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Vasoreactivity in pre- and postmenopausal women: evaluation by pharmacodynamic modeling.

Postmenopausal women experience an increase in cardiovascular mortality and morbidity compared with their premenopausal counterparts. This study was undertaken to develop a pharmacodynamic model to determine whether vascular reactivity in postmenopausal women differed from that in premenopausal women. Eleven subjects in each group were recruited. Graded doses of norepinephrine and insulin were infused via the dorsal hand vein. Venous diameter was measured by ultrasound. Dosage and venous diameter were fit to a Hill-type pharmacodynamic model in which norepinephrine acts as a vasoconstrictor and insulin counteracts varying fractions of norepinephrine constriction. Fitted pharmacodynamic parameters for norepinephrine did not differ uniformly between groups, but at norepinephrine infusion rates between 14 and 46 ng/mL, postmenopausal women demonstrated increased norepinephrine-induced vasoconstriction. Also, the modeled maximal response to insulin (Emaxi) was greater in premenopausal women. By stepwise linear regression, maximal response to insulin was found to be related to menopausal status and diastolic blood pressure. Postmenopausal women showed differences in vasoreactivity that may have important implications in the pathogenesis of hypertension.

Aged↗

Is heritability a risk factor for postmenopausal osteoporosis?

We investigated heritability as a risk factor for the development of osteoporosis in two randomly selected populations of postmenopausal women and their premenopausal daughters. We determined the familial resemblance in bone mass at three sites; the distal forearm, lumbar spine, and proximal femur, premenopausally and with increasing maternal postmenopausal age. We also examined the bone mass of daughters in relation to mothers with and without osteoporotic fractures. Peak bone mass among premenopausal siblings was significantly correlated at all sites (r = 0.30-0.42, p less than 0.001). The same levels of resemblance were found between early postmenopausal mothers and premenopausal daughters. There was no significant difference in bone mass at any skeletal site between daughters of women with either peripheral or spinal fractures and daughters of women without fractures. We also examined familial resemblance with four biochemical markers of bone turnover (fasting urinary calcium and hydroxyproline, both corrected for creatinine, serum alkaline phosphatase, and plasma bone Gla protein). A generally significant resemblance were seen in premenopausal siblings (r = 0.25-0.39, hydroxyproline NS), but not between premenopausal daughters and postmenopausal mothers. We conclude that peak bone mass is hereditary in the distal forearm, lumbar spine, and proximal femur, but the mother-daughter resemblance explains only about 16% of the variability in daughters' bone mass. Furthermore, daughters of women with a moderate state of osteoporotic fractures are not substantially at an increased risk of having a low peak bone mass compared to the daughters of women without fractures.

Absorptiometry, Photon↗

Premenopausal and postmenopausal changes in bone mineral density of the proximal femur measured by dual-energy X-ray absorptiometry.

Total and regional bone mineral density (BMD) of the proximal femur was measured by DXA in 1238 healthy white women. In the 389 premenopausal women, aged 21-54 years, no bone loss was observed before the menopause, except in the femoral neck and Ward's triangle, in which BMD decreased by 0.3%/year (SEE 0.2-0.9%/year, p < 0.001) and 0.6%/year (SEE 0.4-0.8%/year, p < 0.001), respectively. In the postmenopausal women aged 48-75 years, there was a highly significant exponential decay in BMD with age and years since menopause (YSM) in all regions (-0.58 < r < -0.48, p < 0.001). However, YSM was a better predictor of BMD than age. The decrease in BMD in the first 5 years postmenopause reached values of 9-13%. The estimated bone loss after 20 years was 17-30%, greatest in Ward's triangle and smallest in the intertrochanteric region. BMD correlated highly significantly with BMI (0.26 < r < 0.48, p < 0.001). In conclusion, the present study indicates a stable premenopausal bone mass of the proximal femur and a postmenopausal bone loss, which is influenced mainly by YSM within the first 10-15 years after menopause. BMD correlated with body mass index (BMI) in the postmenopausal years, confirming that low BMI constitutes a potential risk factor for osteoporosis.

