交替联合用药治疗绝经后骨质松症及70岁以下老年骨质疏松症临床研究

目的　观察交替应用降钙素 (鲑鱼降钙素 )与二膦酸盐类药物 (固邦 )同时加用钙剂与活性维生素D(海卡洛 )及适当运动 ,治疗绝经后骨质松症及 70岁以下组老年骨质疏松症的疗效。方法　 1 0 3例绝经后骨质疏松症及 70岁以下老年性骨质疏松症患者用降钙素 1～ 3个月 ,同时服用钙剂 ,活性维生素D ,然后停用 1～ 2个月后 ,改服二膦酸盐 3～ 5个月 ,此期间同时服用钙剂及活性维生素D ,并适当运动 ,再停药 1～ 2个月 ,如此一个周期 ,按上述程序重复循环治疗。结果　通过 1 5～ 3年重复程序治疗 ,骨痛症状明显缓解 ,有效率高达 80 %。骨密度 (BMD)值有增高趋势 ,其中腰椎BMD值增加明显为 8 0 % (P <0 0 5 ) ,双髋部平均BMD值增高 6 2 % (P <0 0 5 )骨折率逐年下降。结论　交替联合用降钙素与二膦酸盐类药物同时加用钙剂与活性维生素D治疗绝经后骨质疏松症及 70岁以下老年骨质疏松症 ,能有效的改善骨痛 ,同时BMD值有明显增高趋势 ,降低骨折发生率。     

鲑鱼降钙素治疗老年骨质疏松症的疗效观察

目的　观察鲑鱼降钙素对老年骨质疏松症的治疗效果。方法　将经定量CT(QCT)测定确 诊为骨质疏松且有临床症状的老年患者105例分成两组,鲑鱼降钙素组48例,予鲑鱼降钙素肌肉注射,每 天1次50IU,连用7d后,改为50IU隔天1次,连用14d后,改为50IU每周2次,连用4周为一个疗程,间 隔2个月后再重复,共1年,同时加服钙尔奇D(含元素钙600mg,维生素D125IU)每天1片;钙剂组57 例,单纯口服钙尔奇D每天1片,疗程1年,两组治疗前后均测定2～4腰椎(L2～4)骨密度(BMD),治疗前 后记录临床症状。结果　鲑鱼降钙素组较钙剂组骨痛症状缓解(89.6%和42.1%)效果明显(P<0.01), 鲑鱼降钙素组腰椎BMD治疗后(0.85±0.09)mg/cm3,较治疗前(0.81±0.05)mg/cm3有所升高(P< 0.05);钙剂组BMD无明显改变。结论　鲑鱼降钙素与钙剂联合应用对治疗老年骨质疏松症有缓解临床 症状及增加腰椎BMD的作用。     

阿伦膦酸钠与活性维生素D3对比防治绝经期前SLE患者GIOP

目的对比观察阿伦膦酸钠与活性维生素D3,对无脆性骨折病史的绝经期前系统性红斑狼疮（SLE）患者糖皮质激素诱导骨质疏松（GIOP）的疗效。方法分别依照大、小剂量两种GCs治疗方案入组绝经期前SLE患者（其中门诊病情稳定,长期服用小剂量糖皮质激素GCs治疗者47例;病房初诊,服用大剂量GCs治疗者44例）。每种方案入组患者随机分为钙剂组、钙剂＋活性维生素D3组及钙剂＋阿伦膦酸钠组治疗,分别于第0、3、6个月监测患者骨代谢血清学指标及骨密度值,并记录治疗过程中骨折及股骨头坏死的发生情况。结果（1）小剂量GCs治疗方案：各用药组血清Ca、PO4、ALP水平治疗前后均无显著差异;血清N—MID及B—CT水平,钙剂联合阿伦膦酸钠组治疗后较治疗前显著降低（P〈0．05）;单用钙剂或钙剂联合活性维生素D3组治疗后较治疗前上升,但仅血清N—MID水平差异有统计学意义（P〈0．05）。骨密度值：单用钙剂组,腰椎、单侧股骨及股骨颈BMD值治疗后较治疗前显著降低（P〈0．05）;钙剂联合活性维生素D3组三处BMD值治疗前后差异无统计学意义（P〉0．05）,钙剂联合阿伦膦酸钠组,三处BMD值治疗后较治疗前均显著升高俨〈0．05）。（2）大剂量GCs治疗方案：各用药组血清Ca、PO4、ALP水平治疗前后均无显著差异;血清N—MID及B—CT水平,钙剂联合阿伦膦酸钠组治疗后较治疗前显著降低（P〈0．05）,单用钙剂或钙剂联合活性维生素D3组治疗后较治疗前显著上升（P〈0．05）。骨密度值：单用钙剂组及钙剂联合活性维生素D3组,三处BMD值治疗后较治疗前显著降低（P〈0．05）,钙剂联合阿伦膦酸钠组,治疗前后差异无统计学意义（P〉0．05）。（3）骨折及股骨头坏死的发生：小剂量GCs治疗方案中,各组均无骨折及股骨头坏死的发生;大剂量GCs治疗方案中,单用钙剂或钙剂联用活性维生素D3组均出现股骨头坏死,而钙剂联用阿伦膦酸钠组则无股骨头坏死的发生。结论对于分别服用大、小两种剂量GCs治疗的绝经期前SLE患者,阿伦膦酸钠较活性维生素D3,可以更好地降低骨转换、提高骨密度值,减少股骨头坏死发生的例数。     

