益气温经方联合唑来膦酸治疗原发Ⅰ型骨质疏松症随机对照研究

Evaluation of the Efficacy of Yiqi Wenjing Decotion Combined with Zoledronic Acid on Primary TypeⅠOsteoporosis:A Randomized Controlled Trial

目的观察益气温经方干预原发Ⅰ型骨质疏松患者的疗效。方法本研究于中国临床试验注册中心完成注册(No.ChiCTR200034867)。将180例患者按随机数字表法分成基础用药组、唑来膦酸组和益气温经方组,每组各60例。基础用药组予口服碳酸钙D3片(每日1次,每次1片)和骨化三醇胶囊(每日2次,每次1粒)治疗;唑来膦酸组予基础用药及唑来膦酸(唑来膦酸每年1次,每次5 mg);益气温经方组予基础用药、唑来膦酸及益气温经方(中药每日2次,每次1袋)。4个月为1个疗程(连续服用3个月,停药1个月),试验期间共9个疗程。试验观察治疗前后3、6、12个月的疼痛VAS评分、Tinetti平衡与步态评分、腰背肌和股四头肌肌力;比较治疗前后1、2、3年的骨密度、血清Ⅰ型前胶原氨基端前肽(PINP)、Ⅰ型胶原交联C-末端肽(β-CTX)、骨折率。结果试验过程中,基础用药组脱落7例,唑来膦酸组脱落5例,益气温经组脱落4例,最终有164例患者完成试验。(1)VAS疼痛评分量表:与本组治疗前比较,治疗3、6、12个月后基础用药组、唑来膦酸组及益气温经组VAS均下降(P<0.01);治疗3个月后,与基础用药组比较,益气温经组VAS评分降低(P<0.05);治疗6、12个月后,与唑来膦酸组、基础用药组比较,益气温经组VAS评分降低(P<0.05,P<0.01)。(2)Tinetti平衡与步态评分:与本组治疗前比较,治疗6个月后,益气温经组Tinetti评分上升(P<0.05);治疗12个月后唑来膦酸组、益气温经组Tinetti评分均上升(P<0.01);治疗6、12个月后,与唑来膦酸组、基础用药组比较,益气温经组评分更高(P<0.05,P<0.01)。(3)腰背肌和股四头肌肌力:与治疗前比较,治疗3、6、12个月后益气温经组腰背肌、股四头肌肌力上升(P<0.01,P<0.05)。治疗6个月后,与基础用药组比较,益气温经组腰背肌和股四头肌肌力更高(P<0.05);治疗12个月后,与唑来膦酸组、基础用药组比较,益气温经组腰背肌和股四头肌肌力更高(P<0.05)。(4)骨密度:与本组治疗前比较,治疗1、2年后,唑来膦酸组与益气温经组骨密度均上升(P<0.05);治疗3年后基础用药组骨密度下降,唑来膦酸组和益气温经组上升(P=0.008,P<0.01)。治疗1年后,与基础用药组比较,益气温经组骨密度更高(P=0.01);治疗2年后,与基础用药组比较,益气温经组骨密度更高(P<0.01);治疗3年后,与唑来膦酸组、基础用药组比较,益气温经组骨密度更高(P=0.026,P<0.01)。(5)骨代谢指标:与本组治疗前比较,治疗1、2、3年后唑来膦酸组和益气温经组β-CTX和PINP水平下降(P<0.01,P<0.05)。治疗1年和2年后,与基础用药组比较,益气温经组β-CTX更低(P=0.026,P=0.001);治疗3年后,与唑来膦酸组和基础用药组比较,益气温经组β-CTX更低(P=0.048,P<0.01)。治疗2年后,与基础用药组比较,益气温经组PINP降低(P=0.012);治疗3年后,与唑来膦酸组比较,益气温经组PINP升高(P=0.046),与基础用药组比较,益气温经组PINP降低(P=0.025)。(6)骨折率:治疗第2年内和治疗3年后总计,3组总体骨折率比较,差异有统计学意义(χ^(2)=6.868,P=0.02;χ^(2)=6.275,P=0.043),益气温经组与基础用药组比较降低,差异有统计学意义(P<0.05)。结论唑来膦酸联合基础用药和唑来膦酸联合益气温经方使用,都能提升骨密度、降低β-CTX、PINP、疼痛情况和骨折率,但后者疗效更优;唑来膦酸联合基础用药可以改善下肢平衡及肌力,但联合益气温经方使用效果更显著。