Absorptiometry, Photon↗

Increased bone turnover in late postmenopausal women is a major determinant of osteoporosis.

Changes of bone turnover with aging are responsible for bone loss and play a major role in osteoporosis. Although an increase of bone turnover has been documented at the time of menopause, the subsequent abnormalities of bone resorption and formation and their potential role in determining bone mass in the elderly have not been investigated. To address this issue, we have measured a battery of new sensitive and specific markers of bone turnover in a population-based study of 653 healthy women analyzed cross-sectionally, including 432 women postmenopausal from 1 to 40 years, and the data were correlated with bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA) at different skeletal sites. Bone formation was assessed by serum osteocalcin (OC), serum bone-specific alkaline phosphatase (B-ALP), serum C-propeptide of type I collagen (PICP), and bone resorption by the urinary excretion of two pyridinoline cross-linked peptides (NTX and CTX). Bone turnover increased in perimenopausal women with both irregular menses and elevated serum follicle stimulating hormone (FSH). Menopause induced a 37-52% and 79-97% increase in the bone formation and bone resorption marker levels, respectively (p < 0.0001 except for PICP). In postmenopausal women, bone formation markers did not decrease with age. When resorption markers were corrected by whole body bone mineral content (BMC), the fraction of bone resorbed per day was not correlated with age in postmenopausal women and remained elevated for up to 40 years after menopause. In premenopausal women, the bone turnover rate accounted for only 0-10% of the variation in whole body BMC, total hip, distal radius, and lumbar spine BMD. With increasing time after menopause, the importance of the bone turnover rate as a determinant of bone mass increased at all sites and accounted for up to 52% of the BMD variance in elderly women. Thus, in women 20 years or more postmenopause, bone turnover was higher in those in the lowest quartile than in those in the highest quartile of BMD. In elderly women, 20 years since menopause and over, but not in younger ones, serum PTH was negatively correlated with serum 25-hydroxyvitamin D (r = -0.22, p < 0.05) and explained only 5-8% of the bone turnover variance (p < 0.01-0.001). These data indicate that the overall rates of both bone formation and bone resorption remain high in elderly women. The rate of bone turnover appears to play an increasing role as a determinant of bone mass with increasing time since menopause with a high bone turnover rate being associated with a low bone mass. Thus assessing bone marker levels may be useful in the evaluation of osteoporosis risk. In elderly women, secondary hyperparathyroidism caused in part by reduced serum 25-hydroxyvitamin D appears to be a marginal determinant of an increased bone turnover rate.

Absorptiometry, Photon↗

Relationship between urinary profile of the endogenous steroids and postmenopausal women with stress urinary incontinence.

