Relationship between carotid atherosclerosis and lumbar spine bone mineral density in postmenopausal women

Osteoporosis and increased carotid intima-media thickness (IMT) have been associated with atherosclerosis. We investigated the correlation between carotid IMT and lumbar spine bone mineral density (BMD) in postmenopausal women. We studied the carotid IMT in 175 postmenopausal women, including 43 women (control) with normal spinal BMD, 73 women with osteopenia, and 59 women with osteoporosis. Carotid IMT was assessed by ultrasonography. BMD at the lumbar spine (lumbar 2 to 4 vertebrae) was measured by dual-energy X-ray absorptiometry. Age, years since menopause, and carotid IMT were significantly greater in the osteoporosis group than in the control (all p<0.01) and osteopenia groups (all p<0.01). Estradiol was significantly lower in the osteoporosis group than in the control group (p<0.05). BMD was significantly lower in the osteoporosis group than in the osteopenia or control group (both p<0.01) and in the osteopenia group than in the control group (p<0.01). After adjusting for age, years since menopause, and estradiol, women with osteoporosis had significantly greater carotid IMT than controls (p<0.05). The univariate linear regression analysis revealed that carotid IMT was significantly positively correlated with age, years since menopause, and low-density lipoprotein (LDL) cholesterol (all p<0.05) and was significantly negatively correlated with estradiol and BMD (all p<0.05), but showed no significant association with other clinical variables. In multivariate regression analysis, the carotid IMT was significantly positively correlated with LDL cholesterol (p<0.01) and negatively correlated with BMD (p<0.01), but not with other variables. Carotid atherosclerosis might be associated with lumbar spine bone mass in postmenopausal women, suggesting that postmenopausal women with osteoporosis may have more advanced carotid atherosclerosis than those with a normal bone mass.     

Effects of hormone replacement therapy on bone mineral density in postmenopausal women with primary hyperparathyroidism: four-year follow-up and comparison with healthy postmenopausal women

BACKGROUND: Long-term treatment of patients with asymptomatic primary hyperparathyroidism remains controversial, but the presence of osteoporosis is regarded as an indication for parathyroidectomy. Hormone replacement therapy (HRT) is a possible alternative therapy in osteopenic postmenopausal women with the disorder, and results of short-term studies suggest a beneficial effect on bone mass comparable to that achieved by parathyroidectomy. Longer-term data are required to further assess the efficacy of this treatment in chronic stable primary hyperparathyroidism. METHODS: We report the results of the extension from 2 to 4 years of a randomized, placebo-controlled trial of HRT in postmenopausal women with primary hyperparathyroidism. Of 23 postmenopausal women with primary hyperparathyroidism, 11 received active HRT with conjugated equine estrogen, 0.625 mg/d, and medroxyprogesterone acetate, 5 mg/d, and 12 received placebo. Bone mineral density was measured throughout the skeleton at 6-month intervals using dual-energy x-ray absorptiometry in these women and in 50 normocalcemic age-matched control subjects. None of the 23 patients withdrew during the extension period. RESULTS: Changes in bone mineral density were more positive in those taking HRT than placebo, with the between-group differences at 4 years being 4.6% in the total body, 7.5% in the lumbar spine, 7.4% in the femoral neck, 8.2% in the femoral trochanter, 6.8% in the legs, and 7.0% in the forearm (P<.01). At skeletal sites composed predominantly of cortical bone, there was a progressive divergence of the 2 groups. Biochemical markers of bone turnover remained lower throughout the study in women taking HRT. When rates of bone loss were compared between the placebo group and healthy women of comparable age, bone loss tended to be more marked throughout the skeleton in women with hyperparathyroidism, but only in the total body and its legs subregion was this difference significant. CONCLUSIONS: Hormone replacement therapy is efficacious in the long-term management of osteopenia in postmenopausal women with primary hyperparathyroidism and thus represents an important new therapeutic option for asymptomatic patients who do not have other indications for surgery. Bone loss seems to be accelerated in untreated primary hyperparathyroidism.     

