伊班膦酸钠联合辛伐他汀治疗老年性骨质疏松症的疗效及安全性评估

目的 评价伊班膦酸钠联合辛伐他汀治疗老年性骨质疏松症的疗效及安全性。方法 选择我院2010年3月～2011年6月治疗的老年性骨质疏松症患者94例,遵照知情同意原则并按照随机数字表法分为观察组和对照组,对照组46例采用伊班膦酸钠治疗,观察组48例采用伊班膦酸钠联合辛伐他汀治疗,观察比较两组患者的治疗情况。结果 观察组的总有效率为97.9%,明显高于对照组的82.6%,组间差异有统计学意义（P＜0.05）;治疗后两组患者的骨密度均明显上升,观察组改变更为明显（P＜0.05）;观察组的不良反应发生率为6.3%,对照组为8.7%,两组间差异无统计学意义（P＞0.05）。结论 伊班膦酸钠联合辛伐他汀治疗老年性骨质疏松症的临床疗效满意,不良反应少,能明显升高患者的骨密度,是临床首选的药物治疗方案。     

鲑鱼降钙素注射液与唑来膦酸钠注射液治疗绝经后骨质疏松症的临床疗效对比

目的对比鲑鱼降钙素注射液与唑来膦酸钠注射液在治疗绝经后骨质疏松症的临床疗效研究。方法本研究收集了2010年2月-2016年2月在南昌大学第三附属医院治疗的绝经后骨质疏松症患者82例,分为鲑鱼降钙素注射液治疗组(40例,治疗时间3个月/年,连续3年),唑来膦酸钠注射液组(42例,治疗时间1次/年,5 mg/次,连续3年)。同时口服碳酸钙D3(600 mg/d)、骨化三醇(0.25μg/d)。采集患者基线及治疗3年后骨密度(bone mineral density,BMD)、肾功能、血钙(blood calcium,BC)、血磷(blood phosphorus BP)、骨碱性膦酸酶(bone alkaline phosphatase,BALP);进行组间及治疗前后对照;以视觉模拟标度尺(visual analogue scale,VAS)评分评估骨痛情况,判定临床疗效;对比两组患者不良反应的发生人次及发生率。结果(1)对两组患者肾功能、血钙、血磷、骨碱性膦酸酶水平进行组间及治疗前后比较,差异均无统计学意义,P0.05;(2)两组患者治疗后骨痛评价:两组患者VAS评分均较治疗前降低,但鲑鱼降钙素组VAS评分较唑来膦酸钠组显著降低,差异有统计学意义,P0.05;(3)两组患者治疗后面积骨密度值较治疗前均显著升高,P0.05。唑来膦酸钠组患者腰椎、股骨颈骨密度升高幅度高于鲑鱼降钙素组,两组比较差异有统计学意义,P0.05;(4)在本研究中唑来膦酸钠组不良反应发生率低。结论唑来膦酸钠与鲑鱼降钙素治疗3年均有效提高了绝经后骨质疏松症患者的骨密度,其中唑来膦酸钠组优于鲑鱼降钙素组。两种治疗均有效减轻患者骨痛症状,鲑鱼降钙素组临床疗效优于唑来膦酸钠组。     

