Association of the CT gene (CA) polymorphism with BMD in osteoporotic Mexican women

Calcitonin (CT) plays a role in the pathogenesis of osteoporosis and genetic variations in or adjacent to the CT gene may be associated with loss of bone mineral density (BMD). The correlation between a dinucleotide (cytosine-adenine) repeat polymorphism at the CT locus and BMD was examined in 70 osteoporotic women, 70 non-osteoporotic women and 500 subjects from the Mexican population. The allele A and genotype AA frequencies were significantly higher in osteoporotic women than in non-osteoporotic women (60% vs 32%; p < 0.0001 and 41% vs 14%; p = 0.0007, respectively). Genotype AA was associated with the presence of osteoporosis [odds ratio 2.58; 95% confidence interval (CI); 1.62-4.12]. Likewise, the loss of lumbar BMD and T scores were related to the presence of allele A: subjects with a single A allele displayed lower values for lumbar BMD and T score (84.02% and -1.51, respectively) than those who do not present any A allele (89.61% and -0.88, respectively). Individuals with two alleles A showed the lowest lumbar BMD and T-score values (73.77% and -2.51, respectively). Analysis of potential confounder demonstrated that aging has a significant effect on osteoporosis development (odds ratio 1.1; 95% CI; 1.1052-1.152).     

Elevated arterial stiffness in postmenopausal women with osteoporosis

OBJECTIVES: Osteoporosis and increased pulse wave velocity (PWV) are cardiovascular risk factors. We investigated the relationship between PWV and bone mass in the lumbar spine in postmenopausal women. METHODS: We studied the PWV in 95 women; 38 postmenopausal women with normal spinal bone mineral density (BMD), 32 osteopenic postmenopausal women, and 25 osteoporotic postmenopausal women. The brachial-ankle PWV (baPWV) was measured using an automated device. The BMD of the lumbar spine (L2-L4) was measured using dual-energy X-ray absorptiometry. RESULTS: After adjusting for age and years since menopause, women with osteoporosis had a significantly higher baPWV than those with normal BMD (1500 +/- 220 cm/s versus 1340 +/- 215 cm/s; P < 0.05), but no significant differences in baPWV were seen between the osteoporotic and osteopenic groups or between the osteopenic and normal BMD groups. In univariate regression analysis, the baPWV was significantly negatively correlated with BMD (r = -0.450, P < 0.01), and significantly positively correlated with age (r = 0.601, P < 0.01), years since menopause (r = 0.577, P < 0.01), systolic blood pressure (r = 0.295, P < 0.01), and diastolic blood pressure (r = 0.264, P < 0.05), but was not with other variables. In multivariate regression analysis, the baPWV was significantly correlated with BMD (P < 0.05), but not with other variables. CONCLUSIONS: Postmenopausal women with osteoporosis may have elevated arterial stiffness, suggesting that osteoporotic postmenopausal women may have a higher risk of cardiovascular disease.     

A prospective,randomized, placebo-controlled study of the dose effect of oral estradiol on bone mineral density in postmenopausal Chinese women

OBJECTIVES: One of the long-term consequences of estrogen deficiency in postmenopausal women is an increased risk of osteoporosis. Fractures of the hip and lumbar spine are associated with considerable morbidity and mortality. Estrogen replacement therapy reduces the risk of osteoporosis, but there is no clear agreement on the most appropriate doses to be used. The aim of this study was to compare changes in bone mineral density (BMD) measurements using conventional and lower dose estradiol. METHODS: A prospective, randomized, placebo-controlled 12-month study of the effect of 1 and 2 mg estradiol on BMD in 152 hysterectomized postmenopausal Chinese women with no contraindication to the use of estrogen replacement therapy. RESULTS: Over 12 months, spinal BMD in placebo treated patients decreased by a mean of 2% from baseline (-0.02+/-0.03 g/cm(2)) while it increased by 2% in the 1 mg (0.02+/-0.03 g/cm(2)) and 3% in the 2 mg group (0.03+/-0.03 g/cm(2)). Mean changes in BMD over 12 months in the hip were -0.02+/-0.02 g/cm(2) (-2%), 0.01+/-0.02 g/cm(2) (+1%) and 0.01+/-0.03 g/cm(2) (+1%) in the placebo, 1 and 2 mg estradiol groups, respectively (P<0.05). Relative to placebo, increases in BMD in both 1 and 2 mg groups were statistically significant for both spine and hip (P<0.05). However, there was no significant difference in the increase in BMD between the 1 and 2 mg doses for either lumbar spine or hip (P=0.82, 0.53, respectively). CONCLUSION: The results of our study show that a 1 mg dose of oral estradiol is effective in preventing bone loss in postmenopausal Chinese women.     