AIMS: The aims of this study were to investigate whether endogenous steroid hormones are (1) related to pathogenesis of stress urinary incontinence after menopause, (2) are related to severity of stress urinary incontinence, and (3) are related to prognostic parameters of stress urinary incontinence. METHODS: Twenty post-partum women with clinically diagnosed stress urinary incontinence and 20 age-matched postmenopausal women without stress urinary incontinence (control group) were evaluated. We compared urinary profile of the endogenous steroid hormones patients with stress urinary incontinence and controls, and between grade I and grade II of stress urinary incontinence. We also investigated the relationship between urinary profile of the endogenous steroid hormones and prognostic parameters of stress urinary incontinence (maximal urethral closure pressure, functional urethral length, Valsalva leak point pressure, cough leak point pressure, posterior urethrovesical angle, bladder neck descent, and stress urethral axis). The ages of the patients and those in the control group were 64.3 +/- 5.6 and 57.5 +/- 3.8 years old and the body mass indexes were 24.96 +/- 3.14 and 22.11 +/- 2.73 kg/m2 in patients and in normal subjects, respectively. Nine patients were grade I and 11 were grade II. Estrone and 17beta-estradiol only were detected in all subjects, regardless of control or patient group. It is noteworthy that there were no significant differences (P > 0.05) in the levels of estrone and 17beta-estradiol in the urine of postmenopausal normal subjects compared with in the urine of postmenopausal patients with urinary incontinence. E2/E1 ratio was not different between the two groups (P > 0.05). Among the objective steroids, DHEA, Delta4-dione, Delta5-diol, Te, DHT, 16alpha-DHT, 11-keto An, THDOC, and THB were not detected either in the urine of normal subjects and nor in the urine of the patients. After comparing androgen levels between normal subjects and patients, no significant differences (P>0.05) were detected, except for 5alpha-THB and 5alpha-THF. Neither 5alpha-THB or 5alpha-THF were detected in the patients' urine. Et/An (11beta-OH Et/11beta-OH An) concentration ratios were not significantly different between the two groups, either (P > 0.05). There were not significant differences of concentrations (micromol/g creatinine) of urinary steroids between grade I and grade II of stress urinary incontinence. Pregnanediol was significantly related to bladder neck descent in supine and sitting positions (R = 0.79, P = 0.01, and R = 0.73, P = 0.03, respectively), and pregnanetriol was significantly related to maximal urethral closure pressure and functional urethral length (R = 0.68, P = 0.04, and R = -0.79, P = 0.01, respectively). Androsterone was significantly related to bladder neck descent in supine and sitting positions (R = 0.68, P = 0.04, and R = 0.78, P = 0.01, respectively). 5-AT was significantly related to bladder neck descent in sitting position and stress urethral axis (R = 0.72, P = 0.03, and R = -0.71, P = 0.03). 11-keto Et was significantly related to bladder neck descent in supine and sitting positions and related to stress urethral axis (R = 0.82, P = 0.01, and R = 0.81, P = 0.01, R = -0.67, P = 0.04, respectively). THS was significantly related to bladder neck descent in supine and sitting positions and related to stress urethral axis (R = 0.76, P = 0.02, and R = 0.74, P = 0.02, R = -0.68, P = 0.04, respectively). THE was significantly related to bladder neck descent in sitting position (R = 0.67, P = 0.04).beta-Tetrahydrocortisol/alpha-tetrahydrocortisol (beta-THF/alpha-THF) and alpha-cortol were significantly related to maximal urethral closure pressure and functional urethral length (R = 0.74, P = 0.02, and R = -0.92, P = 0.01; R = 0.71, P = 0.36, and R = -0.87, P = 0.000, respectively). 17beta-estradiol (E2) was significantly related to bladder neck descent in supine position (R = -0.62, P = 0.04) and 17beta-estradiol/estrone (E2/E1) was significantly related to cough leak point pressure (R = 0.79, P = 0.01). In conclusion, the urinary concentrations of endogenous steroid metabolites in postmenopausal patients with stress urinary incontinence were not significantly different from normal patients and were not significantly different between grade I and grade II patients with stress urinary incontinence. Some endogenous steroid metabolites were positively or negatively significantly related to prognostic parameters of stress urinary incontinence.

Adrenal Cortex Hormones↗

Adenomyosis in postmenopausal breast cancer patients treated with tamoxifen: a new entity?

Between September 1, 1989 and October 31, 1994, 173 postmenopausal breast cancer women on tamoxifen treatment were followed up in the authors' institutions. During this period, 14 (8.1%) underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy for various indications. Eight (57.1%) were found to have adenomyosis, of whom one had a large fundal adenomyotic lump and the other seven patients had two to four small microscopic foci of adenomyosis. In this study, the rate of adenomyosis described among those postmenopausal breast cancer patients treated with tamoxifen is nearly three to four times higher than the rate reported in the literature for pre- and postmenopausal women. There is no previous reported increased incidence of adenomyosis in postmenopausal breast cancer patients treated with tamoxifen. Thus, it is suggested that the prolonged and unopposed estrogen-like stimulation by tamoxifen may play a causal role rather than be a casual factor in the development of this pathologic entity.

Adult↗

The contribution of bone loss to postmenopausal osteoporosis.

