阿仑膦酸钠与钙尔奇D分别联合二甲双胍治疗2型糖尿病合并骨质疏松症的疗效对比研究

摘要 目的：对比阿仑膦酸钠与钙尔奇D分别联合二甲双胍治疗2型糖尿病（T2DM）合并骨质疏松症的疗效。方法：选取我院于2016年4月~2019年1月期间收治的109例T2DM合并骨质疏松症患者,根据乱数表法将患者分为钙尔奇D组（n=54,钙尔奇D）和阿仑膦酸钠组（n=55,阿仑膦酸钠）。比较两组患者临床疗效、血糖指标、骨代谢相关指标、腰椎L2~L4及股骨颈的骨密度值。结果：阿仑膦酸钠组治疗1个月后的临床总有效率为83.64%（46/55）,高于钙尔奇D组的62.96%（34/54）（P<0.05）。两组治疗1个月后腰椎L2~ L4、股骨颈的骨密度值均升高,且阿仑膦酸钠组高于钙尔奇D组（P<0.05）。两组治疗1个月后骨钙素（BGP）升高,且阿仑膦酸钠组高于钙尔奇D组（P<0.05）;血清I型胶原C末端肽（s-CTX）、碱性磷酸酶（BAP）、人抗酒石酸酸性膦酸酶 5b（TRAP-5b）则降低,且阿仑膦酸钠组低于钙尔奇D组（P<0.05）。两组治疗1个月后空腹血糖（FPG）、糖化血红蛋白（HbA1c）均降低（P<0.05）,但两组治疗1个月后组间比较无统计学差异（P>0.05）。两组不良反应发生率对比无统计学差异（P >0.05）。结论：与钙尔奇D联合二甲双胍治疗比较,阿仑膦酸钠联合二甲双胍治疗T2DM合并骨质疏松症患者,疗效显著,可有效改善骨代谢指标及骨密度,且不影响降糖效果,具有一定的临床应用价值。     

独活寄生汤联合阿仑膦酸钠对骨质疏松症患者骨代谢指标、血液流变学以及血清炎症因子的影响

摘要 目的：探讨独活寄生汤联合阿仑膦酸钠对骨质疏松症患者骨代谢指标、血液流变学以及血清炎症因子的影响。方法：选取于2017年5月~2019年12月期间我院收治的113例骨质疏松症患者,根据随机数表法将患者分为对照组（n=56）和研究组（n=57）,对照组患者给予阿仑膦酸钠治疗,研究组在对照组的基础上联合独活寄生汤治疗,比较两组患者疗效、骨代谢指标、骨密度（BMD）、血液流变学以及血清炎症因子水平,记录两组治疗期间不良反应发生情况。结果：研究组治疗1个月后的临床总有效率为91.23%（52/57）,高于对照组的76.79%（43/56）（P<0.05）。治疗1个月后两组BMD、血清碱性磷酸酶（ALP）升高,且研究组较对照组高（P<0.05）;两组治疗1个月后血清磷（S-P）、血清钙（S-Ca）组间比较无差异（P>0.05）。治疗1个月后两组全血黏度低切、白介素-6（IL-6）、纤维蛋白原、肿瘤坏死因子-α（TNF-α）、全血黏度高切、白介素-1（IL-1）下降,且研究组低于对照组（P<0.05）。两组不良反应发生率比较无差异（P>0.05）。结论：骨质疏松症患者采用独活寄生汤联合阿仑膦酸钠治疗,疗效确切,可有效改善骨代谢、血液流变学以及血清炎症因子水平,且不增加不良反应发生率。     

