Double-blind, placebo-controlled study of the effects of tibolone on bone mineral density in postmenopausal osteoporotic women with and without previous fractures.

A 2-year placebo-controlled, randomized, two-center prospective study was carried out to assess the effects of tibolone (Org OD14, Livial) on trabecular and cortical bone mass and bone biochemistry parameters in elderly postmenopausal women with and without previous fractures. In total, 107 subjects, 71 with fractures and 36 without fractures, were randomized to tibolone (n = 64) or placebo (n = 43). Their mean age was 63.1 years. Bone mineral density (BMD) (g/cm2) was assessed at baseline and every 6 months for 2 years by dual-energy X-ray absorptiometry (DXA). Mean baseline values were 0.79 and 0.80 for the lumbar spine in the tibolone and placebo groups, respectively, and for the femoral neck 0.64 in both groups. Serum and urinary bone biochemistry parameters were measured concurrently. An analysis of variance (ANOVA) model including center and group was applied. The completers' group was the primary subset for the analysis; the intention-to-treat (ITT) group was also analyzed. Results are expressed as the percentage change at 24 months and the annual rate of change percentage year. The tibolone group showed an overall mean increase (vs. placebo) in BMD at the lumbar spine of 7.2% (p < 0.001) and for the femoral neck 2.6% (p < 0.001). In subjects with previous fractures increases were 6.0% and 4.0% for the lumbar spine and femoral neck, while in those with no fractures, respective changes were 8.9% and 1.1%. Overall changes in the placebo group were 0.9% and -1.6% for the lumbar spine and femoral neck, respectively. A significant fall in bone biochemistry parameters showed that tibolone inhibits osteoclastic activity. In conclusion we have found that tibolone 2.5 mg induces significant increases of trabecular and cortical bone mass in elderly postmenopausal osteoporotic women with and without previous fractures.     

Association of serum leptin with bone mineral density in postmenopausal osteoporotic females

Objective: Present study was designed to find out whether leptin is a predictor of bone mass density (BMD) in premenopausal women (PMW) and postmenopausal osteoporotic women (PMOPW) or it has no association with BMD.

Methods: One hundred and ninety two women (98 PMOPW and 94 PMW) were recruited for this study. The control group was BMI matched with osteoporotic subjects. BMD assessment was done on calcaneus by peripheral ultrasound bone densitometry and T scores were determined. Serum leptin levels were measured by enzyme-linked immunosorbent assay (ELISA).

Results: Serum leptin and BMD values were significantly different in both groups (leptin, 18.56?±?8.65?ng/ml versus 21.64?±?9.80?ng/ml, p?=?0.02) and (BMD, ?0.70?±?0.19 versus ?3.17?±?0.59, p?=?0.000), respectively. In PMOPW serum leptin and BMD were considerably correlated with weight (lep, r?=?0.53, p?=?<0.001; BMD, r?=??0.21, p?=?0.02), BMI (lep, r?=?0.52, p =?<0.001; BMD, r?=??0.27, p?=?0.005), waist circumference (lep, r?=?0.61, p?=?<0.001; BMD, r?=?0.18, p?=?0.04), hip circumference (lep, r?=?0.58, p?=?<0.001).

Multivariate linear stepwise regression analysis showed that weight and BMI in PMW and PMOPW were independent predictors of BMD. Serum leptin level was not found to be the predictor of BMD in both groups.

Conclusion: The present results indicate that body weight and BMI have an impact on BMD while serum leptin is not associated with BMD in PMW and PMOPW.     

Association of vitamin D receptor gene polymorphism with bone mineral density in Slovenian postmenopausal women.

Osteoporosis is a common bone disease which affects one in three women after the 60th year of life and is a major cause of morbidity in older people. To identify patients with osteoporosis, measurement of bone mineral density (BMD) is recommended. The association of BMD with vitamin D receptor (VDR) genotype in Slovenian postmenopausal women was studied. We determined VDR genotype in 102 late postmenopausal women aged 47-77 years. BMD measurements were performed at the level of the lumbar spine (L2-L4) by dual X-ray absorptiometry. Our data show significantly lower BMD in BB women compared to those with bb genotype. The relative distribution of VDR genotypes and alleles in the Slovenian population was 18.6:57.8:23.6% for BB:Bb:bb, respectively. The results are consistent with those of a previous study which found an excellent correlation between BB VDR genotype and low BMD. The data were derived from a relatively small, but ethnically homogeneous population of the same socioeconomic status, with very similar dietary and physical activity habits. Dietary habits in particular seem to be important because of the relatively low calcium intake which may enhance the phenotypic expression of VDR gene polymorphisms.     