We have addressed the relative importance of peak bone mass and subsequent rate of loss in determining postmenopausal women's bone mass in old age, by examining longitudinal measurements of radial mid-shaft bone mass on various samples of healthy white postmenopausal women. Using both the variance estimate of age-specific rates of bone loss and the population variance in bone mass, we determined that rates of loss could contribute importantly to future bone mass. However, since we found a small negative correlation between initial bone mass and rate of loss, it was necessary to estimate the effect of bone loss as the complement of the contribution of initial bone mass. We found that the influence of bone loss (relative to initial bone mass) increases as the women age, such that by about age 70, the contribution of initial bone mass and rate of loss approached equality. However, estimated rates of bone loss were not very stable over time, so it was difficult to identify long-term 'fast-losers'. We conclude that the rate of postmenopausal bone loss is an important contributor to osteoporosis at old age, but it is difficult to identify long-term fast-losers, thereby reducing the clinical value of assessments of rates of change in bone mass early in the postmenopause.

Aged↗

Non-responders to hormone replacement therapy for the prevention of postmenopausal bone loss: do they exist?

Hormone replacement therapy (HRT) prevents postmenopausal bone loss, but the prevalence of non-responders in healthy early postmenopausal women is not known. In order to study this, we reviewed data from three published studies, each carried out in a randomized, placebo-controlled, longitudinal design over 2 year, that used seven hormone replacement therapies. Bone mineral content (BMC) was measured in the distal forearm by single photon absorptiometry. A mathematical model for elimination of measurement errors was applied to published BMC data. After this correction, we found that only 1.2% of early healthy postmenopausal women who are receiving HRT in conventional doses will lose more than 1% of forearm BMC per year. In conclusion, most, if not all, healthy early postmenopausal women who might need HRT against loss of bone will respond positively in forearm BMC to such therapy.

Bone Density↗

The effect of intranasal salmon calcitonin on postmenopausal bone turnover as assessed by biochemical markers: evidence of maximal effect after 8 weeks of continuous treatment.

Although treatment with intranasal salmon calcitonin (sCT) has been shown to effectively inhibit postmenopausal bone loss, there is still controversy over both timing and the duration of its application. In an open prospective study, we therefore assessed the effect of shortterm intranasal sCT on postmenopausal bone turnover, employing biochemical markers of bone metabolism. Ten early postmenopausal, previously untreated women (1-5 years after menopause) with biochemical evidence of increased bone resorption and a low bone mineral density at baseline were treated with intranasal sCT (100 IU B.I.D.) for a period of 3 months. Oral calcium (500 mg/day) was administered simultaneously, and during a further 3 month follow-up interval. Treatment with sCT resulted in a pronounced suppression of bone resorption markers with a maximum effect reached after 8 weeks of therapy: as compared to the respective baseline values, mean levels decreased by -26.2% +/- 3.4% (P < 0.001) for pyridinoline, -32.7% +/- 3.5% (P < 0.001) for deoxypyridinoline, -32.7% +/- 3.3% (P < 0.001) for hydroxyproline, and -24.1% +/- 8.2% (P < 0.001) for the amino-terminal telopeptide. In contrast, changes in bone formation markers of osteocalcin (-14.4% +/- 4.8%, P < 0.05) and C-terminal procollagen type I propetide (-7.9% +/- 3.9%, ns) were much less pronounced. Unexpectedly, after week 8 of the study all resorption markers showed a plateau and a trend to increase, although intranasal sCT was continued for a total of 12 weeks. This effect could not be attributed to the formation of anti-sCT antibodies. After cessation of treatment, both bone formation and resorption markers rapidly returned to baseline levels. Bone mineral density of both spine and hip showed no significant change during the observation period. Our results demonstrate that in postmenopausal women with a high bone turnover, intranasal treatment with 200 IU of sCT effectively reduces bone turnover and maintains bone mass, the maximum effect being reached after 8 weeks of treatment.

Administration, Intranasal↗

Comparison of vitamin D metabolism in early healthy and late osteoporotic postmenopausal women.

