Determinants of one-year response of lumbar bone mineral density to alendronate treatment in elderly Japanese women with osteoporosis

The purpose of this study was to determine factors that could predict the one-year response of the lumbar bone mineral density (BMD) to alendronate treatment in elderly Japanese women with osteoporosis. Eighty-five postmenopausal women with osteoporosis, all of whom were between 55-88 years of age, were treated with alendronate (5 mg daily) for 12 months. Serum calcium, phosphorus, and alkaline phosphatase (ALP) and urinary NTX levels were measured at the baseline and 6 months, and lumbar (L1-L4) BMD was measured by dual energy X-ray absorptiometry at the baseline and 12 months. Multiple regression analysis was used to determine factors that were correlated with the percent change in lumbar BMD at 12 months. Lumbar BMD increased by 8.1 % at 12 months with a reduction in the urinary NTX level by 51.0 % at 6 months. Baseline lumbar BMD (R2=0.226, p < 0.0001) and percent changes in serum ALP and urinary NTX levels (R2=0.044, p < 0.05 and R2=0.103, p < 0.001, respectively) had a negative correlation with the percent change in lumbar BMD at month 12, while the baseline number of prevalent vertebral fractures (R2=0.163, p < 0.001), serum ALP level, and urinary NTX level (R2=0.074, p < 0.05 and R2=0.160, p < 0.001, respectively) had a positive correlation with it. However, baseline age, height, body weight, body mass index, years since menopause, serum calcium and phosphorus levels, and percent changes in serum calcium and phosphorus levels at 6 months did not have any significant correlation with the percent change in lumbar BMD at 12 months. These results suggest that lumbar BMD was more responsive to one-year of alendronate treatment in elderly osteoporotic Japanese women with lower lumbar BMD, more prevalent vertebral fractures, and higher bone turnover, who showed a greater decrease in bone turnover at 6 months, regardless of age, years since menopause, and physique. Alendronate may be efficacious in elderly Japanese women with evident osteoporosis that is associated with high bone turnover, and the percent changes in serum ALP and urinary NTX levels at 6 months could predict the one-year response of lumbar BMD to alendronate treatment.     

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.     

Changes in bone markers after once-weekly low-dose alendronate in postmenopausal women with moderate bone loss

BACKGROUND: High bone turnover, with bone resorption exceeding bone formation, is a major mechanism of postmenopausal osteoporosis. Therefore, inhibition of bone resorption is a rational approach for the prevention of bone loss. The objective of the current study was to determine the short-term efficacy of once-weekly low-dose alendronate in the prevention of bone loss, via bone turnover markers, in early postmenopausal Korean women with moderate bone loss. METHODS: This study involved a 12-week, randomized, double-blind clinical trial that compared the effects of placebo with alendronate 20mg once weekly. All subjects received supplemental calcium 600 mg and vitamin D 400IU daily. We recruited 63 postmenopausal women (ranging from 50 to 65 years of age) with the lowest lumbar spine bone mineral density (BMD) at least 2.0 S.D. below the mean value for young healthy adults. BMD was measured at baseline and serum alkaline phosphatase (ALP), osteocalcin, C-terminal telopeptide of type I collagen (CTX), and osteoprotegerin (OPG) were measured at baseline and 12 weeks after treatment. RESULTS: We randomly assigned 63 women to either placebo or alencronate 20 mg once a week for 3 months. Forty-nine women continued and completed all 3 months. After 3 months, bone resorption markers were significantly decreased in the alendronate group than in the placebo group: CTX -47.2% vs. 15% (p<0.01), ALP 1.6% vs. 25.9% (p=0.01), osteocalcin -29.2% vs. -13.6 (p=0.06). Women who received alendronate showed similar results to those who received placebo with regard to adverse events. CONCLUSION: Once-weekly low-dose alendronate may be a cost-effective and safe method of suppressing bone turnover in early postmenopausal women with moderate bone loss.     

Comparison of the Effects of Alendronate and Alfacalcidol on Hip Bone Mineral Density and Bone Turnover in Japanese Men Having Osteoporosis or Osteopenia with Clinical Risk Factors for Fractures

Purpose

The comparative effects of alendronate and alfacalcidol on bone mineral density (BMD) and bone turnover have already been established in postmenopausal women with osteoporosis. An open-labeled prospective study was conducted to compare the treatment effects of alendronate and alfacalcidol on hip BMD and bone turnover in Japanese men with osteoporosis or osteopenia with clinical risk factors for fractures.

