阿仑膦酸钠联合替勃龙治疗绝经后骨质疏松症疗效分析

目的探讨阿仑膦酸钠联合替勃龙治疗绝经后骨质疏松症的临床疗效。方法回顾性分析自2010-01—2015-12诊治的300例绝经后骨质疏松症,150例采用阿仑膦酸钠联合替勃龙治疗(观察组),150采用阿仑膦酸钠治疗(对照组),比较2组治疗期间不良反应情况、末次随访时临床疗效,治疗前、治疗后6个月、治疗后12个月股骨颈骨密度、骨碱性磷酸酶(BALP)、羟基末端肽(CTX)、钙调节激素25(OH)D3。结果 300例均获得随访,随访时间平均14.34(3~21)个月。治疗期间观察组不良反应较对照组少,末次随访时观察组临床疗效较对照组优,差异有统计学意义(P <0.05)。治疗后6个月、12个月观察组股骨颈骨密度、BALP、CTX、25(OH)D3较对照组明显改善,差异有统计学意义(P <0.05)。结论采用阿仑膦酸钠联合替勃龙治疗绝经后骨质疏松症可提高骨密度,改善骨代谢,临床疗效满意,安全性良好。     

阿仑膦酸钠对绝经后骨质疏松症患者骨代谢指标的影响

目的观察抗骨吸收药物双膦酸盐对绝经后骨质疏松症患者骨代谢状态的影响。方法本研究为回顾性研究,共收集在我院骨质疏松门诊数据库中临床资料完整的女性绝经后骨质疏松症患者152例,其中阿仑膦酸钠治疗组93例(A组),每周给予阿仑膦酸钠70 mg,一次口服;未服用阿仑膦酸钠对照组59例(B组)。分别观察治疗前和治疗后3、6、12个月骨转换生化指标:骨特异性碱性磷酸酶(BAP)、抗酒石酸酸性磷酸酶(TRAP-5b)及25羟维生素D(25(OH)VD)的变化。结果 A组患者经阿仑膦酸钠治疗3个月后BAP和TRAP-5b水平分别较治疗前下降30.60%和32.95%(P0.001)治疗6个月时完全降至女性绝经前水平,并一直维持在此水平至治疗后12个月。B组患者治疗前后BAP和TRAP-5b水平差异无统计学意义。结论绝经后骨质疏松症患者骨代谢处于高转换状态,其BAP及TRAP-5b水平较绝经前明显升高;经阿仑膦酸钠治疗3个月后高转换状态可以明显改善,骨转换指标BAP和TRAP-5b水平回落到绝经前水平。     

运动联合利塞膦酸钠治疗绝经后女性骨质疏松症疗效分析

目的观察广场舞运动联合补充利塞膦酸钠防治绝经后骨质疏松症的疗效。方法 168名绝经后骨质疏松症妇女随机分为实验组和对照组,实验组进行广场舞锻炼联合补充利塞膦酸钠治疗,对照组单纯予以补充利塞膦酸钠治疗。实验前及实验干预后6个月和12个月分别检测两组受试者腰椎L1-4、股骨颈部及Ward区骨密度、VAS疼痛评分、骨代谢指标以及不良反应。结果治疗6个月及12个月,两组患者VAS评分不同程度降低,其中以治疗组骨痛的治疗效果要明显优于对照组(P0.05)。治疗12个月后两组腰椎L1-4、股骨颈部及Ward区骨密度明显升高(P0.05),而治疗组明显高于对照组(P0.05)。治疗后6个月及12月,两组血清OC及NTX I较治疗前比较改善明显(P0.05),和对照组比较,治疗组血清OC及NTX I水平改变更为明显(P0.05);而两组不良反应无明显差异(P0.05)。结论广场舞运动结合补充利塞膦酸钠可以有效改善绝经后骨质疏松症,是一种合适的治疗方案。     