利塞膦酸钠联合雷洛昔芬治疗绝经后骨质疏松症疗效分析

目的观察利塞膦酸钠联合雷洛昔芬治疗绝经后女性骨质疏松症的效果。方法将148例绝经后女性骨质疏松症患者随机分为治疗组和对照组,治疗组给予利塞膦酸钠联合雷洛昔芬治疗,对照组给予利塞膦酸钠治疗。在治疗前及治疗后12个月分别检测两组受试者腰椎及髋部骨密度、血清骨代谢指标、激素水平及研究期间药物不良反应和VAS评分的变化。结果药物治疗后12个月,两组腰椎(L1～4)及左侧股骨颈的骨密度明显增加,治疗组的骨密度显著高于对照组(P0. 05);血清雌激素和孕酮水平均明显下降,皮质醇水平明显上升,与治疗前相比差异有统计学意义(P0. 05),而对照组与治疗前相比差异无统计学意义(P0. 05);治疗后两组血清P1NP及β-CTX较治疗前明显下降、BAP和BGP较治疗前明显上升,比较差异有统计学意义(P0. 05),治疗组较对照组的改善更为明显(P0. 05);治疗后两组患者VAS评分较治疗前显著降低,比较差异有统计学意义(P0. 05),治疗组较对照组降低得更为明显(P0. 05);两组患者在研究期间的药物不良反应无统计学意义(P0. 05)。结论利塞膦酸钠联合雷洛昔芬治疗骨质疏松症较单独使用利塞膦酸钠治疗的效果更为显著,且不增加药物副作用。     

唑来膦酸与阿仑膦酸钠治疗骨质疏松性髋部骨折的临床疗效对比

目的回顾性分析唑来膦酸与阿仑膦酸钠对骨质疏松性髋部骨折患者的临床疗效和安全性比较。方法从2016年1月至2017年10月就诊的骨质疏松性髋部骨折患者中筛选出分别接受唑来膦酸和阿仑膦酸钠治疗至少1年的老年患者作为研究对象,分为观察组(唑来膦酸治疗)和对照组(阿仑膦酸钠治疗)。收集所有患者治疗前及治疗1年后视觉模拟评分(VAS)、股骨骨密度和骨代谢标志物变化情况,进行组间比较,观察药物不良反应和再发骨折情况。结果治疗1年后两组患者术后骨密度明显升高,VAS评分、Ⅰ型胶原氨基端前肽(PINP)、Ⅰ型胶原羧基端肽(CTX)水平较治疗前均显著下降(P均0. 05)。治疗后观察组VAS评分、CTX水平显著低于同期对照组(P0. 05),两组骨密度、PINP、药物不良反应发生率以及再发骨折差异均无统计学意义(P0. 05)。结论唑来膦酸和阿仑膦酸钠用于骨质疏松性髋部骨折均安全有效。但在缓解骨折术后骨痛症状,改善骨代谢,提高患者依从性方面,唑来膦酸优于阿仑膦酸钠。     

唑来膦酸与阿仑膦酸钠预防PKP术后再骨折的效果分析

目的比较分析静脉滴注唑来膦酸与口服阿仑膦酸钠预防经皮椎体后凸成形(PKP)术后预防骨质疏松性再骨折的效果。方法纳入2014-01—2017-12行PKP手术并获得完整随访的92例骨质疏松性胸腰椎压缩骨折,术后进行规范抗骨质疏松治疗,46例在口服碳酸钙D3片、骨化三醇胶丸基础上口服阿仑膦酸钠治疗(阿仑膦酸钠组),46例在基础治疗后静脉滴注唑来膦酸治疗(唑来膦酸组)。结果 92例均获得随访,随访时间平均16(12～24)个月。阿仑膦酸钠组与唑来膦酸组术后3 d疼痛VAS评分、伤椎椎体前缘高度比值、伤椎Cobb角差异无统计学意义(P0.05)。唑来膦酸组再次骨折发生率低于阿仑膦酸钠组,末次随访时骨密度高于阿仑膦酸钠组,差异有统计学意义(P 0.05)。结论 PKP术后出现骨质疏松性再骨折的主要原因是骨质疏松症控制不佳,对于此类患者术后应重视规范抗骨质疏松治疗,而唑来膦酸预防骨质疏松性再骨折的效果明显优于口服阿仑膦酸钠。     

