Month 3 and month 6 measurements of bone mineral density predict the annual outcome in postmenopausal women with osteoporosis in whom alendronate was added to long-term HRT

Objective: To examine the predictive value of bone mineral density measurements done as early as months 3 and 6 after initiation of alendronate therapy (10 mg daily) in osteoporotic women already using long-term hormone replacement therapy. Method: Lumbar spine and femoral neck bone density (DPX by Lunar) were performed at baseline, 3, 6, 12 months of combined therapy. The study group included 45 women at baseline, but 2 dropped-out at day 67 and at month 6 because of gastric complaints, leaving 43 women for analyses. Results: Group characteristics at baseline were as follows: mean age 61±5 years, mean duration of HRT use 7±3 years, lumbar spine bone density 0.863±0.089 g/cm², with a t-score of −2.75±0.8 S.D., and femoral neck density 0.706±0.085 g/cm² with a t-score of −2.28±0.7 S.D. Bone density increased during 1 year of combined therapy, totaling a 3.2% gain for the spine and a 2.4% gain for the femur. Most of the annual change was already observed at month 3: 2.1% for the spine and 1.4% for the femur. Moreover, the baseline to month 6 percentage difference showed a very good correlation with the yearly outcome (r=0.74, P<0.001 for both spine and femur). When different arbitrary cut-off definitions for a successful treatment (1%, 1.5% or 2% gain in density) were used in analyses, in the majority of cases the bone density at 1 year, whether elevated or not, could be predicted by months 3 and 6 results. Although urine deoxypyridinoline decreased throughout the study period, demonstrating a significant time trend (P=0.001), the baseline to month 3 changes did not correlate with baseline to annual bone density results. Conclusions: In specific clinical settings when patients or physicians are looking for a good way to anticipate whether additional alendronate in hormone users would turn out to be beneficial, bone density measurements performed as early as 3–6 months after initiation of therapy might give the answer.     

Ultra low-dose hormone replacement therapy and bone protection in postmenopausal women

OBJECTIVES: The aim of the present study was to evaluate the effects of low doses of hormone replacement therapy (HRT) in normal young postmenopausal women. METHODS: In an open trial healthy, non-obese postmenopausal women received for 2 years a low-dose continuous combined HRT (LD-HRT) containing 1mg estradiol+0.5 mg norethisterone acetate each pill for 28 days, or 0.5 mg of 17beta-estradiol and 0.25 mg of norethisterone acetate (Ultra low dose, Ultra-LD-HRT) along with 1000 mg of calcium per day. Control group consisted of women receiving only 1000 mg of calcium per day, for 2 years. Menopausal symptoms were evaluated by the Green climacteric scale for the first 12 weeks of the study while bleeding profiles, bone mineral density (BMD) and bone turnover were assessed for 24 months. RESULTS: LD-HRT and Ultra-LD-HRT were effective in reducing menopausal clinical symptoms. In the control group, BMD significantly (P<0.05) decreased at the spine (-2.8+/-0.2%), and femoral neck (-2.8+/-0.7%). In LD-HRT treated group BMD showed a significant (P<0.05) increase at the spine (5.2+/-0.7%), and femoral neck (2.8+/-0.4%) after 24 months. In the Ultra-LD-HRT treated women spine and femoral neck BMD showed a significant (P<0.05) increase (2.0+/-0.3 and 1.8+/-0.3%, respectively) after 24 months. In these women treated with LD-HRT and Ultra-LD-HRT the BMD values were significantly (P<0.05) different from those measured in calcium-treated women. CONCLUSIONS: LD-HRT and Ultra-LD-HRT can alleviate subjective symptoms providing an effective protection against the postmenopausal decrease of BMD.     