渐进性抗阻训练对绝经后骨质疏松患者骨密度及骨代谢标记物的影响

目的观察渐进性抗阻训练对绝经后骨质疏松症(postmenopausal osteoporosis,PMO)患者骨密度和骨代谢标记物的影响,同时观察对患者疼痛的缓解作用。方法将30例PMO患者分为渐进性抗阻训练组(15例)以及对照组(15例)。两组患者均给予常规药物治疗,即碳酸钙D3+骨化三醇胶丸+阿伦膦酸钠(抗骨吸收药物)。而渐进性抗阻训练组患者还接受了渐进性抗阻训练。3个月后比较两组患者骨密度、骨代谢标记物和疼痛症状的变化情况。结果 (1)治疗前,两组患者的骨密度、骨代谢标记物水平以及疼痛评分差异均无统计学意义;(2)治疗3个月,两组患者的腰椎骨密度及左股骨近端骨密度均有所增加,但训练组变化要高于对照组(P0.05);(3)治疗3个月,两组患者的骨代谢标记物均有所降低。其中,两组患者的骨形成标记物未见差异,但训练组的骨吸收标记物水平要低于对照组(P0.05);(4)治疗3个月,两组患者的疼痛评分均显著下降,但训练组评分同样低于对照组(P0.05)。结论渐进性抗阻训练能抑制PMO患者的骨吸收过程,提升患者骨密度,并且能有效缓解患者的疼痛症状。     

早期预防性治疗对绝经后骨质疏松症影响的动物实验研究

目的评价早期预防性抗骨吸收治疗对绝经后骨质疏松症骨量、骨代谢指标和骨组织形态的变化特点,提供早期监测和预防绝经后骨质疏松症的依据.方法以去卵巢大鼠为实验对象、抑制骨吸收的唑来膦酸注射液为赋形药物,建立绝经后骨质疏松症的动物模型.选取44只3个月龄雌性SD大鼠,除假手术组行假手术外,其余各组均行双侧卵巢切除.假手术组(sham)、去势对照组(ovx)以安慰剂处理,其余两组分别在去势后3d、1个月给予唑来膦酸注射液(zoledronic acid,ZOL) 500μg/kg静脉单次注射,分别在实验开始、术后1个月及术后3个月测定大鼠股骨骨密度(BMD),收集血清测定I型前胶原氨基端前肽(PINP)、抗酒石酸酸性磷酸酶5b (TRACP-5b)的值变化,并光镜下观察大鼠股骨病理学变化,图像分析系统观察骨形态计量学静态指标骨小梁面积百分率(TBV)、骨小梁厚度(Tb.Th)、骨小梁间距(Tb.sp)的变化.结果应用去卵巢大鼠成功建立绝经后骨质疏松模型.去势对照组在1个月股骨BMD、血清PINP和TRACP-5b、TBV、Tb.Th及Tb.sp等指标变化上和正常对照组存在显著性差异(P＜0.01);去势3d即行ZOL治疗者和假手术对照组的BMD、骨代谢、骨形态学指标比较变化无显著性差异(P＞0.05);1个月后开始ZOL治疗者仅部分恢复骨密度,血清PINP、TRACP5b、骨组织形态指标变化和早期治疗组比较存在非常显著性差异(P＜0.01),且其骨小梁连接有明显的退变.结论骨代谢指标可用于抗骨吸收治疗的疗效监测;去势大鼠早期进行预防性抗骨吸收治疗,能抑制其骨量的丢失,减慢骨小梁退变,恢复骨密度.     