We studied 20 healthy premenopausal women aged 36.5 +/- 4.0 years (mean +/- 1 SD), 123 healthy postmenopausal women aged 50.0 +/- 2.4 years, and 103 postmenopausal women aged 65.1 +/- 5.6 years with symptomatic osteoporosis (forearm and spinal fracture). Serum levels of vitamin D metabolites [25(OH)D, 24,25(OH)2D3, and 1,25-(OH)2D] were compared with (1) bone mass in the forearm (single photon absorptiometry) and in the spine (dual photon absorptiometry); (2) biochemical indices of bone formation (serum alkaline phosphatase, plasma bone Gla protein), and bone resorption (fasting urinary hydroxyproline); and (3) other biochemical estimates of calcium metabolism (serum calcium, serum phosphate, 24-hour urinary calcium, intestinal absorption of calcium). The present study revealed no difference in any of the vitamin D metabolites between the premenopausal women, the healthy postmenopausal women and the osteoporotic women as a group. The concentrations of 1,25(OH)2D and 25(OH)D were significantly lower in patients with spinal fracture than in those with forearm fracture. In the early postmenopausal women serum 1,25(OH)D was related to forearm bone mass (r = -0.20; P less than 0.05), intestinal calcium absorption (r = 0.18; P less than 0.05), and 24-hour urinary calcium (r = 0.21; P less than 0.05); serum 25(OH)D was related to spinal bone mass (r = 0.23; P less than 0.01). In the osteoporotic women, serum vitamin D metabolites were not related to bone mass, but 1,25(OH)2D was related to bone Gla protein (r = 0.33; P less than 0.001), serum phosphate (r = -0.27; P less than 0.01), and 24-hour urinary calcium (r = 0.43; P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

24,25-Dihydroxyvitamin D 3↗

The relationship between bone mineral density and ultrasound in postmenopausal and osteoporotic women.

The aim of this cross-sectional study was to use a novel method of data analysis to demonstrate that patients with osteoporosis have significantly lower ultrasound results in the heel after correcting for the effect of bone mineral density (BMD) measured in the spine or hip. Three groups of patients were studied: healthy early postmenopausal women, within 3 years of the menopause (n = 104, 50%), healthy late postmenopausal women, more than 10 years from the menopause (n = 75, 36%), and a group of women with osteoporosis as defined by WHO criteria (n = 30, 14%). Broadband ultrasound attenuation (BUA), speed of sound (SOS) and Stiffness wer measured using a Lunar Achilles heel machine, and BMD of the lumbar spine and left hip was measured using dual-energy X-ray absorptiometry (DXA). SOS, BUA and Stiffness were regressed against lumbar spine BMD and femoral BMD for all three groups combined. The correlation coefficients were in the range 0.52-0.58, in agreement with previously published work. Using a calculated ratio R, analysis of variance demonstrated that the ratio was significantly higher in the osteoporotic group compared with the other two groups. This implied that heel ultrasound values are proportionately lower in the osteoporotic group compared with the other two groups for an equivalent value of lumbar spine and femoral neck BMD. We conclude that postmenopausal bone loss is not associated with different ultrasound values once lumbar spine or femoral neck BMD is taken into account. Ultrasound does not give additional information about patterns of bone loss is postmenopausal patients but is important in those patients with osteoporosis and fractures.

Absorptiometry, Photon↗

Administration of a supplement containing both calcium and vitamin D is more effective than calcium alone to reduce secondary hyperparathyroidism in postmenopausal women with low 25(OH)vitamin D circulating levels.