A longitudinal evaluation of the effect of two doses of tibolone on bone density and metabolism in early postmenopausal women.

Tibolone, a steroid with tissue-specific activities, can reduce the bone resorption that takes place after the menopause. The present calcium-controlled, 2-year study aimed to evaluate the effect of two doses of oral tibolone, 1.25 mg and 2.5 mg, on bone loss in early postmenopausal women. The subjects were randomly allocated to one of the three groups, namely tibolone 2.5 mg (n = 30), tibolone 1.25 mg (n = 30) and a control group (n = 30). All subjects received 1000 mg of calcium per day. In the control group, vertebral and femur bone mineral density (BMD) decreased significantly (p < 0.05) after 12 and 24 months. In both tibolone groups, vertebral and femur BMD increased significantly (p < 0.05) increased after 12 and 24 months. In the control group, bone turnover markers (urinary excretion of hydroxyproline/creatinine and plasma osteocalcin levels) remained constant, while in both tibolone groups these markers showed similar significant decreases (p < 0.05) after 12 and 24 months. After 24 months, body weight increased in the control group (p < 0.05), while smaller increments were evident in the tibolone groups. Symptom scores in the control group did not show any significant modification during the study. In contrast, the administration of 2.5 mg tibolone was significantly (p < 0.05) effective in reducing hot flushes and other symptoms. The tibolone 1.25 mg group yielded similar results (even if it was proportionally less efficient) to the higher dose. It is concluded that tibolone is effective, even at lower doses, in relieving climacteric symptoms and preventing a decrease in spine and femur BMD in early postmenopausal women.     

Serum lipid levels and bone mineral density in Greek postmenopausal women

Contradictory results have been reported regarding a relationship between serum lipid levels and bone mineral density. The purpose of this study was to further investigate a possible relationship between those parameters in Greek postmenopausal women. A total of 591 patients followed at a tertiary hospital were examined for seven different lipid factors in relation to dual-emission X-ray absorptiometry measurements at the lumbar spine. Lipoprotein-a was the only lipid measurement that univariately showed an almost significant trend of association with bone mass category (analysis of variance [ANOVA] p value 0.062 for Ln(Lipoprotein-a)). In multiple regression, it was noted that a non-significant negative trend of association of high density lipoprotein (HDL) cholesterol and Apolipoprotein AI with lumbar T-score (p value 0.058 and 0.075, respectively). In age subgroup analysis, Lipoprotein-a and Ln(Lipoprotein-a) presented a negative correlation with lumbar T-score for women with age ≥ 53 years (p value 0.043 and 0.070, respectively), while a negative correlation of HDL and Apolipoprotein AI levels with lumbar T-score remained in women with age < 53 years (p value 0.039 and 0.052, respectively). The findings do not support a strong relationship between lipid levels and bone mass measurements.     

Low levels of endogenous estradiol protect bone mineral density in young postmenopausal women.

OBJECTIVE: Low levels of endogenous estrogens may play a role in the protection of bone mineral density (BMD) in healthy postmenopausal women. The aim of this study was to evaluate the effect of endogenous estradiol and testosterone on bone mass in young and older healthy postmenopausal women. METHODS: The study involved 99 postmenopausal women aged 55-75 years. The BMDs of the lumbar spine, proximal femur and total skeleton were determined. Measurements were taken of serum calcium, bone alkaline phosphatase, Crosslaps, estradiol, estrone, sex hormone binding globulin, testosterone, bioavailable testosterone and urine calcium. Estradiol was measured using a sensitive assay with a lower detection limit at 5 pg/ml. RESULTS: A multivariate analysis showed that the BMD of the lumbar spine was significantly predicted by estradiol (p < 0.05), and testosterone (p < 0.0001). Likewise, testosterone was found to be an independent predictor of the BMD of the total femur (p < 0.001) and the total skeleton (p < 0.001). The population was divided into two groups: < or = 65 (Group 1) and > 65 years (Group 2) of age and also stratified according to estradiol levels: > 10 and < or = 10 pg/ml. Significant differences in BMD were found in women in Group 1 in whom estradiol levels higher than 10 pg/ml were associated with a higher BMD of the lumbar spine (+ 14%, p < 0.01), proximal femur (+ 6%, p < 0.05) and total skeleton (+ 7%, p < 0.05) compared with women with estradiol levels below 10 pg/ml. Bone alkaline phosphatase levels (p < 0.05) and serum Crosslaps (not significant) were lower in women in Group 1 with a level of estradiol more than 10 pg/ ml. CONCLUSION: Endogenous estradiol levels higher than 10 pg/ml and testosterone protected bone mass in healthy postmenopausal women under 65 years of age. These results were not observed in the group of older women.     

