Body mass index (BMI) and parameters of bone formation and resorption in postmenopausal women

OBJECTIVES: Aim of this study was to evaluate increased body mass index (BMI) as an anthropometric factor, predisposing to lower rates of bone turnover or changes in bone balance after menopause. MATERIAL AND METHODS: For this purpose, we calculated BMI, and measured spinal (BMD(SP)) and femoral bone mineral density (BMD(FN)) and biochemical markers of bone formation (serum osteocalcin (S-OC), serum procollagen type I C propeptide (S-PICP), serum bone-specific alkaline phosphatase (S-B-ALP)) and resorption (urine N- and C-terminal cross-linking telopeptide of type I collagen (U-NTX-I and U-CTX-I), pyridinoline (U-PYD) and deoxypyridinoline (U-DPD)) in 130 healthy postmenopausal women, aged 46-85 years. Bone balance indices were calculated by subtracting z-scores of resorption markers from z-scores of formation markers, to evaluate bone balance. RESULTS: S-PICP ( r = -0.297, P = 0.002), S-OC ( r = -0.173, P = 0.05) and bone balance indices (zPICP-zDPD) and (zPICP-zPYD) were negatively correlated with BMI (r = -0.25, P = 0.01 and r = -0.25, P = 0.01 and r = -0.21, P = 0.037) and with BMD(SP) (r = -0.196, P = 0.032 and r = -0.275 and P = 0.022). Women were grouped according to their BMI, in normals (BMI < 25 kg/m2), overweight (BMI = 25-30 kg/m2, and obese (BMI > 30 kg/m2). Overweight and obese women had approximately 30% lower levels of S-PICP compared to normals (68.11 +/- 24.85 and 66.41 ng/ml versus 97.47 +/- 23.36 ng/ml, respectively; P = 0.0001). zPICP-zDPD, zPICP-zCTX-I and zPICP-zPYD were significantly declined in obese women compared to normals (P = 0.0072, 0.02 and 0.0028). CONCLUSIONS: We conclude that in postmenopausal women, BMI is inversely associated with levels of collagen I formation marker, serum PICP. In obesity formation of collagen I was reduced, in favor of degradation, but since this finding is not followed by simultaneous decrease in bone mineral density, it seems that increased body weight may have different effects on mature estrogen-deficient bone and extraskeletal tissues containing collagen I.     

Association of the calcitonin gene (CA) polymorphism with bone mass and bone responsiveness to hormone therapy in postmenopausal Korean women

OBJECTIVE: To evaluate the relationship between cytosine-adenine (CA) polymorphism of the calcitonin gene, serum calcitonin levels, bone mineral density (BMD) and bone responsiveness to hormone therapy (HT). DESIGN: Calcitonin (CA) polymorphism, serum calcitonin, and BMD at the lumbar spine and proximal femur were determined in 430 postmenopausal Korean women. In all, 181 women were treated with sequential HT for 2 years. RESULTS: Four major calcitonin alleles were present with a frequency greater than 5%: 122 base pair (bp) 61.3%, 108 bp 25.1%, 110 bp 7.0%, and 124 bp 6.2%. There were no differences in the BMD at the lumbar spine and proximal femur in postmenopausal women with zero, one, or two copies of major alleles. Serum calcitonin levels in women with two copies of the 108 bp allele were significantly higher than those in women with zero or one copy of the 108 bp allele. The annual rate of positive change of BMD at the femoral neck after HT was significantly higher in women homozygous for the 108 bp allele than in women with zero or one copy of the 108 bp allele, but the number of copies of the major calcitonin alleles was not significantly associated with HT-responsiveness. CONCLUSION: The calcitonin (CA) polymorphism is one of the genetic factors that may affect BMD changes at the femoral neck after HT in Korean women.     