BACKGROUND AND AIMS: Supplementation of postmenopausal women with calcium alone or calcium-vitamin D association was suggested to have positive effects on bone turnover and bone density, as well as to lower fracture incidence. The beneficial effect appears to be mediated by a reduction in parathyroid hormone secretion. Our aim was to compare the respective efficacy of calcium and calcium-vitamin D supplements in reducing serum parathyroid hormone levels in postmenopausal women with prevalent low 25(OH)vitamin D levels. METHODS: One hundred consecutive ambulatory postmenopausal women with serum 25(OH)vitamin D levels below 18 ng/mL were included in a randomized, prospective, open label study. For a duration of 90 days, the women were randomly assigned to a daily supplementation of either one tablet of calcium gluconolactate and carbonate (500 mg calcium), or one powder-pack of an association of calcium carbonate (500 mg calcium), citric acid (2.175 gr) and cholecalciferol (200 IU). Changes observed during the 90 days of the study in circulating PTH levels were the primary endpoint, while changes in serum 25(OH)D levels were assessed as secondary endpoint. RESULTS: A significant difference was observed between the calcium-vitamin D (CaD) and the calcium (Ca) only groups for changes occurring during the 90 days of the study in PTH (-14.5+/-40% and +2.5+/-46%) (p=0.009) and 25(OH)D (+67+/-77% and +18+/-55%) (p<0.001) circulating levels. PTH changes between baseline and day 90 were significant in the CaD group, but not in the Ca group. The odds ratio for a patient in group Ca to experience an absolute (<12 ng/mL) deficiency in circulating 25(OH)vitamin D levels, compared to a group CaD patient was statistically increased (OR: 3.22, 95% CI: 1.33-7.80). CONCLUSIONS: Our results support the recommendation of supplementing postmenopausal women with low circulating levels of 25(OH)vitamin D with a combination of calcium and vitamin D, rather than with calcium alone.

Aged↗

The role of parathyroid hormone in the pathogenesis, prevention and treatment of postmenopausal osteoporosis.

Parathyroid hormone (PTH) is the principal regulator of bone remodeling in the adult skeleton. The acute in vivo effect of PTH is to increase bone resorption, although sustained increases in its circulating levels accelerate both formation and resorption. These divergent effects have focused attention on PTH as a factor contributing to bone loss in some postmenopausal women, as well as interest in its role as therapy for the disease. Sustained increases in PTH are classically seen in primary hyperparathyroidism. While still controversial, increasing evidence suggests that primary hyperparathyroidism is associated with increased rates of bone loss, particularly from cortical sites in the skeleton. It is clear that the remodeling space is increased in primary hyperparathyroidism, and that surgical correction of the disease leads to substantial increases in bone mass in patients with osteoporosis. Recently, secondary hyperparathyroidism has emerged as an important contributor to increased rates of bone turnover and bone loss in postmenopausal women. The etiology of secondary hyperparathyroidism in postmenopausal women is complex, and is probably related to alterations in vitamin D metabolism and tissue responsiveness to 1,25(OH)2vitamin D. PTH has emerged at the forefront of anabolic therapies for the treatment of postmenopausal osteoporosis. When given as a single agent, intermittent daily subcutaneous administration of PTH induces consistent gains in trabecular bone mass with more varying effects on the cortical envelope. However, recent therapeutic trials employing a second agent, most notably estrogen, give hope that this approach may provide the first truly efficacious anabolic therapy for this devastating disease.

Aged↗

Prevention of early postmenopausal bone loss with cyclical etidronate.

Cyclical etidronate has been shown to be effective in the treatment of established postmenopausal osteoporosis but less is known about its effects on early menopausal bone loss. The aim of the study was to establish the effects of cyclic etidronate therapy on spinal and proximal femoral bone mineral loss in early postmenopausal women. One hundred and seven women who were within 6 months to 3 years of the menopause were recruited into a 2-year, randomised, placebo-controlled, double-blind trial. Spinal bone mineral density was within 2 SD of the age-matched mean reference value at baseline. Bone mineral density in the lumbar spine and proximal femur was assessed by dual energy X-ray absorptiometry at baseline and thereafter at 6 monthly intervals for 2 years. Urinary collagen cross-links (deoxypyridinoline and pyridinoline) were measured at the same time points. Seventy-seven women completed the study. At the end of the treatment period, the mean bone mineral density change from baseline in the treated group was +0.14% and -0.06% in the lumbar spine and femoral neck, respectively, compared to -1.49 and -2.22 in the control group. Overall, there was a significant difference between the two groups at both these sites (p=0.01 and 0.001, respectively). No significant differences between the groups were demonstrated at the greater trochanter or Ward's triangle. The conclusion was that cyclical etidronate therapy prevents bone loss in the spine and femoral neck in early postmenopausal women. It provides a safe and effective therapeutic option for the prevention of postmenopausal osteoporosis in women who are unwilling or unable to tolerate hormone replacement therapy.