骨疏康治疗骨质疏松性脊椎压缩性骨折64例临床观察

目的 观察中药骨疏康在骨质疏松性脊椎压缩骨折治疗中的作用。方法 对94例临床诊断为骨质疏松性脊椎压缩骨折患者进行随机对照单盲研究。其中治疗组64例,服用骨疏康颗粒和钙制剂加维生素D;对照组30例服用钙制剂和维生素D治疗,持续6个月。治疗结束时进行疗效评价。疗效以腰背痛消失情况和躯体活动是否受限,以及下地活动时间、行走距离为判断指标。结果 治疗组64例中,显效51例(79.7％),有效11例(17.2％),无效2例(3.1％);对照组30例中,显效19例(63.3％),有效10例(33.3％),无效1例(3.3％)。经统计学处理,两组显效率差异显著(P<0.05),治疗组优于对照组。结论骨疏康可以有效治疗骨质疏松性脊椎压缩骨折引起的疼痛,加快骨折愈合。     

唑来膦酸预防芳香化酶抑制剂引起骨丢失的临床研究*

目的:探讨唑来膦酸预防绝经后乳腺癌患者芳香化酶抑制剂内分泌治疗引起骨丢失的效果。方法:选取2005年6 月至2007年6 月天津医科大学附属肿瘤医院63例绝经后激素受体阳性乳腺癌患者,随机分为治疗组（唑来膦酸与芳香化酶抑制剂连用）和对照组（单用芳香化酶抑制剂）。 随访24个月,观察不同时期两组患者腰椎（L2～L4）前后位骨密度,骨量减少和骨质疏松发生率的变化。结果:治疗6 个月,唑来膦酸组腰椎的骨密度与单用芳香化酶抑制剂组相比有增高趋势,但差异无统计学意义（P=0.099）。 两组骨丢失事件的发生没有统计学差异（骨量减少:P=0.124,骨质疏松:P=0.573）。 12个月时,治疗组腰椎骨密度较对照组明显升高（P=0.008）,治疗组骨量减少和骨质疏松的发生率低于对照组（骨量减少:P=0.048,骨质疏松:P=0.042）。 24个月时,治疗组的腰椎骨密度明显高于对照组（P=0.000）。 治疗组骨量减少和骨质疏松的发生率明显低于对照组（骨量减少:P=0.027,骨质疏松:P=0.011）。 治疗期间,除治疗组骨痛发生率与对照组相比较高外（P=0.039）,两组的不良事件的发生率相似（P>0.05）。结论:唑来膦酸对芳香化酶抑制剂内分泌治疗引起的骨丢失有明显的预防作用,且不良反应轻微,安全有效,耐受性好。      

骨疏康对去卵巢雌鼠骨质疏松症防治作用的研究

目的 为验证骨疏康颗粒防治原发性骨质疏松症(POP)的疗效和探讨其治疗机理。方法 以切除卵巢雌性大鼠复制绝经后骨质疏松症模型,观察该药对去卵巢大鼠抗失骨作用。实验分为模型组、骨疏康组、尼尔雌醇组和正常对照组。术后1周开始灌胃治疗,持续12周。结果 实验性骨质疏松症大鼠一般状态、器官指数、腰椎骨矿含量、胫骨骨组织形态计量学、股骨生物力学性能等指标明显异常,病理光镜和计算机图像分析显示POP病变典型。骨疏康颗粒对上述改变有明显缓解作用,综合疗效优于对照西药。结论 骨疏康颗粒可通过体内多方位调节作用达到预防和抑制骨质疏松症的发生和发展,具有较好的应用前景。     