二磷酸盐促进假体周围骨溶解后假体翻修骨整合的实验研究

目的:评价阿仑膦酸钠对新西兰大白兔假体周围发生骨溶解后,再进行对新西兰大白兔假体翻修骨整合的影响。方法:选取雄性新西兰大白兔30只,随机分成3组(正常组,实验组,对照组,每组10只)。正常组在胫骨松质骨区域植入钛合金假体,实验组和对照组分别植入钛合金假体和钛颗粒,饲养8周后,三组统一进行假体翻修。实验组用阿仑磷酸钠治疗8周后取材,对照组和正常翻修组也分别进行取材。通过假体推出力学实验、硬组织切片观察,评价阿仑磷酸钠对假体周围翻修后骨整合的影响。结果:假体推出力学实验结果显示,实验组假体最大推出载荷明显大于对照组(P0.01)。硬组织学切片通过苦味酸--品红染色,利用图像分析仪器统计假体周围骨整合的面积实验组假体周围骨量明显优于对照组假体周围骨量(P0.05)。结论:二磷酸盐-阿仑磷酸钠可以提高假体翻修后假体周围骨整合。     

胰岛素联合阿仑膦酸钠对2型糖尿病骨质疏松症患者骨代谢的影响

目的:研究胰岛素联合阿仑膦酸钠对2型糖尿病(T2DM)骨质疏松症患者骨代谢的影响。方法:选择从2010年1月到2015年7月在医院治疗的T2DM合并骨质疏松症患者208例纳入本次研究。依照随机数字表法将患者划分成单用胰岛素组(对照1组)、单用二甲双胍组(对照2组)、二甲双胍及阿仑膦酸钠组(对照3组)以及胰岛素及阿仑膦酸钠组(联合组)各52例,各组在常规补钙治疗的基础上分别给予对应治疗措施,比较各组治疗前后骨代谢相关指标,以及各组治疗过程中的不良反应。结果:组内相比,治疗后联合组的骨密度(BMD)、血清骨特异型碱性磷酸酶(BAP)及骨钙素(BGP)明显高于治疗前,人抗酒石酸酸性磷酸酶5b(TRAP-5b)明显低于治疗前,差异有统计学意义(P0.05);而其他三组治疗前后的BMD、BAP、TRAP-5b和BGP相比,差异均不显著(P0.05)。组间相比,治疗后联合组的BMD、BAP及BGP明显高于其他三组,TRAP-5b明显低于其他三组,差异有统计学意义(P0.05)。各组的不良反应总发生率比较,差异均无统计学意义(均P0.05)。结论:利用胰岛素以及阿仑膦酸钠联合治疗T2DM合并骨质疏松症患者,具有较好的疗效,同时还可有效改善其骨代谢指标水平,值得在临床上予以推广。     

阿伦膦酸钠与阿法骨化醇联合治疗妇女绝经后骨质疏松症的疗效

目的:探讨妇女绝经后骨质疏松症(PMO)应用阿伦膦酸钠(ALN)与阿法骨化醇联合治疗的临床效果。方法:选取我院门诊2013年1月~2015年3月收治的98例PMO患者,按照数字随机表法均分为两组。对照组:在常规钙剂基础上,给予阿法骨化醇治疗;观察组:在对照组基础上,给予ALN治疗。记录比较两组治疗前后Ward三角区、股骨颈及腰椎L2~L4骨密度(BMD)水平,治疗前后翻身、前屈后伸及自发性腰背痛视觉模拟评分法(VAS)评分,治疗前后血清骨钙素(BGP)、骨碱性磷酸酶(BALP)、Ⅰ型胶原C端肽(CTX)及抗酒石酸酸性磷酸酶5b(TRACP-5b)水平,用药期间不良反应。结果:观察组治疗后Ward三角区、股骨颈及腰椎L2~L4 BMD水平与治疗前比较,均明显改善(P0.05),且观察组改善程度更加明显(P0.05);观察组治疗后翻身、前屈后伸及自发性腰背痛VAS评分与治疗前比较,均显著降低(P0.01),且观察组改善程度更为显著(P0.01);观察组治疗后血清BGP、BALP、CTX及TRACP-5b水平与治疗前比较,均显著下降(P0.01),且观察组改善幅度更为显著(P0.01)。结论:妇女PMO应用ALN与阿法骨化醇联合治疗更能显著提高BMD水平,缓解患者疼痛症状,改善骨代谢指标,疗效切实,安全可靠,具有较高临床参考价值。     