Absorptiometry, Photon↗

[Dissection or irradiation of the axilla in postmenopausal patients with breast cancer? Long-term results and long-term effects in 655 patients].

BACKGROUND: Until 1993 postmenopausal women with breast cancer did not receive adjuvant chemotherapy in our institution even if axillary nodes were involved. So in these patients axillary dissection had no diagnostic value for further treatment. Therefore we started a prospective study in which dissection of axillary nodes was replaced by irradiation in postmenopausal cN0 patients. PATIENTS AND METHODS: From 1986 to 1993 we irradiated 655 patients with breast cancer after breast conserving surgery (BET). In all 144 cN1- and all 209 premenopausal cN0-patients axillary dissection was recommended. Of 302 postmenopausal cN0 patients 129 had breast surgery in our institution. In a total of 129 patients axillary dissection was replaced by irradiation (AxRT-group). They were compared with all 173 patients referred from other hospitals for irradiation after both breast conserving surgery and axillary dissection (AxOP-group). Dissected patients with gross tumor involvement of the axilla or less than eight nodes removed had additional axillary irradiation. Patients age, tumor size, vessel-, muscle- or skin invasion and grading were similar in both groups (Table 1). However, in the AxRT-group there were more patients with negative hormone receptors, multifocal and medial sited tumors. Late complications after dissection and/or irradiation of the axilla were evaluated in 502 patients free of locoregional relapse and with a minimal follow up of 3 years (median 9.5 years). RESULTS: After 5, 10 and 15 years tumor free survival rates were 90%, 82% and 79% in the AxOP-group vs 91%, 82% and 80% in the AxRT-group, respectively (p = 0.95) (Figure 1). Overall survival (p = 0.98) (Figure 2), local (p = 0.47) and axillary control (p = 0.12) were equal in both groups (Figures 3 and 4). However, serious problems like lymphedema of the arm, pain, mobility impairment occurred in 26% patients following axillary dissection but only in 1% after axillary irradiation. No difference in late sequelae after axillary dissection with or without irradiation could be detected (26 vs 27%) (Table 2). CONCLUSION: In postmenopausal cN0-patients axillary dissection should be replaced by axillary irradiation, since it offers the same chance for cure with much lower morbidity.

Aged↗

[Hormone replacement and selective estrogen receptor modulators (SERMS) in the prevention and treatment of postmenopausal osteoporosis].

For many years, hormone replacement therapy (HRT) has been regarded as one of the most reliable means of prophylaxis and treatment for postmenopausal osteoporosis. As HRT ameliorates menopausal symptoms, it is widely prescribed among early postmenopausal women. A variety of different modes of replacement that suit each individual requirement are available in terms of schedule (cyclic or combined application of gestagens) and route of application (oral or transdermal). HRT effectively prevents spinal bone loss and delays bone loss at the hip up to a very old age. With continued use after menopause, HRT might theoretically halve the incidence of vertebral and hip fractures. However, long-term use or use of HRT in old age is rarely practiced, and the actual benefit of a transient use for future fracture prevention remains unclear. Raloxifene is the first member of the novel class of selective estrogen receptor modulators (SERMs) that has been approved for the prophylaxis and treatment of postmenopausal osteoporosis. It combines the positive effects of estrogen on the skeleton with estrogen-antagonistic effects on sex tissues. Thus, raloxifene maintains bone mass and decreases the incidence of vertebral fractures in osteoporotic women, but avoids many of the side effects that are responsible for the poor long-term compliance to HRT such as resumption or continuation of regular menses, breast tenderness, or breast cancer. It even markedly reduces the risk of breast cancer. Both estrogen and raloxifene are characterized by a large number of extraskeletal effects that have to be taken into account when counseling postmenopausal women on the use of these agents for the prevention or treatment of osteoporosis.