Clinical usefulness of endometrial screening by ultrasound in asymptomatic postmenopausal women

Objective: The aim of the present study was to evaluate the clinical usefulness of routine use of endometrial ultrasound in asymptomatic, bleeding-free postmenopausal women. Methods: We retrospectively reviewed the data of 850 postmenopausal women subjected to hysteroscopy, focusing our attention on those cases (148) with an ultrasound indication of endometrial thickening. Results: In 850 postmenopausal women, we identified 27 (3.2%) endometrial adenocarcinomas. In these subjects, the indication for office hysteroscopy was abnormal uterine bleeding in 24 (24/27; 88.9%) cases; pathological pap smear with abnormal endometrial cells in 2 (2/27; 7.4%) cases and thickened endometrium upon transvaginal ultrasound (tvUS) only in one (1/27; 3.7%) patient. On the other hand, 148 hysteroscopies were performed on the basis of the tvUS indication in otherwise asymptomatic (bleeding free) postmenopausal women; only 1(0.7%) of these presented an adenocarcinoma. Conclusion: Our findings show that the use of tvUS as a screening tool for endometrial pathology in asymptomatic postmenopausal women generates 93.2% false positive results, so that most of these women undergo this second level invasive procedure uselessly. Our data suggest that, in asymptomatic postmenopausal women, endometrial ultrasound evaluation is not worthwhile as a screening tool, such as it is considered in common clinical practice. The present results call for a larger prospective trial to further elucidate this controversial issue.     

Beta-blockers reduce bone resorption marker in early postmenopausal women

BACKGROUND: There is evidence to suggest that beta-blockers used in the management of cardiovascular disease may also modulate bone metabolism and reduce bone fragility. AIM: The study aimed to determine the association between beta-blocker use, serum markers of bone turnover and bone loss in early postmenopausal women. SUBJECTS AND METHODS: In this observational study, we evaluated beta-blocker exposure in association with serum levels of C-telopeptide and bone-specific alkaline phosphatase, and rates of bone loss. Beta-blocker use, concomitant therapy and lifestyle were documented for 197 women (50-59 years), 175 of whom had changes in whole body bone mineral density monitored over a 2-year period. RESULTS: Twenty-four beta-blocker users were identified at baseline. After controlling for concomitant use of hormone therapy, C-telopeptide levels were 6.7% lower among beta-blocker users (p=0.02). No association was detected between bone-specific alkaline phosphatase and beta-blocker use. Analysis of 15 beta-blocker users and 152 non-users identified 2 years post-baseline showed that levels of C-telopeptide but not bone-specific alkaline phosphatase were predictors of adjusted rates of bone loss (p=0.008 and p>0.05, respectively). Adjusted rates of bone loss were-0.001+/-0.026 g cm(-2) over 2 years for the users and-0.004+/-0.025 g cm(-2) over 2 years for non-users, but this difference was not significant. CONCLUSION: Beta-blockers might suppress bone resorption with relative preservation of bone formation. A study with greater power is required to determine whether ss-blocker use is associated with lower rates of bone loss.     

PIXI bone density screening for osteoporosis in postmenopausal women

OBJECTIVES: The aim of this study was to evaluate a pragmatic screening programme for osteoporosis based on the identification of known risk factors. A secondary aim was to assess the validity of peripheral instantaneous X-ray imager (PIXI) scanning against dual energy X-ray absorptiometry (DEXA) in women identified as having osteopenia. METHODS: A cross-sectional two stage screening programme. The study was carried out in 14 practices in Surrey. Women aged 60-80 years of age were screened with a questionnaire. Those identified with one or more risk factors were offered a PIXI scan of the ankle in their own surgery. Those with an intermediate score on PIXI scan were offered a DEXA scan of hip, spine and forearm. RESULTS: Four thousand six hundred and forty-six women completed questionnaires, 2688 had a PIXI scan and 553 were found to be at high risk of osteoporosis. Multivariate analysis identified the three most important risk factors associated with increased risk of osteoporotic fracture as age, a previous fracture and the presence of a stooped posture. Hormone replacement therapy (HRT) was shown to be protective. Twenty three percent of women with an intermediate score on PIXI scan were found to have osteoporosis on DEXA scan of hip and spine. CONCLUSIONS: PIXI scanning proved acceptable, practicable but only had moderate comparability with DEXA. The findings suggest that patients over the age of 60 years with a history of a fracture or evidence of spinal collapse are likely to have osteoporosis and should be offered screening. HRT past the menopause would seem to confer benefit and the recent reduction in its use may lead to increasing numbers of women suffering osteoporotic fractures.     