阿仑膦酸钠联合脂多糖引发巨噬细胞炎症反应的机制研究

目的:阐明阿仑膦酸钠以及阿仑膦酸钠联合脂多糖引发巨噬细胞炎症反应的分子机制,进一步探究双膦酸盐类药物相关性颌骨坏死发生的相关机制。方法:选取小鼠单核巨噬细胞白血病细胞Raw264.7和小鼠骨髓来源的巨噬细胞BMDM作为细胞模型,分为对照组、脂多糖组、阿仑膦酸钠组以及阿仑膦酸钠联合脂多糖组,分别检测Caspase1,IL-1β及IL-18的表达水平,用Western blot检测Raw264.7细胞中Caspase1的蛋白水平变化,用流式观察BMDM细胞中Caspase1荧光强度变化。结果:除了BMDM细胞中阿仑膦酸钠联合脂多糖组IL-1β的表达水平相比阿仑膦酸钠组没有增加外(P0.05),Raw264.7和BMDM细胞中阿仑膦酸钠联合脂多糖组Caspase1,IL-1β及IL-18的m RNA表达水平均高于对照组(P0.05)和阿仑膦酸钠组(P0.05)。Raw264.7细胞中阿仑膦酸钠联合脂多糖组cleaved Caspase 1蛋白表达水平最高。BMDM细胞中阿仑膦酸钠联合脂多糖组Caspase 1荧光强度最高。然而加入组蛋白去甲基化酶抑制剂GSK-J4后,在Raw264.7和BMDM细胞中,阿仑膦酸钠联合脂多糖组Caspase1,IL-1β及IL-18的m RNA表达水平均有下降(P0.05)。结论:阿仑膦酸钠联合脂多糖可以加剧阿仑膦酸钠的炎症反应,促进Caspase1,IL-1β及IL-18的表达,并在一定程度受到表观遗传的调控,提示感染及炎症因素可能对双膦酸盐类药物相关性颌骨坏死(BRONJ)的发生发展具有促进作用,同时提示我们可以在表观遗传方向寻找治疗BRONJ的新靶点。     

利塞膦酸钠对去卵巢大鼠正畸牙齿移动期间破骨细胞中FAK蛋白表达的影响

目的:探讨利塞膦酸钠对去卵巢大鼠正畸牙齿移动期间破骨细胞中FAK蛋白表达的影响。方法:将30只雌性大鼠随机分为3组:假手术组、VOX组(卵巢切除+等量注射生理盐水)和利塞膦酸钠治疗组(切除卵巢+每3天腹膜内注射利塞膦酸钠),各10只。通过数字卡尺测量牙齿移动距离。通过蛋白质印迹检测FAK、I型胶原和整合素-β1蛋白表达水平。使用EXA-3000双能X射线BMD测量仪,测量左股骨BMD。通过RT-qPCR检测TRACP、RANKL和BMP-2 mRNA表达水平。结果:第1~3月时,与假手术组相比,VOX组大鼠体重和牙齿移动距离均增加(P<0.05),而与VOX组相比,利塞膦酸钠治疗组大鼠体重和牙齿移动距离均降低(P<0.05)。与假手术组相比,VOX组FAK、I型胶原和整合素-β1蛋白表达水平、tBMD、pBMD、mBMD和dBMD值以及TRACP、RANKL和BMP-2 mRNA水平均显著降低(P<0.05),而与假手术组和VOX组相比,利塞膦酸钠治疗组以上指标均显著增加(P<0.05)。结论:利塞膦酸钠通过调控整合素-β1/FAK信号通路,对去卵巢大鼠的骨吸收、骨质流失和骨强度降低有有效的抑制作用,可以预防和抑制卵巢切除引起的骨质疏松症的作用,这为骨质疏松症的临床治疗提供了新的依据。     

