUS) of the heel was estimated and 18 age-, BMI- and oestrogen status matched healthy women served as controls. In all the patients serum BGP and UFC were measured at the time of diagnosis of CS. Compared to their matched controls, BMD in the forearm and BUA values in the heel did not differ in the premenopausal women with CS, while in the postmenopausal group BMD in the forearm was decreased (P < 0.05) but not BUA. Apart from a weak negative correlation between serum BGP and BMD in the ultradistal site of the forearm in premenopausal women (P = 0.05), serum BGP and UFC did not show significant correlation with BMD or BUA. BMD in the forearm is reduced only in postmenopausal women with newly diagnosed endogenous CS, while BUA in the heel is unaffected in both pre- and postmenopausal patients. Moreover, serum BGP and UFC do not seem to be relevant markers for assessing bone loss in the peripheral skeleton at the time of diagnosis of hypercortisolemia.

Racial differences in the effect of early milk consumption on peak and postmenopausal bone mineral density.

Studies of the effect of milk consumption on bone density have focused on white women. The applicability to other races is unclear. This study of 4316 women found a racial difference in the effect of early milk consumption on bone. Further study is required to evaluate the etiology of this difference. Early milk consumption has been found to influence bone mineral density positively throughout life. Previous studies leading to this finding focused on white women; there are no data to support the view that black women also gain an equivalent benefit from early milk consumption. Using data from the Third National Health and Nutrition Examination Survey (NHANES III), we analyzed the relationship between reported childhood and teenage milk consumption and current hip bone mineral density at four sites (femoral neck, trochanter, intertrochanter, and total hip) among postmenopausal and 20- to 39-year-old non-Hispanic white (NHW) and black (NHB) women. Potential confounding variables were accounted for in the analysis. Controlling for age and body mass index, teenage milk consumption was significantly associated with higher bone mineral density at all four sites among both postmenopausal and 20- to 39-year-old white women, but was not associated with bone mineral density at any site among black women. A similar pattern was observed for childhood milk intake. The interaction between race and teenage milk consumption significantly explained postmenopausal bone mineral density at all sites, whereas the interaction between race and teenage milk consumption was significant at two of the four sites among the 20- to 39-year-old women. The results show racial differences in the effect of early milk consumption on peak and postmenopausal bone mineral density.

Association of molecular variants, haplotypes, and linkage disequilibrium within the human vitamin D-binding protein (DBP) gene with postmenopausal bone mineral density.

Possible contribution of vitamin D-binding protein (DBP) gene for determination of BMD was tested by characterizing 13 SNPs in 384 adult Japanese women. When the effect of a specific single SNP was tested, five SNPs (-39C>T, IVS1+827C>T, IVS1+1916C>T, IVS1-1154A>G, and IVS11+1097G>C) correlated with BMD significantly at various levels. The chromosomal dosage of one haplotype (T-C-C-G-T-C in -39C>T, IVS1+827C>T, IVS1+1916C>T, IVS1-1154A>G, D432E, and IVS11+1097G>C) displayed significant correlation with adjusted radial BMD (r = 0.15, p = 0.008; n = 331). Multiple regression analyses revealed a most significant correlation with the combination of IVS1+827C>T and D432E (r2 = 0.029, p = 0.005). These results indicate a complex combined effect of several SNPs within the DBP gene that might underlie susceptibility to low radial BMD and osteoporosis. Osteoporosis results from the interplay of multiple environmental and genetic determinants. The gene encoding vitamin D-binding protein (DBP), a key factor for regulating calcium homeostasis through the vitamin D endocrine system, is a probable candidate for conferring susceptibility to osteoporosis. To test a possible contribution of the DBP gene for determination of bone mineral density (BMD) of adult women, we have characterized 13 single nucleotide polymorphisms (SNPs) within the DBP gene in DNA from 384 adult Japanese women and attempted to correlate specific SNPs with BMD. Sixteen major haplotypes accounted for 80% of the variations, indicating allelic complexity in this genomic region. Pairwise linkage disequilibrium (LD), measured by the D' and r2 statistics, demonstrated a general pattern of decline with increasing distance, but individual LD values within small genomic segments were diverse. Regression analysis for adjusted BMD revealed significant correlation with respect to five of them (-39C>T, IVS1+827C>T, IVS1+1916C>T, IVS1-1154A>G, and IVS11+1097G>C) at various levels. An intronic SNP (IVS11+1097G>C) with the highest significance of association (p = 0.006) showed significant LD with four SNPs located around the first exon (r2 values > 0.18, D' > 0.5). A non-synonymous coding SNP, D432E, showed a comparable level of correlation, but it was in a moderate LD only with IVS11+1097G>C. The chromosomal dosage of one haplotype (T-C-C-G-T-C in -39C>T, IVS1+827C>T, IVS1+1916C>T, IVS1-1154A>G, D432E and IVS11+1097G>C) estimated in each subject displayed significant correlation with adjusted radial BMD (r = 0.15, p = 0.008; n = 331). Furthermore, multiple regression analyses revealed that the most significant correlation was achieved for the combination of IVS1+827C>T and D432E (r2 = 0.029, p = 0.005). These results indicate a complex combined effect of several SNPs within the DBP gene that might underlie susceptibility to low radial BMD and osteoporosis.