Tibolone (Livial) enhances warfarin-induced anticoagulation in postmenopausal women

OBJECTIVE: To investigate the potential drug interaction between tibolone and warfarin in healthy postmenopausal women. METHODS AND RESULTS: The study was designed as a double-blind, randomized, placebo-controlled, two-way crossover study in postmenopausal women. After stabilization of the International Normalized Ratio (INR; a standardized prothrombin time, PT) between 1.4 and 2.0 with warfarin, subjects were randomized to receive either tibolone (2.5mg/day) or placebo for 21 days. After a 7-day wash-out period (during which warfarin treatment was continued) the treatments were crossed over. Primary efficacy parameters were INR and coagulation Factors II, VII, VIIa and X (means of measurements at Days 18 and 20 and Days 46 and 48). Treatment with tibolone induced a statistically significant increase in INR (estimate of mean difference=0.40; P=0.002), and a statistically significant decrease in coagulation factors. Treatments were generally well tolerated and no clinically significant adverse events were observed. CONCLUSIONS: Tibolone enhances warfarin-induced anticoagulation in postmenopausal women, as reflected by increases in INR and decreases in coagulation Factors II, VII, VIIa and X, compared to placebo. It is advisable to monitor for changes in coagulation status during (and after discontinuation of) simultaneous use of tibolone and warfarin.     

Anthropometry fails in classifying bone mineral status in postmenopausal women

This study tested two hypotheses: (1) that simple anthropometric parameters can be used to identify patients at risk of decreased bone mineral content and (2) that an inverse relationship exists between waist:hip ratio (WHR) and bone mineral density (BMD). Bone mineral content (BMC) and BMD were evaluated by dual-energy X-ray absorptiometry in 1873 free-living women. Of these, 1819 (97%) were post-menopausal. One thousand and thirteen women (54%) had normal BMD, 705 (38%) osteopenia and 155 (8%) osteoporosis. Body weight (Wt), body mass index and arm muscle and fat areas were significantly lower in osteoporotics than osteopenics (p < 0.0001) and in these latter than controls (p < 0.0001). However, values of WHR were similar in all groups (p = ns). Body weight was the anthropometric parameter better correlated with BMC (rho = 0.650, p < 0.0001) and only Wt and age were identified as significant predictors of bone mineral status (normal-BMD/osteopenic/osteoporotic) at polytomous logistic regression (p = 0.0001 for each). However, Wt could not be employed as an indicator of bone mineral status at the individual level because of high variations in BMC for the same level of Wt. Under- (< 5th percentile) and normal-Wt (5th-95th percentile) women had the same frequency of osteopenia (39%) while it was lower in over-Wt (> 95th) women (13%). The frequency of osteoporosis was higher in under- than normal-Wt women (37 vs 7%) and none of the over-Wt women had osteoporosis. This study shows that: (1) simple anthropometric measurements cannot be used to select subjects at risk of decreased BMC and, (2) BMD does not vary with WHR.     

Association of the vitamin D receptor start codon polymorphism (FokI) with bone mineral density in postmenopausal Korean women