Superiority of alfacalcidol compared to vitamin D plus calcium in lumbar bone mineral density in postmenopausal osteoporosis

In a randomized multicenter, double-blind, double-dummy, parallel group study a comparison of the efficacy and safety of 1 μg alfacalcidol to 880 IU vitamin D plus calcium carbonate (1 g calcium) once daily per os was performed on 148 postmenopausal osteoporotic Caucasian patients with normal vitamin D serum levels for 18 months. Bone mineral density (BMD) was measured at baseline, 12 and 18 months. Safety parameters were followed during the entire study period. Sixty-nine (90.8%) in the alfacalcidol group and 67 (93.1%) in the vitamin D group were included in the ITT analysis. Lumbar BMD in the alfacalcidol group increased by 0.017 g/cm² (2.33%) and 0.021 g/cm² (2.87%) from baseline (P<0.001) at 12 and 18 months, respectively, whereas in the vitamin D plus calcium group the increase was 0.005 g/cm² (0.70%) from baseline (N.S.) at both 12 and 18 months. The higher changes from baseline in the alfacalcidol group, as compared to the changes in the vitamin D plus calcium group at both 12 and 18 months, were found to be statistically significant (P=0.018, 0.005). A small increase of mean femoral BMD was achieved in both groups (N.S.). Adverse events were similar in both groups. No significant differences were noted between the groups in serum calcium. In conclusion, alfacalcidol was found to be superior in significantly increasing lumbar BMD as compared to vitamin D plus calcium while safety characteristics were found to be similar in both treatments.     

Exercise and lumbar spine bone mineral density in postmenopausal women: a meta-analysis of individual patient data

BACKGROUND: Low bone mineral density (BMD) at the lumbar spine is a major public health problem among postmenopausal women. We conducted a meta-analysis of individual patient data (IPD) to examine the effects of exercise on lumbar spine BMD in postmenopausal women. METHODS: IPD were requested from a previously developed database of summary means from randomized and nonrandomized trials dealing with the effects of exercise on BMD. Two-way analysis of variance tests with pairwise comparisons (p < or =.05) and 95% confidence intervals (CIs) were used to determine the statistical significance for changes in lumbar spine BMD. RESULTS: Across 13 trials that included 699 subjects (355 exercise, 344 control), a statistically significant interaction was found between test and group (F = 15.232, p =.000). Pairwise comparisons (Bonferroni t tests) revealed a statistically significant increase in final minus initial BMD for the exercise group ( +/- SD = 0.005 +/- 0.043 g/cm(2), t = 2.46, p =.014, 95% CI = 0.001-0.009) and a statistically significant decrease in final minus initial BMD for the control group ( +/- SD = -0.007 +/- 0.045 g/cm(2), t = -3.051, p =.002, 95% CI = -0.012--0.002). Changes were equivalent to an approximate 2% benefit in lumbar spine BMD (exercise, +1%, control, -1%). CONCLUSIONS: The results of this IPD meta-analysis suggest that exercise helps to improve and maintain lumbar spine BMD in postmenopausal women.     

Prevention of femoral and lumbar bone loss with hormone replacement therapy and vitamin D3 in early postmenopausal women: a population-based 5-year randomized trial

The long term effects of hormone replacement therapy (HRT) and vitamin D3 (Vit D) on bone mineral density (BMD) were studied. A total of 464 nonosteoporotic early postmenopausal women from the Kuopio Osteoporosis Study (n = 13100) were randomized to four groups: 1) HRT (sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate, 2) Vit D3 (300 and 100 IU/day during the fifth year), 3) HRT and Vit D combined, and 4) placebo. Lumbar (L2-L4) and femoral neck BMD were determined by dual x-ray absorptiometry (DXA) at baseline and after 2.5 and 5 yr of treatment. Intention to treat analysis (n = 464) showed that after 5 yr, lumbar BMD remained unchanged in the HRT and HRT plus Vit D groups [+0.2% (P = 0.658) and +0.9% (P = 0.117), respectively], whereas lumbar BMD decreased by 4.6% in the Vit D group and by 4.5% in the placebo group (P < 0.001 in both). The loss of femoral neck BMD was less in the HRT (-1.4%; P = 0.005) and HRT plus Vit D (-1.3%; P = 0.003) groups than in the Vit D and placebo groups (-4.3%; P < 0.001 in both). Among those 370 women who complied with the 5-yr treatment, the effect was more pronounced: lumbar BMD had increased by 1.5% in the HRT (P = 0.009) and by 1.8% in the HRT plus Vit D group (P = 0.005), with a plateau after 2.5 yr, whereas lumbar BMD had decreased in both the Vit D and placebo groups (4.6% and 4.7%; P < 0.001, respectively). Femoral neck BMD decreased again less in the HRT (-0.4%) and HRT plus Vit D (-0.6%) groups than in the Vit D and placebo groups (-4.4% in both). This study confirms the positive long term effect of HRT on BMD also seen in intention to treat analysis. The data suggest that low dose vitamin D3 supplementation does not prevent bone loss in healthy, nonosteoporotic, early postmenopausal women, and it confers no benefit additional to that of HRT alone.     