Relationship between adolescent amenorrhea and climacteric osteoporosis

OBJECTIVES: The relationship between climacteric osteoporosis and disturbances in menstrual cycle during adolescence was examined. METHODS: Seven hundred and seventy-one questionnaires were shared out among women visiting the outpatient department for climacteric complaints for the first time between 2001 and 2004. Questions revealed the age, age at menarche and menopause, the regularity or irregularity of menstrual cycle during adolescence and adult ages. The bone mineral density was examined using the Dual Energy X-ray Absorptiometry (DEXA) method on the lumbar spine. RESULTS: Six hundred and thirty-five of the 771 questionnaires were suitable for analysis. Osteoporosis was observed in 30.1% of the cases. Age, age at the menarche or at the menopause did not alter in the subgroups with or without osteoporosis. The incidence and severity of osteoporosis were significantly higher in patients reporting secondary amenorrhea during adolescent ages (42.1%; average BMD of the lumbar spine 71.6+/-3.9), as compared to the patients with normal cycle (30.4%; average BMD of the lumbar spine 84.8+/-7.8). No correlation between the occurrence of osteoporosis and the frequency of menstrual cycle during adulthood was observed. CONCLUSIONS: Secondary amenorrhea during the years of adolescence might play a role in the development of more severe osteoporosis in menopause.     

Bone mineral density in breast cancer patients with positive estrogen receptor tumor status

AIM: The aim was to investigate bone mineral density (BMD) in breast cancer patients with positive estrogen receptor (ER) tumor status. METHODS: The participants were 110 postmenopausal breast cancer patients with positive estrogen receptor (ER+) tumor status. Two hundred and sixty-one age-matched, healthy postmenopausal women, all of whom were selected from our pooled data, served as controls. Age, age at menopause, years since menopause (YSM), height, weight, and body mass index (BMI, wt/ht(2)) were recorded. Lumbar spine (L2-4) BMD and Z-score were assessed by dual-energy X-ray absorptiometry. RESULTS: Bone mineral density in breast cancer patients was significantly higher than that in controls (0.89+/-0.12 g/cm(2) versus 0.84+/-0.16 g/cm(2), P<0.01). The Z-score in breast cancer patients was also higher than that in controls (110+/-13.6% versus 100+/-9.8%, P<0.001). Higher BMD and Z-score in breast cancer patients remained significant after adjusting for age, YSM, and BMI (P<0.05). CONCLUSIONS: Postmenopausal breast cancer patients with positive ER tumor status have higher BMD. Positive ER tumor status may be associated with higher cumulative exposure to estrogen.     

Bone mass and bone diminution of the axial and peripheral skeleton in normal and osteoporotic Austrian females.

Measurements of bone mass were performed in 133 healthy Austrian women using the quantitative computed tomography technique of the lumbar spine and single photon absorptiometry of the distal forearm. The data were compared with those of 110 Austrian females with osteoporotic spine fractures. A significant difference in mean bone density of the lumbar spine was observed between normal and osteoporotic patients in every decade, whereas forearm measurements showed statistical differences in the seventh and eighth decade but not in the sixth decade. Compared to age matched controls, bone mass of osteoporotic women showed the following diminution: sixth decade: distal forearm: -12.7%, spine: -46.8%; seventh decade: distal forearm: -19.0%, spine: -36.7%, eighth decade: distal forearm: -15.4%, spine: -33.7%. It appears that postmenopausal osteoporosis involves greater loss of bone in the spine in the first decade after menopause and slows down after this period, whereas loss of forearm bone mineral density (BMD) increases with advancing age.     