A theoretical analysis of the relative influences of peak BMD, age-related bone loss and menopause on the development of osteoporosis.

Factors that determine a post-menopausal woman's bone mineral density (BMD) include her mass at the time of skeletal maturity (peak BMD), menopause and the rate of loss she experiences as she ages. Understanding the relative influence of each of these factors may help identify important preventive treatments and provide new ways to identify women at risk for osteoporosis. In this analysis we utilize a computer model of the bone remodeling process to predict the relative influences of peak BMD, menopause and age-related bone loss on the development of osteoporosis. The delay in the onset of osteoporosis (defined as BMD <2.5 SD from the young adult mean) caused by modifying peak BMD, age-related bone loss or the age at menopause is quantified. A 10% increase in peak BMD is predicted to delay the development of osteoporosis by 13 years, while a 10% change in the age at menopause or the rate of non-menopausal bone loss is predicted to delay osteoporosis by approximately 2 years, suggesting that peak BMD may be the single most important factor in the development of osteoporosis.

Lean body mass and bone mineral density in physically exercising postmenopausal women

Objectives: To investigate whether the relative contribution of body composition (lean and fat mass component) to postmenopausal bone mineral density (BMD) differs between women participating in physical exercise and sedentary women. Methods: Subjects were 45 postmenopausal women participating in regular physical exercise and 89 sedentary controls aged 50–60 years. Baseline characteristics included age, height, weight, body mass index (BMI, Wt/Ht 2), age at menopause, and years since menopause (YSM). Body fat mass, percentage of body fat, lean body mass, and lumbar spine BMD (L2-4) were measured by dual-energy X-ray absorptiometry. Results: Although age, height, weight, BMI, and YSM did not differ between the two groups, lean body mass and lumbar spine BMD were significantly higher ( P<0.05 and <0.001, respectively), while body fat mass and percentage of body fat mass were significantly lower in exercising women than in sedentary controls ( P<0.05 and <0.05, respectively). In exercising women, BMD was positively correlated with lean body mass ( r=0.415, P<0.01) but not with body fat mass ( r=0.155, NS). Conversely, in sedentary controls, BMD was correlated with body fat mass ( r=0.251, P<0.05) and lean body mass ( r=0.228, P<0.05). Conclusions: Lean body mass is a more significant determinant of postmenopausal BMD in physically exercising women than in sedentary women.

Association between a functional interleukin-6 gene polymorphism and peak bone mineral density and postmenopausal bone loss in women: the ofely study