The effect of low dose nylestriol-levonorgestrel replacement therapy on bone mineral density in women with postmenopausal osteoporosis

OBJECTIVE: Recently our studies have shown that nylestriol in combination with levonorgestrel prevented bone loss, decreased bone turnover rate and increased the maximal loading of bone without obvious side effects in retinoic acid (RA) induced osteoporotic rats. In addition to the animal experiments, we evaluate the effect of Compound Nylestriol Tablet (CNT) on bone mineral density (BMD) in women with postmenopausal osteoporosis. Compound Nylestriol Tablet, which contains 0.5 mg of nylestriol (cyclopentylethinyl estriol) and 0.15 mg of levonorgestrel per tablet, was authorized as a new anti-osteoporotic agent for clinical trial in postmenopausal osteoporosis. METHODS: One year's clinical observation was performed in 191 eligible patients who were randomly divided into two groups (A and B). In group A, 119 patients were treated for one year with CNT (one tablet per week) and in group B, 72 patients with placebo. Bone mineral density of lumbar antero-posterior spine (L1-L4), lateral spine, total hip and total forearm positions including radius+ulna at the ultra distal areas, mid areas, and one-third areas, were measured before and after treatment. Biochemical parameters and effects of CNT on uterus, and breast were observed. RESULTS: We found that patients treated with CNT had a significant decrease of bone loss in total forearm, including radius+ulna at the ultra distal, mid, and 1/3 areas compared with control subjects (all P < 0.05). An improved BMD tendency could be seen at the lumbar spine. There were no differences in the observed biochemical variables. No side-effects on uterus, or mammary glands observed. None of the patients had uterine bleeding or vertebral fractures during one year's CNT treatment. CONCLUSION: These data suggested that CNT is effective, safe and convenient in treating postmenopausal osteoporosis.     

Prospective 10-year study of the determinants of bone density and bone loss in normal postmenopausal women,including the effect of hormone replacement therapy

OBJECTIVE: To prospectively assess bone density and the factors determining the rate of bone loss over a 10-year period of postmenopausal life. DESIGN: Prospective, observational study. METHODS: One hundred and four normal White postmenopausal women, baseline mean age 59 years (range 47-71 years) completed the study (mean duration of follow-up 10.2 years, range 9.4-10.6 years). None had diseases or were taking medications affecting bone metabolism at entry to the study. Information was collected on medical, fracture and smoking history, alcohol use, dietary calcium intake and physical activity. Body composition and bone density were measured by dual-energy X-ray absorptiometry at baseline and at 10 years. Biochemical, haematological and hormonal analyses were performed. RESULTS: Twenty-four percent of the women started hormone replacement therapy (HRT) during the study period; most of these remained on therapy at follow-up. The mean duration of therapy was 6.6 years (range 2.8-10.4 years). The use of HRT was associated with significant gains in bone density (total body + 3.0%, trochanter + 4.2%, Ward's triangle + 4.4%, spine + 10.5%) and a significant reduction in vertebral fracture risk [standardized risk ratio compared with non-HRT users 0.42 (confidence interval 0.18-0.83)]. HRT use was not associated with greater weight gain than that occurring in other members of the cohort. The baseline and follow-up bone densities in the non-HRT users were highly correlated (0.82 < or = r < or = 0.91, P < or = 0.0001) and baseline bone density accounted for the majority of the variance in the 10-year results. Multivariate analyses showed that the independent correlates of rate of change of bone density were weight and fat mass (both baseline values and changes during follow-up), time after menopause, sex hormone concentrations, urinary calcium loss, PTH levels and haemoglobin concentration (which may reflect nutrition and health). CONCLUSIONS: Bone density is highly predictable over an extended period of time in normal postmenopausal women. Maintenance of body weight and good health reduce bone loss. HRT is effective for treating osteoporosis, with improvement in bone density and reduction in vertebral fractures. Good compliance with HRT long-term is achievable. These findings are relevant to deciding the frequency of bone density measurement, and in advising women regarding prevention and treatment of postmenopausal bone loss.     