Osteoporosis affects component positioning in computer navigation-assisted total knee arthroplasty

Although computer-assisted navigation in total knee arthroplasty (TKA) has many advantages, undetected tracker pin movement can result in poor lower limb alignment and component position. Osteoporosis may be an underlying cause of tracker pin movement. The present prospective case-control study compared 6-month radiographic outcomes in 44 osteoporotic and 56 non-osteoporotic knees undergoing navigation TKAs. Osteoporotic knees were defined as those having a T-score of -2.5 or less either in the femoral neck or lumbar spine or both. At postoperative 6 months' follow-up, the average coronal tibial component position was greater valgus in osteoporotic group than in nonosteoporotic group (non-osteoporotic=varus 0.7°±1.8°; osteoporotic=valgus 1.2°±3.4°; p=0.041). Multiple linear regression analysis showed that being in the osteoporotic group was a predictor of tibial coronal component position (β=0.321, p=0.039). In addition, preoperative lumbar spine bone mineral density was found to be a predictor of coronal and sagittal alignments of the tibial component (β=0.406, p=0.015, β=-0.463, p=0.007). The present study found that osteoporosis affected tibial component position in computer-assisted navigation TKA. Clinicians should be particularly aware of the possibility of undetectable tracker pin movement during navigation TKA in osteoporotic knees.     

Prevention of postmenopausal bone loss with long-cycle hormone replacement therapy

OBJECTIVE: Postmenopausal bone loss and osteoporotic fractures can be prevented by hormone replacement therapy (HRT). However, opposed HRT may increase the risk of breast cancer above that associated with estrogen alone and in non-hysterectomized women estrogen substitution alone increases the risk of uterine cancer, which triggered renewed interest in long-cycle HRT regimens (estrogen replacement therapy with progesterone-free intervals up to 6 months). The effects on bone of such long-cycle HRT regimens are unknown. The objective of the present study was to compare the effects on bone and the endometrium of long-cycle HRT and conventional HRT. METHODS: Seventy-three healthy non-hysterectomized postmenopausal women were randomized to either conventional HRT (estradiol (E2) 2 mg/d during 12 days, E2 2 mg/d plus 1 mg/d of norethisterone acetate (NETA) during 10 days, E2 1 mg/d for 6 days) or long-cycle HRT treatment (two cycles with E2 2 mg/d during 28 days, followed by one cycle of conventional HRT and repeated every 3 months). Primary endpoint was the change in bone mineral density (BMD) at the lumbar spine (LS) over 24 months. RESULTS: BMD at LS increased significantly versus baseline in both treatment groups (conventional HRT +3.8 +/- 0.6%, long-cycle HRT +3.3 +/- 0.5%, p < 0.0001 for both) with no significant difference between treatment groups over 24 months. Similar significant BMD increases versus baseline were observed at the femoral neck, while biochemical markers of bone turnover (osteocalcin and deoxypyridinoline) were significantly decreased over 24 months. There were no endometrial or breast related adverse events reported. CONCLUSION: Long-cycle HRT may be a valid alternative to conventional HRT with regard to protection against postmenopausal bone loss.     

Bone mineral density and prediction of non-osteoporotic disease

It is widely recognized that bone mineral density (BMD) is one of the best predictors of osteoporotic fractures. Sex hormone status clearly affects bone either directly or indirectly and a longer estrogen exposure appears to be a major determinant of postmenopausal BMD. Accordingly, several studies have led to the hypothesis that BMD might represent a marker of the accumulated lifetime exposure of estrogen and therefore be used as a predictor factor of the risk of other postmenopausal conditions such as breast cancer or cardiovascular diseases (CVD).     

