双膦酸盐治疗26例成骨不全症的疗效分析

Efficacy of bisphosphonates on osteogenesis imperfecta in 26 patients

目的回顾分析使用双膦酸盐(bisphosphonates,BPs)治疗成骨不全症(osteogenesis imperfecta,OI)的疗效并对比不同用药年限、给药途径及起始治疗年龄的疗效差异。方法选取2019年1月至2021年12月就诊于上海交通大学医学院附属第六人民医院骨质疏松和骨病专科接受BPs治疗的26例OI患者,年龄4~67岁,中位年龄12.5岁,其中男17例,女9例。观察治疗前后及治疗过程中骨代谢指标、生化指标、骨密度(bone mineral density,BMD)、脆性骨折发生率等变化。结果26例患者使用阿仑膦酸钠、唑来膦酸或伊班膦酸钠治疗1~5年,给药途径为口服或静脉滴注。用药1年、2~3年及3年以上患者的腰椎BMD分别较基线增加了14.89%、70.73%、64.17%,股骨颈BMD分别增加了12.21%、42.58%、65.28%,全髋BMD分别升高了13.75%、38.95%、94.28%,用药>3年组的股骨颈及全髋BMD增长率显著高于用药1年组(P=0.028、0.002)。不同用药年限患者治疗后脆性骨折次数均下降,且下降幅度(%)及绝对值(次/年)差异无统计学意义(P=0.410、0.459)。口服和静脉用药患者骨钙素(osteocalcin,OC)下降幅度及各部位BMD改善程度相近,且2组患者脆性骨折发生次数均较基线显著减少。未成年组(年龄<18岁)患者治疗结束时腰椎、股骨颈、全髋BMD增加64.64%、45.31%和54.00%,且年均脆性骨折次数较基线减少。成年组(年龄≥18岁)患者治疗结束时骨转换生化标志物(bone turnover biomarkers,BTMs)水平显著下降,腰椎、股骨颈、全髋BMD无显著增加(P=0.393、0.567、0.473),但脆性骨折较基线显著减少(P<0.001)。结论不同用药年限对预防新发脆性骨折疗效相近,用药年限越长,对BMD的改善越显著;口服与静脉用药对新发脆性骨折及BMD的改善疗效相近;未成年OI患者接受BPs可显著增加BMD,未成年及成年患者接受BPs治疗均能预防新发脆性骨折。

Objective To retrospectively analyze the efficacy of bisphosphonates(BPs)in the treatment of osteogenic imperfecta(OI)patients,and to compare the differences in efficacy among different treatment duration,administration methods and age at treatment initiation.Methods Totally 26 OI patients who received BPs treatment in department of osteoporosis and bone disease of Shanghai Jiao Tong University Affiliated Sixth People s Hospital from January,2019 to December,2021 were selected in the study with the median age of 12.5 years(range,4-67 years)including 17 males and 9 females.Changes in bone metabolism and biochemical indicators,bone mineral density(BMD),and fragility fractures rates before,after and during the treatment were observed.Results A total of 26 patients were treated with alendronate sodium,zoledronic acid or ibandronate sodium for 1 to 5 years,administered orally or intravenously.Lumbar spine BMD of patients treated with medication for 1 year,2-3 years and more than 3 years increased by 14.89%,70.73%,and 64.17%,respectively,compared to the baseline.Femoral neck BMD increased by 12.21%,42.58%,and 65.28%,respectively.Total hip BMD increased by 13.75%,38.95%,and 94.28%,respectively.The growth rate of femoral neck and total hip BMD in the medication group treated for more than 3 years was significantly higher than that in the medication group treated for 1 year(P=0.028,0.002).The frequency of fragility fractures after treatment declined in patients with different medication durations,and there was no significant difference in the extent of decline(%)and absolute value(times/year)(P=0.410,0.459).The decrease in osteocalcin(OC)and the improvement degrees of BMD at various sites were comparable in patients receiving oral and intravenous medications,and the occurrence frequency of fragility fractures in both groups was significantly reduced compared with the baseline.The BMD of lumbar spine,femoral neck and total hip increased by 64.64%,45.31%and 54.00%at the end of treatment in the juvenile group,and the average annual number of fragility fractures decreased compared with baseline.At the end of treatment,the level of bone turnover biomarkers(BTMs)in the adult group decreased significantly,and BMD in the lumbar spine,femoral neck,and total hip did not increase significantly(P=0.393,0.567,and 0.473),but fragility fractures were significantly reduced from baseline(P<0.001).Conclusion The efficacy of different medication durations in preventing new fragility fractures is similar.The longer the medication duration is,the more significant the improvement in BMD is.Oral and intravenous medication have similar improvement effects on newly developed fragility fractures and BMD.Underage OI patients receiving BPs can significantly increase BMD,and BPs treatment can prevent new fragility fractures in both underage and adult patients.