绝经后妇女腰椎和髋部骨密度变化的临床研究及意义

目的研究绝经后妇女骨密度（ＢＭＤ）变化情况及与骨质疏松的关系。方法用双能Ｘ线骨密度测量仪（ＤＥＸＡ）检测１４４名绝经后妇女腰椎和髋部的ＢＭＤ。结果妇女绝经后骨矿物含量随增龄逐渐下降，髋部各区域的骨丢失高于腰椎，以Ｗａｒｄ三角最明显，其顺序为Ｗａｒｄ三角＞股骨颈＞股骨粗隆＞腰椎２～４（Ｌ２～Ｌ４）。绝经年限与腰椎和髋部的ＢＭＤ呈明显负相关，在绝经１０年内呈线性下降，以后下降相对缓慢。结论妇女绝经后松质骨骨量丢失明显，在临床检测中，髋部骨密度的测量对妇女绝经后骨质疏松早期诊断及预防骨折有重要意义。     

Effect of combined risedronate and hormone replacement therapies on bone mineral density in postmenopausal women

Both hormone replacement therapy (HRT) and bisphosphonates are efficacious in the prevention and treatment of postmenopausal osteoporosis. Combined therapy with bisphosphonate and HRT is likely to be used in clinical practice, and limited data are available regarding its efficacy and safety. This was a 1-yr, double blind, placebo-controlled study in which 524 postmenopausal women received daily treatment with conjugated equine estrogens (0.625 mg) alone or in combination with risedronate (5 mg). Women who had not undergone hysterectomy received medroxyprogesterone acetate (up to 5 mg, daily or cyclically) at the discretion of the investigator. The primary efficacy end point was the percent change from baseline in mean lumbar spine bone mineral density (BMD) at 1 yr. Changes in BMD at the proximal femur and forearm, bone turnover markers, and histology and histomorphometry were also assessed. At 12 months, significant (P < 0.05) increases from baseline in lumbar spine BMD were observed in both treatment groups (HRT-only, 4.6%; combined risedronate-HRT, 5.2%); the difference between the two groups was not statistically significant. Both therapies led to significant increases in BMD at 12 months at the femoral neck (1.8% and 2.7%, respectively), femoral trochanter (3.2% and 3.7%), distal radius (1.7% and 1.6%), and midshaft radius (0.4% and 0.7%). The differences between groups were statistically significant (P < 0.05) at the femoral neck and midshaft radius. Both combined risedronate-HRT and HRT-only produced significant decreases in the biochemical markers of bone turnover, with somewhat greater decreases in the combined treatment group. Bone biopsy data showed normal bone structure and normal mineralization with either treatment. Expected decreases in bone turnover were observed and were greater in the combined treatment group (68-79% reduction relative to baseline values, P < 0.005). Overall, combined treatment had a safety profile similar to that of HRT-only, including bone and gastrointestinal safety profiles. In conclusion, the combined treatment with risedronate and HRT had a favorable effect on BMD similar to that of HRT alone at the lumbar spine and slightly, but significantly, greater than that of HRT alone at the femoral neck and midshaft radius. The combined treatment was well tolerated, and there were no adverse effects on the skeleton.     

Relationship between brachial arterial endothelial function and lumbar spine bone mineral density in postmenopausal women.