深度解读 商业地图——骨质疏松症治疗药物编

今后,全球的骨质疏松症治疗药物的市场将会发生什么变化呢。 现在,在全球占首位的公司是拥有销售额第一的产品阿仑膦酸钠水合物（通用名,商品名“FOSAMAX”．下同）的美国Merck公司。阿仑膦酸钠水合物2006年的销售额约为3580亿日元。但是,阿仑膦酸钠水合物的专利将于2008年期满。证券分析师中有人预测2010年该药剂的销售额将缩减为1／5,专利期满的影响看来不小。     

阿仑膦酸钠联合化疗对多发性骨髓瘤患者骨代谢的影响

目的:研究阿仑膦酸钠联合化疗对多发性骨髓瘤患者骨代谢的影响。方法:选取2011年4月到2014年4月我院收治的多发性骨髓瘤患者130例,按照随机数字表法将患者分为研究组和对照组,每组65例,对照组给予化疗,研究组在对照组的基础上给予阿仑膦酸钠,比较两组骨特异性碱性磷酸酶(BAP)、骨钙素(OC)、I型前胶原氨基肽(PINP)、血钙(Ca)、血磷(P)、β胶原特殊序列(β-CTx)以及碱性磷酸酶(ALP)。结果:治疗后研究组OC、PINP和BAP均显著高于治疗前和对照组,比较差异均有统计学意义(P0.05);治疗后研究组β-CTx显著低于治疗前和对照组,比较差异均有统计学意义(P0.05)。结论:阿仑膦酸钠联合化疗治疗多发性骨髓瘤患者能显著改善其的骨代谢,值得临床推广。     

磷酸三钙磨损颗粒诱导小鼠假体周围骨细胞损伤的作用

目的：研究磷酸三钙（TCP）磨损颗粒是否能诱导小鼠颅骨假体周围骨细胞损伤,并探讨其作用机制。方法：36只雄性ICR小鼠随机分为3组（n=12）：假手术组（Sham）、模型（TCP）组和3-甲基腺嘌呤（3-MA）组,采用TCP磨损颗粒30 mg置于小鼠颅骨中缝骨膜外缝合皮肤构建小鼠颅骨溶解模型。3-MA处理组小鼠于术后第2天颅顶皮下注射自噬的特异性抑制剂3-MA （1.0 mg/kg）,2 d 1次,2周后处死动物取血清和颅骨。Micro-CT分析各组小鼠颅骨骨密度（BMD）、骨体积分数（BVF）和骨吸收孔（porosity）数;HE染色和流式细胞术检测各组假体周围骨细胞活性及凋亡情况;ELISA法检测各组血清中骨细胞特征蛋白牙本质基质蛋白（DMP-1）和骨硬化蛋白（SOST）水平;Western blot法检测各组假体周围骨细胞中DMP-1、SOST和自噬关键分子Beclin-1及微管相关蛋白1轻链3（LC-3）等蛋白的表达。结果：与Sham组比较,TCP组假体周围骨细胞活性明显降低,骨细胞死亡及凋亡显著增加（P<0.05）,血清SOST水平及其蛋白表达明显增加,而血清DMP-1水平及其蛋白表达显著减少（P<0.05）,Beclin-1表达增加,LC-3I向LC-3Ⅱ转换明显增加;与TCP组比较,3-MA组假体周围骨细胞损伤明显加重,骨细胞凋亡显著增加（P<0.05）。结论：TCP磨损颗粒可通过激活凋亡和自噬而诱导假体周围骨细胞损伤,促进假体周围骨溶解和关节无菌性松动。     