Genetic factors play an important role in determining bone mass and several genes are involved in this process. Interleukin-6 (IL-6) is a candidate gene for regulation of bone mineral density (BMD) and it has been suggested recently that novel IL-6 −174 G/C allelic variants may be associated with peak BMD in young men and with bone resorption in elderly women. In this study, we assessed the relationships between IL-6 gene polymorphism, peak BMD, rate of postmenopausal BMD loss, and bone turnover in women. BMD was measured by dual-energy X-ray absorptiometry in 255 healthy premenopausal women, aged 31–57 years. BMD loss at the forearm was measured over 4 years in 298 healthy untreated postmenopausal women, 50–88 years (mean 64 years). We also measured levels of serum osteocalcin, bone alkaline phosphatase, and N-propeptide of type I collagen for bone formation and three markers of bone resorption, including urinary and serum C-terminal cross-linking telopeptide of type I collagen and urinary N-terminal telopeptide of type I collagen, in both pre- and postmenopausal women at baseline. In premenopausal women we found a significant association between IL-6 genotypes and BMD at the whole body (analysis of variance [ANOVA], p = 0.03), femoral neck (p = 0.03), trochanter (p = 0.014), Ward’s triangle (p = 0.03), and total hip (p = 0.006), with subjects having the CC genotype showing 3%–7% higher BMD levels than their GG counterparts. However, after matching women with CC and GG genotypes for body height the differences decreased (2%–4%), and were no longer significant (p = 0.10–0.23). In postmenopausal women the mean rate of loss at the ultradistal radius was significantly associated with IL-6 genotypes (ANOVA, p = 0.049), with women having the CC genotype showing a significantly greater rate of bone loss (p < 0.05) compared with their GC and GG counterparts. After adjustment for weight changes, the difference in the rate of ultradistal radius bone loss between genotypes decreased and was not significant (p = 0.06 for CC vs. GG). A similar trend was observed for distal radius bone loss (p = 0.10, ANOVA), but not for the middle radius. We found no significant association between genotypes, bone turnover markers in premenopausal women, and either bone turnover or BMD in postmenopausal women. We conclude that this new functional IL-6 polymorphism was weakly associated with level of peak BMD and the rate of forearm trabecular postmenopausal bone loss in this cohort of healthy French women. IL-6 genotypes accounted only for a small proportion of the interindividual variation of both peak BMD and rate of bone loss and were not significant after adjustment for height and changes in body weight, respectively, suggesting that part of the effect may have been due to the differences in body size. Larger long-term studies are necessary to assess adequately the relationships between IL-6 genotype, rate of bone loss, and risk of fracture.

The oxidative metabolism of estradiol conditions postmenopausal bone density and bone loss.

Because lifelong exposure to estrogen is a strong determinant of bone mass, we asked whether metabolic conversion of estrogen to either inactive or active metabolites would reflect postmenopausal bone mineral density (BMD) and rate of bone loss. Biochemical markers of inactive estrogen metabolites, urinary 2-hydroxyestrogen (2OHE1) and 2-methoxyestrogen (2MeOE1), and active metabolites, urinary 16alpha-hydroxyestrone (16alphaOHE1), estradiol (E2), and estriol (E3), were determined in 71 untreated, healthy postmenopausal women (age, 47-59 years) followed prospectively for 1 year. Urinary 2MeOE1 was correlated negatively with baseline vertebral (anteroposterior [AP] projection, r = -0.23 andp < 0.05; lateral view, r = -0.27 and p < 0.05) and proximal femur bone density measured by dual-energy X-ray absorptiometry (DXA; total, r = -0.38 and p < 0.01; neck, r = -0.28 and p = 0.02; trochanter, r = -0.44 and p < 0.01). BMDs of women in the lowest quartile of urinary 2MeOE1 (< 15 ng/g) were significantly higher than those in the highest quartile at all skeletal sites (p < 0.05). Likewise, women in the lowest quartile of urinary 2OHE1/16alphaOHE1 ratio (< 1.6) did not experience bone loss after 1 year, in contrast to women in the higher quartiles. We propose that the rate of inactivation of estrogens through 2-hydroxylation may contribute to postmenopausal osteoporosis.

The correlation between parity, lactation and the postmenopausal bone mineral density

The correlation between parity, lactation and the postmenopausal bone mineral density

Review: Tibolone is as effective as estrogens for postmenopausal symptoms and bone mineral density

Source Citation Moore RA. Livial: a review of clinical studies. Br J Obstet Gynaecol. 1999 Mar 19;106(Suppl):1-21.

Differences in bone resorption after menopause in Japanese women with normal or low bone mineral density: quantitation of urinary cross-linked N-telopeptides.

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 bone mineral density in postmenopausal white Iowans.

