阿德福韦酯致低血磷性骨软化症2例分析

Two cases of hypophosphataemic osteomalacia due to adefovir dipivoxil treatment

目的探讨长期服用小剂量阿德福韦酯导致低血磷性骨软化症的临床特点。方法对大连大学附属中山医院2015年2月至6月收治的2例长期口服阿德福韦酯(10 mg/d)导致低血磷性骨软化症患者的临床资料进行回顾性病例分析。结果2例患者分别为75岁男性和79岁女性,均因全身骨痛、肌肉无力和行走困难2年就诊,既往均有慢性乙型肝炎病史,分别口服阿德福韦酯(10 mg/d)8年和4年;化验提示低磷血症(男患为0.44 mmol/L,女患为0.47 mmol/L),低钾血症(男患为3.0mmol/L,女患为3.1 mmol/L),血碱性磷酸酶升高(男患为227 IU/L,女患为566 IU/L),25(OH)D降低(男患为18.16 ng/ml,女患为3 ng/ml),尿常规检测提示尿蛋白及尿糖为阳性,骨密度均提示骨质疏松,影像学显示多发性骨折。停服阿德福韦酯,补充钙剂、骨化三醇、氯化钾和中性磷溶液等治疗,患者生化指标逐渐恢复正常,骨痛及肌肉无力减轻,行走较正常。结论长期服用小剂量阿德福韦酯可以导致低血磷性骨软化症,应定期监测血电解质、肾脏功能、尿常规及骨密度,一旦出现阿德福韦酯相关的肾损伤,应停用阿德福韦酯,并纠正电解质紊乱,以避免引起低血磷性骨软化症。

Objective To investigate the clinical characteristics of hypophosphatemic osteomalacia due to long-term oral administration of low-dose adefovir dipivoxil（ ADV）.Methods The clinical data of 2 hypophosphatemic osteomalaeia patients with long-term oral administration of ADV（ 10 mg/d）,from Feb 2015 to Jun 2015,was retrospectively analyzed.Results One75-year old male patient and the other 79-year old female patient were hospitalized with 2-year chief complaint of systemic bone pain,muscle weakness and walking difficulty.They were suffering from chronic hepatitis B and treated with a low-dose of ADV（ 10 mg /d） for 8 and 4 years,respectively.Laboratory tests showed hypophosphatemia（ 0.44 mmol/L in the male,0.47 mmol/L in the female）,hypopotassemia（ 3.0 mmol/L in the male,3.1 mmol/L in the female）,increased alkaline phosphatase（ 227 IU /L in the male,566 IU/L in the female）,decreased 25-（ OH） vitamin D（ 18.16 ng/ml in the male,3ng/ml in the female）,proteinuria,and glycosuria.In addition,they both had osteoporosis and multiple fractures.After the withdrawal of ADV,they received calcitriol,calcium carbonate,potassium chloride,and neutral phosphate solution.The blood biochemical results returned to normal,the bone pain and muscle weakness relieved,and walk was normal.Conclusion Hypophosphatemic osteomalacia could be induced by long-term ADV oral administration in patients suffering from chronic hepatitis B.Electrolyte,renal function,and bone density should be monitored regularly.Once the renal injury associated with ADV was confirmed,the patients should stop taking ADV and correct electrolyte disorder,in order to inhibit the induction of hypophosphataemic osteomalacia.