Alendronate Therapy in Men With Primary Hyperparathyroidism

ObjectiveTo determine the skeletal effects of alendronate therapy in men with primary hyperparathyroidism (PHPT) in comparison with those in postmenopausal women.MethodsThere essentially are no published data on the effects of bisphosphonate therapy in men with PHPT. We previously conducted a double-blind, randomized, single-crossover trial of alendronate, 10 mg daily, in PHPT and reported that alendronate significantly increases bone mineral density (BMD) at 12 months relative to baseline values. That study sample included both women (n = 28) and men (n = 9) and both premenopausal (n = 4) and postmenopausal (n = 24) women. Study subjects were randomly assigned to receive either alendronate or placebo during the first year, and all subjects received alendronate during the second year. Among the men, 3 received alendronate and 6 received placebo during the first year. The current analysis focuses on the skeletal effects of alendronate therapy in the 9 men during their first year of treatment versus the 6 men during their first year while receiving placebo as well as the 24 postmenopausal women during their first year of alendronate therapy. Paired t tests comparing baseline and 12-month data were performed for the 9 treated men and the 6 control subjects; unpaired t tests were used to compare the 9 treated men and the 24 treated women.ResultsAlendronate therapy for 1 year (n = 9) resulted in a 4.8% increase in BMD at the lumbar spine (P = .1) in comparison with the men who received 1 year of placebo (n = 6). Relative to baseline, men receiving alendronate showed a significant 4.4% gain in BMD at the lumbar spine (P = .009) and a 2.95% gain in total hip BMD (P = .027). A 47% decline in serum levels of bone-specific alkaline phosphatase activity was also noted with alendronate therapy (P = .003). Changes in BMD in the male population were similar to previously reported effects of alendronate therapy in postmenopausal women with PHPT.ConclusionAlendronate therapy in men with PHPT is associated with improvements in BMD and reductions in bone turnover. These data, similar to the findings in postmenopausal women with PHPT, suggest that aminobisphosphonates may be of value in providing skeletal protection for men with PHPT. Further study is needed to confirm skeletal protection and fracture efficacy in this population. (Endocr Pract. 2009;15:705-713)     

Effects of Long-Term Alendronate Treatment on a Large Sample of Pediatric Patients with Osteogenesis Imperfecta

Objective: Osteogenesis imperfecta (OI) is a group of inherited diseases characterized by reduced bone mass, recurrent bone fractures, and progressive bone deformities. Here, we evaluate the efficacy and safety of long-term treatment with alendronate in a large sample of Chinese children and adolescents with OI.Methods: In this prospective study, a total of 91 children and adolescents with OI were included. The patients received 3 years' treatment with 70 mg alendronate weekly and 500 mg calcium daily. During the treatment, fracture incidence, bone mineral density (BMD), and serum levels of the bone turnover biomarkers (alkaline phosphatase [ALP] and cross-linked C-telopeptide of type I collagen [β-CTX]) were evaluated. Linear growth speed and parameters of safety were also measured.Results: After 3 years of treatment, the mean annual fracture incidence decreased from 1.2 ± 0.8 to 0.2 ± 0.3 (P<.01). BMD at the lumbar spine and femoral neck significantly increased by 74.6% and 39.5%, with their BMD Z-score increasing from -3.0 to 0.1 and from -4.2 to -1.3, respectively (both P<.01 vs. baseline). In addition, serum ALP and β-CTX levels decreased by 35.6% and 44.3%, respectively (both P<.05 vs. baseline). Height significantly increased, but without an obvious increase in its Z-score. Patient tolerance of alendronate was good.Conclusion: Three years' treatment with alendronate was demonstrated for the first time to significantly reduce fracture incidence, increase lumbar spine and femoral neck BMD, and decrease bone turnover biomarkers in Chinese children and adolescents with OI.Abbreviations:ALP = alkaline phosphataseβ-CTX = cross-linked C-telopeptide of type I collagenBMD = bone mineral densityBP = bisphosphonateDXA = dual-energy X-ray absorptiometry25OHD = 25-hydroxyvitamin DOI = osteogenesis imperfectaPTH = parathyroid hormone     