Osteoporosis is a major health problem for older individuals. For women, development of osteoporosis is a function of the accretion of "peak" bone mass in the third decade, age at menopause, and rate of bone loss with aging. Low bone mineral density (BMD) is a major risk factor for osteoporosis and fracture. The purpose of this study was to identify life style, nutritional, medical, and genetic predictors of low BMD in postmenopausal Iowa women. One hundred thirty-four postmenopausal White women ranging in age from 57 to 81 years were included in this case-control study. Bone mineral density was measured at the femoral neck, using dual photon X-ray absorptiometry (Hologic 2000 QDR). Sixty-six women with BMD measurements below 0.68 g/cm2 (the bottom quartile of the BMD distribution in the population from which participants were recruited), and 68 women with values at or above 0.83 g/cm2 (the top quartile of the BMD distribution in the same population) were included. Information about environmental, nutritional, medical, and life style modifiers of BMD was obtained by written questionnaire and telephone interview. To assess familial factors that might influence BMD, we obtained a detailed family history for each participant. In addition, we tested the hypothesis that allelic variation at the Vitamin D receptor (VDR), and the type I collagen gene (COL1A1 and COL1A2) loci influence BMD. Weight, loss of height, age, and age at menopause were strong predictors of BMD in our population. After adjustment for these differences, we found no effect of genotype at the COL1A1, COL1A2, and VDR loci on BMD. Bone mineral density is a complex trait that is influenced by several different modifiers; in the present study, weight was the best predictor of postmenopausal BMD. While several studies suggest that VDR genotype is an important determinant of BMD, we did not find this association in our population, nor did we identify an association between allelic variation at the type I collagen gene loci and BMD. Identification of genes that determine body mass index may provide additional insight into risk factors for low BMD, and osteoporotic fractures.

Physical activity in adolescence and bone density in periand postmenopausal women: A population-based study

The association between sports participation during adolescence and peri- and postmenopausal bone mineral density (BMD) was examined among 2025 women aged 48–58 years. Adolescent recreational and competitive sporting activities were registered with a self-administered questionnaire. Altogether, 881 (43.5%) women stated that they had taken part in sports during their adolescence. BMD was measured using dual X-ray absorptiometry (DXA) in lumbar vertebrae 2–4 and the left femoral neck. The unadjusted BMD was 2.4% higher ( p = 0.001) and the adjusted BMD was 1.4% higher in the spine ( p = 0.015 after adjusting for age, weight, time from menopause to densitometry, and duration of estrogen replacement therapy) among women who had taken part in sports during their adolescence compared to women who had been inactive. There was no significant difference in femoral neck BMD between these groups. The results of this population-based study suggest that intense recreational physical activity in adolescence could play some role in preventing axial osteoporosis in later life.

Decreased serum IGF-I and dehydroepiandrosterone sulphate may be risk factors for the development of reduced bone mass in postmenopausal women with endogenous subclinical hyperthyroidism.

Postmenopausal women with endogenous subclinical hyperthyroidism seem to have reduced bone mass, which does not correlate with serum thyroid hormone levels. Relative insufficiencies of IGF-I and dehydroepiandrosterone sulphate (DHEAS) might be additional risk factors for low bone density in these patients. We measured IGF-I, IGF-binding protein-3 (IGFBP-3) and DHEAS levels together with bone mineral density (BMD) of the femoral neck and lumbar spine in women with an autonomously functioning thyroid nodule. Sixty-three women were classified as subclinical hyperthyroid (31 pre- and 32 postmenopausal) and 39 as overt hyperthyroid (16 pre- and 23 postmenopausal) and results were compared with data obtained from 41 age-matched euthyroid healthy women. In premenopausal women BMD was reduced only in the overt hyperthyroid group, and only in the spine, to 92% (P < 0.05). Serum IGF-I as well as IGFBP-3 were increased in the manifest hyperthyroid group, to 157% (P < 0.001) and 129% (P < 0.05) respectively, whereas DHEAS levels did not change in either premenopausal patient group. In postmenopausal women BMD was significantly reduced both in the subclinical hyperthyroid group (spine to 90% and femoral neck to 88%; P < 0.05), as well as in the hyperthyroid group (spine to 78% and femoral neck to 86%; P < 0.01). In contrast to premenopausal women, serum IGF-I and IGFBP-3 did not change in the two groups who were postmenopausal and serum DHEAS levels were reduced to 58% (P < 0.001) in both postmenopausal groups with subclinical as well as overt hyperthyroidism. In the same two groups of patients, serum IGF-I and DHEAS levels correlated with BMD (femoral neck; both r = 0.50, P < 0.05). In conclusion, women with a solitary autonomous thyroid nodule with subclinical hyperthyroidism have reduced BMD only if they are postmenopausal. This is probably due to the effect of subtle increases in thyroid hormone production together with lack of oestrogen protection of the skeleton. But additional risk factors for the development of enhanced bone loss might be a state of relative IGF-I and DHEAS insufficiency in these patients as well as in postmenopausal women with overt hyperthyroidism.