74例老年骨质疏松患者应用鲑鱼降钙素联合阿仑膦酸钠治疗的疗效观察

目的　评估联合应用鲑鱼降钙素与阿仑膦酸钠治疗缓解老年性骨质疏松症患者骨关节疼痛及血清骨钙素(BGP)、降钙素(CT)及骨密度(BMD)水平的变化。方法 联合应用鲑鱼降钙素和阿仑膦酸钠治疗本院收治的74例老年性骨质疏松症患者,给予鲑鱼降钙素50IU肌肉注射,隔日1次,连续使用15次后改为口服阿仑膦酸钠1粒/周,共经6个月治疗,采用数字模拟评分法(VAS)比较治疗前、后全身骨关节疼痛程度,治疗前、后骨钙素、降钙素及第2～第4腰椎(L2-4 )、股骨颈、Ward区骨密度水平的变化,并进行统计学分析。结果 鲑鱼降钙素联合阿仑膦酸钠治疗老年性骨质疏松症患者6个月后,对缓解骨关节疼痛症状疗效良好,治疗前与治疗后比较差异显著(P<0.01);治疗前后骨密度、血清骨钙素和降钙素水平均有显著差异（P<0.05）。结论 鲑鱼降钙素联合阿仑膦酸钠治疗老年性骨质疏松症使血清降钙素的水平明显升高,骨钙素水平明显降低,能显著减轻患者骨关节疼痛,改善症状,并增加骨密度,对老年性骨质疏松症有明显的疗效。     

甲状旁腺激素(1-34)和阿仑膦酸钠治疗骨质疏松症合并类风湿关节炎疗效的对比研究

目的比较甲状旁腺激素(parathyroid hormone,PTH)(1-34)和阿仑膦酸钠(alendronate,ALN)治疗骨质疏松症合并类风湿关节炎(rheumatoid arthritis,RA)女性患者的疗效。方法选取98例于2017年2月至2017年11月在我院就诊诊断为骨质疏松症合并RA的绝经后女性患者。按照治疗方案将患者分为PTH组和ALN组,两组患者分别接受特立帕肽或阿仑膦酸钠治疗,观察治疗6个月后两组患者骨密度和骨代谢指标的改变。结果在两组治疗6个月后,腰椎的骨密度较治疗前均有显著增加(P0.05)。与ALN组相比,PTH组治疗6个月腰椎骨密度的平均变化百分比显然更高;而股骨颈骨密度仅在PTH组显著增加。结论甲状旁腺激素(1-34)在短期治疗骨质疏松症合并类风湿女性患者时,效果较阿仑膦酸钠更佳。     

阿仑膦酸钠治疗绝经后妇女骨质疏松症临床分析

目的评价阿仑膦酸钠片治疗绝经后妇女骨质疏松症的临床疗效、安全性、依从性。方法对50例患骨质疏松症的绝经后妇女随机分为治疗组30例,服用阿仑膦酸钠,1次/周;对照组20例,服用钙尔奇D片,1次/天,两组疗程均为6个月。结果阿仑膦酸钠治疗组骨密度定量测定较治疗前有明显提高（P〈0.01）,疼痛症状改善;总有效率93.5%,与钙尔奇D组比较有统计学意义（P〈0.05）。结论阿仑膦酸钠治疗绝经后妇女骨质疏松症疗效好。     

阿仑膦酸钠治疗COPD患者骨质疏松症的疗效及对肺功能的影响

目的 评价阿仑膦酸钠治疗慢性阻塞性肺疾病(COPD)患者骨质疏松症的近期临床疗效及对肺功能的影响。方法 COPD患者38例，经骨密度检查，并根据WHO诊断标准确诊为骨质疏松症，连续服用阿仑膦酸钠和碳酸钙，于治疗6个月后复测患者骨密度、肺功能以及血清钙、磷、碱性磷酸酶(ALP)、血清骨钙素(BGP)和晨尿游离脱氧吡啶啉排泄率(Dpd／Cr)；在服药期间每月在门诊随诊1次，观察患者临床症状、血常规及肝肾功能等生化指标。结果 治疗6个月后患骨痛症状改善，FEV1及FEV1％有显著提高，腰椎正、侧位、左股骨颈、左股骨近端及Ward’s三角的骨密度均有不同程度增高。治疗前FEV1、治疗后FEV1变化值／XFEV1与腰椎正、侧位骨密度变化值△APL1-4及△LatL2-4间呈正相关。治疗后血清钙、BGP水平升高；血清磷、ALP水平及晨尿Dpd／Cr值均下降。无严重的副作用及过敏反应。结论 阿仑膦酸钠是治疗COPD合并骨质疏松症的安全有效的药物，可提高患者骨密度，也有利于肺通气功能的改善，特别适合于病情较重或有骨折的患者。     