低频脉冲电磁场治疗原发性骨质疏松症的临床观察

目的观察低频脉冲电磁场对原发性骨质疏松症患者的治疗作用。方法对60例原发性骨质疏松症患者进行低频脉冲电磁场治疗,每次40min,1次/d,每周治疗5次,共24周为1个疗程,观察其治疗作用。结果治疗后在48例有疼痛症状的患者中,疼痛消失或缓解43例(P<0.05),总有效率为89.6%。血清骨钙素水平提高5.8%。6个月后复查显示平均腰椎(L2-4)骨密度提高0.56%,平均股骨颈骨密度提高1.38%,平均大转子骨密度提高了1.29%,平均髋部Wards三角区骨密度提高1.87%(P均<0.05)。治疗过程中及治疗后无1例出现不良反应。治疗前后患者血常规、肝肾功能、血钙、血磷均在正常范围内。结论PEMFs能缓解原发性骨质疏松症患者疼痛症状,改善骨代谢以及提高骨密度。     

绝经前早期乳腺癌患者于内分泌治疗中采用钙及维生素D对减少骨量的作用分析

目的 探讨绝经前早期乳腺癌患者于内分泌治疗中采用钙及维生素D对减少骨量的作用.方法 截选78例绝经前早期乳腺癌患者作为本次研究对象.所有研究对象均采用内分泌治疗,并于治疗前检测2组腰椎、全髋及股骨颈处骨密度情况.按照随机数字表法将研究对象分为对照组与治疗组,各39例.对照组不采用任何补充治疗,治疗组采用钙及维生素D辅助治疗.2组均治疗12个月,并再次检测2组骨密度,观察治疗安全性.结果 治疗12个月后,对照组腰椎骨密度较治疗前明显下降,与治疗组比较,P<0.05.2组患者全髋关节骨密度均较治疗前显著下降,而对照组下降更显著,P<0.05.治疗组患者腰椎、股骨颈骨密度较治疗前比较,P>0.05.对照组患者治疗前、后股骨颈骨密度比较,P>0.05;且与治疗组比较,P>0.05.治疗期间未发生不良反应.结论 于内分泌治疗绝经前早期乳腺癌期间及时补充钙及维生素D可有效减少患者骨量丢失,尤其是腰椎,从而对预防患者骨质疏松症的发生具有重要意义.     

Reduced CpG island methylation of the TBC1D8 gene may predict risk for osteoporosis in Chinese postmenopausal women

Objective: In this study, we collected samples from postmenopausal women aged >60 y and evaluated bone mineral density (BMD) in addition to other biochemical variables to evaluate risk factors for osteoporosis. Furthermore, we investigated whether an association exists between the CpG island methylation levels in the promoter region of the TBC1D8 gene and osteoporosis incidence. Our goal was to identify contributing factors to the pathogenesis of osteoporosis and provide a theoretical basis for osteoporosis testing and therapy.Materials and Methods: We used questionnaires to collect data from Chinese Han women in their communities. The following parameters were measured: uric acid, high density lipoprotein, low density lipoprotein, fasting blood glucose, serum creatinine, serum calcium, serum phosphorus, alkaline phosphatase, P1NP, β-CTX, PTH, 25(OH)D and bone mineral density from lumbar spine 1 to 4, femoral neck, and total hip. DNA was also extracted to assess the methylation level of the TBC1D8 gene.Conclusions: Our findings suggest that a lower body mass index (BMI) infrequent exercise and certain sleep durations may be associated with osteoporosis. In addition, higher serum creatinine, β-CTX and PTH and lower 25(OH)D levels may be associated with osteoporosis. In Chinese Han postmenopausal women, decreased methylation of the TBCF1D8 gene promoter CpG islands is associated with osteoporosis. Finally, we also observed that TBC1D8 is negatively correlated with high density lipoprotein in postmenopausal women with osteoporosis.     