Materials and Methods

One hundred twelve men with osteoporosis or osteopenia with clinical risk factors for fractures (mean age: 71.4 years) were randomly divided into two groups of 56 patients each: the alendronate (5 mg daily) and alfacalcidol (1 µg daily) groups. The BMD of the total hip, urinary level of cross-linked N-terminal telopeptides of type I collagen (NTX), and serum levels of bone-specific alkaline phosphatase (BSAP) were measured during the 12-month-treatment period.

Results

Forty-five patients in the alendronate group and 42 patients in the alfacalcidol group completed the trial. Alendronate increased BMD (+2.3% at 12 months) following reductions in the urinary level of NTX (-46.4% at 3 months) and serum level of BSAP (-34.1% at 12 months), while alfacalcidol sustained BMD (-1.9% at 12 months) as well as the urinary level of NTX (+13.2% at 3 months) and serum level of BSAP (+1.8% at 12 months).

Conclusion

The present study confirmed that alendronate has better efficacy than alfacalcidol (active control) in increasing hip BMD and reducing bone turnover in Japanese men with osteoporosis or osteopenia with clinical risk factors for fractures.     

骨代谢相关基因多态性与盐酸雷洛昔芬对绝经后骨质疏松妇女骨密度和骨转换指标影响的关系

目的了解骨代谢相关基因多态性与盐酸雷洛昔芬( raloxifene,RLX)对绝经后骨质疏松妇女骨密度(bone mineral density, BMD)和骨转换指标影响的关系.方法为随机、对照和双盲试验,入选47～74岁68例无亲缘关系的绝经后骨质疏松汉族妇女,随机分为RLX组和安慰剂组(各34例),RLX组日服RLX 60 mg,安慰剂组服与RLX外观一致的安慰剂,共1年.在服药前、服药后6月和12月时,检测BMD和骨转换指标包括血清1型胶原羧基末端肽(C-telopeptide, CTX)和骨钙素(osteocalcin, BGP).分析雌激素受体1基因(estrogen receptor 1 gene,ESR1)Xba Ⅰ和PvuⅡ位点、ESR2基因RasⅠ位点、维生素D受体基因(vitamin D receptor, VDR)FokⅠ和CDX2结合位点的多态性. 结果共58例完成整个试验,研究结束时RLX组腰椎2～4(L2～4)、全髋部和大转子BMD增加的百分数,以及血清CTX和BGP水平下降的百分数与安慰剂组比较差异均有统计学意义(P<0.05或P<0.01).治疗后12个月,RLX组VDR FokⅠ FF基因型者(n=8)全髋部和大转子BMD值平均下降各为1.98%±4.86%和2.26%±4.73%,而Ff/ff基因型者(n=21)平均增加各为2.52%±2.75%和2.74%±2.97%(P<0.05);ESR1 PvuⅡ位点PP/Pp基因型者(n=17)全髋部BMD明显增加(2.12%±2.78%),而pp基因型者(n=12)呈下降(-1.34%±3.73%)(P<0.05).但上述5个位点多态性与安慰剂组各指标变化均无相关性. 结论 RLX对绝经后骨质疏松妇女BMD的作用受VDR基因FokⅠ和ESR1基因PvuⅡ多态性的调节.在临床选择该药物时,可根据应用对象的基因型做有益决策之用.     

Lipid, glucose and homocysteine metabolism in women treated with a GnRH agonist with or without raloxifene