We undertook this study in order to examine the association between bone mineral density (BMD) and a polymorphism at the first of two potential translation initiation codons in the vitamin D receptor (VDR) gene. This polymorphism was detected by restriction fragment length polymorphism analysis, using polymerase chain reaction (PCR) and the restriction endonuclease FokI. The f allele indicates the presence of the FokI site, and the F allele its absence. The FokI genotype was determined in 174 postmenopausal Korean women, aged 43–71 years. The distribution of FokI genotypes in Koreans was found not to differ significantly from those found in Caucasians and Japanese, although it does differ significantly from that found in the black American population. We observed a significant association between the FokI polymorphism and lumbar BMD; P = 0.048, analysis of covariance [ANCOVA], but no association with femoral neck BMD (P = 0.505, ANCOVA). Those with the ff genotype had a 13.3% lower BMD in the lumbar spine than the FF subjects. In addition, a significantly higher prevalence of the ff genotype was observed in osteoporotic compared with osteopenic or normal women (P = 0.036, χ² test). These data suggest that the ff genotype of the VDR gene correlates with decreased BMD in the lumbar spine in postmenopausal Korean women. Received: May 8, 2000 / Accepted: June 7, 2000     

Osteoporosis and bone metabolism in postmenopausal women with osteoarthritis of the hand

OBJECTIVE: Osteoarthritis and osteoporosis are two major health problems affecting postmenopausal women. Epidemiological observations seem to demonstrate a possible inverse relationship between osteoarthritis and osteoporosis. Erosive osteoarthritis (EOA) of the hand is a destructive form of primary osteoarthritis. This study evaluated bone mineral density and bone metabolism changes in erosive and nonerosive hand osteoarthritis women. DESIGN: Fifty-five women (mean age, 59 years; body mass index, 23 +/- 1.4 kg/m) who had been postmenopausal for an average of 9 years and who presented with hand osteoarthritis according to American College of Rheumatology criteria were enrolled in the study; 15 women showed clinical and radiological evidence of hand EOA. Twenty women matched for age, age at menopause, and body mass index formed the control group. Bone mineral density (g/cm) was measured at the hip and lumbar spine using dual-energy x-ray absorptiometry. Serum and urinary calcium and phosphate, serum 25-hydroxyvitamin D, parathyroid hormone, osteocalcin, and urinary breakdown products of bone matrix (CrossLaps) were analyzed. RESULTS: Women with hand EOA had a statistically significant lower T- and Z-score L2-L4 value than non-hand EOA women and controls (P < 0.01). Moreover, postmenopausal women with hand EOA had higher significant percentage of osteoporosis at lumbar spine when compared with non-hand EOA postmenopausal women and controls. Any statistically significant difference in osteocalcin and CrossLaps serum levels was noted among women with hand EOA, hand osteoarthritis, and controls. CONCLUSIONS: Our data suggest that postmenopausal women with clinical and radiological EOA are at risk for development of osteoporosis.     

Simple adnexal cysts in postmenopausal women: conservative management

Objective: To evaluate the expectant management of asymptomatic small, anechoic, simple ovarian cysts diagnosed by echography in postmenopausal women. To gain insight in the natural history of these cysts. Method: Thirty six postmenopausal women with asymptomatic ovarian cysts (from 1.5 to 5.0 cm) diagnosed by ultrasonography and with a CA 125 serum level within the normal range and a non-suspicious color Doppler were followed conservatively. Visits were scheduled at 8–10 weeks of the diagnosis, at 6-month intervals twice and annually thereafter. Results: The follow-up period extended from 4 to 70 months with an average of 31.5 months. There were no cases of cyst enlargement. The cysts remained unchanged in 29 cases (80.5%), decreased in size in four cases (11.1%) and disappeared in three cases (8.3%). Conclusion: We think that the possibility of malignant transformation of one of these cysts is remote and the benefits of conservative management greatly outweighs its risks.     

Significance of incidentally thick endometrial echo on transvaginal ultrasound in postmenopausal women

Postmenopausal bleeding is "cancer until proven otherwise." A thin distinct endometrial echo on transvaginal ultrasound has a risk of malignancy of 1 in 917 and does not require an endometrial biopsy. If the endometrial echo is poorly visualized, then in such women, saline infusion sonohysterography is an appropriate next step. The prevalence of asymptomatic endometrial thickening (mostly due to inactive polyps) is high, approximately 10% to 17% of postmenopausal women. The risk of malignancy in such polyps is low (approximately 0.1%), and in structures that mimic polyps, it is also low (0.3%). The incidence of serious complications from an operative intervention in such postmenopausal women is not insignificant (1.3%-3.6%). Thus, automatic intervention in such women, without any high-risk status, is not warranted.     