Effects of tamoxifen on bone mineral density and metabolism in postmenopausal women with early-stage breast cancer

At the present time, tamoxifen is the most widely used anti-estrogen for adjuvant therapy and metastatic disease in postmenopausal women with breast cancer, a population at high risk for osteoporosis. This prospective study was designed to evaluate the effect of adjuvant tamoxifen on bone mineral density and all biochemical markers concomitantly in women with early-stage breast cancer in one study. Using dual-energy X-ray absorptiometry, prior to and 12 mo after tamoxifen treatment, bone mineral density in lumbar spine and femoral neck was measured in 44 women with T1-T2N0M0 estrogen-receptor-positive breast cancer receiving adjuvant treatment with tamoxifen 20 mg/d. Biomarkers that can affect bone mineral metabolism were measured before and after 3 and 12 mo of tamoxifen treatment. Bone mineral density was minimally increased in lumbar spine and femoralneck after 12 mo treatment with tamoxifen (p=0.79 and 0.55, respectively). No differences were found in serum levels of calcium, phosphate, creatinine, ALAT, albumin, LDH, calcitonin, or estradiol. A significant decrease in osteocalcin levels was found after 3 and 12 mo (p≤0.01). TSH and PTH levels were increased (p≤0.05) after 3 mo, returning to baseline after 12 mo. In conclusion, tamoxifen has an estrogen-like effect on bone metabolism in postmenopausal women and is associated with preservation of bone mineral density in lumbar spine and femoral neck. Changes in serum concentration of biochemical markers may reflect decreased bone turnover or bone remodeling and add to the understanding of tamoxifen’s effect on bone mineral density.     

绝经后早期乳腺癌患者术后一年内发生骨密度减低的相关因素分析

目的 探讨影响绝经后早期乳腺癌患者术后一年内发生骨密度减低的相关因素。方法 对242 例绝经后早期乳腺癌患者临床资料进行回顾性分析,并对骨密度减低的相关因素进行单因素及多因素Logistic回归分析。结果 对影响骨密度减少的10项指标进行单因素分析,显示年龄、BMI、绝经年限、AI内分泌治疗、雌二醇水平与骨密度减低显著相关（P＜0.05）;多因素Logistic回归分析显示绝经年限长、AI内分泌治疗、雌二醇低水平是骨密度减低的主要影响因素（P＜0.05）。结论 绝经后乳腺癌患者骨密度减低的主要影响因素是绝经年限长、AI内分泌治疗、雌二醇低水平,对于合并这些危险因素的乳腺癌患者,在临床工作中要足够重视并进行预防性和针对性治疗。     

Bone health in postmenopausal women with early breast cancer: How protective is tamoxifen?

Breast cancer is a leading threat to women's health. Tamoxifen, the most successful selective estrogen receptor modulator, has been used in hormonal therapy for three decades. Along with its therapeutic effect on breast cancer, tamoxifen also demonstrates potential benefits for bone health. However, the extent and quality of such benefits have not been systematically evaluated. We conducted a comprehensive literature search and identified 27 peer-reviewed articles investigating the relationship between tamoxifen and bone health in postmenopausal women with early stage breast cancer. The majority of studies reported that tamoxifen therapy alone protected against the loss of spinal bone mineral density. The bones in the hip also benefited from tamoxifen treatment while there was no evidence demonstrating tamoxifen's protection against bone loss in arms. When tamoxifen was combined with chemotherapy, it was found to partially prevent or reverse the bone loss resulting from chemotherapy. Patients with a history of hormone replacement therapy experienced bone loss while patients without the history had increased bone mineral density during tamoxifen therapy. Despite an apparent impact of tamoxifen on bone mineral density, the few available studies of tamoxifen and bone fractures appear to suggest no protective effect but an increase in fracture incidence. More investigation is necessary to clarify the discrepancy between bone mineral density and fracture in postmenopausal breast cancer patients treated with tamoxifen.     

Prevention of anastrozole-induced bone loss with monthly oral ibandronate during adjuvant aromatase inhibitor therapy for breast cancer