伊班膦酸钠和阿仑膦酸钠对绝经后骨质疏松的干预研究

目的评价伊班膦酸钠和阿仑膦酸钠对绝经后骨质疏松骨量变化的作用。方法 64例年龄47～80岁,的绝经后骨质疏松妇女随机分为两组,Ⅰ组予以口服伊班膦酸钠150 mg,每月一次;Ⅱ组服用阿仑膦酸钠70 mg,每周一次,两组患者均每天服用钙剂0.6 g及维生素D 200 IU,治疗时间1年,治疗前后测量腰椎及髋部骨密度,评价伊班膦酸钠及阿仑磷酸钠对绝经后骨质疏松骨量变化的作用。结果Ⅰ组治疗半年和1年后,患者腰椎骨量较治疗前分别增加了6.25%和9.64%,(P<0.05),Ⅱ组治疗半年和1年后,患者腰椎骨量较治疗前分别增加了6.82%和11.4%,(P<0.05),两组患者治疗1年后髋部骨量较治疗前也有所增加,以腰椎骨量增加最为明显。结论两种双磷酸盐治疗绝经后骨质疏松均能显著改善患者骨量,临床疗效相近,但伊班膦酸钠临床耐受性较好。     

PKP联合阿伦膦酸钠维D3治疗绝经后骨质疏松性椎体压缩骨折

目的探讨经皮椎体后凸成形术(PKP)联合阿伦膦酸钠维D3治疗绝经后骨质疏松椎体压缩骨折的临床疗效。方法回顾性分析自2017-10—2018-10采用PKP治疗的90例绝经后骨质疏松椎体压缩骨折,48例PKP术后单存口服钙剂治疗(对照组),42例PKP术后口服钙剂联合使用阿伦膦酸钠维D3片治疗(观察组),比较2组术后3 d、6个月疼痛VAS评分与ODI指数,比较2组术后6个月密度T值。结果90例均顺利完成手术与药物治疗,随访时间12~24个月,平均16.9个月。术后3 d2组疼痛VAS评分、ODI指数比较差异无统计学意义(P>0.05),术后6个月观察组疼痛VAS评分、ODI指数、骨密度T值较对照组优,差异有统计学意义(P<0.05)。结论PKP联合阿伦膦酸钠维D3治疗绝经后骨质疏松性椎体骨折临床疗效显著,可以明显缓解患者腰背部疼痛,提高患者生活质量,增加患者骨密度。     

甲状旁腺激素(1-34)联合伊班膦酸钠治疗严重骨质疏松症的临床研究

目的甲状旁腺激素(parathyroid hormone,PTH)(1-34)联合伊班膦酸钠治疗严重骨质疏松症效果临床观察。方法98例严重绝经后骨质疏松症合并骨骼疼痛患者随机分为治疗组和对照组,治疗组使用PTH联合伊班膦酸钠治疗,对照组单纯予以伊班膦酸钠治疗,为期12个月。分别检测两组受试者腰椎及髋部骨密度、血清骨代谢指标治疗前后的改变。结果药物治疗6个月后两组患者腰椎L1~4及股骨粗隆、左侧股骨颈、Ward三角区的骨密度明显增加,且12个月后骨密度进一步增加,显著高于对照组(P0.05);药物治疗12个月后两组血清及碱性磷酸酶(ALP)、血清Ⅰ型胶原C末端肽(s-CTX)、血清抗酒石酸酸性磷酸酶-5b(TRACP-5b)、血清骨源性碱性磷酸酶(BAP)及血清骨钙素(OC)水平均显著改变,且治疗组对ALP及s-CTX、BAP、OC及TRACP-5b影响更明显(P0.05),而两组血钙(Ca)及血磷(P)治疗前后无明显差异(P0.05)。结论PTH联合伊班膦酸钠使用能有效提高严重骨质疏松症患者髋部及腰椎骨密度,改善骨代谢。     

伊班膦酸钠干预绝经后骨质疏松骨量的研究

目的 评价伊班膦酸钠对绝经后骨质疏松骨量变化的作用.方法 32例年龄47～80岁的绝经后骨质疏松妇女,腰椎、股骨颈或股骨总量骨密度T值≤-2.5SD,予以口服伊班膦酸钠150 mg,每月1次,每天服用钙剂0.5 g,治疗时间1年,治疗前后测量腰椎及髋部骨密度,评价伊班膦酸钠对绝经后骨质疏松骨量变化的作用.结果 伊班膦酸钠治疗半年后,患者腰椎骨量较治疗前显著升高(P<0.05),未见明显不良反应,患者有较好的耐受性和持续性.结论 伊班膦酸钠治疗绝经后骨质疏松能显著改善患者骨量,临床使用安全、方便.     