BACKGROUND: Osteoporosis and endothelial dysfunction have been associated with atherosclerosis. The correlation between brachial arterial endothelial function and lumbar spine bone mineral density (BMD) in postmenopausal women will be investigated. METHODS AND RESULTS: The endothelial function in 85 postmenopausal women, including 28 women with normal spinal BMD, 27 women with osteopenia, and 30 women with osteoporosis were studied. Brachial arterial flow-mediated vasodilatation (FMD) after reactive hyperemia was assessed by ultrasonography. The BMD at the lumbar spine (lumbar 2 to 4 vertebrae) was measured by dual-energy X-ray absorptiometry. Age, years since menopause, and FMD were significantly greater in the osteoporosis group than in the normal BMD group (p<0.01, p<0.05, and p<0.05, respectively). The BMD was significantly lower in the osteoporosis group than in the osteoporosis or normal BMD group (both p<0.01). After adjusting for age and years since menopause, women with osteoporosis had significantly lesser FMD than those with normal BMD (p<0.05). The univariate linear regression analysis revealed that brachial arterial FMD was significantly positively correlated with BMD (r=0.31, p<0.01), but showed no significant association with other clinical variables. In multivariate regression analysis, the FMD was significantly positively correlated with BMD (p<0.01), but not with other variables. CONCLUSIONS: Postmenopausal women with osteoporosis might have impaired brachial arterial endothelial function, suggesting that brachial artery endothelial function might be associated with lumbar spine bone mass in postmenopausal women.     

Monofluorophosphate combined with hormone replacement therapy induces a synergistic effect on bone mass by dissociating bone formation and resorption in postmenopausal women: a randomized study.

Sodium fluoride stimulates bone formation and has been used to treat osteoporosis for decades despite debate about the antifracture efficacy. Hormone replacement therapy (HRT) results in only modest increases in bone mineral density (BMD). However, for women with low bone mass, the ideal therapy should not only inhibit bone resorption but simultaneously stimulate bone formation to increase bone mass above the fracture threshold. We thus performed a randomized, double-blind, placebo-controlled intervention study to prospectively investigate the effect of a low dose of fluoride, in combination with HRT, on BMD and biochemical markers of bone turnover. One hundred healthy postmenopausal women (60-70 yr old) were thus randomly assigned to: 1) HRT [transdermal 17beta-estradiol, releasing 50 microg/day; plus oral norethisterone acetate (NETA), 1 mg/day]; or 2) oral monofluorophosphate (MFP; equivalent to fluoride, 20 mg/day); or 3) HRT+MFP; or 4) placebo, for 96 weeks. All participants received a calcium supplement of 1000 mg/day. Sixty-eight women completed the study. We found a pronounced, linear increase in spinal BMD during treatment with HRT+MFP [11.8% (1.7% SEM)], which was significantly greater than the increase in the HRT group [4.0% (0.5% per yr); P < 0.05]. MFP produced a smaller increase [2.4% (0.6% per yr)], whereas there was no change in the placebo group [0.0% (0.5% SEM)]. Similar changes were found at the other skeletal sites (distal forearm, hip, and total body). Markers of bone formation showed a fall in the HRT group, which was significantly more pronounced than in the combined HRT+MFP group. A nonsignificant increase was found in the MFP group, whereas the placebo group showed a decrease caused by calcium treatment. The marker of bone resorption decreased significantly more in the HRT and the HRT+MFP groups than in the placebo group but tended to increase in the MFP group. In conclusion, this study shows, by use of biochemical markers of bone turnover, that bone resorption and formation may be dissociated, as a result of actions of two compounds with diverging effects on bone turnover. Furthermore, the synergistic effects of relatively low doses of the compounds suggested statistically and clinically significant increases in trabecular and probably also cortical bone. Adverse effects were relatively rare and mild.     

Alveolar and postcranial bone density in postmenopausal women receiving hormone/estrogen replacement therapy: a randomized,double-blind,placebo-controlled trial