T score of trabecular and cortical bone in normal postmenopausal women

Objective: The T score of the cortical and trabecular bone compartments (T score of BMD_Trab and T score of BMD_Corti) was calculated in healthy postmenopausal women to determine which bone compartment loses more bone mass. Material and methods: A total 134 healthy postmenopausal women (mean age 55.1±6.4 years) and 67 healthy premenopausal women (mean age 36.0±8.6 years) were studied. Determinations were made using peripheral quantitative computed tomography (pQCT) of the nondominant forearm. The postmenopausal women were divided into groups by years since menopause (YSM): two early postmenopausal groups: <5 YSM and 6–10 YSM; and two late postmenopausal groups: 11–20 YSM and >20 YSM. Results: There was a significant correlation between the T score of BMD_Trab and the T score of BMD_Corti (P<0.0001). Both correlated negatively and significantly with age (P<0.001 and P<0.0001, respectively) and neither correlated with weight. The Wilcoxon test showed no significant differences between the trabecular and cortical T scores in the overall group of women. By YSM, only the >20 YSM group showed significant differences (P<0.005). The ANOVA post hoc Bonferroni/Dunn test showed a gigficant difference in the T score of BMD_Trab by YSM only in the <5 YSM versus 11–20 YSM groups (P=0.007) and in the <5 YSM versus >20 YSM groups (P<0.0001). The T score of BMD_Corti by YSM differed significantly only between the <5 YSM versus 11–20 YSM groups (P<0.0001) and between the 11–20 YSM and >20 YSM groups (P<0.005). Conclusion: In contrast with what has been postulated in recent studies, our results showed that postmenopausal bone loss was similar in the cortical and trabecular bone compartments in the first 20 years after menopause. Trabecular bone loss was greater than cortical bone loss in late menopause (>20 years).     

两种膦酸盐药物预防绝经后妇女骨量丢失的比较

羟乙膦酸二钠（羟膦Ｅｔｉｄｒｏｎａｔｅ）和氯屈膦酸二钠（氯膦 Ｃｌｏｄｒｏｎａｔｅ）是近年来我 国合成生产的 ３类新药,本文对其抗骨量丢失作用进行比较,探讨其防治骨量丢失的效果及其患者的依从性,为临床医师选择防治骨质疏松药物提供参考。 受试者均为绝经１年以上的妇女,腰２－４骨密度低于女性骨峰值 ＩＳＤ以上,无糖尿病等内分泌代谢疾患、实验前３个月无雌激素、降钙素、活性维生素Ｄ服用史、１年内未接受过氟化物及膦酸盐类药物、肝肾功能正常。研究分为实验一：组１、组２每日各服羟膦２００ｍｇ或安慰剂共两周,继之各…     

Association of the osteoprotegerin gene polymorphisms with bone mineral density in postmenopausal women

OBJECTIVES: Osteoprotegerin (OPG) is a recently discovered member of the tumour necrosis factor receptor superfamily. It plays a crucial role in the control of bone resorption and its gene could therefore be a good candidate gene for osteoporosis. The aim of our work was to find polymorphisms in the OPG gene and to investigate their possible contribution to the genetic susceptibility to osteoporosis by testing for their association with bone mineral density (BMD). METHODS: The whole OPG gene coding region was screened for the presence of polymorphisms in a group of 60 osteoporotic women by single-strand conformation polymorphism analysis (SSCP) approach. Association of the discovered polymorphisms with bone mineral density was investigated in 136 Slovenian postmenopausal women. RESULTS: We detected eight OPG gene polymorphisms that were confirmed by direct DNA sequencing, deletion 4752_4753delCT and nucleotide substitutions 1181G>C, 1217C>T, 1284G>A, 4501C>T, 6893A>G, 6950A>C and 8738T>A. Nucleotide substitutions 1284G>A and 8738T>A have not been previously described. Polymorphisms 4752_4753delCT, 6893A>G and 6950A>C were in complete linkage and the same was true for 1217C>T and 4501C>T. The association with BMD was found only for polymorphism 1181G>C. Subjects with genotype 1181GG had significantly lower lumbar spine BMD than subjects displaying 1181GC. CONCLUSIONS: By our approach we detected eight polymorphisms in the OPG gene. According to our analysis polymorphism 1181G>C is associated with BMD and could therefore be considered as an element of genetic susceptibility to osteoporosis.     

Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis

BACKGROUND: Once-daily injections of parathyroid hormone or its amino-terminal fragments increase bone formation and bone mass without causing hypercalcemia, but their effects on fractures are unknown. METHODS: We randomly assigned 1637 postmenopausal women with prior vertebral fractures to receive 20 or 40 microg of parathyroid hormone (1-34) or placebo, administered subcutaneously by the women daily. We obtained vertebral radiographs at base line and at the end of the study (median duration of observation, 21 months) and performed serial measurements of bone mass by dual-energy x-ray absorptiometry. RESULTS: New vertebral fractures occurred in 14 percent of the women in the placebo group and in 5 percent and 4 percent, respectively, of the women in the 20-microg and 40-microg parathyroid hormone groups; the respective relative risks of fracture in the 20-microg and 40-microg groups, as compared with the placebo group, were 0.35 and 0.31 (95 percent confidence intervals, 0.22 to 0.55 and 0.19 to 0.50). New nonvertebral fragility fractures occurred in 6 percent of the women in the placebo group and in 3 percent of those in each parathyroid hormone group (relative risk, 0.47 and 0.46, respectively [95 percent confidence intervals, 0.25 to 0.88 and 0.25 to 0.861). As compared with placebo, the 20-microg and 40-microg doses of parathyroid hormone increased bone mineral density by 9 and 13 more percentage points in the lumbar spine and by 3 and 6 more percentage points in the femoral neck; the 40-microg dose decreased bone mineral density at the shaft of the radius by 2 more percentage points. Both doses increased total-body bone mineral by 2 to 4 more percentage points than did placebo. Parathyroid hormone had only minor side effects (occasional nausea and headache). CONCLUSIONS: Treatment of postmenopausal osteoporosis with parathyroid hormone (1-34) decreases the risk of vertebral and nonvertebral fractures; increases vertebral, femoral, and total-body bone mineral density; and is well tolerated. The 40-microg dose increased bone mineral density more than the 20-microg dose but had similar effects on the risk of fracture and was more likely to have side effects.     

Administration of dehydroepiandrosterone (DHEA) enhances visual-spatial performance in postmenopausal women

The current article examines the effect of administering dehydroepiandrosterone (DHEA) on visual-spatial performance in postmenopausal women (N = 24, ages 55-80). The concurrent reduction of serum DHEA levels and visual-spatial performance in this population, coupled with the documented effects of DHEA's androgenic metabolites on visual-spatial performance, suggests that DHEA administration may enhance visual-spatial performance. The current experiment used a double-blind, placebo-controlled crossover design in which 50 mg of oral DHEA was administered daily in the drug condition to explore this hypothesis. Performance on the Mental Rotation, Subject-Ordered Pointing, Fragmented Picture Identification, Perceptual Identification, Same-Different Judgment, and Visual Search tasks and serum levels of DHEA, DHEAS, testosterone, estrone, and cortisol were measured in the DHEA and placebo conditions. In contrast to prior experiments using the current methodology that did not demonstrate effects of DHEA administration on episodic and short-term memory tasks, the current experiment demonstrated large beneficial effects of DHEA administration on Mental Rotation, Subject-Ordered Pointing, Fragmented Picture Identification, Perceptual Identification, and Same-Different Judgment. Moreover, DHEA administration enhanced serum levels of DHEA, DHEAS, testosterone, and estrone, and regression analyses demonstrated that levels of DHEA and its metabolites were positively related to cognitive performance on the visual-spatial tasks in the DHEA condition.