小剂量阿德福韦酯导致低血磷性骨软化症两例并文献总结

Two cases of hypophophataemic osteomalacia induced by the small dose of adefovir dipivoxil,and literature review

目的分析小剂量阿德福韦酯（ADV）导致低血磷性骨软化症的临床特点、治疗及预后。方法结合我院诊断的两例服用阿德福韦酯后发生低血磷性骨软化症患者资料和国内外文献，对该症的临床特点、治疗、预后和早期诊断进行总结。结果服用小剂量阿德福韦酯治疗慢性乙型肝炎导致低血磷性骨软化症患者共12例，男9例，女3例，均来自亚洲人群，年龄在（22—74）岁，服用阿德福韦酯（18～64）个月发现低血磷，血磷波动在（0．37～0．79）mmoL／L，血钙正常或偏低，血钾偏低，且均有不同程度的骨质疏松，予补充钙剂、骨化三醇、欧思美等治疗预后良好。结论小剂量阿德福韦酯所致低血磷性骨软化症临床相对少见，容易漏诊，凡服用阿德福韦酯的患者，无论剂量大小，均应定期检查血肌酐、血钙、血磷及骨密度，以监测是否发生肾损害及低血磷性骨软化症，以期早期诊断，一旦各项指标异常应立即停药，同时可换用其他抗病毒药，如干扰素、恩替卡韦等。

Objective To analyze the clinical characteristics, treatment, and prognosis of hypophosphatemia osteomalacia induced by the small dose of adefovir dipivoxil. Methods According to the clinical data of two cases of hypophosphatemia osteomalacia induced by the small dose of adefovir dipivoxil, who were diagnosed in our hospital, and combining with domestic and overseas literatures, we summarized the clinical characteristics, treatment, prognosis, and the early diagnosis of this disease. Results There were 12 patients with hypophosphatemia osteomalacia induced by small dose of adefovir dipivoxil, which was used for the treatment of chronic hepatitis B, including 9 males and 3 females. All these patients were Asian, with age from 22 to 74 years old. Hypophosphatemia was found after taking adefovir dipivoxil for 18-64 months. And the concentration of phosphorus ranged from 0. 37 to 0. 79 mmol/L. The serum calcium level was normal or low, and the serum potassium level was low. They all had varying degrees of osteoporosis. The prognosis was good after taking calcium, calcitriol, and strontium ranelate. Conclusion The hypophosphatemia osteomalacia induced by small dose of adefovir dipivoxil is rarely in clinical practice, which can be easily missed. Those patients who takes adefovir dipivoxil, no matter what the dosage is, should take periodical examination including serum creatinine, serum calcium, blood phosphorus, and bone mineral density to monitor the occurrence of renal damage and hypophosphatemia, in order to make an early diagnosis. Adefovir dipivoxil should be discontinued immediately when any index showing abnormal. Other anti-viral drugs can be used, icluding interferon, entecavir, etc.