葛根素联合阿仑膦酸钠治疗绝经后骨质疏松症的效果观察

目的探索葛根素联合阿仑膦酸钠对绝经后骨质疏松症的影响。方法 148例绝经后骨质疏松症患者随机分为治疗组(n=74)和对照组(n=74)。对照组给予阿仑膦酸钠治疗,治疗组给予葛根素联合阿仑膦酸钠治疗,为期治疗6个月。检测治疗后两组患者髋部及腰椎的骨密度改变,同时测定血清雌二醇(estradiol,E2)、骨代谢指标[骨钙素(osteocalcin,BGP)、骨源性碱性磷酸酶(bone alkaline phosphatase,BALP)、抗酒石酸酸性磷酸酶-5b(tartrate-resistant acid phosphatase-5b,TRAP-5b)]、免疫因子[白细胞介素-6(interleukin-6,IL-6)、转化生长因子-β(transforming growth factor-β,TGF-β)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)以及白细胞-10(IL-10)]水平的变化,并记录治疗期间出现的药物不良反应。结果治疗前,两组的骨密度、骨代谢指标和免疫因子比较差异无统计学意义(P0.05)。治疗6个月后,两组髋部及腰椎骨密度都有不同程度的升高,其中治疗组骨密度变化更明显,和对照组比较差异有统计学意义(P0.05);同时各组血清BALP、BGP、TRAP-5b、IL-10、IL-6和TNF-α水平均降低,TGF-β1及E2水平均升高,而治疗组改变更明显,两组比较差异有统计学意义(P0.05)。两组患者治疗均未发现明显药物不良反应。结论葛根素联合阿仑膦酸钠可以通过降低骨转换率及减少免疫因子表达来改善绝经后女性骨质疏松患者髋部及腰部的骨密度,且安全性高。     

Zoledronic acid enhances bone-implant osseointegration more than alendronate and strontium ranelate in ovariectomized rats

Summary

This study was designed to compare the effects of alendronate (ALN), strontium ranelate (SR), and zoledronic acid (ZOL) on bone-implant osseointegration in ovariectomized rats. Histological examination and biomechanical tests show that ZOL, ALN, and SR enhance bone-implant osseointegration; ALN and SR have similar effects, while ZOL enhances bone-implant osseointegration more than ALN and SR

Introduction

This study aims to compare the effects of ALN, SR, and ZOL on bone-implant osseointegration in ovariectomized rats.

Methods

Sixty female Sprague–Dawley rats were included in this study. Of them, 48 rats were ovariectomized (OVX) and assigned to four groups: OVX (OVX?+?Veh), ALN (OVX?+?ALN), SR (OVX?+?SR), and ZOL (OVX?+?ZOL). And another 12 rats were sham-operated as a control group (Sham). Four weeks after ovariectomy, HA-coated titanium implants were inserted into the tibias bilaterally in all rats. Then the rats in groups ALN, SR, and ZOL were systemically administrated with alendronate (7 mg/kg/week, orally), strontium ranelate (500 mg/kg/day, orally), or a single injection of zoledronic acid (0.1 mg/kg, iv), respectively. Twelve weeks after implantation, all rats were sacrificed to get the femurs and tibias. Histological examination and biomechanical tests were used to evaluate bone-implant osseointegration in all groups.

Results

ALN, SR, and ZOL significantly increased distal femoral BMD when compared with group OVX; ZOL increased BMD significantly more than ALN and SR (P?<?0.05). Significant increase of bone-to-implant contact and peri-implant bone fraction were observed in groups ALN, SR, and ZOL when compared with group OVX (P?<?0.05). Groups ALN and SR were inferior to groups ZOL and Sham (P?<?0.05) in bone-to-implant contact and peri-implant bone fraction. Similar results were found in biomechanical testing (max pushout force).