Association of the estrogen receptor alpha gene polymorphisms with osteoporosis in the Mexican population

The estrogen receptor gene (ER alpha) has been implicated in the development of osteoporosis. In this study, the association of two ER alpha gene polymorphic markers (a TA dinucleotide repeat and a single nucleotide polymorphism, G2014A) with osteoporosis was tested in 70 osteoporotic women, 70 non-osteoporotic women and 500 subjects from the Mexican population. According to the genetic analysis of the Mexican population using eight unlinked polymorphic markers, we found that our population is structured into three subpopulations; therefore, the allele-phenotype relationship was analyzed with a statistical method that considered population stratification. We found that the G2014A polymorphism is associated with the presence of osteoporosis while the TA dinucleotide repeat is not. The G allele and the GG genotype frequencies of the G2014A marker were significantly higher in osteoporotic than in non-osteoporotic women. Likewise, subjects bearing the G allele in heterozygous or homozygous displayed lower values for lumbar bone mineral density and T score than those who did not present any G allele. The effect of confounders for osteoporosis on the association of G allele-osteoporosis was ruled out. In summary, we conclude that the G2014 polymorphism may become a useful marker for genetic studies of osteoporosis in the Mexican population.     

Changes in bone mineral density during and after 3 years' use of tamoxifen or toremifene

OBJECTIVES: To study the effects of tamoxifen and toremifene on bone mineral density (BMD) in postmenopausal women with breast cancer. METHODS: Seventy patients with stage II-III breast cancer were randomized to start either tamoxifen (n = 36; 20 mg per day) or toremifene (n = 34; 40 mg per day) for 3 years. BMD in the lumbar spine and in the proximal femur was measured by dual-energy X-ray absorptiometry both before and during the treatment and 1 year after the discontinuation of the anti-estrogens. RESULTS: The baseline BMD measurements were comparable between the groups. In 3 years, lumbar BMD decreased by 1.7% in tamoxifen (P = 0.048) and 3.0% in toremifene (P = 0.001) users (ns between the groups), and femoral neck BMD by 0.9% (P = 0.040) and 1.3% (P = ns), respectively. The use of hormone replacement therapy (HRT) until the diagnosis of breast cancer was associated with decreases in lumbar BMD during anti-estrogen regimen (4% at 3 years) in contrast to unchanged lumbar BMD in women with no previous use of HRT. During the 1st year after the cessation of anti-estrogen, lumbar BMD did not change at all in either group whereas femoral BMD decreased in both the groups at the rate of 1.5-3.2%, as expected. CONCLUSIONS: We conclude that tamoxifen (20 mg) and toremifene (40 mg) have similar bone-sparing efficacy that in lumbar spine extends up to 1 year after the cessation of these regimens. This effect is not seen in lumbar spine BMD in those postmenopausal women who discontinue HRT at the time of breast cancer diagnosis.     

Screening for osteoporosis after breast cancer: For whom,why and when

Osteoporosis and breast cancer are common diseases in postmenopausal women. Bone and the breast are both estrogenic dependent tissues and different surrogate markers for osteoporosis are opposite of those for the risk of breast cancer. In particular, numerous studies have reported a positive relationship between high bone mineral density (BMD) and a greater risk of breast cancer. On the other hand, most treatments in early breast cancer women including ovarian suppression treatments (chemotherapy, surgery or GnRH agonists) and aromatase inhibitor (AI) therapy induce a profound and rapid suppression of estrogen levels thereby increasing the rate of bone loss. Nevertheless, their impact on the risk of fracture is still questionable, especially in postmenopausal women with no osteoporosis at baseline. The purpose of this minireview is to examine the relationship between breast cancer and the risk of fracture and to discuss a screening strategy for osteoporosis after breast cancer.     

Tofupill/Femarelle (DT56a): a new phyto-selective estrogen receptor modulator-like substance for the treatment of postmenopausal bone loss

OBJECTIVE: To evaluate the efficacy of Tofupill/Femarelle (DT56a), a novel phyto-selective estrogen receptor modulator (SERM), in preserving bone mineral density (BMD) in postmenopausal women. DESIGN: The study sample consisted of 98 healthy, postmenopausal women who were randomly allocated, on a double-blind basis, to receive either 644 mg/d DT56a (study group) or 344 mg/d DT56a supplemented with calcium (low-dose group) for 12 months. Each participant was assessed with a comprehensive health questionnaire, a detailed physical, and laboratory and pelvic sonogram examinations at entry and every 3 months thereafter. BMD was assessed by dual-energy x-ray absorptiometry (Lunar) of the lumbar spine and femoral neck before the study began and after 12 months of treatment. RESULTS: After 12 months of treatment, BMD had increased in the study group by 3.6% in the lumbar spine (P = 0.039) and by 2.0% in the femoral neck (NS). In the low-dose group, BMD had decreased in the lumbar spine by 0.6% (NS) and by 0.6% in the femoral neck (NS). Comparison of the change in bone density between the groups yielded a significant difference for the lumbar spine (P = 0.037). Neither group showed a change in endometrial thickness and sex hormone levels nor reported any side effects of treatment. CONCLUSIONS: Tofupill treatment in postmenopausal women increases BMD without unwanted estrogenic effect. Tofupill appears to be a promising phyto-SERM for the prevention of postmenopausal osteoporosis.     