Administration, Oral↗

Dental panoramic radiograph as a tool to detect postmenopausal women with low bone mineral density: untrained general dental practitioners' diagnostic performance.

The detection of postmenopausal women with low bone mineral density (BMD) is an important strategy to reduce the incidence of osteoporotic fracture. Recent studies suggested that incidental findings on dental panoramic radiographs may be used as a tool to detect women with low BMD. However, little is known whether this finding is sufficiently assessed by untrained general dental practitioners (GDPs). The purpose of this study was to investigate: (1) the observer agreement and (2) the diagnostic efficacy in detecting women with low BMD, when untrained GDPs assess the appearance (normal or eroded) of the mandibular inferior cortex on dental panoramic radiographs of postmenopausal women. Twenty-seven GDPs were asked to classify the appearance of the mandibular inferior cortex on dental panoramic radiographs of 100 postmenopausal women who had completed BMD assessments of the lumbar spine and of the femoral neck. Intra-and inter-observer agreements were analyzed with kappa statistics. The diagnostic efficacy (sensitivity, specificity and predictive values) was analyzed by comparing two groups classified by the mandibular inferior cortex (women with normal and women with eroded mandibular inferior cortex) with those classified by BMD (women with normal BMD and women with osteopenia or osteoporosis). The mean sensitivity and specificity were 77% and 40%, respectively, when BMD of the lumbar spine was used as standard and 75% and 39%, respectively, when BMD of the femoral neck comprised the standard. Nineteen untrained GDPs (70%) presented a moderate to almost perfect intra-observer agreement. We conclude that dental panoramic radiograph may be used in clinical dental practice to identify postmenopausal women who have undetected low BMD and should undergo further testing with bone densitometry.

Aged↗

Soy protein consumption and bone mass in early postmenopausal Chinese women.

Recent interest has been shown in the potential beneficial effects of phytoestrogens on bone health. As the early years of menopause are a period of rapid bone loss, and the risk for osteoporosis increases substantially, the habitual intake of soy protein and isoflavones may play a role in the retardation of bone loss. This paper reports the results of the baseline cross-sectional analysis of the association between dietary soy protein intake and bone mineral density/content in a population-based study of Chinese women. The sample comprised 454 healthy Chinese women (mean age 55.1 +/- 3.57) within the first 12 years of postmenopause. We estimated the dietary intake of soy protein and isoflavones, and other key nutrients, including dietary protein and calcium, using the quantitative food frequency method. Bone mineral density (BMD) and content (BMC) at the spine, hip and total body were measured with a dual energy X-ray densitometer (Hologic 4500A). Soy protein consumption was categorized as quartiles of intake, and related to BMD values at the spine and hip, and BMC of total body. Stratified analyses were carried out among women within or at least 4 years postmenopausal. We observed few differences in BMD/BMC values among the intake quartiles in women within the first 4 years of menopause. However, among the later postmenopausal women, we noted a dose-response relationship with increasing higher BMD values at the trochanter, intertrochanter as well as the total hip and total body with increasing soy protein intake quartiles (P<0.05 from tests for trend). The BMD values differed by about 4-8% between the first and fourth soy protein intake quartiles. Though women from the fourth intake quartile had a 2.9% higher BMD value compared with those from the first intake quartile, the difference was not statistically significant. Stepwise multiple linear regression analyses showed the association between soy intake quartiles and hip BMD as well as total body BMC values remained after adjusting for body weight, which was retained in the final model. Analyses based on soy isoflavones content yielded similar results. This study demonstrated that, among women after the initial few years postmenopausal, soy protein/isoflavones intake had a modest but significant association with hip BMD as well as total body BMC. The effects of soy protein and soy isoflavones on bone health should be further explored in populations with habitual dietary soy intake.

Analysis of Variance↗