Conclusions

In rats losing bone rapidly after ovariectomy, systemic administration of ZOL, ALN, and SR causes better bone-implant osseointegration when compared to OVX; ALN and SR have similar positive effects on osseointegration, while ZOL, that was given in a dose with more positive BMD effect than that of ALN or SR, causes better osseointegration than either ALN or SR.     

A single zoledronic acid infusion reduces bone resorption markers more rapidly than weekly oral alendronate in postmenopausal women with low bone mineral density

Early data suggest that an annual i.v. infusion of zoledronic acid (ZOL) might have therapeutic use in women with osteoporosis. In this randomized, double-blind, double-dummy, multicenter, 24-week trial, we evaluated the onset of action of a single infusion of ZOL 5 mg (n=69) compared with weekly oral alendronate (ALN) 70 mg (n=59) in postmenopausal women with low bone mineral density (T score< or =-2 by DXA) as assessed by reductions in urine N-telopeptide of type I collagen (NTX) at week 1. The effects of these therapies on other markers of bone turnover, patient preference for once yearly i.v. vs. oral weekly treatment, and adverse events were also assessed. At week 1, ZOL 5 mg resulted in a significantly greater reduction in mean urine NTX from baseline than ALN 70 mg (P<0.0001). Significantly greater reduction in urine NTX and serum beta-C-telopeptide of type I collagen (beta-CTX) were also observed in the ZOL 5 mg group at all post-baseline time points. Bone-specific alkaline phosphatase (BSAP) levels showed a more gradual reduction in both the ZOL 5 mg and ALN 70 mg groups, reaching premenopausal range by week 12. A comparable proportion of patients reported adverse events in each treatment group (ZOL 5 mg, 91.3%; ALN 70 mg, 86.4%). Transient, flu-like symptoms were the most common adverse events in the ZOL 5 mg group and resulted in a higher frequency of adverse events in this group during the first 3 days of treatment. After 3 days, adverse event rates were similar in the 2 groups. The majority of patients, including those experiencing flu-like symptoms, expressed a preference for annual i.v. therapy (66.4%) compared with weekly oral therapy (19.7%). We conclude that a single i.v. infusion of ZOL 5 mg reduced urine NTX levels more rapidly than weekly oral ALN 70 mg. The majority of study patients preferred an i.v. treatment regimen of ZOL 5 mg over weekly osteoporosis therapy with ALN 70 mg.     

Cancer treatment dosing regimens of zoledronic acid result in near‐complete suppression of mandible intracortical bone remodeling in beagle dogs

Bisphosphonate doses used in cancer treatment are substantially higher than those used for osteoporosis. Little is known about the effects of these high doses on tissue‐level remodeling suppression. The aim of this study was to assess the effects of cancer dosing regimens of zoledronic acid on tissue‐level bone remodeling at different skeletal sites. Skeletally mature female beagle dogs were treated with monthly intravenous infusions of vehicle (VEH, saline) or zoledronic acid (ZOL, 0.067 mg/kg); an additional group of animals was treated daily with oral alendronate (ALN, 0.2 mg/kg/day). Doses of ZOL and ALN were, on a milligram per kilogram basis, consistent with those used for cancer and osteoporosis, respectively. Following either 3 or 6 months of treatment, animals were euthanized, and mandible, rib, and tibia were processed for dynamic bone histology. There was no evidence of oral lesions or bone matrix necrosis in the mandibles of any animals. After 3 months, the rate of intracortical bone remodeling in the mandible was significantly suppressed with ZOL (?95%) compared with VEH; by 6 months, ZOL had produced nearly complete suppression (?99%) compared with VEH. ZOL also significantly suppressed remodeling in the rib cortex at both 3 (?83%) and 6 (?85%) months compared with VEH; tibia cortex bone formation rate was nonsignificantly lower with ZOL treatment (?68% to ?75%). Remodeling suppression in ZOL‐treated animals was significantly greater than in ALN‐treated animals at both the mandible and the rib; ALN and VEH were not different for any of the assessed parameters at any of the sites. Compared across skeletal sites, the absolute level of remodeling suppression with ZOL treatment was significantly greater at sites with higher remodeling, whereas the percent reduction was similar among the sites. These results document nearly complete intracortical remodeling suppression resulting from monthly intravenous zoledronic acid dosing, with changes being most dramatic at the mandible. Copyright © 2010 American Society for Bone and Mineral Research     