Denosumab

Denosumab is a fully human monoclonal IgG(2) antibody that binds to receptor activator of nuclear factor-κB ligand (RANKL) and inhibits bone resorption due to RANKL-mediated osteoclastogenesis. In Europe, subcutaneous denosumab is indicated for cancer treatment-induced bone loss in men with prostate cancer and in postmenopausal women with breast cancer. In a large (n= 1468), well designed, multinational, phase III trial in adult patients with prostate cancer who were receiving androgen-deprivation therapy, bone mineral density (BMD) at the lumbar spine was significantly improved from baseline after 24 (primary endpoint) and 36 months of treatment with subcutaneous denosumab (60 mg once every 6 months), relative to that with placebo. Moreover, the risk of new vertebral fracture was significantly reduced by 62% in the denosumab group compared with the placebo group. In breast cancer patients receiving aromatase inhibitor therapy (n =252), subcutaneous denosumab (60 mg once every 6 months) significantly improved BMD at the lumbar spine from baseline after 12 (primary endpoint) and 24 months of treatment relative to placebo in a pivotal phase III trial. There were significant improvements in BMD at all skeletal sites, including the lumbar spine, total hip, and femoral neck, after 24 and 36 months' denosumab treatment in prostate cancer patients and after 12 and 24 months' treatment in breast cancer patients. In general, these improvements occurred irrespective of baseline characteristics, including age, duration of hormone ablation therapy, and baseline BMD. Denosumab treatment was generally well tolerated for up to 24 months in breast cancer patients and for up to 36 months in prostate cancer patients.     

Prevention of osteoporosis and uterine effects in postmenopausal women taking raloxifene for 5 years

OBJECTIVE: Raloxifene hydrochloride (60 mg/day) is a selective estrogen receptor modulator indicated for the prevention and treatment of postmenopausal osteoporosis. Raloxifene treatment for 3 years increases bone mineral density (BMD) and, unlike tamoxifen (a triphenylethylene selective estrogen receptor modulator), does not stimulate the endometrium in healthy postmenopausal women. The effect of longer duration of treatment with raloxifene is not known. Therefore, the main objectives of these analyses are (1) to compare the effect of 5 years of treatment with raloxifene (60 mg/day) with placebo in terms of the likelihood of developing osteoporosis and (2) to evaluate the effect of 5 years of raloxifene treatment on the endometrium and incidence of vaginal bleeding. DESIGN: The current analyses include integrated data from two identically designed, prospective, double-blinded trials including postmenopausal women (mean age, 55 years) randomly assigned to either placebo (n = 143) or raloxifene (60 mg/day; n = 185). Osteoporosis and osteopenia were diagnosed according to World Health Organization criteria, using the manufacturer's database for the lumbar spine and the National Health and Nutrition Examination Survey's 1998 reference base for the hip. Endometrial thickness was determined using transvaginal ultrasonography. Clinical diagnoses of endometrial hyperplasia or endometrial cancer were confirmed by blinded review of histopathology reports. RESULTS: Compared with the case of placebo, raloxifene treatment for 5 years reduced bone turnover markers (osteocalcin: -10.9%, P < 0.001; bone-specific alkaline phosphatase: -7.2%, P = 0.042; urinary C-telopeptide: -11.1%, P = 0.034) and was associated with increased BMD in the lumbar spine (2.8%; P < 0.001) and total hip BMD (2.6%; P < 0.001). Women taking raloxifene were less likely to develop osteoporosis (relative risk [RR] for raloxifene v placebo: 0.13; 95% CI: 0.00, 0.37; P = 0.001) or osteopenia (RR: 0.23; 95% CI: 0.00, 0.81; P = 0.038) at the lumbar spine and were more likely to convert to normal BMD status at the lumbar spine (RR: 4.01; 95% CI: 1.34, 11.23; P = 0.043) and total hip (RR: 3.92; 95% CI: 1.12,14.27; P = 0.011) at 5 years, compared with the case of placebo. Raloxifene also significantly reduced total cholesterol (-5.5%; P < 0.001) and low-density lipoprotein cholesterol (-8.7%; P < 0.001), compared with the case of placebo. No significant changes in high-density lipoprotein cholesterol (P = 0.257) or triglycerides (P = 0.620) were detected. Incidence of hot flashes was higher among women taking raloxifene compared with those taking placebo [raloxifene, 47 (28.8%); placebo, 21 (16.8%); P = 0.017]. Women taking placebo or raloxifene reported a similar incidence of vaginal bleeding (P = 0.999) or of mean endometrial thickness of more than 5 mm at baseline and at each visit, up to the 5-year endpoint (P >/= 0.349). No diagnoses of endometrial hyperplasia or endometrial cancer were made in either treatment group. CONCLUSIONS: Five years of raloxifene treatment in healthy postmenopausal women preserves BMD, significantly reduces the likelihood of development of osteoporosis, and was not associated with an increased rate of vaginal bleeding, endometrial hyperplasia, or endometrial carcinoma, compared with the case of placebo.     