BACKGROUND: Although GnRH analogues are widely used to treat a variety of sex hormone-related diseases, little is known about their effect on metabolism. Therefore, we have evaluated the effect of a GnRH analogue, administered with or without raloxifene, on serum levels of lipoproteins, glucose, insulin and homocysteine (Hcy). METHODS: One hundred premenopausal women with symptomatic uterine leiomyomas were initially enrolled and randomized to receive 3.75 mg/28 days leuprolide acetate depot associated with 60 mg/day raloxifene hydrochloride (group A) or 1 placebo tablet/day (group B) for six cycles of 28 days. At entry and at cycle 6, subjects underwent anthropometric measurements, including body mass index and waist-to-hip ratio measurements, and blood chemistry assays for serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), glucose, insulin, Hcy, vitamin B(12) and folate concentrations. Insulin resistance was evaluated with the homeostasis model assessment (HOMA) score. RESULTS: Baseline parameters were similar in the two groups. At cycle 6, TC, HDL-C, LDL-C and TG levels were significantly increased (P < 0.05) in group B. In group A, LDL-C levels were unchanged, and TC, HDL-C and TG levels were increased (P < 0.05). Serum TC and LDL-C levels differed (P < 0.05) between the groups. Glucose levels were unchanged between and within groups, whereas insulin levels and HOMA scores increased (P < 0.05) versus baseline in group B. Post-treatment Hcy levels were higher (P < 0.05) versus baseline in group B; they were unchanged in group A. Serum vitamin B(12) and folate concentrations were unchanged in both groups. CONCLUSIONS: GnRH analogues alter serum lipoprotein and Hcy levels and increase insulin resistance. These acute metabolic changes may be prevented or reduced by raloxifene.     

骨髓间充质干细胞干预治疗骨质疏松症中的骨组织生物力学性能

目的以雷洛昔芬干预治疗骨质疏松为对照,用生物力学性能指标验证骨髓间充质干细胞(bone mesenchymal stem cells,BMSCs)干预治疗骨质疏松动物的效果。方法取6月龄雌性SD大鼠88只,随机分为骨质疏松动物模型组22只,正常对照组22只,雷洛昔芬干预组22只,骨髓间充质干细胞干预组22只。以摘除大鼠卵巢的方法建立骨质疏松动物模型。动物饲养4周后,分别以骨髓间充质干细胞和雷洛昔芬对骨质疏松动物进行干预治疗。于给药6周后检测各组大鼠血清Ca、P、碱性磷酸酶(alkaline phosphatase,ALP),并取胫骨进行剪切实验,取股骨进行冲击实验,测试肱骨的骨密度(bone mineral density,BMD)。结果骨髓间充质干细胞干预组肱骨BMD,血清Ca、ALP,胫骨各项剪切力学性能指标和股骨各项冲击力学性能指标大于模型组及雷洛昔芬干预组,其血清P小于模型组及雷洛昔芬干预组(P<0.05)。结论骨质疏松动物通过以骨髓间充质干细胞干预后,肱骨BMD,血清Ca、ALP,骨的强度和韧性可以得到一定恢复。     

Prevention of bone loss in postmenopausal women treated with lasofoxifene compared with raloxifene

OBJECTIVE: Osteoporosis is a significant health problem in postmenopausal women. Consequently, new and effective therapies are being sought to preserve bone mass and prevent osteoporosis in this population of women. The objective of this study was to compare the effects of lasofoxifene with raloxifene and placebo on indices of bone health in postmenopausal women. DESIGN: A randomized, double-blind, placebo- and active treatment-controlled study of 2 years duration was conducted. Women included 410 postmenopausal women aged 47 to 74 years. The four treatment groups were: lasofoxifene 0.25 mg/day, or 1.0 mg/day, raloxifene 60 mg/day, or placebo daily. All women received daily calcium and vitamin D supplements. The primary endpoint was percent change from baseline to 2 years in lumbar spine bone mineral density (BMD) in all women having baseline and at least one follow-up bone density measurement. Total hip BMD, biochemical markers of bone turnover, low-density lipoprotein cholesterol, and safety were also evaluated in all women. RESULTS: Both doses of lasofoxifene significantly increased lumbar spine BMD compared with raloxifene (P < or = 0.05) and with placebo treatment (P < or = 0.05). Least squares mean increases (95% CI) from baseline in lumbar spine BMD, compared with placebo, were 3.6% (1.9, 5.2) for lasofoxifene 0.25 mg/day, 3.9% (2.4, 5.5) for lasofoxifene 1.0 mg/day, and 1.7% (0.3, 3.0) for raloxifene. The two doses of lasofoxifene and raloxifene were equally effective at increasing total hip BMD. Lasofoxifene and raloxifene significantly reduced the levels of biochemical markers of bone turnover compared with placebo. In general, the effects of lasofoxifene were greater than the responses to raloxifene. At 2 years, lasofoxifene significantly (P < or = 0.05) reduced low-density lipoprotein cholesterol levels by 20.6% and 19.7% with 0.25 mg/day and 1 mg/day, respectively, compared with raloxifene (12.1%) and placebo (3.2%). Lasofoxifene and raloxifene had a similar adverse event profile with low rate of discontinuations due to adverse events. CONCLUSIONS: Lasofoxifene may be an effective and well-tolerated treatment option for the prevention of bone loss in postmenopausal women.     