阿仑膦酸钠对绝经后骨质疏松合并骨关节炎患者骨强度的影响

目的探讨阿仑膦酸钠对绝经后骨质疏松症(postmenopausal osteoporosis,PMOP)合并骨关节炎(osteoarthritis,OA)患者骨强度的影响。方法选取华北理工大学附属医院骨质疏松门诊2016年5月至2019年10月诊治的144例患者,根据其诊断分为OP+OA组(73例)和OP组(71例)。两组患者口服阿仑膦酸钠(1次/周),连续治疗12个月。比较两组患者治疗前后股骨颈截面面积(CSA)、股骨颈截面转动力矩(CSMI)、股骨颈截面模量(Z)、股骨颈皮质厚度(CT)、股骨颈屈曲应力比(BR)、骨密度、疼痛视觉模拟评分(VAS)、Lysholm膝关节评分、生化指标变化。结果两组患者治疗后CSA、CSMI、Z、腰椎和股骨颈骨密度、Lysholm膝关节评分高于治疗前(P<0.05),而在治疗12个月后OP+OA组患者腰椎、股骨颈骨密度高于OP组(P<0.05)。两组患者治疗后BR、VAS评分低于治疗前(P<0.05),而在治疗后12个月OP+OA组患者BR、VAS评分低于OP组(P<0.05)。结论阿仑膦酸钠应用于绝经后骨质疏松合并骨关节炎患者治疗,不仅可以提高骨密度、改善关节症状,还能提高髋部骨强度。     

阿仑膦酸钠治疗男性骨质疏松症的临床研究

目的 观察阿仑膦酸钠治疗男性骨质疏松症的疗效和安全性。方法 ３７例男性骨质疏松症患者,选用阿仑膦酸钠治疗６个月。比较治疗前后患者疼痛、骨密度、血生化指标和副反应的变化。结果 经６个月治疗后,患者疼痛明显改善,腰椎、股骨颈和髋部骨密度增加,尿钙与尿肌酐比值（Ｃａ／Ｃｒ）及尿羟脯氨酸与尿肌酐比值（Ｈｏｐ／Ｃｒ）降低,副反应轻微且耐受性好。结论 阿仑膦酸钠治疗男性骨质疏松症疗效显著、安全性好。     

骨胶原肽对老年骨质疏松症患者骨密度和骨代谢指标的影响

目的观察骨胶原肽对老年骨质疏松症患者的骨密度和血清骨代谢指标水平的影响。方法 138例老年骨质疏松症患者纳入本研究,将其随机分为治疗组和对照组,每组各69例。对照组患者应用阿仑膦酸钠治疗,治疗组患者给予骨胶原肽联合阿仑膦酸钠治疗,治疗为期12个月。检测治疗前和治疗12个月后两组患者腰椎正位(L1-L4)、左股骨颈的骨密度、血清血钙、血磷、骨碱性磷酸酶(bone alkaline phosphatase,BALP)和抗酒石酸酸性磷酸酶-5b(tartrate-resistant acid phosphatase-5b,TRAP-5b)水平变化情况以及治疗有效率和不良反应。结果治疗12个月后,治疗组腰椎正位、左股骨颈的骨密度患者均明显高于对照组,差异均有统计学意义(P0.05);治疗12个月后,两组患者血清BALP及血磷水平较治疗前明显降低,血清TRAP-5b及血钙水平均较治疗前明显升高,和治疗前比较差异均有统计意义(P0.05);而治疗组较对照组改善更为明显(P0.05)。治疗组的患者治疗有效率优于对照组(P0.05),而不良反应无明显差异(P0.05)。结论骨胶原肽联合阿仑膦酸钠能安全有效提高老年骨质疏松症患者的骨密度,改善骨代谢。     

Early changes in urinary cross-linked N-terminal telopeptides of type I collagen level correlate with 1-year response of lumbar bone mineral density to alendronate in postmenopausal Japanese women with osteoporosis