Lifetime high calcium intake increases osteoporotic fracture risk in old age

Caloric restriction prolongs life span. Calcium restriction may preserve bone health. In osteoporosis, bone mineral density (BMD) has significantly decreased, due to a lack of osteoblast bone formation. Traditional osteoporosis prevention is aimed at maximizing BMD, but the lifetime effects of continuously maintaining a high BMD on eventual bone health in old age, have not been studied. Strikingly, in countries with a high mean BMD, fracture rates in the elderly are significantly higher than in countries with a low mean BMD. Studies show that this is not based on genetic differences. Also, in primary hyperparathyroidism, on the brink of osteoporosis, BMD levels may be significantly higher than normal. Maybe, BMD does not represent long term bone health, but merely momentary bone strength. And maybe, maintaining a high BMD might actually wear out bone health. Since osteoporosis particularly occurs in the elderly, and because in osteoporotic bone less osteoblasts are available, the underlying process may have to do with ageing of osteoblastic cells. In healthy subjects, osteoblastic bone cells respond to the influx of calcium by composing a matrix upon which calcium precipitates. In the process of creating this matrix, 50-70% of the involved osteoblasts die. The greater the influx of calcium, the greater osteoblast activity, and the greater osteoblast apoptosis rate. An increased osteoblast apoptosis rate leads to a decrease in the age-related osteoblast replicative capacity (ARORC). In comparison to healthy bone, in osteoporotic bone the decrease in the replicative capacity of osteoblastic cells is greater. Due to the eventual resulting lack of osteoblast activity, micro-fractures cannot be repaired. Continuously maintaining a high BMD comes with continuously high bone remodeling rates, which regionally exhaust the ARORC, eventually leading to irreparable microfractures. Regarding long time influences on bone health, adequate estrogen levels are known to be protective against osteoporosis. This is generally attributed to its inhibiting influence on osteoclast activity. Instead, its net effects on osteoblast metabolism may be the key to osteoporosis prevention. Adequate estrogen levels inhibit osteoblast activity, calcium apposition and osteoblast apoptosis rate, preserving the ARORC. CONCLUSION: Regarding osteoporosis prevention, ARORC better than BMD represents bone health. Regarding ARORC, adequate estrogen levels are protective, opposing the similar effects of hyperparathyroidism and a high calcium diet. Tests need to be performed in mice to assess the lifetime effects of a high versus a low calcium diet, on eventual bone fracture toughness.     