Zoledronic Acid Versus Alendronate In The Treatment of Children With Osteogenesis Imperfecta: A 2-Year Clinical Study

Objective: Bisphosphonates have been demonstrated to increase the bone mineral density (BMD) of osteogenesis imperfecta (OI) patients. We aimed to compare the efficacy and safety of intravenous zoledronic acid and oral alendronate in patients with OI.Methods: A total of 161 patients with OI ranging from 2 to 16 years old were included and randomized at a 2:1 ratio to receive either weekly oral alendronate (ALN) 70 mg or a once-yearly infusion of zoledronic acid (ZOL) for 2 years. The primary endpoints were percentage change from baseline in lumbar spine (LS) BMD and change in Z-scores of LS BMD.Results: A total of 136 patients with OI completed the 2-year clinical study, 90 of whom were assigned to receive ALN, while 46 received ZOL treatment. The percentage change in LS BMD was 60.01 ± 7.08% in the ALN group and 62.04 ± 5.9% in the ZOL group (P = .721). The corresponding BMD Z-score increased by 0.50 ± 0.05 in the ALN group and 0.71 ± 0.06 in the ZOL group (P = .013). ZOL was superior to ALN in reducing the clinical fracture rate (hazard ratio, 0.23; 95% confidence interval, 0.118 to 0.431). There was no difference in the incidence of severe side effects between the two groups.Conclusion: A once-yearly 5 mg infusion of ZOL and weekly oral ALN had similar effects in increasing BMD and reducing bone resorption in children and adolescents with OI. ZOL was superior to ALN in reducing the clinical fracture rate.Abbreviations: 25OHD = 25-hydroxyvitamin D; ALN = alendronate; ALP = alkaline phosphatase; β-CTX = cross-linked C-telopeptide of type I collagen; BMD = bone mineral density; BP = bisphosphonate; FN = femoral neck; LS = lumbar spine; OI = osteogenesis imperfecta; SAE = severe adverse event; ZOL = zoledronic acid     

Alendronate increases bone mineral density in patients with symptomatic primary hyperparathyroidism

Primary hyperparathyroidism (PHPT) is often associated with low bone mineral density (BMD). An open-labeled, prospective trial was conducted to determine whether alendronate (ALN), 10 mg daily, maintains or improves BMD in patients with advanced PHPT. All patients had symptomatic PHPT and met surgical guidelines however refused surgery. Nineteen patients was treated with alendronate for 2 years. The primary outcome index, BMD, was measured at the lumbar spine (LS) and femoral neck (FN) every 6 months by dual-energy x-ray absorptiometry. Serum calcium, phosphorous and PTH, and urinary calcium excretion were monitored every 3 months. Treatment with alendronate over 2 years was associated with a significant (5.3+/-0.4%; p<0.01) increase in LS BMD in comparison with baseline. FN BMD increased significantly at 24 months with alendronate by 2.5%+/-0.7 (p<0.01) from baseline. Serum calcium, phosphorus and PTH, and urine calcium excretion did not change with alendronate therapy. In PHPT, alendronate significantly increases BMD at the LS and FN at 24 months from baseline values with stable serum calcium and PTH levels. Alendronate may be a useful alternative to parathyroidectomy in symptomatic PHPT among those with low BMD, who are candidates for surgery but either decline or for whom surgery is contraindicated.     