阿仑膦酸钠与雷洛昔芬对牙槽骨吸收的影响

背景：研究证明阿仑膦酸钠与雷洛昔芬对骨质疏松有抑制作用。 目的：建立实验性大鼠骨质疏松及牙槽骨吸收模型,评价阿仑膦酸钠与雷洛昔芬对骨吸收的防治作用。 方法：56只雌性SD大鼠建立骨质疏松及牙槽骨吸收的动物模型,实验动物分组：①去势+结扎组和单纯结扎组又分别分为3个亚组：阿仑膦酸钠组、雷洛昔芬组和非用药组。②单纯去势非用药组。③假手术组做空白对照。建模手术后第5日开始灌胃给药,1次/d,治疗3个月。用血生化指标、骨密度测量及组织形态学方法进行药效评价。 结果与结论：阿仑膦酸钠治疗组较雷洛昔芬组有更强的降低去势组碱性磷酸酶和血钙的作用;提高去势组骨密度。结果证实阿仑膦酸钠与雷洛昔芬均能减少骨质丢失,从而可以防止骨质疏松及病理性牙槽骨骨吸收,且阿仑膦酸钠作用较好。     

Once-weekly alendronate 70 mg and raloxifene 60 mg daily in the treatment of postmenopausal osteoporosis

OBJECTIVE: To compare the efficacy and tolerability of once-weekly (OW) alendronate (ALN) 70 mg and raloxifene (RLX) 60 mg daily in the treatment of postmenopausal osteoporosis. DESIGN: This 12-month, randomized, double-blind study enrolled 456 postmenopausal women with osteoporosis (223 ALN, 233 RLX) at 52 sites in the United States. Efficacy measurements included lumbar spine (LS), total hip, and trochanter bone mineral density (BMD) at 6 and 12 months, biochemical markers of bone turnover, and percent of women who maintained or gained BMD in response to treatment. The primary endpoint was percent change from baseline in LS BMD at 12 months. Adverse experiences were recorded to assess treatment safety and tolerability. RESULTS: Over 12 months, OW ALN produced a significantly greater increase in LS BMD (4.4%, P < 0.001) than RLX (1.9%). The percentage of women with > or = 0% increase in LS BMD (ALN, 94%; RLX, 75%; P < 0.001) and > or =3% increase in LS BMD (ALN, 66%; RLX, 38%; P < 0.001) were significantly greater with ALN than RLX. Total hip and trochanter BMD increases were also significantly greater (P < or =0.001) with ALN. Greater (P < 0.001) reductions in N-telopeptide of type I collagen and bone-specific alkaline phosphatase were achieved with ALN compared with RLX at 6 and 12 months. No significant differences in the incidence of upper gastrointestinal or vasomotor adverse experiences were seen. CONCLUSION: ALN 70 mg OW produced significantly greater increases in spine and hip BMD and greater reductions in markers of bone turnover than RLX over 12 months. A greater percentage of women maintained or gained BMD on ALN than RLX. Both medications had similar safety and tolerability profiles.     

Relationship between BMD, dental panoramic radiographic findings and biochemical markers of bone turnover in diagnosis of osteoporosis