Intravenous zoledronic acid 5 mg in the treatment of postmenopausal women with low bone density previously treated with alendronate

This randomized, double-blind, double-dummy, multicenter trial assessed safety and efficacy of a single dose of IV zoledronic acid (ZOL) 5 mg vs. oral alendronate (ALN) 70 mg weekly in postmenopausal women with low bone mineral density (BMD) who had previously been treated with ALN. Postmenopausal women who were receiving oral ALN for at least 1 year immediately prior to randomization and with lumbar spine or femoral neck BMD T-score values < or = -2.0 prior to initiation of ALN were randomized to one 15-min IV infusion of ZOL 5 mg plus 52 weeks of oral placebo (n=113) or one IV infusion of placebo plus 52 weeks of oral ALN 70 mg (n=112). End points included percent change in lumbar spine BMD from baseline to month 12 and relative change from baseline in urine N-telopeptide of type I collagen (NTX), serum C-telopeptide of type I collagen (CTX), amino terminal propeptides of type I collagen (PINP), and bone-specific alkaline phosphatase (bone ALP) over 12 months. Adverse events, bone histomorphometry and microscopic appearance, and patient preference for the 2 treatment regimens were also assessed. In this study, a single infusion of ZOL 5 mg maintained BMD 12 months following the switch from oral ALN in women with osteoporosis. The mean duration of prior ALN therapy at baseline was 4 years. Mean biomarker levels in the ALN 70-mg group remained at or close to baseline levels for the duration of the study. In the ZOL 5-mg group, mean biomarker levels were reduced from baseline after 3 months, returned to baseline after 6 months, and increased thereafter but remained within the premenopausal range. The overall rates of adverse events were comparable in the 2 groups (ZOL 5 mg, 86.7%; ALN 70 mg, 80.4%). Headache occurred more commonly within the first 3 days after infusion with ZOL 5 mg (12.4%) than with ALN 70 mg (6.3%). Bone biopsies indicate that both treatments decrease excessive remodeling seen in osteoporosis. The majority (78.7%) of patients expressed preference for once yearly infusion over weekly oral therapy. We conclude that patients can be switched from oral ALN to ZOL 5 mg infusion with maintenance of therapeutic effect for at least 12 months and that patients prefer a once yearly infusion to weekly oral therapy.     