阿仑膦酸钠治疗绝经后骨质疏松症的疗效与耐受性

目的评价阿仑膦酸钠对改善中国绝经后骨质疏松症患者骨密度和骨转换指标的疗效与耐受性。方法对274例绝经后骨质疏松症妇女进行前瞻性、多中心、自身前后对照研究。患者年龄49-82(平均65.0±6.3)岁,绝经年限3-34(平均15.3±6.8)年。予日服阿仑膦酸钠10 mg及元素钙500 mg,疗程6个月,观察腰椎及髋部骨密度、身高、骨转换生化指标尿Ⅰ型胶原氨基末端肽/肌酐(NTX/Cr)、血钙、磷、碱性磷酸酶浓度、肝肾功能及不良反应,以判断药物的疗效和耐受性。用双能X线骨密度仪测量骨密度,用酶联免疫吸附法测量尿NTX/Cr,用自动分析仪检测生化指标。结果阿仑膦酸钠治疗6个月后,患者腰椎2-4、股骨颈、wards三角及大转子骨密度显著增加,增幅分别达4.1%、2.5%、3.3%及2.4%(均P<0.001)。治疗后血碱性磷酸酶及尿NTX/Cr浓度快速、显著下降,降幅达52.2%和26.7%(P<0.001)。患者身高无明显改变,仅1例外伤后足趾骨新发骨折,钙磷水平、血尿常规及肝肾功能在正常范围内波动,12例(4.4%)出现与治疗有关的腹胀、返酸、腹痛等轻度胃肠道反应。结论阿仑膦酸钠是治疗中国绝经后骨质疏松症安全而有效的药物。     

Raloxifene therapy interacts with serum osteoprotegerin in postmenopausal women

OBJECTIVES: Osteoprotegerin (OPG) is a protein expressed by osteoblasts that, linking the receptor activator of nuclear factor kappaB (RANK) ligand (RANKL), produced by osteoblasts, blocks the process of osteoclastic differentiation and modulates osteoclastic apoptosis. Raloxifene (RAL) stimulates the production of OPG from osteoblasts, as demonstrated in vitro, carring out their antiresorption activity, at least in part, as means of the OPG/RANK/RANKL system. The aim of this study was to evaluate in vivo if the RAL treatment of postmenopausal women was associated to changes in serum OPG; moreover, to evaluate the serum changes of bone turnover modulators interleukin-6 (IL-6) and C-telopeptides of type-1 collagen (CrossLaps). METHODS: A prospective, randomized, placebo-controlled study was designed. A group of consecutive healthy postmenopausal women (n=40) referred to II Menopause Centre of the Department of Gynaecology of Second University of Naples for climacteric syndrome was enrolled and divided in two groups: (n=20) postmenopausal women received for 6 months oral raloxifene (60 mg/day) versus (n=20) postmenopausal women received placebo tablets. RESULTS: Serum OPG levels in postmenopausal women after RAL treatment are statistically significant increased (P<0.001) versus baseline (P=0.007) versus placebo. CONCLUSIONS: These in vivo data demonstrate that RAL could improve osteoporosis, also through an increase of OPG production by osteoblasts.     

Bone turnover and its relationship with bone mineral density in pre- and postmenopausal women with or without fractures