OBJECTIVE: Mandibular indices, measured on panoramic radiographs, may be useful screening implements for low skeletal bone mass density (BMD). Recent studies suggest that radiographic examination of mandible may constitute an effective process for the early diagnosis of osteoporosis. Biochemical markers of bone turnover may be of value for prediction of individual bone loss and they may help in predicting risk of fracture in elderly women. In contrast to the vast information available on dental radiographic findings and BMD only scarce data exist on the relationship between panoramic mandibular indices and biochemical markers. The aim of this study was to examine the diagnostic performance of dental panoramic radiography and biochemical markers of bone turnover in relation to BMD at the spine in a group of postmenopausal women. SUBJECTS AND METHODS: An assessment of the number of lost teeth, mandibular cortical width (MCW) at the mental region and morphologic classification of mandibular inferior cortex (MIC grade) was performed on dental panoramic radiographs in a group of 141 postmenopausal women 38-81 years of age. BMD at the lumbar spine was measured by dual energy X-ray absorptiometry. BMD values were categorized as normal (T-score greater than 1.0), and as indicative of osteopenia (T-score -1.0 to -2.5) or osteoporosis (T-score less than -2.5) according to the World Health Organization classification. Serum bone alkaline phosphatase (BAP) was measured with an enzyme immunoassay. Cross-linked N-telopeptides of type I collagen (NTx) corrected for creatinine secretion, was measured with a competitive-inhibition enzyme-linked immunosorbent assay ELISA. RESULTS: In our study, a decrease in MCW by 1mm increases the likelihood of osteopenia or osteoporosis to 47% (p-value<0.05), having taken into consideration the effect of the years elapsed since menopause. The increase of alkaline phosphatase (ALP) per unit increase the likelihood of osteopenia or osteoporosis to 14% (p-value<0.05), having checked the effect of the years since menopause. A decrease in MCW by 1mm increases the likelihood of moderately or severely eroded cortex to 97% (p-value<0.001). The increase in ALP per 1 unit increases the likelihood of moderate or severe erosion per 10% (p-value<0.05), taking into account the years since menopause. CONCLUSIONS: Our results suggest that dentists have sufficient clinical and radiographic information that enables them to play a significant role in early diagnosis of osteoporosis in postmenopausal women. Panoramic radiographs and biochemical markers of bone turnover may be of value for prediction of individual bone loss and they may help in predicting risk of fracture in elderly women.     

Effect of estrogen replacement on insulin sensitivity,serum lipid and bone resorption marker in hypogonadal males

Recent reports of osteoporosis in congenital estrogen deficiency in humans from estrogen resistance or aromatase deficiency have called attention to the importance of estrogen in males. It is the purpose of the present study to evaluate the effects of low- dose estrogen on glucose, lipid and bone metabolism in males with hypogonadism. Nine Thai males with primary or secondary hypogonadism were included in the study. Testosterone was discontinued at least 8 weeks before the study. The subjects received 0.3 mg of conjugated equine estrogen (CEE) daily for 4 weeks. Serum C-terminal telopeptide of type 1 collagen (CTX), total cholesterol (TC), LDL cholesterol (LDL-C), HDL cholesterol (HDL-C), triglyceride (TG) and parameters related to insulin sensitivity were measured at baseline and 4 weeks after treatment. Insulin sensitivity was assessed by frequent intravenous glucose tolerance test. The mean age of subjects was 35.77 years (22-70 years). Insulin sensitivity index (SI) did not change significantly after the administration of CEE (P=0.09). Likewise, no change in acute insulin response (AIR(glucose)) was detected. However, glucose effectiveness (SG) significantly decreased after CEE (P<0.05). No significant change in serum TC, LDL-C, HDL-C or TG was detected. In regard to bone turnover, serum CTX significantly decreased after CEE administration (P<0.05). We concluded that low-dose estrogen administration in hypogonadal males for 4 weeks causes a decrease in bone turnover and an increase in glucose effectiveness. No effect on serum lipid concentrations or insulin sensitivity and secretion was detected.     

Placebo-controlled multicenter study of oral alendronate in postmenopausal osteoporotic women. FOSIT-Study-Group. Fosamax International Trial