BACKGROUND: We conducted a 3-year, double-blind, randomized, placebo-controlled study to determine whether the positive effects of hormone/estrogen replacement therapy (H/ERT) on postcranial bone density are accompanied by similar positive effects on oral bone mass. METHODS: A total of 135 postmenopausal women (aged 41-70 years) with no evidence of moderate or severe periodontal disease were randomized to receive daily oral conjugated estrogen (Premarin; 0.625 mg) alone or in combination with medroxyprogesterone acetate (Prempro; 0.625 and 2.5 mg, respectively) or placebo. All subjects received calcium carbonate (1000 mg/d) and cholecalciferol (400 [corrected] IU/d) supplements. The primary efficacy end points were the changes in alveolar crest height and alveolar bone density. Alveolar crest height was measured on bite-wing radiographs, and changes in alveolar bone mass were assessed by means of digital-subtraction radiography. Postcranial bone density was measured in the lumbar spine and left proximal femur by means of dual-energy x-ray absorptiometry. RESULTS: Hormone/estrogen replacement therapy significantly increased alveolar bone mass compared with placebo (+1.84% vs +0.95% [P =.04]), and tended to improve alveolar crest height (+4.83% vs +3.46% [P =.34]). Bone mineral density of the proximal femur significantly increased in the H/ERT compared with the placebo group (total proximal femur, +3.59% vs +0.22% [P =.001]; neck, +2.05% vs -0.34% [P =.02]; trochanter, +3.49% vs +0.08% [P<.001]), but not the lumbar spine (+1.01% vs +0.17% [P =.39]). Changes in alveolar bone mass correlated with bone density changes in the total femur (r = 0.28 [P =.02]) and femoral trochanter (r = 0.25 [P =.04]) in the H/ERT but not in the placebo group. CONCLUSIONS: Postcranial and oral bone mass were increased in postmenopausal women receiving H/ERT. Improvement in oral bone health constitutes an additional benefit of H/ERT.     

Comparison of the effect of alendronate on lumbar bone mineral density and bone turnover in men and postmenopausal women with osteoporosis

The purpose of the present study was to compare the effect of alendronate treatment on lumbar bone mineral density (BMD) and bone turnover in men and postmenopausal women with osteoporosis. Sixty men with primary or secondary osteoporosis and 318 women with postmenopausal osteoporosis were treated with alendronate. The primary end points were lumbar BMD and urinary cross-linked N-terminal telopeptides of type I collagen (NTX) and serum alkaline phosphatase (ALP) levels. The secondary end point was the incidence of vertebral and nonvertebral fractures. Forty-seven (78.3%) men and 254 (79.9%) women who could complete the 12-month trial were analyzed. The mean ages of men and postmenopausal women were 69.1 and 70.4 years, respectively. Both men and postmenopausal women showed higher levels of urinary NTX as compared with normal range of premenopausal women. Alendronate treatment decreased urinary NTX level by 39.2% in men and 45.4% in postmenopausal women at 3 months and serum ALP level by 17.8 and 21.0%, respectively, at 12 months. Following reduction in bone turnover markers, lumbar BMD increased 5.8 and 7.6% in men and postmenopausal women, respectively, at 12 months. Reduction in urinary NTX level and increase in lumbar BMD were smaller in men than in postmenopausal women. The incidence of vertebral and nonvertebral fractures was 10.6 and 8.5%, respectively, in men and 8.3 and 7.5%, respectively, in postmenopausal women, with no significant difference in these incidences between them. These results suggested that alendronate treatment effectively increased lumbar BMD from baseline in men with primary or secondary osteoporosis following reduction in bone turnover, although its efficacy did not appear to be greater than in postmenopausal women with osteoporosis. We have no funding sources; we have no conflict of interest.     

Retraction Note: Comparison of the effect of alendronate on lumbar bone mineral density and bone turnover in men and postmenopausal women with osteoporosis

Clinical Rheumatology - A correction to this paper has been published: https://doi.org/10.1007/s10067-021-05788-3     

Melatonin improves bone mineral density at the femoral neck in postmenopausal women with osteopenia: a randomized controlled trial

Melatonin is known for its regulation of circadian rhythm. Recently, studies have shown that melatonin may have a positive effect on the skeleton. By increasing age, the melatonin levels decrease, which may lead to a further imbalanced bone remodeling. We aimed to investigate whether treatment with melatonin could improve bone mass and integrity in humans. In a double‐blind RCT, we randomized 81 postmenopausal osteopenic women to 1‐yr nightly treatment with melatonin 1 mg (N = 20), 3 mg (N = 20), or placebo (N = 41). At baseline and after 1‐yr treatment, we measured bone mineral density (BMD) by dual X‐ray absorptiometry, quantitative computed tomography (QCT), and high‐resolution peripheral QCT (HR‐pQCT) and determined calciotropic hormones and bone markers. Mean age of the study subjects was 63 (range 56–73) yr. Compared to placebo, femoral neck BMD increased by 1.4% in response to melatonin (P < 0.05) in a dose‐dependent manner (P < 0.01), as BMD increased by 0.5% in the 1 mg/day group (P = 0.55) and by 2.3% (P < 0.01) in the 3 mg/day group. In the melatonin group, trabecular thickness in tibia increased by 2.2% (P = 0.04), and volumetric bone mineral density (vBMD) in the spine, by 3.6% (P = 0.04) in the 3 mg/day. Treatment did not significantly affect BMD at other sites or levels of bone turnover markers; however, 24‐hr urinary calcium was decreased in response to melatonin by 12.2% (P = 0.02). In conclusion, 1‐yr treatment with melatonin increased BMD at femoral neck in a dose‐dependent manner, while high‐dose melatonin increased vBMD in the spine. Further studies are needed to assess the mechanisms of action and whether the positive effect of nighttime melatonin will protect against fractures.     