Objective: This work was carried out in order to investigate possible relationships between bone turnover rate, as evaluated by bone biomarkers and skeletal mass, as evaluated by bone mineral density (BMD). Method: Fifty-eight normal women and 30 female patients with osteoporotic fractures were enrolled. Three groups were defined: (1) fertile subjects (n=24), mean age 33.7±8.1 years; (2) postmenopausal women (n=32, including 11 patients with fractures) whose BMD values, in terms of T score, were less than −2.5 S.D. below the young adult mean obtained in our laboratory (mean age 61.7±7.9 years; and years since menopause (ysm), 12.6±8.3); (3) postmenopausal women (n=32, including 19 patients with fractures) whose BMD values in terms of T score, were below −2.5 S.D. (mean age 62.9±8.6 years; and ysm 15.9±9.0). Groups II and III characterised, by inclusion criteria, by significant different mean BMD values, were similar as far as chronological and menopausal age were considered. Metabolic tests included a short urine collection to determine calcium, hydroxyproline, cross-linked N-telopeptides of type I collagen (NTx) and creatinine (Cr); half-way through this collection, a blood sample was taken for the measurement of total alkaline phosphatase activity (ALP) and tartrate-resistant acid phosphatase activity (TRAP). BMD at lumbar spine was evaluated. Results: There were significant differences amongst the three groups in mean ALP (P<0.001, by analysis of variance) TRAP (P<0.006) and NTx/Cr (P<0.001) values, but not as far as mean values of calcium/Cr or hydroxyproline/Cr ratios were concerned. Considering the group as a whole, there were significant inverse correlations between NTx/Cr, ALP, TRAP and BMD controlling for both age (r=−0.392, P<0.001; r=−0.447, P<0.001 and r=−0.327, P<0.002, respectively) and ysm (r=−0.374, P<0.001; r=−0.474, P<0.001 and r=−0.333, P<0.002). Conclusions: Our results indicate, that, even after controlling for both ageing and oestrogen status, there is an inverse relationship between bone mass (that at a given time represents the balance of all previous metabolic events) and a biochemical marker (which reflects bone turnover at the time of examination). These findings are in line with the belief that increased bone turnover should be regarded as a risk factor for osteoporosis. Furthermore, our results indicate that, unless there is no increase of hepatic isozyme, total ALP still maintains a possible role as a first analysis to evaluate bone turnover before requesting markers with greater specificity, sensitivity but also more expensive and whose analysis is sometimes time-consuming.     

The values of urinary NTx in postmenopausal women undergoing HRT; the role of additional alendronate therapy

Objective: To determine the changes in levels of urinary NTx at the end of the 6th month of oral and transdermal hormone replacement therapy (HRT) and the effects of additional alendronate therapy for osteoporotic women. Method: Of 66 postmenopausal women 23 were treated with oral estradiol+norethisterone acetate (E+P), and 22 were treated with transdermal estradiol+norethisterone acetate. The third group consisted of 21 women with osteoporosis (bone mineral density<100 mg/cm³) and treated with oral E+P plus alendronate 10 mg/day. Result: Significant decreases of urinary NTx levels were seen after HRT in all study groups (P<0.05). But the decline of NTx levels was not different between the oral and transdermal HRT groups (P>0.05). There was no additional decrease in the levels of NTx with alendronate therapy (P>0.05) but NTx excretion diminished more in patients with high baseline levels. Conclusion: The decline of NTx at the end of the 6th month of HRT reflects the decrease of bone resorption and it is not related to the route of administration.     

Effects of continuous combined hormone replacement therapy and clodronate on bone mineral density in osteoporotic postmenopausal women: A 5-year follow-up

Objective

To determine the effects of HRT with or without clodronate on bone mineral density (BMD) change and bone turnover markers.

Design

Prospective, partly randomized trial.

Setting

Kuopio University Hospital, Finland.

Population

167 osteoporotic women (61 ± 2.7 years; T-score ≤ −2.5 SD).

Methods

Estradiol 2 mg + NETA 1 mg, randomization to additional 800 mg clodronate (n = 55, HT + C-group) or placebo (n = 55, HT-group); if contraindications to HRT, clodronate (n = 57, C-group).

Main outcome measures

BMD by DXA after 1, 3 and 5 years, serum osteocalcin (OC) and bone-specific alkaline phosphatase (BAP) at the baseline and after 3 years.

Results

After 5 years, adjusted lumbar BMD increased by 4.2% in the HT-group and 3.7% in the HT + C-group. The C-group showed a decrease of −1.1%, the total difference being 5.3% and 4.8% between HT, HT + C vs. C-group, respectively (p < 0.001). In the femoral neck, the adjusted 5-year BMD benefit was 1.3% and 2.4% in the HT- and HT + C-groups, respectively, the net loss of BMD in the C-group was −3.3% (p < 0.05 between HT + C vs. C). By 3 years, OC decreased by 55.0%, 70.3% and 53.8% in the HT-, HT + C- and C-groups, respectively (p < 0.001 vs. baseline). The significant decreases of BAP were 39.4% in the HT-group, 42.1% in the HT + C-group and 30.2% in the C-group with no significant differences between the groups after adjustments.