Determinants of radial bone density as measured by PQCT in pre- and postmenopausal women: the role of bone size.

The aim of the present study was to examine the influence of anthropometric, hormonal, and geometric factors on the variability of radial bone mineral density (BMD) in women. In 583 healthy pre- and postmenopausal females (aged 40-60 years) radial total (BD) and trabecular BMD (TBD) was measured by peripheral quantitative computerized tomography at the nondominant distal forearm. In addition, 29 women who had suffered a Colles' fracture after minor trauma were also evaluated. There was no age-dependent change in radial BD and TBD before menopause. We found a negative correlation between BMD and age and years since menopause (YSM) in postmenopausal women (BD = 422.73 - 2.342 age - 6.308YSM; r = 0.36, p = 0.0001, n = 128). The variation of YSM, body mass index (BMI), and age accounted for 20% of the variability of BD in postmenopausal women. In contrast, in premenopausal women, only 3% of the variability could be explained by anthropometric variables. Bone mineral content (BMC) and bone area, but not BMD at the distal radius, were significantly correlated to grip strength (r = 0.25, p = 0.006 for BMC, r = 0.26, p = 0.003 for area). The cross-sectional bone area of the CT slice showed a significant increase with aging (y = 263.02 + 1.25x; r = 0.14, p = 0.0009). There was a strong negative correlation between bone area and BD and TBD (y = 516.04 - 0.668x; r = -0.57, p < 0.0001 for BD). If BMD is normalized for BA, variation is reduced by 32% (for BD) and 10% (for TBD), respectively. Women with Colles' fracture had a significantly lower TBD normalized for BA (fracture group [-0.71 +/- 0.88] vs. normals (0.03 +/- 0.99]; p = 0.00009). Our results show that YSM and BMI are predictors of postmenopausal BMD. However, radial BMD is influenced strongly by geometric variables such as cross-sectional bone area.

Postmenopausal bone mineral density: relationship to calcium intake,calcium absorption, residual estrogen, body composition, and physical activity

Physical and lifestyle data were collected from 62 postmenopausal women who had declined hormone replacement therapy. Potential predictor variables were examined for their associations with bone mineral density (BMD) of the lumbar spine and femoral neck as assessed by dual x-ray absorptiometry. Body weight demonstrated the strongest association with lumbar BMD; lean body mass demonstrated the strongest association with femoral BMD. Together with the natural logarithm of the number of years since menopause (ln YSM) these anthropometric variables explained 36 and 34% of the variability of femoral and lumbar BMD, respectively. Serum estradiol levels demonstrated a weak positive association with BMD, which lost statistical significance after adjustment for body mass. Similarly, cardiovascular fitness was positively associated with femoral BMD prior to but not following adjustment for body mass. Controlling for years since menopause and body mass, the product of dietary calcium and calcium absorption demonstrated a weak positive correlation with femoral BMD (partial r = 0.30). The intake of tea was positively and significantly associated with both bone density measurements. In multiple regression analysis, femoral BMD was best explained by the lean body mass, ln YSM, and the daily intake of tea (r2 = 0.50). Similarly, lumbar BMD was best explained by body weight, ln YSM, and intake of tea (r2 = 0.44). Body mass is a major predictor of postmenopausal bone density at the hip and spine. A positive association between dietary calcium and BMD was detected only by taking into account the intestinal absorptive efficiency.

The heritability of bone mineral density, ultrasound of the calcaneus and hip axis length: a study of postmenopausal twins.