OBJECTIVES: To evaluate effects on bone mineral density (BMD), safety, and tolerability of a single daily dose of alendronate (10 mg), administered for 1 year to postmenopausal women with osteoporosis. METHODS: This interim analysis includes the first approximately 20% of patients to complete treatment in a large, placebo-controlled study (the Fosamax International Trial (Fosit)), which enrolled 1908 patients from 34 countries. Patients < or = 85-year-old with osteoporosis (lumbar spinal BMD > or = 2 S.D. below mean for mature premenopausal Caucasian women) were randomly assigned to treatment with alendronate or placebo once daily in the morning; all patients received supplemental calcium (500 mg/day). Dual-Energy X-ray Absorptiometry (DXA) was used to measure BMD in spine and proximal femur. RESULTS: A total of 297 patients had BMD data available for analysis. Patients treated with alendronate showed progressive increase of BMD during treatment. At 12 months, mean BMD had increased significantly (P < 0.001) at the lumbar spine (5.6%), trochanter (3.6%), and femoral neck (2.6%) in the alendronate group. Increases in BMD were significantly (P < 0.001) greater than in the placebo group at all sites. Among 442 patients assessed for safety, there were no statistically or clinically significant differences between treatment groups in the incidence of adverse events, including upper gastrointestinal adverse events, or laboratory abnormalities. CONCLUSIONS: Results of this multinational study show that oral alendronate, administered as 10 mg once daily for 1 year, is generally well tolerated and produces significant, progressive increases in BMD at the lumbar spine and proximal femur of postmenopausal women with osteoporosis.     

伊班膦酸钠间断静脉输注治疗北京绝经后骨质疏松症的疗效

 目的 评价新一代双膦酸盐类药物伊班膦酸钠间断静脉输注对北京绝经后骨质疏松症的疗效及安全性。方法 研究纳入绝经后骨质疏松女性60例,年龄48~74岁,绝经年限3~32年,随机分为2组,治疗组每3个月静脉输注伊班膦酸钠2mg,对照组每周口服阿仑膦酸钠70mg,疗程12个月。疗效指标为腰椎及髋部骨密度（采用双能X线骨密度仪测量）、骨吸收指标血I型胶原羧基末端肽（酶联免疫吸附法测量）及骨形成指标碱性磷酸酶（自动分析仪酶法检测）。安全性指标包括血尿生化指标、心电图及不良反应。结果 59例患者完成研究。治疗12个月后,伊班膦酸钠组腰椎2-4、股骨颈及大转子骨密度增幅达6.3%,2.5%和0.1% (腰椎P <0.001,股骨颈P <0.01)。阿仑膦酸钠组腰椎、股骨颈及大转子骨密度改变率为 3.7%,4.9和-0.5% (腰椎和股骨颈P <0.001)。两组间治疗前后骨密度均无明显差别。伊班膦酸钠和阿仑膦酸钠治疗后ALP及CTX浓度均快速、显著下降,ALP降低15.8%和17.2%,CTX降低78.1%及43.2%（均P <0.001）。两组血钙磷水平、肝肾功能在正常范围内,伊班膦酸钠组常见的不良反应是首次输液后肌肉疼痛和低热,占26.7%,反酸、上腹不适是阿仑膦酸钠组主要的不良反应,占13.3%,患者可以耐受这些轻度的不良反应。结论 新一代双膦酸类药物伊班膦酸钠对于治疗绝经后骨质疏松症是安全而有效的。     

绝经后妇女骨质疏松患者血清IGF-1、IGFBP-3与骨密度及骨代谢指标的关系

目的： 探讨胰岛素样生长因子-1（IGF-1）和胰岛素样生长因子结合蛋白-3（IGFBP-3）与绝经后妇女骨密度及骨代谢指标之间的关系。方法： 通过检测90例绝经后妇女骨质疏松患者及70例绝经后骨量正常的健康对照组血清IGF-1、IGFBP-3、骨钙素（BGP）、I型胶原异构C端肽（β-CTX）、雌激素（E₂）、降钙素（CT）、甲状旁腺激素（PTH）、钙（Ca）、磷（P）等指标，然后同用双能X线骨密度仪检测的两组研究对象的腰椎（L2-L4）侧位、左股骨颈骨密度进行比较。结果： 绝经后骨质疏松组妇女腰椎、股骨颈骨密度显著低于对照组（均P<0.01）；血清IGF-1、IGFBP-3、E₂、CT、BGP水平均低于对照组（均P<0.01）；血清β-CTX、PTH均高于对照组（均P<0.01），血清Ca、P两组之间无差异（均P>0.05）。骨质疏松组和对照组腰椎侧位、左股骨颈BMD均与IGF-1、IGFBP-3、E₂、BGP、CT水平呈正相关，与β-CTX、PTH水平呈负相关，而与血钙、血磷无明显关系。结论： IGF-1、IGFBP-3、E₂、BGP、CT、β-CTX、PTH血清水平与腰椎、左股骨质具有明显的相关性，通过检测上述指标可考虑作为筛查绝经后妇女是否容易患有骨质疏松症的一项有价值的生化参考指标。     

