双膦酸盐治疗成骨不全症达药物假期时患者临床特点

Clinical characteristics of patients with osteogenesis imperfecta entering drug holiday of bisphosphonates

目的研究双膦酸盐(bisphosphonates,BPs)治疗成骨不全症(osteogenesis imperfecta,OI)骨密度(bone mineral density,BMD)达正常而进入药物假期患者的临床特点。方法回顾性分析2004年1月至2015年12月在北京协和医院治疗的OI患者,纳入BPs治疗后BMD达正常而停药的35例OI儿童为停药组,以年龄、性别、疗程匹配且因BMD仍低而继续治疗的35例OI儿童为对照组,应用双能X线吸收检测法测量BMD,并测定血清碱性磷酸酶(alkaline phosphatase,ALP)和Ⅰ型胶原羧基端交联肽(β-cross linked C-telopeptide of type 1 collagen,β-CTX)的浓度,对比分析两组基线、治疗期间及停药时BMD、骨转换生化指标的差异。结果停药组平均治疗4年BMD达正常而停药,该组基线腰椎、股骨颈、全髋BMD明显高于对照组[(543±229)mg/cm^2vs.(419±182)mg/cm^2、(513±241)mg/cm^2vs.(300±231)mg/cm^2、(573±216)mg/cm^2vs.(328±226)mg/cm^2],停药组治疗前年骨折次数低于对照组[(1.3±2.6)次vs.(2.1±3.5)次,P<0.05];治疗4年时,两组各部位BMD均较基线增加,但BMD变化率无明显差异,新发年骨折次数及血ALP、β-CTX降低率差异均无统计学意义(均P>0.05);在停药时,停药组腰椎、股骨颈、全髋BMD仍明显高于对照组[(1 065±129)mg/cm^2vs.(803±170)mg/cm^2、(944±92)mg/cm^2vs.(674±140)mg/cm^2、(941±92)mg/cm^2vs.(687±140)mg/cm^2,均P<0.01]。结论 BPs能够增加不同病情OI患者的BMD,降低骨折率和骨转换生化指标。病情较轻的OI患者接受平均4年BPs治疗后有望BMD达正常而停药,而病情较重的OI患者则需BPs治疗更长时间。

Objective To analyze the clinical characteristics of patients with osteogenesis imperfecta （OI） who entered drug holiday when their bone mineral density （BMD） achieved normal range after the treatment of bisphos- phonates （BPs）. Methods We retrospectively analyzed OI patients who received treatment in Peking Union Medical College Hospital （PUMCH） from January 2004 to December 2015. Thirty five children with OI were included as drug- discontinuation group who achieved normal BMD after BPs treatment. The other 35 children with OI acted as control group, who continued BPs treatment because of low BMD patients in two groups matched in age, gender, and treatment duration. Before and after treatment, BMD were measured by dual energy X-ray absorptiometry （DXA） , and serum levels of alkaline phosphatase （ALP） , and 13-cross linked C-telopeptide of type 1 collagen （13-CTX） were also tested. BMD and bone turnover biomarkers were compared between the two groups. Results It took an average of 4 years to achieve normal BMD for drug-discontinuation group. At baseline, BMD at lumbar spine, femoral neck, and total hip in drug-discontinuation group [ （543±229）, （513±241） and （573±216） mg/cm2 ] were higher than those in control group [ （419±182） , （300±231） , and （328±226） mg/cm2） ] , and the annual fracture incidence were less than that in control group [ （1.3±2.6） vs. （2. 1±3.5） ] （P〈0. 05）. During 4 years of treatment, there were no differences in increase rate of BMD, decrease of annual fracture incidence and bone turnover biomarkers between two groups （all P〉0. 05）. When BPs was discontinuated, BMD at lumbar spine, femoral neck, and total hip in drug-discontinuation group [ （1 065±129） , （944±92） and （941±92） mg/cm2] were higher than those in control group [ （803±170）, （674±140） and （687-＋140） mg/cm^2, all P〈0.01J. Conclusions BPs could significantly increase BMD, reduce fracture incidence and bone turnover biomarkers in patients with OI. Mild OI patients may have a chance to achieve normal BMD and enter the drug holiday after 4 years of BPs treatment. Severe OI patients need to receive longer period treatment of BPs.