Association of homocysteine,vitamin B12, and folate with bone mineral density in postmenopausal women: a meta-analysis

Background

The relationship of homocysteine (Hcy), folate, and vitamin B12 with bone mineral density (BMD) has been investigated in postmenopausal women. However, the relationship is still controversial.

Purpose

To evaluate the association of Hcy, folate, vitamin B12 and BMD in postmenopausal women with a meta-analysis.

Methods

We searched for all published articles indexed in Medline (1950–2012), Embase (1974–2012), and China National Knowledge Infrastructure (1994–2012). Any case–control or cohort study relating to Hcy, vitamin B12, folate, and BMD was included, and the data were extracted independently by two reviewers. Criteria for inclusion were the assessment of Hcy, vitamin B12, folate, and BMD in postmenopausal women as outcomes. We performed this meta-analysis with Review Manager 5.1 software. Odds ratios and 95 % confidence intervals (CI) were used to evaluate the results.

Results

Six eligible studies were selected for meta-analysis. Our analysis suggested that vitamin B12 and Hcy levels were significantly higher in postmenopausal osteoporosis (PMOP) group than that in controls (P = 0.007, <0.05; 95 % CI 3.06–19.38 and P = 0.0003, <0.05; 95 % CI 0.75–2.52, respectively). Folate level was lower in PMOP group than that in controls, but this difference was not statistically significant (P = 0.09, 95 % CI ?3.33 to 0.25).

Conclusions

Hcy and vitamin B12, but not folate, were related to BMD in PMOP. Extra vitamin B12 may not play a protective role for osteoporosis in postmenopausal women. Future studies are needed to confirm them, especially the relationship between increased vitamin B12 and BMD.     

Hot flushes, bone mineral density, and fractures in older postmenopausal women

OBJECTIVE: To assess whether greater severity of hot flushes is associated with bone loss or fracture risk in older postmenopausal women. METHODS: This study is a secondary analysis of 3,167 postmenopausal women in the Multiple Outcomes of Raloxifene Evaluation trial. Baseline hot flush severity was assessed by self-report. Femoral neck and lumbar spine bone density was assessed by dual-energy X-ray absorptiometry. Vertebral and nonvertebral fractures were determined radiographically and by interview. Baseline bone density, 3-year bone loss, baseline prevalent fractures, and 3-year fracture incidence were examined in women with varying hot flush severity. RESULTS: After adjusting for other characteristics, greater severity of hot flushes was associated with higher, rather than lower, baseline bone density (adjusted mean femoral neck bone density=0.633, 95% confidence interval [CI] 0.614-0.652 g/cm2, versus 0.611, 95% CI 0.608-0.613 g/cm2 for women with "severe" versus "minimal" hot flushes). Women with more severe hot flushes were less likely to have a baseline fracture (odds ratio 0.64, 95% CI 0.48-0.84, for vertebral fracture in women with moderate or severe versus minimal hot flushes). The 3-year annualized change in bone density did not differ among women with varying hot flush severity (P>.40 for all). Hot flush severity was not related to incident vertebral or nonvertebral fracture (P>.05 for all). CONCLUSION: Among osteoporotic women who are 5 or more years postmenopausal, greater severity of persistent hot flushes is not associated with progressive bone loss or risk of fracture, despite previous research linking hot flushes to bone loss during early menopause. LEVEL OF EVIDENCE: II.     

影响绝经后妇女骨密度变化的候选基因研究

目的探讨有关候选基因对绝经后妇女骨密度变化的影响。方法对205例绝经后妇女,应用双能X线骨密度仪测定腰椎和股骨颈骨密度。采用PCR测序法,检测护骨素基因多态性;采用PCR-限制性片段长度多态性方法,检测甲状旁腺激素、降钙素受体、骨钙素及瘦素受体基因多态性;采用PCR-琼脂糖凝胶电泳法,检测瘦素基因多态性。结果在护骨素基因第1外显子中,发现1个G-1181C单核苷酸多态性。在校正年龄及体重指数对骨密度的影响后,携带护骨素基因CC型及甲状旁腺激素基因bb型妇女的腰椎骨密度较高,分别为(1.042±0.142)g/cm2及(1.196±0.133)g/cm2。降钙素受体、骨钙素、瘦素及瘦素受体基因与骨密度之间无相关关系。经多元逐步回归分析,护骨素、甲状旁腺激素及骨钙素基因与腰椎骨密度变异有关,甲状旁腺激素基因与股骨颈骨密度的变异有关。结论护骨素及甲状旁腺激素基因与绝经后妇女骨量变异有一定关系,降钙素受体、骨钙素、瘦素及瘦素受体基因与绝经后妇女骨密度变异无关。护骨素基因可能是绝经后妇女发生骨量减少的遗传性标记。     