The purpose of this study was to determine whether early changes in the urinary levels of cross-linked N-terminal telopeptides of type I collagen (NTX) during alendronate treatment would be correlated with the 1-year response of lumbar bone mineral density (BMD) in postmenopausal Japanese women with osteoporosis. One hundred five postmenopausal women with osteoporosis, aged 54–88 years, were treated with alendronate (5mg daily) for 12 months. The urinary NTX levels were measured by enzyme-linked immunosorbent assay at the baseline and at 3, 6, and 12 months, and lumbar (L1–L4) BMD was measured by dual-energy X-ray absorptiometry using the Hologic QDR 1500W equipment at the baseline and at 12 months. The mean percent reduction in urinary NTX level at 3, 6, and 12 months was 36.8%, 49.5%, and 49.0%, respectively, the extent of reduction at 6 and 12 months being greater than that at 3 months, and the mean percent increase of the lumbar BMD at 12 months was 8.2%. Single regression analysis showed a significant correlation between the percent reductions in the urinary NTX level at 3, 6, and 12 months of treatment and the percent increase of the lumbar BMD at 12 months (r = 0.200, P < 0.05; r = 0.341, P < 0.001; and r = 0.338, P < 0.001, respectively). Thirty percent of the patients were labeled as poor responders at 3 months, with the reduction in the urinary NTX level being less than the minimum significant change (MSC); 61% of these patients showed a greater reduction in the urinary NTX level, exceeding the MSC, at 6 months. These results suggest that the changes in the urinary NTX levels at 3 and 6 months after the start of alendronate treatment at the dose of 5mg daily may be correlated with the 1-year response of the lumbar BMD in postmenopausal Japanese women with osteoporosis. In other words, the greater the reduction of the urinary NTX level at 3 and 6 months after the start of alendronate treatment, the greater can be the expected increase of the lumbar BMD after 12 months of treatment. In this study, 70% of the patients were good responders, who showed a reduction of the urinary NTX level exceeding the MSC at 3 months. Among the remaining 30% poor responders, about 60% showed satisfactory reduction of the urinary NTX level, exceeding the MSC, at 6 months after the start of treatment with alendronate.     

Effect of alendronate on bone mineral density and bone turnover markers in post-gastrectomy osteoporotic patients

Alendronate decreases the urinary levels of cross-linked N-terminal telopeptides of type I collagen (NTX; about 45% at 3 months) and serum levels of alkaline phosphatase (ALP; about 27% at 24 months), leading to an increase in lumbar spine bone mineral density (BMD; about 9% at 24 months) in postmenopausal Japanese women with osteoporosis. However, the effectiveness of oral bisphosphonates on osteoporosis remains to be established in patients who have undergone a gastrectomy. The objective of the present case series study was to examine the effect of alendronate on BMD and bone turnover markers in post-gastrectomy osteoporotic patients. Sixteen patients (3 men and 13 postmenopausal women) with osteoporosis, who had undergone a gastrectomy (mean age: 69.1 years), were recruited in our outpatient clinic. All the patients were treated with alendronate (5 mg daily or 35 mg weekly) for 24 months. The effects of alendronate on lumbar spine (women) or total hip (men) BMD and urinary NTX and serum ALP levels were examined. A total or partial gastrectomy had been performed for eight patients each. The mean duration after surgery was 16.0 years. With alendronate therapy, urinary NTX levels significantly decreased at 3 months (−27.0%). Serum ALP levels decreased (−12.1%) and lumbar spine BMD increased (+5.2%), but total hip BMD did not significantly change (+0.6%) at 24 months. No severe adverse events were observed, and alendronate therapy was well tolerated. These results suggest that alendronate mildly increases lumbar spine BMD by mildly reducing bone turnover in osteoporotic patients after a gastrectomy.     

Treatment with once-weekly alendronate 70 mg compared with once-weekly risedronate 35 mg in women with postmenopausal osteoporosis: a randomized double-blind study.

Once-weekly alendronate 70 mg and once-weekly risedronate 35 mg are indicated for the treatment of postmenopausal osteoporosis. These two agents were compared in a 12-month head-to-head trial. Greater gains in BMD and greater reductions in markers of bone turnover were seen with alendronate compared with risedronate with similar tolerability. INTRODUCTION: The nitrogen-containing bisphosphonates, alendronate and risedronate, are available in once-weekly (OW) formulations for the treatment of postmenopausal osteoporosis. A 12-month, head-to-head study was performed to compare these agents in the treatment of postmenopausal women with low BMD. MATERIALS AND METHODS: A total of 1053 patients from 78 U.S. sites were randomized to OW alendronate 70 mg (N = 520) or risedronate 35 mg (N = 533), taken in the morning after fasting. Endpoints included BMD changes over 6 and 12 months at the hip trochanter, total hip, femoral neck, and lumbar spine (LS); percent of patients with predefined levels of change in trochanter and LS BMD at 12 months; and change in biochemical markers of bone turnover at 3, 6, and 12 months. Tolerability was evaluated by adverse experience (AE) reporting. RESULTS: Significantly greater increases in hip trochanter BMD were seen with alendronate (3.4%) than risedronate (2.1%) at 12 months (treatment difference, 1.4%; p < 0.001) as well as 6 months (treatment difference, 1.3%; p < 0.001). Significantly greater gains in BMD were seen with alendronate at all BMD sites measured (12-month difference: total hip, 1.0%; femoral neck, 0.7%; LS, 1.2%). Significant differences were seen as early as 6 months at all sites. A greater percentage of patients had > or =0% (p < 0.001) and > or =3% (p < 0.01) gain in trochanter and spine BMD at 12 months with alendronate than risedronate. Significantly greater (p < 0.001) reductions in all biochemical markers of bone turnover occurred with alendronate compared with risedronate by 3 months. No significant differences were seen between treatment groups in the incidence of upper gastrointestinal AEs or AEs causing discontinuation. CONCLUSIONS: In this 12-month, head-to-head trial of alendronate and risedronate, given in accordance with the approved OW regimens for treatment of osteoporosis in postmenopausal women, alendronate produced greater gains in BMD and greater reductions in markers of bone turnover than risedronate. The greater antiresorptive effect of alendronate was seen as early as 3 months, and the tolerability profiles were similar.     