碳酸钙D3、骨化三醇联合唑来膦酸对2型糖尿病合并原发性骨质疏松症患者骨密度和骨痛的影响

目的分析探讨碳酸钙D3、骨化三醇联合唑来膦酸对2型糖尿病(type 2 diabetes mellitus,T2DM)合并原发性骨质疏松症老年患者骨密度和骨痛的影响。方法选取我院2014年5月至2015年5月期间收治的T2DM合并原发性骨质疏松症老年患者220例,将所有患者按照随机数字表法随机分为对照组和试验组,所有患者均给予骨化三醇和碳酸钙D3进行治疗,其中试验组患者使用碳酸钙D3、骨化三醇联合唑来膦酸进行治疗。所有患者均持续治疗3年,3年后观察两组患者的骨密度(bone mineral density,BMD)及骨痛视觉模拟评分(visual analogue scale,VAS)评分情况,比较两组患者的不良反应发生情况。结果两组患者治疗前的骨密度情况并无明显差异(P均0. 05);治疗三年后,两组患者的骨密度均比治疗前有所增加(P0. 05),试验组患者的骨密度显著优于同期对照组患者(P均0. 05)。两组患者治疗前的VAS评分并无明显差异(P 0. 05);经过三年的治疗后,两组患者的VAS评分均显著低于本组治疗前(P0. 05),试验组患者的VAS评分显著低于同期对照组患者(P0. 05)。试验组患者在治疗期间没有新发骨折出现,而对照组患者则有1例出现左侧股骨颈骨折;试验组患者在静注唑来膦酸注射液后有5例出现轻微的头疼、乏力、发热、感冒等症状,在服用塞来昔布洛索洛芬后症状缓解。结论对T2DM合并原发性骨质疏松症老年患者采取碳酸钙D3、骨化三醇联合唑来膦酸进行治疗能够有效增加患者的骨密度,改善其骨痛VAS评分,效果显著,值得在临床上加以推广运用。     

二甲双胍联合阿仑膦酸钠治疗骨质疏松症合并2型糖尿病的临床疗效

目的观察二甲双胍联合阿仑膦酸钠对骨质疏松症合并2型糖尿病的影响。方法将120例绝经后骨质疏松症合并2型糖尿病患者随机分为治疗组(n=60)和对照组(n=60)。对照组给予阿仑膦酸钠治疗,治疗组给予阿仑膦酸钠联合二甲双胍治疗,为期治疗6个月。检测治疗后两组患者髋部及腰椎骨密度和视觉模拟评分法(visual analogue scale,VAS)评分改变,同时测定血清骨代谢指标骨特异性碱性磷酸酶(bone-specific alkaline phosphatase,B-ALP)和抗酒石酸酸性磷酸酶-5b(tartrate resistant acid phosphatase-5b,TRACP-5b)水平的变化,记录药物的不良反应。结果治疗前两组的骨密度、骨代谢指标和VAS评分比较没有统计学意义(P0.05)。治疗3个月和6个月后,两组髋部及腰椎密度都有不同程度的升高(P0.05),治疗组的骨密度提高较对照组更为显著(P0.05)。同时,各组血清B-ALP和TRACP-5b水平、VAS评分均降低(P0.05),治疗组的骨代谢指标和VAS评分改善较对照组更为显著(P0.05)。而两组之间的不良反应比较无明显差异(P0.05)。结论二甲双胍增加阿仑膦酸钠治疗骨质疏松症合并2型糖尿病临床疗效显著。     

Efficacy and safety of a once‐yearly i.v. Infusion of zoledronic acid 5 mg versus a once‐weekly 70‐mg oral alendronate in the treatment of male osteoporosis: A randomized,multicenter, double‐blind,active‐controlled study

Zoledronic acid (ZOL) has shown beneficial effects on bone turnover and bone mineral density (BMD) in postmenopausal osteoporosis. This study compared the efficacy and safety of a once‐yearly i.v. infusion of ZOL with weekly oral alendronate (ALN) in men with osteoporosis. In this multicenter, double‐blind, active‐controlled, parallel‐group study, participants (n = 302) were randomized to receive either once‐yearly ZOL 5 mg i.v. or weekly oral ALN 70 mg for 24 months. Changes in BMD and bone marker levels were assessed. ZOL increased BMD at the lumbar spine, total hip, femoral neck, and trochanter and was not inferior to ALN at 24 months [least squares mean estimates of the percentage increases in lumbar spine BMD of 6.1% and 6.2%; difference approximately 0.13; 95% confidence interval (CI) 1.12–0.85 in the ZOL and ALN groups, respectively]. At month 12, the median change from baseline of markers for bone resorption [serum β‐C‐terminal telopeptide of type I collagen (β‐CTx) and urine N‐terminal telopeptide of type I collagen (NTx)] and formation [serum N‐terminal propeptide of type I collagen (P1NP) and serum bone‐specific alkaline phosphatase (BSAP)] were comparable between ZOL and ALN groups. Most men preferred i.v. ZOL over oral ALN. The incidence of adverse events and serious adverse events was similar in the treatment groups. It is concluded that a once‐yearly i.v. infusion of ZOL 5 mg increased bone density and decreased bone turnover markers similarly to once‐weekly oral ALN 70 mg in men with low bone density. © 2010 American Society for Bone and Mineral Research.     