Prediction of bone mass density variation by bone remodeling markers in postmenopausal women with vitamin D insufficiency treated with calcium and vitamin D supplementation

The aim of this study was to determine whether early changes in bone markers could predict long-term response in bone mineral density (BMD) after calcium (500 mg) and vitamin D (400 IU) supplementation twice daily in ambulatory elderly women with vitamin D insufficiency (25-hydroxyvitamin D, <12 ng/ml). One hundred and ninety-two women (mean age, 75 +/- 7 yr) were randomized to receive either the supplementation (n = 95) or a placebo (n = 97) in a double-blind, controlled clinical trial for 1 yr. In comparison with the placebo group, supplementation significantly increased BMD, normalized 25-hydroxyvitamin D and significantly decreased intact PTH and bone remodeling markers. The initial values of telopeptide cross-links were correlated with improvement in total body BMD [urinary N-telopeptides (NTX), r = 0.38; C-telopeptides (CTX), r = 0.32; serum CTX, r = 0.28], and the 3-month changes in the same markers were correlated with improvement in total body (urinary N-telopeptides, r = -0.29; serum CTX, r = -0.26) and vertebral BMD (CTX, r = -0.26; all P < 0.05). We concluded that short-term changes in bone resorption markers can predict long-term variations in BMD in elderly women with vitamin D insufficiency receiving calcium and vitamin D supplementation.     

Effects of tibolone and cyclic hormone replacement therapy on glucose metabolism in non-diabetic obese postmenopausal women: a randomized study

OBJECTIVE AND METHODS: To study the effects of hormone replacement therapy on glucose metabolism, 31 obese (body mass index > or =27 kg/m(2)) postmenopausal women were randomized to treatment with tibolone (2.5 mg once daily; TIB; n=16) or to oestradiol valerate (2 mg daily)-dydrogesterone (20 mg daily for 2 weeks every 3 months; ED; n=15) for 12 months. Oral (OGTTs) and intravenous glucose tolerance tests (IVGTTs) and a euglycaemic hyperinsulinaemic clamp were performed before and at 6 and 12 months of treatment. RESULTS: TIB decreased the rates of whole body glucose uptake (WBGU) at 6 (P=0.04) and 12 months (P<0.001), but it did not have a significant effect on glucose tolerance. In OGTTs, serum insulin and C-peptide concentrations 2 h after the oral glucose load were increased (P<0.001 and P=0.05 respectively) at 12 months of treatment with TIB, but no changes in the areas under the curve (AUC) of insulin or C-peptide were observed. Furthermore, TIB did not have a significant effect on insulin secretion, the metabolic clearance rate (MCR) of insulin or hepatic insulin extraction. Treatment with ED did not modify the rates of WBGU, but it increased the MCR of insulin (P=0.017) and hepatic insulin extraction (P<0.001) and tended to decrease the insulin AUC (P=0.07). Moreover, glucose tolerance slightly deteriorated during this treatment (P=0.02). Although early phase insulin secretion evaluated by the serum C-peptide response at 30 min in the OGTT increased (P=0.046), the first-phase insulin response during the IVGTT decreased (P=0.05) during ED treatment. CONCLUSIONS: Despite the impairment in peripheral insulin sensitivity, TIB treatment had a neutral effect on glucose tolerance, possibly due to a compensatory decrease in endogenous glucose production. The increased demand on insulin induced by ED, due to both a stimulatory effect on pancreatic beta cells and increased insulin metabolism, may explain the slightly detrimental effect on glucose tolerance with this treatment.