Objective To observe the effect of Yiqi Wenjing Decotion(YQWJD)on patients with primary typeⅠosteoporosis.Methods The protocol was registered in the Chinese Clinical Trial Registry(No.ChiCTR200034867).According to the random number table method,180 patients were randomly assigned into three groups,basic medication group,zoledronic acid group and YQWJD group,60 cases in each group.The basic medication group was given oral calcium carbonate D3 tablets(1 tablet once a day)and calcitriol capsule(1 tablet twice a day),the zoledronic acid group was given basic medicine and zoledronic acid(zoledronic acid once a year,each time 5 mg),and the YQWJD group was given basic medicine,zoledronic acid and YQWJD(once 1 bag,twice a day).A course of treatment was given every 4 months(taking it continuously for 3 months and stopping the drug for one month).There were 9 courses during the trial period.After treatment for 3,6,12 months,the VAS pain score,Tinetti balance and gait score,and muscle strength of lumbar dorsal muscle and quadriceps were compared,and after treatment for 1,2,3 years,the bone mineral density(BMD),procollagenⅠn-terminal propeptide(PINP),β-C-terminal telopeptide of typeⅠcollagen(β-CTX)and bone fracture rate were compared.Results During the trial,7 cases in the basic medication group,5 cases in the zoledronic acid group and 4 cases in the YQWJD group dropped out.Finally,164 patients completed the trial.(1)VAS pain score scale.Compared with before treatment,after 3,6,12 months of treatment,VAS score in the basic medication group,zoledronic acid group and YQWJD group decreased(P<0.01).After 3 months treatment,compared with the basic medication group,the VAS score in the YQWJD group decreased(P<0.05).Compared with the zoledronic acid group and the basic medication group after 6 and 12 months treatment,the VAS score decreased in the YQWJD group(P<0.05,P<0.01).(2)Tinetti balance and gait score.Compared with before treatment,the Tinetti score of YQWJD group increased after 6 months treatment,and the Tinetti score of zoledronic acid group and YQWJD group increased after 12 months treatment(P<0.01).Compared with the zoledronic acid group and the basic medication group after 6 and 12 months treatment,the Tinetti score increased in the YQWJD group(P<0.05,P<0.01).(3)Muscle strength of lumbar dorsal muscle and quadriceps.Compared with before treatment,the muscle strength of lumbar dorsal muscle and quadriceps femoris increased after 3,6,12 months treatment(P<0.01,P<0.05).After 6 months of treatment,compared with the basic treatment group,the muscle strength of lumbar dorsal muscle and quadriceps femoris in YQWJD group was higher(P<0.05).The muscle strength of lumbar dorsal muscle and quadriceps femoris in YQWJD group was higher than those in zoledronic acid group and basic medication group after 12 months treatment(P<0.05).(4)BMD.Compared with before treatment,after 1 and 2 years of treatment,the BMD of zoledronic acid group and YQWJD group increased(P<0.01).After 3 years of treatment,BMD of the basic medication group decreased,while zoledronic acid group and YQWJD group increased(P=0.008,P<0.01).After 1 year of treatment,compared with the basic medication group,the BMD of the YQWJD group was higher(P=0.01).After 2 years,compared with the basic medication group,the BMD of the YQWJD group increased(P<0.01).After 3 years,compared with the zoledronic acid group and the basic medication group,the BMD of the YQWJD group was also higher(P=0.026,P<0.01).(5)Bone Metabolism Index.Compared with before treatment,the levels ofβ-CTX and PINP in zoledronic acid group and YQWJD group decreased after 1,2,3 years of treatment(P<0.01,P<0.05).After 1 and 2 years of treatment,compared with the basic medication group,theβ-CTX in the YQWJD group was lower(P=0.026,P=0.001);after 3 years of treatment,compared with the zoledronic acid group and the basic medication group,theβ-CTX in the YQWJD group decreased(P=0.048,P<0.01).After 2 years of treatment,compared with the basic medication group,the PINP in the YQWJD group decreased(P=0.012);after 3 years of treatment,compared with the zoledronic acid group,the PINP in the YQWJD group increased(P=0.046),and compared with the basic medication group decreased(P=0.025).(6)Fracture rate.In the second year of treatment and after 3 years of treatment,the overall fracture rate of the three groups was significantly different(χ^(2)=6.868,P=0.02;χ^(2)=6.275,P=0.043).Compared with the basic medication group,the fracture rate of the YQWJD group was lower(P<0.05).Conclusion Zoledronic acid combined with basic drugs and zoledronic acid combined with YQWJD can both increase BMD,and reduceβ-CTX,PINP,pain and fracture rate,but the latter has better efficacy.Zoledronic acid combined with basic drugs can improve lower extremity balance and muscle strength,but combined with YQWJD has more significantly effect.