Conclusions

In postmenopausal women with osteoporosis, HRT increased spinal and femoral BMD, but the combination of HRT and clodronate did not offer an extra gain of bone mass.     

Identification of the risk factors for osteoporosis among postmenopausal women

ObjectivesThe aim of this study was to determine the effect of different durations of menopause at the time of bone mineral density (BMD) measurement and of different age at menopause intervals on the prevalence of osteopenia and osteoporosis among untreated postmenopausal women. We also assessed related factors leading to low BMD.MethodsA total of 2769 postmenopausal women who had not taken any anti-osteoporosis treatment and/or hormone replacement therapy were divided into three groups according to duration of menopause at the time of BMD measurement. The women were also evaluated in four different age groups according to their age at menopause onset. Multinomial logistic regression analysis was used to determine related factors leading to low BMD. Investigated parameters include demographic characteristics, plasma glucose, lipids, and lipoproteins.ResultsAccording to World Health Organization (WHO) criteria, among 2769 patients, 449 (16.2%) were identified as having osteoporosis, 1085 (39.2%) as having osteopenia, and 1235 (44.6%) as having normal BMD. Osteoporosis was determined in 10.6% and 16.2% of women with menopause duration of 0–3 years and 4–7 years, respectively, whereas this rate was 31.9% in women with menopause duration of over 7 years (p = 0.001). The percentages for osteopenia remained constant among the three different menopause durations (0–3 years: 37.2%, 4-7 years: 42.1%, and >7 years: 40.9%). Thirty percent of women with age at onset of <40 years were osteoporotic. However, the percentages of women with osteoporosis among the other age groups were similar (40–46 years: 18.3%, 47–52 years: 14.1%, and >52 years: 15.4%). The percentages for osteopenia remained relatively constant among the four age groups (36.7, 40, 39.1 and 39%). According to the multinomial logistic regression analysis, duration of menopause at the time of BMD test and parity were positively correlated with both osteoporosis and osteopenia, while glucose level was negatively correlated with both osteoporosis and osteopenia. Age at menopause was negatively correlated only for osteoporosis. Low-density lipoprotein cholesterol (LDL-c) level may be accepted as a clinically significant factor for osteopenia (OR: 1.01; CI_95%: 1.00–1.02). No differences were determined in the prevalence of osteopenia and osteoporosis in women with menopause duration of >7 years when evaluated according to the four menopause age groups as described before (p = 0.74). Contribution to the regression model was 0.8% by age at menopause, 5.6% by menopause duration at time of BMD measurement, 5.8% by both factors.ConclusionAccording to our results, osteoporosis is related more to the duration of menopause at the time of BMD measurement rather than the age at menopause among untreated postmenopausal women. High parity was determined as another risk factor for low BMD.     

Bone loss during oestriol therapy in postmenopausal women

In contrast to all other oestrogens examined thus far oestriol hemisuccinate (12 mg/day) did not prevent bone loss in 28 postmenopausal women. The average bone loss, however, was somewhat less than expected from placebo studies, while the bone loss achieved by a group taking 4–6 mg/day was equal to that achieved by previous placebo groups. To be an effective agent for prevention of post-menopausal osteoporosis oestriol would have to be prescribed in daily doses considerably in excess of 12 mg.     