2型糖尿病男性患者骨代谢指标与骨密度的相关性研究

目的：探讨2型糖尿病男性患者骨密度与骨代谢生化指标间的关系。方法：选取我科2014年1月至2015年12月入院的2型糖尿病男性患者102例,采用双能X线骨密度仪,测定腰椎(L2~L4)、股骨上端[包括股骨颈(Neck)、华氏三角(Ward)及股骨粗隆(Troch)]和全身的骨密度(bone mineral density, BMD)值;根据T值将这些患者分为骨量正常组(44例)、骨量减少组(36例)和骨质疏松组(29例),采用酶联免疫法测定各组碱性磷酸酶(alkaline phosphatase,ALP)、N-端中段骨钙素(N-MID-OT)、总Ⅰ型胶原氨基端延长肽(type 1 amino-terminal propeptide,tP1NP)和β胶原特殊序列(β-CTX)的浓度,比较三组骨代谢指标的变化,并对BMD与各项骨代谢指标进行相关性分析。结果：随着骨密度的降低,骨代谢指标的水平逐渐增高,其中,N-MID-OT和β-CTX的水平在三组间的差异皆有统计学意义(P<0.05);tP1NP在骨质疏松组和其余两组有统计学差异(P<0.05);ALP在三组间无统计学差异(P>0.05)。骨量减少组中,N-MID-OT与Neck、Troch及全身的BMD呈负相关(r=?0.754,?0.663,?0.743;P<0.05),β-CTX与Ward的BMD呈负相关(r=?0.273;P<0.05);骨质疏松组中, N-MID-OT与所有部位的BMD呈负相关(r=?0.736,?0.562,?0.715,?0.521,?0.436;P<0.05),β-CTX与Neck、Ward及全身的BMD呈负相关(r=?0.532,?0.614,?0.764;P<0.05)。结论：2型糖尿病男性患者骨密度与骨代谢指标呈负相关,两者联合评估有助于早期预防骨质疏松。     

Prevention of osteoporosis and uterine effects in postmenopausal women taking raloxifene for 5 years

OBJECTIVE: Raloxifene hydrochloride (60 mg/day) is a selective estrogen receptor modulator indicated for the prevention and treatment of postmenopausal osteoporosis. Raloxifene treatment for 3 years increases bone mineral density (BMD) and, unlike tamoxifen (a triphenylethylene selective estrogen receptor modulator), does not stimulate the endometrium in healthy postmenopausal women. The effect of longer duration of treatment with raloxifene is not known. Therefore, the main objectives of these analyses are (1) to compare the effect of 5 years of treatment with raloxifene (60 mg/day) with placebo in terms of the likelihood of developing osteoporosis and (2) to evaluate the effect of 5 years of raloxifene treatment on the endometrium and incidence of vaginal bleeding. DESIGN: The current analyses include integrated data from two identically designed, prospective, double-blinded trials including postmenopausal women (mean age, 55 years) randomly assigned to either placebo (n = 143) or raloxifene (60 mg/day; n = 185). Osteoporosis and osteopenia were diagnosed according to World Health Organization criteria, using the manufacturer's database for the lumbar spine and the National Health and Nutrition Examination Survey's 1998 reference base for the hip. Endometrial thickness was determined using transvaginal ultrasonography. Clinical diagnoses of endometrial hyperplasia or endometrial cancer were confirmed by blinded review of histopathology reports. RESULTS: Compared with the case of placebo, raloxifene treatment for 5 years reduced bone turnover markers (osteocalcin: -10.9%, P < 0.001; bone-specific alkaline phosphatase: -7.2%, P = 0.042; urinary C-telopeptide: -11.1%, P = 0.034) and was associated with increased BMD in the lumbar spine (2.8%; P < 0.001) and total hip BMD (2.6%; P < 0.001). Women taking raloxifene were less likely to develop osteoporosis (relative risk [RR] for raloxifene v placebo: 0.13; 95% CI: 0.00, 0.37; P = 0.001) or osteopenia (RR: 0.23; 95% CI: 0.00, 0.81; P = 0.038) at the lumbar spine and were more likely to convert to normal BMD status at the lumbar spine (RR: 4.01; 95% CI: 1.34, 11.23; P = 0.043) and total hip (RR: 3.92; 95% CI: 1.12,14.27; P = 0.011) at 5 years, compared with the case of placebo. Raloxifene also significantly reduced total cholesterol (-5.5%; P < 0.001) and low-density lipoprotein cholesterol (-8.7%; P < 0.001), compared with the case of placebo. No significant changes in high-density lipoprotein cholesterol (P = 0.257) or triglycerides (P = 0.620) were detected. Incidence of hot flashes was higher among women taking raloxifene compared with those taking placebo [raloxifene, 47 (28.8%); placebo, 21 (16.8%); P = 0.017]. Women taking placebo or raloxifene reported a similar incidence of vaginal bleeding (P = 0.999) or of mean endometrial thickness of more than 5 mm at baseline and at each visit, up to the 5-year endpoint (P >/= 0.349). No diagnoses of endometrial hyperplasia or endometrial cancer were made in either treatment group. CONCLUSIONS: Five years of raloxifene treatment in healthy postmenopausal women preserves BMD, significantly reduces the likelihood of development of osteoporosis, and was not associated with an increased rate of vaginal bleeding, endometrial hyperplasia, or endometrial carcinoma, compared with the case of placebo.     