PURPOSE: The aromatase inhibitor anastrozole is a highly effective well-tolerated treatment for postmenopausal endocrine-responsive breast cancer. However, its use is associated with accelerated bone loss and an increase in fracture risk. The ARIBON trial is a double-blind, randomized, placebo-controlled study designed to evaluate the impact of bisphosphonate treatment on bone mineral density (BMD) in women taking anastrozole. EXPERIMENTAL DESIGN: BMD was assessed in 131 postmenopausal, surgically treated women with early breast cancer at two U.K. centers. Of these, 50 patients had osteopenia (T score -1.0 to -2.5) at either the hip or lumbar spine. All patients were treated with anastrozole 1 mg once a day and calcium and vitamin D supplementation. In addition, osteopenic patients were randomized to receive either treatment with ibandronate 150 mg orally every month or placebo. RESULTS: After 2 years, osteopenic patients treated with ibandronate gained +2.98% (range -8.9, +19.9) and +0.60% (range -9.0, +6.9) at the lumbar spine and hip, respectively. Patients treated with placebo, however, lost -3.22% (range -16.0, +4.3) at the lumbar spine and -3.90% (range -12.3, +7.2) at the hip. The differences between the two treatment arms were statistically significant at both sites (P < 0.01). At 12 months, urinary n-telopeptide, serum c-telopeptide, and serum bone-specific alkaline phosphatase levels declined in patients receiving ibandronate (30.9%, 26.3%, and 22.8%, respectively) and increased in those taking placebo (40.3%, 34.9%, and 37.0%, respectively). CONCLUSIONS: Monthly oral ibandronate improves bone density and normalizes bone turnover in patients treated with anastrozole.     

Breast-related effects of selective estrogen receptor modulators and tissue-selective estrogen complexes

A number of available treatments provide relief of menopausal symptoms and prevention of postmenopausal osteoporosis. However, as breast safety is a major concern, new options are needed, particularly agents with an improved mammary safety profile. Results from several large randomized and observational studies have shown an association between hormone therapy, particularly combined estrogen-progestin therapy, and a small increased risk of breast cancer and breast pain or tenderness. In addition, progestin-containing hormone therapy has been shown to increase mammographic breast density, which is an important risk factor for breast cancer. Selective estrogen receptor modulators (SERMs) provide bone protection, are generally well tolerated, and have demonstrated reductions in breast cancer risk, but do not relieve menopausal symptoms (that is, vasomotor symptoms). Tissue-selective estrogen complexes (TSECs) pair a SERM with one or more estrogens and aim to blend the positive effects of the components to provide relief of menopausal symptoms and prevention of postmenopausal osteoporosis without stimulating the breast or endometrium. One TSEC combination pairing conjugated estrogens (CEs) with the SERM bazedoxifene (BZA) has completed clinical development and is now available as an alternative option for menopausal therapy. Preclinical evidence suggests that CE/BZA induces inhibitory effects on breast tissue, and phase 3 clinical studies suggest breast neutrality, with no increases seen in breast tenderness, breast density, or cancer. In non-hysterectomized postmenopausal women, CE/BZA was associated with increased bone mineral density and relief of menopausal symptoms, along with endometrial safety. Taken together, these results support the potential of CE/BZA for the relief of menopausal symptoms and prevention of postmenopausal osteoporosis combined with breast and endometrial safety.     

Effective inhibition of aromatase inhibitor-associated bone loss by zoledronic acid in postmenopausal women with early breast cancer receiving adjuvant letrozole: ZO-FAST Study results

BACKGROUND: Letrozole is safe and effective in postmenopausal women with estrogen receptor-positive early breast cancer, but long-term aromatase inhibitor use may cause bone loss and increase fracture risk. This study evaluated an immediate or delayed strategy of bone protection therapy with zoledronic acid. METHODS: A total of 1065 patients who were receiving adjuvant letrozole were randomized to immediate-start or delayed-start zoledronic acid (4 mg intravenously biannually for 5 years). The delayed group received zoledronic acid if lumbar spine or total hip T-score decreased below -2.0 or when a nontraumatic fracture occurred. The primary endpoint was change in lumbar spine bone mineral density (BMD) at Month 12. Secondary endpoints included changes in total hip BMD, serum bone turnover markers, and safety at Month 12. RESULTS: Lumbar spine BMD increased from baseline in the immediate arm, while it decreased from baseline in delayed-arm patients. At Month 12, the differences between the groups in lumbar spine and total hip BMD were 5.7% (P < .0001; 95% confidence intervals [CI], 5.2% to 6.1%), and 3.6% (P < .0001; 95% CI, 3.3 to 4.0%), respectively. Both regimens were well tolerated with few serious adverse events. Bone pain was higher in the immediate group, as expected, because some patients experienced acute-phase reactions after zoledronic acid infusion. CONCLUSIONS: At 12 months, immediate zoledronic acid therapy prevented bone loss in postmenopausal women who were receiving adjuvant letrozole.