阿仑膦酸钠治疗37例绝经后骨质疏松症的疗效及观察

观察阿仑膦酸钠对绝经后骨质疏松症的治疗效果与安全性。以37例43～85岁自然绝经三年以上的骨质疏松症妇女为研究对象,每日服用阿仑膦酸钠l0mg及元素钙500mg,观察治疗前后骨密度改变、尿I型胶原氨基末端肽,肌酐、身高、血钙、磷、碱性磷酸酶浓度的改变,以了解疗效。观察服用阿仑膦酸钠前后血、尿常规、肝肾功能、血电解质和便潜血的变化以了解药物的安全性。采用双能X线骨密度仪测定腰椎后前位和髋部骨密度,尿NTX／Cr采用ELISA法,血常规和其他血生化指标的检测,通过自动分析仪完成,便潜血检查采用单克隆抗体法完成。阿仑膦酸钠治疗6个月后,腰椎2～4、股骨颈、Ward's三角区及大转子部位BMD值有显著上升,增加率分别达4．9％、3．4％、5．3％及3．6％。治疗前后患者血钙水平无明显改变,血磷、碱性磷酸酶及NTX／Cr浓度快速、显著下降,提示阿仑膦酸钠能够有效降低骨转换。患者治疗前后身高无明显改变。研究观察期内仅1例患者外伤后发生左足趾骨骨折,余患者均未发生新骨折。患者服药前后血、尿、便常规及肝肾功能、电解质结果均在正常范围内波动,仅1例患者出现了与本药物可能有关的轻度胃肠道不良反应。阿仑膦酸钠是治疗中国绝经后骨质疏松症妇女的安全有效性药物。     

Comparison of effect of treatment with etidronate and alendronate on lumbar bone mineral density in elderly women with osteoporosis

The purpose of this open-labeled prospective study was to compare the treatment effects of cyclical etidronate and alendronate on the lumbar bone mineral density (BMD), bone resorption, and back pain in elderly women with osteoporosis. Fifty postmenopausal women with osteoporosis, age ranging from 55 to 86 years (mean: 70.7 years), were randomly divided into two groups with 25 patients in each group: the cyclical etidronate group (etidronate 200 mg daily for 2 weeks every 3 months) and the alendronate group (5 mg daily). The BMD of the lumbar spine (L1-L4) measured by DXA, the urinary cross-linked N-terminal telopeptides of type I collagen (NTX) level measured by the enzyme-linked immunosorbent assay, and back pain evaluated by the face scale score were assessed at baseline, 6 months, and 12 months. There were no significant differences in baseline characteristics including age, body mass index, years since menopause, lumbar BMD, urinary NTX level, and face scale score between the two treatment groups. Etidronate treatment sustained the lumbar BMD following a reduction in the urinary NTX level and improved back pain, while alendronate treatment reduced the urinary NTX level more significantly, resulting in an increase in the lumbar BMD, and similarly improved back pain. No serious adverse events were observed in either group. This study confirmed that alendronate treatment had a greater efficacy than etidronate treatment in increasing the lumbar BMD through the reduction of bone resorption in elderly women with osteoporosis.     

Trimegestone in a low-dose, continuous-combined hormone therapy regimen prevents bone loss in osteopenic postmenopausal women

OBJECTIVE: To determine the efficacy of estrogen + progestogen therapy with 1 mg 17beta-estradiol and 0.125 mg trimegestone in the prevention of postmenopausal osteoporosis. DESIGN: For this study, 360 healthy, postmenopausal women with osteopenia [lumbar spine bone mineral density (BMD) between -1.0 and -2.5 SD of the premenopausal mean value] were enrolled in a 2-year prospective, randomized study, and 70% completed. Treatments were 1 mg 17beta-estradiol + 0.125 mg trimegestone (n = 179) or placebo (n = 181), given as daily oral therapy. All received a daily supplement of 500 mg calcium and 400 IU vitamin D. BMD measurements at the lumbar spine, total hip, and femoral neck as well as blood and urinary biochemical markers of bone turnover (serum osteocalcin), serum bone-specific alkaline phosphatase, serum CrossLaps, and urinary CrossLaps took place regularly. RESULTS: BMD increases relative to placebo were 6.3%, 3.9%, and 3.8% at the lumbar spine, total hip, and femoral neck, respectively (all P < 0.001). The biochemical markers of bone turnover were suppressed accordingly. Serum CrossLaps and urinary CrossLaps decreased rapidly, by 52% and 54%, respectively, whereas serum osteocalcin and serum bone-specific alkaline phosphatase revealed a more retarded decrease of 40% and 33%, respectively. Of the women receiving hormone therapy, 75% had amenorrhea from the first cycle, and 5% withdrew prematurely due to metrorrhagia or mastalgia. CONCLUSION: This new estrogen + progestogen therapy is efficient in increasing BMD in an osteopenic postmenopausal population. Furthermore, it is well tolerated, with few adverse events and an early bleeding control, which is likely to improve compliance to the treatment over the long term.     

