12例低磷性骨软化症误诊误治临床分析

Misdiagnosis and mistreatment of 12 hypophosphatemic osteomalacia patients

目的比较不同原因低磷性骨软化症(hypophosphatemic osteomalacia,HO)患者的临床特征并解释其机制,分析误诊误治原因,总结诊断方法和治疗规范。方法回顾分析我科2008年7月至2016年10月收治的12例HO的临床资料。结果 12例HO,7例阿德福韦酯相关(ADVO),2例肿瘤相关(TIO),3例散发性。所有患者均表现为多发骨关节疼痛,伴肌肉疲劳无力。患者血磷降低(0.32～0.63 mmol/L),碱性磷酸酶(AKP)升高(136～528 U/L)、总I型胶原氨基端延长肽(PINP)亦升高(39.6～156.7 ng/ml)。ADVO患者的血尿酸常低于正常(72.7～196.4μmol/L),TIO及散发性HO患者血尿酸则大多正常,分别为(331.4～364.5μmol/L)及(138.7～352.7μmol/L)。ADVO尿糖常升高(2.8～11.0 mmol/L),尿蛋白亦升高(0.3～0.7 g/L),TIO及散发性HO尿糖均正常(<1.7 mmol/L),尿蛋白亦正常(<0.1 g/L)。12例中有10例曾被误诊,其中误诊为原发性骨质疏松4例,脊柱关节病5例,膝关节退行性变1例。ADVO患者均停用阿德福韦酯,改用恩替卡韦,同时补充碳酸钙、骨化三醇及磷酸盐治疗(2周至3个月);TIO患者予手术切除肿瘤,1例同时予补充磷酸盐2周;散发性HO长期间断补充中性磷。12例疼痛及肌无力症状均逐渐缓解并最终消失。结论临床表现为全身多发骨关节疼痛,生化提示低血磷、高碱性磷酸酶的患者,均应想到HO可能。临床诊断为HO的患者,伴低尿酸血症、非糖尿病性糖尿和蛋白尿考虑ADVO;不伴低尿酸血,尿常规正常的患者应进一步追问家族史及完善相关影像检查鉴别TIO和遗传性及散发性HO。

Objective To compare clinical features of hypophosphatemic osteomalacia(HO)patients with different causes and explain the relevant mechanism,to analyze the causes of misdiagnosis and mistreatment,and to summarize the diagnostic methods and treatment criteria.Methods From July 2008 to October 2016,clinical data of 12 patients with HO were reviewed and analyzed.Results Of the 12 patients with HO,7 were adefovir dipivoxil related(ADVO),2 were tumor-induced(TIO),and 3 were sporadic.All patients complained of multiple bone and joint pain,and muscle weakness.Laboratory tests showed hypophosphatemia(0.32-0.63 mmol/L),higher level of alkaline phosphatase(AKP)(136-528 U/L)and total type I collagen amino-terminal extended peptide(PINP)(39.6-156.7 ng/ml).While ADVO had lower level of uric acid(72.7-196.4μmol/L).Most of TIO and sporadic HO patients showed normal uric acid(331.4-364.5μmol/L)and(138.7-352.7μmol/L).ADVO often had higher level of glycosuria(2.8-11.0 mmol/L)and albuminuria(0.3-0.7 g/L),but TIO and sporadic HO had normal glycosuria(<1.7 mmol/L)and albuminuria(<0.1 g/L).Of the 12 cases,10 were misdiagnosed:4 primary osteoporosis,5 spondyloarthropathy,1 knee degenerative disease.Treatment of ADVO:adefovir dipivoxil was withdrawed;Entecavir was used;supplementation of calcium carbonate,calcitriol and phosphate(2 weeks-3 months).TIO patients:surgical resection of the tumor,and 1 was also with supplementation of phosphate for 2 weeks.Sporadic HO:long-term supplementation of calcium carbonate,calcitriol and phosphate.Clinical symptoms of12 patients ameliorated and eventually disappeared.Conclusions For patients with systemic multiple bone and joint pain,hypophosphatemia,increased blood alkaline phosphatase,HO should be considered.For patients(clinically diagnosed HO)with lower level of uric acid and higher level of glycosuria and albuminuria,ADVO should be considered.Family history and further relevant image examination are needed to identify IO,hereditary or sporadic HO.