Cost-Minimization Study Comparing Annual Infusion of Zoledronic Acid or Weekly Oral Alendronate in Women With Low Bone Mineral Density

Cost-minimization study to assess the annual direct costs of 2 antiresorptive strategies in postmenopausal women with low bone mineral densities (BMDs). Patients were randomly assigned to receive 70 mg of oral weekly alendronate or a 1-time 5 mg of intravenous zoledronic acid. All medical and nonmedical direct costs were recorded for 1 yr. Student's t-test or the Chi-squared test was used. A total of 101 postmenopausal women were enrolled with a mean age of 58.3 ± 7.6 yr and a postmenopausal period of 13.5 ± 8.3 yr. A total of 50 patients completed 1 yr of alendronate and 51 patients received zoledronic acid. At baseline, no differences were seen between the 2 groups in anthropometric measures, comorbidities, and bone mineral density. The costs for medical attention for low bone mass were $81,532 (US Dollars) for the alendronate group and $69,251 for the zoledronic acid group; the cost per patient was $1631 in the alendronate group vs $1358 in the zoledronic acid group (p < 0.0001). Therefore, zoledronic acid treatment provided an annual savings of 15% of the direct costs compared with oral alendronate treatment. Moreover, there was a significant increase in lumbar spine T-scores in the zoledronic acid group when compared with the alendronate group. Annual zoledronic acid infusion as an antiresorptive treatment in women with low BMD provides significant monetary savings when compared with weekly alendronate therapy for 1 yr. Zoledronic acid infusion is also linked to higher increase in BMD and compliance.     

In Vitro and In Vivo Responses to High and Low Doses of Nitrogen-Containing Bisphosphonates Suggest Engagement of Different Mechanisms for Inhibition of Osteoclastic Bone Resorption

The effects of nitrogen-containing bisphosphonates (N-BPs) on osteoclasts (Ocs) may differ with dose and regimen. N-BPs reduce Oc bone resorption by inhibiting the enzyme farnesyl diphosphate synthase (FPPS), an effect counteracted by geranylgeraniol (GGOH), which restores geranylgeranylation downstream of FPPS. We assessed GGOH effects on inhibition of bone resorption by the N-BPs alendronate (ALN), ibandronate (IBN), and zoledronate (ZOL) in an assay of rabbit Oc resorption of bovine cortical bone. GGOH blocked inhibition of resorption at low, but not high, N-BP concentrations, with a 14- to 20-fold increase in IC₅₀ values for each N-BP. In vivo, growing male rats were administered doses calculated to mimic bioavailable exposures in daily (ALN, IBN), weekly (ALN), monthly (IBN), and yearly (ZOL) clinical regimens. Tibiae were harvested at 48 h, and metaphyses were analyzed. With lower ALN and IBN doses, Oc numbers rose by 26–48 %, morphology was normal, and there was no increase in apoptotic Ocs. In contrast, with higher IBN and ZOL doses, bone-associated Ocs were generally rounded in appearance and numbers of nuclei/Oc versus vehicle increased 42 and 31 %, respectively (P < 0.05). With ZOL, there was no rise in Oc number, but there was a 6.5-fold increase in apoptotic Ocs versus vehicle and a ≥13.5-fold increase versus lower-dose ALN or IBN (P < 0.05). With higher-dose IBN there was no rise in Oc number but 7- and 14-fold increases in Oc apoptosis versus low-dose ALN and IBN (P < 0.02). These results suggest that different mechanisms may come into play across the dosing spectrum of N-BPs.