Population based studies have demonstrated that having a first degree relative with a hip fracture is predictive of future hip fractures. Postmenopausal bone mineral density (BMD), ultrasound of calcaneus and hip axis length are associated with hip fracture, with the association for ultrasound and hip axis length being independent of BMD. The aim of this study was to determine the genetic component of these three important risk factors. We performed a classical twin study using 500 normal female twins, 128 identical and 122 non-identical pairs, aged 50 to 70 years. We measured bone mineral density at multiple sites, hip axis length (distance from the inner rim of the acetabulum to the greater trochanter), broadband ultrasound attenuation and velocity of sound of the calcaneus. Bone density had a strong genetic component at all sites with estimates of heritability ranging from 0.46 to 0.84. Hip axis length and velocity of sound had major genetic components with estimates of 0.62 and 0.61 respectively, which remained virtually unchanged after adjustment for bone mineral density. Broadband ultrasound attenuation had a moderate genetic component with an estimate of 0.53, which was reduced further to 0.45 after adjustment for BMD. In summary, all three bone measurements, which are independently associated with hip fracture, are independently heritable. This study suggests that a combination of different genetic factors acting on the structure, dimensions and density of bone may explain the importance of family history as a risk factor for hip fracture.

Postmenopausal bone mineral density: relationship to calcium intake,calcium absorption, residual estrogen, body composition, and physical activity

Physical and lifestyle data were collected from 62 postmenopausal women who had declined hormone replacement therapy. Potential predictor variables were examined for their associations with bone mineral density (BMD) of the lumbar spine and femoral neck as assessed by dual x-ray absorptiometry. Body weight demonstrated the strongest association with lumbar BMD; lean body mass demonstrated the strongest association with femoral BMD. Together with the natural logarithm of the number of years since menopause (ln YSM) these anthropometric variables explained 36 and 34% of the variability of femoral and lumbar BMD, respectively. Serum estradiol levels demonstrated a weak positive association with BMD, which lost statistical significance after adjustment for body mass. Similarly, cardiovascular fitness was positively associated with femoral BMD prior to but not following adjustment for body mass. Controlling for years since menopause and body mass, the product of dietary calcium and calcium absorption demonstrated a weak positive correlation with femoral BMD (partial r = 0.30). The intake of tea was positively and significantly associated with both bone density measurements. In multiple regression analysis, femoral BMD was best explained by the lean body mass, ln YSM, and the daily intake of tea (r2 = 0.50). Similarly, lumbar BMD was best explained by body weight, ln YSM, and intake of tea (r2 = 0.44). Body mass is a major predictor of postmenopausal bone density at the hip and spine. A positive association between dietary calcium and BMD was detected only by taking into account the intestinal absorptive efficiency.

Tamoxifen reduces bone turnover and prevents lumbar spine and proximal femoral bone loss in early postmenopausal women

Although widely used for its anti-estrogen properties tamoxifen has estrogen like effects on a number of tissues including bone and liver. Previous studies suggest a preservation of lumbar spine density in postmenopausal women but the effect on the hip had not been addressed. To determine whether tamoxifen prevents bone loss in the early postmenopausal period bone mineral density at the lumbar spine and femoral neck was measured using dual energy X-ray absorptiometry at presentation and 6 monthly thereafter for 1 year in a prospective controlled study. Also indices of bone turnover, serum osteocalcin and urinary hydroxyproline excretion, were assessed. Fifteen early postmenopausal women with Stage I or II breast cancer treated with tamoxifen and 21 normal postmenopausal women were studied. Sex hormone binding globulin and antithrombin III levels in serum were also measured as indices of the hepatic estrogenic activity. Tamoxifen (20 mg daily) prevented bone loss at the femoral neck and lumbar spine. Median rates of change in bone mineral density (%/year) for the tamoxifen group were +0.09%/year in the lumbar spine and 1.4%/year in the femoral neck compared with -2.3%/year and -1.8%/year for the control group (P = 0.04 and 0.03, respectively). Tamoxifen resulted in a significant decrease in both serum osteocalcin and urinary hydroxyproline by 6 months of treatment and this effect persisted for the 12 months of observation. An increase in sex hormone binding globulin and a decline in antithrombin III levels was also observed. These data indicate that, in recently, postmenopausal women tamoxifen prevented bone loss at both the lumbar spine and femur and reduced bone turnover.