Prevention of Bone Loss After Withdrawal of Tamoxifen

ObjectiveTamoxifen has antiestrogenic effects in the breast and estrogenlike activity in the skeletons of post-menopausal women. We hypothesized that post-menopausal women with breast cancer would experience a rapid decline in bone mineral density (BMD) after stopping tamoxifen, similar to that seen with estrogen withdrawal. The objective of this study was to assess, in a randomized, double-blind, placebo-controlled trial, whether administration of alendronate (70 mg weekly) would prevent bone loss associated with tamoxifen discontinuation.MethodsPostmenopausal women with breast cancer were randomly assigned to receive alendronate or placebo for 1 year within 3 months after withdrawal of tamoxifen therapy. We initiated a randomized, double-blind, placebo-controlled trial of alendronate (70 mg weekly) in an effort to prevent bone loss associated with discontinuation of tamoxifen therapy. Patients treated with aromatase inhibitors were excluded from the study. BMD at the spine, hip, and forearm was measured at baseline and at 12 months. Analyses employed repeated-measures analysis of variance.ResultsPatient accrual was considerably limited by the substantial increase in use of aromatase inhibitors during the enrollment period. The study patients (N = 11) had similar baseline BMD T-scores in the alendronate (n = 6) and placebo (n = 5) subgroups. After 1 year, tamoxifen withdrawal was associated with a significant decline in BMD at the femoral neck, which appeared to be prevented by weekly administration of alendronate (-5.2% versus 0.1%; P = .02). Levels of urinary N-telopeptide, a marker of bone turnover, increased by 48% in study subjects in the placebo group (P < .01), whereas weekly alendronate treatment was associated with a 52% decline (P < .01) in this bone resorption marker.ConclusionDifferences in BMD and bone turnover were evident despite the small sample size. These data suggest that postmenopausal women with breast cancer completing tamoxifen therapy warrant an evaluation of their skeletal health and that bisphosphonate therapy may be useful in preventing bone loss associated with discontinuation of tamoxifen. (Endocr Pract. 2008;14:162-167)     

Comparative effects of alendronate and alfacalcidol on cancellous and cortical bone mass and bone mechanical properties in ovariectomized rats.

The purpose of the present study was to compare the effects of alendronate and alfacalcidol on cancellous and cortical bone mass and bone mechanical properties in ovariectomized rats. Twenty-six female Sprague-Dawley rats, 7 months of age, were randomized by the stratified weight method into four groups: the sham-operated control (Sham) group and the three ovariectomy (OVX) groups, namely, OVX + vehicle, OVX + alendronate (2.5 mg/kg, p.o., daily), and OVX + alfacalcidol (0.5 mug/kg, p.o., daily). At the end of the 8-week experimental period, bone histomorphometric analyses of cancellous bone at the proximal tibial metaphysis and cortical bone at the tibial diaphysis were performed, and the mechanical properties of the femoral distal metaphysis and femoral diaphysis were evaluated. OVX decreased cancellous bone volume per total tissue volume (BV/TV), and the maximum load of the femoral distal metaphysis, as a result of increases in serum osteocalcin (OC) levels, and also the number of osteoclasts (N.Oc), osteoclast surface (OcS) and bone formation rate (BFR) per bone surface (BS), and BFR/BV, without any effect on cortical area (Ct Ar), or maximum load of the femoral diaphysis. Alendronate prevented this decrease in cancellous BV/TV by suppressing increases in N.Oc/BS, OcS/BS, BFR/BS, and BFR/BV, without any apparent effect on Ct Ar, or maximum load of the femoral distal metaphysis and femoral diaphysis. On the other hand, alfacalcidol increased cancellous BV/TV, Ct Ar, and the maximum load of the femoral distal metaphysis and femoral diaphysis, by mildly decreasing trabecular BFR/BV, maintaining trabecular mineral apposition rate and osteoblast surface per BS, increasing periosteal and endocortical BFR/BS, and preventing an increase in endocortical eroded surface per BS. The present study clearly showed the differential skeletal effects of alendronate and alfacalcidol in ovariectomized rats. Alendronate prevented OVX-induced cancellous bone loss by suppressing bone turnover, while alfacalcidol improved cancellous and cortical bone mass and bone strength by suppressing bone resorption and maintaining or even increasing bone formation.