Related factors in bone mineral density of lumbal and femur in natural postmenopausal women

Objective: To assess possible factors affecting the bone mineral density (BMD) in postmenopausal women. Methods: A retrospective analysis of 267 cases with spontaneous menopause within 3 years of period was performed. None of the enrolled cases were taken any hormone replacement therapy and/or treatment for osteoporosis. BMD measurements were done in lumbal vertebral (L1–L4) and left femur (neck, intertrochanteric and ward triangle) via dual energy X-ray absorbtiometry (DEXA) method, yielding corresponding T-scores of above-mentioned areas. In addition, age at menarche, parity, menopausal age, duration of postmenopausal state, lactation, physical activity, cigarette smoking, dietary calcium intake, oral contraceptive use and body mass index (BMI) were determined. Results: There were no relationships between BMD and age at menarche, parity, menopausal age, lactation, physical activity, smoking, dietary calcium intake and oral contraceptive use. Two associated factors with BMD were BMI and time since menopause. BMI was found to be positively and time since menopause was negatively correlated with BMD of both lumbal region and femur. Conclusions: BMD changes and its related factors should be kept in mind during postmenopausal years. Therefore, adequate peak bone mass and related life style measures should be achieved to confront osteoporosis-related symptoms and its consequences.     

Effect of daily hormone therapy and alendronate use on bone mineral density in postmenopausal women

OBJECTIVE: To evaluate the effect of daily oral and transdermal hormone therapy alone or in combination with alendronate on bone mineral density in postmenopausal women. DESIGN: Comparative prospective clinical study. SETTING: Outpatient clinic of a training and research hospital. PATIENT(S): One hundred seventy-three consecutive postmenopausal women with no previous hormone therapy and a bone mineral density T score <-1 SD were randomly enrolled. INTERVENTION(S): Oral conjugated estrogen, alone or with alendronate, or transdermal estrogen, alone or with alendronate, given for 1 year. All patients also received medroxyprogesterone acetate and calcium. MAIN OUTCOME MEASURE(S): Bone density measurement at L2 to 4 region by dual-energy X-ray absorptiometry. RESULTS: At the end of 1 year, significant increase in bone density measurements were seen in all groups. Oral conjugated estrogen and transdermal estrogen have the same effect on bone mineral density loss. Hormone therapy alone stabilized the bone mineral density loss. Hormone therapy together with alendronate resulted in better values in all groups. CONCLUSION: Hormone therapy is adequate in osteopenic women. However, hormone therapy plus alendronate is advantageous in women with considerable bone mineral density loss.     

Comparison of bone mineral density and its variables between premenopausal and postmenopausal women

Objectives

To compare the bone mineral density (BMD) and its variables in premenopausal and postmenopausal women.

Methods

In this cross sectional study, 62 premenopausal and 62 postmenopausal apparently healthy women were evaluated by a questionnaire. The dietary intake of calcium was evaluated by 24 hours recall method and using table for proximate principle of common Indian food by Indian Council of Medical Research (ICMR). BMD at lumbar spine, femoral neck and Ward’s triangle were measured by dual energy X-ray absorptiometry (DXA). A correlation between BMD and various variables were calculated for each of the two groups.

Results

The mean age of premenopausal and postmenopausal women was 32.46±7.8 and 51.74±7.1 years respectively. The body mass index (BMI), height and weight were comparable in both the groups. The daily intake of calcium was significantly higher in premenopausal women (p<0.01). Approximately, 17% of the postmenopausal women and 9.6% of the premenopausal women were having osteoporosis; 28.56% of the postmenopausal women and 43.54% of the premenopausal women were having osteopenia at the lumbar spine. The BMD at lumber spine was found to be statistically significantly higher in premenopausal women than that in postmenopausal women (p=0.03). BMD at lumbar spine, femoral neck and Ward’s triangle were positively correlated with height, weight, BMI in premenopausal as well in postmenopausal women.

Conclusion

A significant number of women had osteopenia during premenopausal period and osteoporosis in postmenopausal phase. By increasing awareness towards bone health in second and third decade, morbidity of osteoporosis can be reduced.