椎体成形术联合阿仑膦酸钠治疗老年骨折疏松性椎体压缩性骨折的近期疗效分析

目的观察椎体成形术联合阿仑膦酸钠治疗老年骨折疏松性椎体压缩性骨折的近期临床治疗效果。方法选择本院老年骨质疏松性椎体压缩性骨折患者43例,所有患者均在C臂引导下行经皮椎体成形术,术后43例患者根据治疗方案不同分为对照组(n=20)和研究组(n=23),对照组采取常规使用钙剂及维生素D3抗骨质疏松治疗,研究组在对照组药物使用基础上加用阿仑膦酸钠抗骨质疏松治疗,疗程均为12个月。术前及术后不同随访时间点测骨密度(BMD);ELISA法检测血清骨保护素(OPG)变化情况;采用疼痛视觉模拟评分(VAS)评估患者疼痛程度;Oswestry功能障碍指数(ODI)评估活动能力,并分析骨折椎体高度及Cobb角变化情况。结果所有手术均顺利完成,术后安返病房,随访时间为13~21个月,平均16.7月。相比椎体成形术前,研究组患者术后3、6、12月较对照组BMD及OPG均有一定程度增高(0.05);经阿仑膦酸钠治疗3月后,研究组VAS评分及ODI评分均显著低于对照组,且后续不同随访时间点VAS评分及ODI评分均能有效维持(0.05)。相比椎体成形术前,所有患者术后椎体前缘高度、中部高度优于术前椎体高度(0.05);且治疗3月后,研究组椎体前缘高度、中部高度较优于对照组(0.05);相比对照组,研究组Cobb角明显减小(0.05)。结论椎体成形术联合阿仑酸钠治疗老年骨折疏松性椎体压缩性骨折效果较为显著,术后持续使用阿仑膦酸钠治疗能一定程度增加椎骨骨密度,抑制骨保护素的降低进而防止骨破坏,可有效治疗骨质疏松及预防骨质疏松性骨折再次发生,适合临床推广应用。     

Comparison of effects of alendronate and raloxifene on lumbar bone mineral density, bone turnover, and lipid metabolism in elderly women with osteoporosis

PURPOSE: To compare the effects of alendronate and raloxifene on lumbar bone mineral density (BMD), bone turnover, and lipid metabolism in elderly women with osteoporosis. SUBJECTS AND METHODS: One hundred twenty-two postmenopausal women with osteoporosis (mean age: 69.4 years) were randomly divided into 2 groups of 61 patients: the alendronate group and the raloxifene group. BMD of the lumbar spine, urinary level of cross-linked N-terminal telopeptides of type I collagen (NTX), and serum levels of alkaline phosphatase (ALP), total cholesterol (TC), high and low density lipoprotein cholesterols (LDL-C and HDL-C, respectively), and triglycerides (TG) were measured during the 12-month-treatment period. RESULTS: The trial in 50 patients in the alendronate group and 52 patients in the raloxifene group could be completed. Both alendronate and raloxifene increased lumbar BMD (+8.0% and +2.4% at 12 months, respectively), followed by reductions of urinary NTX level and serum ALP level; however, the effects of alendronate were more pronounced than those of raloxifene. Only raloxifene reduced the serum levels of TC and LDL-C (-3.9% and -7.7% at 12 months, respectively), without any significant effect on the serum HDL-C and TG levels. CONCLUSION: The present study confirmed the efficacy of alendronate greater than raloxifene in increasing lumbar BMD through its effect on marked reduction of the bone turnover more than by raloxifene, and some beneficial effects of raloxifene on lipid metabolism in elderly women with osteoporosis.     