Association between respiratory function and osteoporosis in pre- and postmenopausal women

OBJECTIVE: To investigate the relationships between respiratory function and osteoporosis, 132 premenopausal and 98 postmenopausal women were evaluated. METHODS: Bone mineral density (BMD) was measured with dual-energy X-ray absorptiometry. Pulmonary function and anthropometric parameters were measured using a spirometer and a body composition analyzer. RESULTS: Lumbar spine and proximal femur BMDs in postmenopausal women with forced expiratory volume in 1s (FEV1) > or = 92.0% averaged 0.83 +/- 0.12 g/cm2 and 0.67 +/- 0.11 g/cm2, which were significantly above the values (0.76 +/- 0.14 g/cm2 and 0.61 +/- 0.12 g/cm2, P < 0.05) in those with FEV1 <92.0%. The prevalences of osteoporosis at lumbar spine and proximal femur were 59.2 and 46.9% in the postmenopausal women with peak expiratory flow rate (PEFR) <5.12 l/s, significantly higher than those of osteoporosis at the corresponding sites in the women with > or = 5.12 l/s (36.7 and 20.4%, P < 0.05). Lumbar spine and proximal femur BMDs were positively correlated with FEV1 (r = 0.28, P < 0.05; r = 0.31, P < 0.05) and PEFR (r = 0.35, P < 0.05; r = 0.23, P < 0.05) in postmenopausal women; however, no significant correlations were observed in premenopausal women. CONCLUSION: Pulmonary function seems to be more closely associated with BMD in postmenopausal women than in premenopausal women. Poor respiratory function may be an indicator of postmenopausal women at increased risk of osteoporosis.     

Difference in the effect of adiposity on bone density between pre- and postmenopausal women

Objectives: Elevated bone mineral density (BMD) in obese women is partially attributable to the higher circulating estrogen levels derived from extraglandular aromatization in adipose tissue. However, it remains unclear whether there is an effect of overall adiposity on BMD in both pre- and postmenopausal women. The difference in the effect of overall adiposity on BMD between pre- and postmenopausal women was investigated. Materials and methods: Subjects were 296 premenopausal women with regular menstruation and 233 postmenopausal women. Age, age at menarche, years since menopause (YSM, in postmenopausal women), weight, height, and body mass index were recorded. Total fat mass amount, lean mass amount, and percentage of body fat were measured by whole body scanning with dual-energy X-ray absorptiometry (DEXA). Lumbar spine BMD (L2–L4) was measured by DEXA. In each group, significant determinants of BMD were investigated using univariate and stepwise multiple regression analysis. Results: In postmenopausal women, YSM, lean mass amount, total fat mass amount, and height were significant determinants of BMD (R²=0.273, P<0.001). In premenopausal women, only two variables including lean mass amount and age at menarche were significant determinants of lumbar spine BMD (R²=0.110, P<0.001), but total fat mass amount and percentage of body fat were not significant determinants of BMD. Conclusion: The effect of overall adiposity on BMD is more prominent in postmenopausal women than in premenopausal women.     

Trait anxiety and tamoxifen effects on bone mineral density and sex hormone- binding globulin

OBJECTIVE: Tamoxifen therapy preserves BMD of the lumbar spine and increases levels of SHBG. We assessed whether trait anxiety, a factor linked with a reactive endocrine system, is associated with differential changes in BMD and SHBG levels in response to tamoxifen therapy. METHODS: Postmenopausal women (N= 140) with axillary-node-negative breast cancer participated in a 2-year randomized, double-blind, placebo-controlled trial of tamoxifen (10 mg twice a day). Levels of BMD and SHBG were assessed at baseline and at 3, 6, 12, 18, and 24 months. RESULTS: Trait anxiety predicted tamoxifen-induced changes in lumbar spine BMD; high levels of trait anxiety were associated with significantly greater lumbar spine BMD at 3, 12, and 24 months (p values <.05) for women on tamoxifen therapy. High anxiety also was associated with lower levels of SHBG for women using tamoxifen at 3, 12, 18, and 24 months (p values <.05). CONCLUSIONS: Trait anxiety is associated with greater preservation of lumbar spine BMD in response to tamoxifen and with a suppression of tamoxifen-induced increases in SHBG. Trait anxiety and other affective traits may serve as indicators of underlying physiological processes that moderate the effects of estrogen receptor modulators (such as tamoxifen) in clinical trials. Such data may help to elucidate the physiological mechanisms responsible for some of the variation in individual responses to treatment.