胰岛素、阿仑膦酸钠治疗新诊断老年糖尿病骨质疏松症患者骨密度及骨转换指标的研究

目的通过观察胰岛素、阿仑膦酸钠干预,观察在糖尿病骨质疏松症治疗12个月后股骨颈(Femur Neck)骨密度(BMD)及骨特异性碱性磷酸酶(BAP)、骨钙素(BGP)、抗酒石酸酸性磷酸酶-5b(TRAP-5b)等血清骨转换指标的变化。方法选取在我院治疗的糖尿病骨质疏松症患者128例,随机分成4组,即对照组(METF)、胰岛素组(INSU)、二甲双胍+阿仑膦酸钠组(METF+ALEN)、胰岛素+阿仑膦酸钠组(INSU+ALEN),每组同时服用钙尔奇D片作为基础用药,分别于服药前及服药12月后,测定4组患者股骨颈BMD及血BAP、BGP、TRAP-5b,分析治疗前后以及治疗组与对照组间的差异。结果 INSU+ALEN组治疗12月可见患者骨密度较前增加,治疗前后有统计学意义(P0.05),METF、INSU组较前无明显改变,治疗前后无统计学意义(P0.05),METF+ALEN组治疗12月可见患者BMD较前略有增加,治疗前后无统计学意义(P0.05),INSU+ALEN组治疗后BMD的增加明显高于其它组(P均0.05)。INSU+ALEN治疗组患者治疗12月后血清BAP、BGP显著升高(P0.05),TRAP-5b显著降低(P0.05);将上述指标与对照组、其它治疗组比较,BAP、BGP、TRAP-5b差异显著(P均0.01);METF、INSU、METF+ALEN组治疗12月可见患者血清BAP、BGP较前略有增加,TRAP-5b略有降低,治疗前后无统计学意义(P0.05)。结论胰岛素是糖尿病骨质疏松症首选治疗,可增加骨量,预防骨丢失。阿仑膦酸钠能抑制骨吸收,促进骨形成,减缓骨量丢失,提高骨密度,二者联用可有效防治糖尿病骨质疏松症。     

The Efficacy and Tolerability of Alendronate in Postmenopausal Osteoporotic Chinese Women: A Randomized Placebo-Controlled Study

Osteoporosis is a growing health problem in Asian women and it is expected that half of the world's hip fractures will occur in Asia in 50 years' time. As the use of hormonal replacement therapy (HRT) is extremely low in postmenopausal Asian women, nonhormonal agents will be more acceptable for the treatment and prevention of osteoporosis. The efficacy, tolerability, and acceptability of alendronate, an amino-bisphosphonate, for Asian women was evaluated in 70 osteoporotic southern Chinese women in a prospective, randomized, double-blind study. The subjects were randomized to receive either alendronate 10 mg daily or placebo, plus calcium supplementation 500 mg daily. The baseline L 1–4 and hip bone mineral density (BMD) were similar between both groups. At the end of 1 year, there was an increase of 5.8% in the lumbar spine BMD and 3.4% at the total hip with alendronate treatment when compared with baseline values (P < 0.001). Alendronate treatment for 1 year resulted in significant improvement in BMD at all sites measured when compared with placebo. There was also marked reduction in serum alkaline phosphatase (ALP) and urinary n-telopeptide (NTx) in the alendronate group when compared with the placebo group (ALP 25% versus 2%, NTx 75% versus 14%, both P < 0.005). The changes in ALP and NTx at 6 and 12 months correlated with the change in BMD at all sites measured at 1 year (P all <0.05). Alendronate was well tolerated and accepted, although two cases of gastric ulcer were reported. We conclude that alendronate is an effective and well-accepted agent for the treatment of osteoporosis in Asian women. Received: 30 September 1999 / Accepted 6 April 2000     