Rationale for using raloxifene to prevent both osteoporosis and breast cancer in postmenopausal women

Both osteoporosis with fracture and breast cancer are important health issues for postmenopausal women. It is well known that estrogen and estrogen receptors (ERs) play an important role in the pathogenesis of both diseases. In past decades, hormone therapy (HT), mainly estrogen plus progestin (EPT), has been frequently used for the purpose of preventing and treating postmenopausal osteoporosis because of its efficacy, but it also contributes to a significant increase in breast cancer. Currently, there is a dilemma regarding the use of estrogen for postmenopausal women. Fortunately, an increasing understanding of the action of estrogen has led ultimately to the design of new drugs that work by virtue of their interaction with the ER; these drugs have come to be known as selective estrogen receptor modulators (SERMs), and are not only effective in preventing osteoporosis and managing those with osteoporosis, but also in decreasing the incidence of breast cancer. Among these SERMs, raloxifene may be the most attractive agent based on the evidence from five recent large trials (Multiple Outcomes of Raloxifene Evaluation [MORE], Continuing Outcomes Relevant to Evista [CORE], Raloxifene Use for the Heart [RUTH], Study of Tamoxifen and Raloxifene [STAR], and Evista Versus Alendronate [EVA]). The former three trials showed that raloxifene not only decreases the incidence of osteoporosis-associated fractures, but also has efficacy in breast cancer prevention. The head-to-head comparison with the anti-fracture agent alendronate (EVA trial) and the chemoprevention agent tamoxifen (STAR trial) further confirmed that raloxifene is a better choice. We concluded that since there is an absence of a therapeutic effect on relieving climacteric symptoms and there is the presence of a potential risk of thromboembolism in the use of raloxifene, this drug can be prescribed for clear indications, such as the management of osteoporosis, the prevention of fracture, and decreasing the incidence of invasive breast cancer, with careful monitoring for thromboembolism. It is reasonable to use raloxifene as an appropriate medicine that targets climacteric symptom-free postmenopausal women because of its overall favorable risk-benefit safety profile using the global index proposed by the Women's Health Initiation (WHI).     

绝经妇女外周血单个核细胞骨代谢调控因子表达变化

目的:探讨绝经妇女雌激素水平下降所致免疫细胞骨代谢调控因子变化。方法:纳入绝经妇女、未绝经妇女各30例,电化学发光法检测血清雌二醇(E2)水平;RT-PCR法检测外周血单个核细胞(PBMC)中雌激素受体(ERα、ERβ)、白细胞IL-6、TNFα-。核因子κB受体活化因子配基(RANKL)、核因子κB受体活化因子(RANK)mRNA表达;ELISA检测血清IL-6、TNFα-蛋白含量;双能X线骨密度仪检测腰椎2~4(L2-4)前后位骨密度(BMD)。结果:与未绝经组比较,绝经妇女E2水平明显下降,腰椎BMD显著降低(P<0.05),外周血单个核细胞ERα、ERβmRNA表达明显降低(P<0.05),IL-6、TNFα-、RANKL、RANKmRNA表达明显升高(P<0.05),IL-6及TNFα-血清蛋白含量明显升高(P<0.05)。相关性分析显示PBMC中ERα、ERβmRNA表达与血清E2水平、腰椎BMD呈显著正相关性(P<0.05),PBMC中IL-6、TNFα-、RANKL、RANKmRNA表达与血清E2水平、腰椎BMD呈显著负相关性(P<0.05)。结论:绝经后妇女雌激素水平下降伴随着外周血免疫细胞雌激素受体转录水平下降,同时,炎性骨吸收调控因子和溶骨性细胞因子表达升高,这种变化可能在绝经后骨丢失中发挥重要作用。     

Interest of biochemical markers of bone turnover for long-term prediction of new vertebral fracture in postmenopausal osteoporotic women