Relationship between PTH,sex steroid and bone turnover marker measurements and bone density in recently postmenopausal women

OBJECTIVE: It is conceivable that, since menopause accelerates the continuous bone loss determined by age, a specific configuration of bone mass determinants during the first postmenopausal years occurs. METHODS: To establish their value as indicators of bone mass in women with recent natural menopause, we assessed relationships between bone mineral density (BMD) and age, menopausal age, body mass index (BMI), PTH, sex steroid hormones (estradiol and testosterone), and several markers of bone turnover in urine (N-telopeptide and calcium/creatinine ratio) or serum (osteocalcin (OC), total alkaline phosphatase (ALP), total and ionic calcium (iCa), phosphate (P) and magnesium (Mg)) for a group of 118 women (mean of three measurements per subject) attending a third-level menopause unit. Multivariate analysis was used in addition to Pearson's correlation to detect relationships between variables. RESULTS: Several significant associations were detected between variables under Pearson's correlation analysis, but only a few were confirmed under multivariate analysis. Thus, among the clinical traits, age was the main predictor of BMD for femoral neck (P<0.05). Estradiol (E(2)) was the only parameter that attained significance as a predictor for lumbar spine BMD (P<0.05), whereas PTH and NTx levels emerged as predictors of BMD for femoral neck (P<0.05). CONCLUSION: In this group of recently postmenopausal women, hormonal status, as defined by E(2) and PTH, and a resorption marker (NTx), revealed, together with age, as the only significant predictors of BMD.     

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.     

Effect of raloxifene and clodronate on bone density in postmenopausal osteoporotic women

The aim of the present study was to determine the safety and efficacy of combined therapy with raloxifene (RLX) and clodronate (CLD) in postmenopausal women. We enrolled 45 women with postmenopausal osteoporosis. The patients were randomly assigned to two different therapeutic groups: RLX 60 mg/day (n = 23) and RLX 60 mg/day plus CLD 100 mg intramuscularly (i.m.) once every 10 days (n = 22); 1 g of calcium and 800 IU of vitamin D3 were also given daily to both groups. Lumbar and femoral bone mineral density (BMD) were assessed at baseline and after 12 months of therapy using the dual X-ray absorptiometry technique (Norland XR36). We measured the bone turnover markers NTx and CTx, bone alkaline phosphatase (BAP) and osteocalcin at baseline and after 12 months of therapy. Our data demonstrate that 1 year of combined RLX+CLD therapy induced a higher increase in lumbar BMD than treatment with RLX alone as well as a major decrease in bone resorption markers, suggesting an additive effect of CLD on bone mass and inhibition of bone turnover. Furthermore, after 1 year of therapy levels of bone formation markers (osteocalcin and BAP) had increased in both groups, but the increase in osteocalcin and BAP was significantly higher in the RLX+CLD treated group, suggesting that, in addition to its inhibitory effects on resorption, CLD might also have stimulatory effects on mature osteoblast activity.