Effect of walking exercise on bone metabolism in postmenopausal women with osteopenia/osteoporosis

The purpose of this prospective study was to determine whether moderate walking exercise in postmenopausal women with osteopenia/osteoporosis would affect bone metabolism. Fifty postmenopausal women, aged 49–75 years, with osteopenia/osteoporosis were recruited: 32 women entered the exercise program (the exercise group) and 18 served as controls (the control group). The exercise consisted of daily outdoor walking, the intensity of which was 50% of maximum oxygen consumption, with a duration of at least 1h with more than 8000 steps, at a frequency of 4 days a week, over a 12-month period. Lumbar (L2–L4) bone mineral density (BMD) was measured at the baseline and every 6 months with dual-energy X-ray absorptiometry (DXA) in both groups. Serum bone-specific alkaline phosphatase (BAP) and urinary cross-linked N-terminal telopeptides of type I collagen (NTX) levels were measured at baseline and at months 1, 3, 6, 9, and 12 by EIA and ELISA, respectively, in the exercise group, and urinary NTX level was measured at the baseline and every 6 months in the control group. There were no significant differences in baseline characteristics including age, height, body weight, bone mass index, years since menopause, lumbar BMD, and urinary NTX level between the two groups. Although no significant changes were observed in lumbar BMD and the urinary NTX level in the control group, lumbar BMD in the exercise group was increased as compared with the control group, but was sustained from the baseline. In the exercise group, the urinary NTX level rapidly responded to walking exercise from month 3, and this reduction was sustained until month 12, followed by reduction in the serum BAP level. A moderately negative correlation was found between the percent change in the urinary NTX level at month 3 and that in lumbar BMD at month 12 in the exercise group. This study clearly demonstrates that the mechanism for the positive response of lumbar BMD to moderate walking exercise in postmenopausal women with osteopenia/osteoporosis appears to be the suppression of bone turnover, and that an early change in the urinary NTX level may be useful to predict the long-term response of increasing lumbar BMD to exercise, although its efficacy for lumbar BMD may be quite modest.     

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。     

Effect of ONO‐5334 on Bone Mineral Density and Biochemical Markers of Bone Turnover in Postmenopausal Osteoporosis: 2‐Year Results From the OCEAN Study

Cathepsin K inhibitors, such as ONO‐5334, are being developed for the treatment of postmenopausal osteoporosis. However, their relative effects on bone resorption and formation, and how quickly the effects resolve after treatment cessation, are uncertain. The aim of this study was to examine the efficacy and safety of 24‐month treatment with ONO‐5334 and to assess the effect of treatment cessation over 2 months. We studied 197 postmenopausal women with osteoporosis or osteopenia with one fragility fracture. Patients were randomized to ONO‐5334 50 mg twice daily, 100 mg or 300 mg once daily, alendronate 70 mg once weekly (positive control), or placebo for 24 months. After 24 months, all ONO‐5334 doses were associated with increased bone mineral density (BMD) for lumbar spine, total hip, and femoral neck (p < 0.001). ONO‐5334 300 mg significantly suppressed the bone‐resorption markers urinary (u) NTX and serum and uCTX‐I throughout 24 months of treatment and to a similar extent as alendronate; other resorption marker levels remained similar to placebo (fDPD for ONO‐5334 300 mg qd) or were increased (ICTP, TRAP5b, all ONO‐5334 doses). Levels of B‐ALP and PINP were suppressed in all groups (including placebo) for approximately 6 months but then increased for ONO‐5334 to close to baseline levels by 12 to 24 months. On treatment cessation, there were increases above baseline in uCTX‐I, uNTX, and TRAP5b, and decreases in ICTP and fDPD. There were no clinically relevant safety concerns. Cathepsin K inhibition with ONO‐5334 resulted in decreases in most resorption markers over 2 years but did not decrease most bone formation markers. This was associated with an increase in BMD; the effect on biochemical markers was rapidly reversible on treatment cessation. © 2014 American Society for Bone and Mineral Research.