Objective: To analyse the interest of baseline levels and short-term (3-months) changes in serum osteocalcin (BGP), serum bone-specific alkaline phosphatase (BALP) and urinary C-telopeptide of type I collagen/creatinine ratio (U-CTX) to predict 3-years changes in bone mineral density (BMD) and spinal deformity index (SDI) in postmenopausal osteoporotic women. Methods: Data were derived from a cohort of 603 osteoporotic women corresponding to the placebo arm of a 3-years prospective, double-blind study. Results: Baseline values of BALP, BGP and U-CTX were negatively and significantly correlated with baseline spinal BMD. Significant correlations were also observed between the changes in BMD observed after 36 months at the spine and baseline BALP (r=0.20, P=0.0001), BGP (r=0.09, P=0.05) and U-CTX (r=−0.11, P=0.02). At 3 years, 71 women (15.9%) showed an increase in their SDI, corresponding to the occurrence of at least one new vertebral deformity. Baseline values of the four bone turnover markers (BTM) were not significantly related to the occurrence of new vertebral deformities. However, when considering the changes in the BTM observed after 3-months of follow-up, BGP (P=0.003) and U-CTX (P=0.047) were identified as significant predictors of an increase of SDI. The associated odds ratios (95% confidence interval (CI)) were 10.922 (2.218–53.78) for unit changes of log BGP and 1.369 (1.003–1.867) for unit changes of log U-CTX. The relative risk (RR) (IC 95%) of having a new vertebral fracture over 36 months was 0.31 (0.15–0.65) when being in the lowest quartile of 3-months changes in BGP as compared with the highest. Conclusion: We conclude that two sequential measurements of BGP and U-CTX performed at 3-months intervals could be of interest to identify postmenopausal osteoporotic women with the highest risk to present new vertebral deformities.     

Weight loss improves biomarkers endothelial function and systemic inflammation in obese postmenopausal Saudi women

BackgroundAlthough postmenopausal associated disorders are important public health problems worldwide, to date limited studies evaluated the endothelial function and systemic inflammation response to weight loss in obese postmenopausal women.ObjectiveThis study was done to evaluate the endothelial function and systemic inflammation response to weight loss in obese postmenopausal Saudi women.ResultsThe values of body mass index(BMI), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP), inter-cellular adhesion molecule (ICAM-1), vascular cell adhesion molecule (VCAM-1) and plasminogen activator inhibitor-1 activity (PAI-1:Ac) were significantly decreased in group (A), while changes were not significant in group (B). Also, there were significant differences between mean levels of the investigated parameters in group (A) and group (B) after treatment.ConclusionWeight loss ameliorates inflammatory cytokines and markers of endothelial function in obese postmenopausal Saudi women.     

Serum cathepsin K as a marker of bone metabolism in postmenopausal women treated with alendronate

Context

Cathepsin K is a member of the cysteine protease family that cleaves both helical and telopeptide regions of collagen I, the major type of collagen in bone. Measurement of circulating levels of cathepsin K may be useful to assay the number or function of osteoclasts.

Objective

The aim of the study was to evaluate the role of serum cathepsin K as a biochemical marker of bone metabolism in patients with postmenopausal osteoporosis before and after treatment with alendronate.

Design, setting and participants

The study was a case–control and prospective study with postmenopausal osteoporotic women including a total number of 86 subjects. Serum cathepsin K was determined in 46 women with postmenopausal osteoporosis before and after 3, 6 and 12 months of treatment with alendronate. Basal serum cathepsin K levels were also compared between premenopausal healthy women (n = 20), postmenopausal women without osteoporosis (n = 20) and osteoporotic women. In addition, serum carboxyterminal cross-linked telopeptide of type I collagen (CTX), osteocalcin (OC) and bone-specific alkaline phosphatase (bALP) were measured.

Main outcome measure

Changes in cathepsin K serum levels after alendronate treatment.

Results

Serum cathepsin K levels were higher in postmenopausal women with osteoporosis (9.4 ± 11 pmol/L) compared with healthy postmenopausal women (6.8 ± 8.1 pmol/L; p < 0.01) and premenopausal women (6.3 ± 5.0 pmol/L, p < 0.01). Serum cathepsin K decreases gradually after alendronate treatment (17% at 3 months, 22% at 6 months and 41% at 12 months, p < 0.01). In contrast, the treatment resulted in early and sustained reductions in serum CTX.

Conclusion

We conclude that serum cathepsin K seems to provide additional information on bone metabolism in postmenopausal women treated with alendronate.