阿德福韦酯致Fanconi综合征并继发低磷性骨软化症4例

 目的  探讨阿德福韦酯相关性Fanconi综合征继发低磷性骨软化症的临床特点。方法  报道4例阿德福韦酯相关性Fanconi综合征继发低磷性骨软化症,并进行相关文献复习,总结其临床特点。结果  4例患者均表现为不同程度骨关节疼痛、肌无力,既往乙肝病史,服用阿德福韦酯抗病毒治疗3~6年不等,血液检查示低血磷,同时合并不同程度低血钾、低血尿酸,尿检示糖尿及蛋白尿,诊断为阿德福韦酯相关性Fanconi综合征并继发低磷性骨软化症。复习文献发现,阿德福韦酯治疗所致Fanconi综合征继发低磷性骨软化症有剂量、时间依赖性及可逆性特点,应用小剂量阿德福韦酯(10 mg/d)后出现Fanconi综合征多见于亚裔男性。患者常因骨关节疼痛起病,首诊科室多为骨科及风湿科,确诊周期长,易漏诊、误诊。结论  凡服用阿德福韦酯的患者,无论剂量大小,均应定期进行相关检查,如血钙、血磷、尿常规与尿生化等,以监测是否发生Fanconi综合征并继发低磷性骨软化症。     

低剂量阿德福韦酯致低血磷性骨软化症的临床特点及治疗分析

目的 探讨低剂量阿德福韦酯(10 mg/d)所致低血磷性骨软化症的临床特点及其治疗方法,以提高临床医生对该病的认识.方法 回顾性分析2011年4月-2012年7月本院确诊的4例低剂量阿德福韦酯致低血磷性骨软化症患者的临床资料,总结其临床特点及治疗方法.结果(1)4例患者中,3例为男性,发病年龄为38～68岁,病程为2～24个月.发病时阿德福韦酯持续用药时间为8～94个月.(2)首发症状以足跟负重痛最为常见(3/4).主要表现为进行性骨痛(4/4),最常累及足跟和胫前(3/4);踝关节痛(4/4);身高变矮(2/4).查体发现2例有胸廓、骨盆挤压痛.病史:1例合并高血压,1例长期大量饮酒.(3)实验室检查可见低磷血症(4/4)、高尿磷(4/4)、血碱性磷酸酶(ALP)增高(3/4).影像学检查:双能骨密度及X线检查显示骨质疏松(4/4);骨扫描可见颅骨、四肢长骨骨皮质普遍放射性增高(3/4).(4)治疗:停用阿德福韦酯,改为恩替卡韦抗病毒;口服中性磷溶液、阿法迪三胶囊、钙尔奇D片.4～16周时患者的血磷恢复正常,8～20周骨关节痛缓解.随访至11～73周,除1例合并右股骨不全骨折外,其余患者均恢复正常行走能力.结论 低剂量阿德福韦酯可导致低血磷性骨软化症.对长期服用阿德福韦酯者老年人、饮酒、合并慢性病者,用药期间应定期监测,尤其是血磷、ALP水平及肾功能、尿常规,以尽早发现,及时给予中性磷治疗.     

低剂量阿德福韦酯致低血磷性骨软化症的临床特点及治疗分析

目的探讨低剂量阿德福韦酯(10 mg/d)所致低血磷性骨软化症的临床特点及其治疗方法,以提高临床医生对该病的认识。方法回顾性分析2011年4月—2012年7月本院确诊的4例低剂量阿德福韦酯致低血磷性骨软化症患者的临床资料,总结其临床特点及治疗方法。结果 (1)4例患者中,3例为男性,发病年龄为38～68岁,病程为2～24个月。发病时阿德福韦酯持续用药时间为8～94个月。(2)首发症状以足跟负重痛最为常见(3/4)。主要表现为进行性骨痛(4/4),最常累及足跟和胫前(3/4);踝关节痛(4/4);身高变矮(2/4)。查体发现2例有胸廓、骨盆挤压痛。病史:1例合并高血压,1例长期大量饮酒。(3)实验室检查可见低磷血症(4/4)、高尿磷(4/4)、血碱性磷酸酶(ALP)增高(3/4)。影像学检查:双能骨密度及X线检查显示骨质疏松(4/4);骨扫描可见颅骨、四肢长骨骨皮质普遍放射性增高(3/4)。(4)治疗:停用阿德福韦酯,改为恩替卡韦抗病毒;口服中性磷溶液、阿法迪三胶囊、钙尔奇D片。4～16周时患者的血磷恢复正常,8～20周骨关节痛缓解。随访至11～73周,除1例合并右股骨不全骨折外,其余患者均恢复正常行走能力。结论低剂量阿德福韦酯可导致低血磷性骨软化症。对长期服用阿德福韦酯者老年人、饮酒、合并慢性病者,用药期间应定期监测,尤其是血磷、ALP水平及肾功能、尿常规,以尽早发现,及时给予中性磷治疗。     

阿德福韦酯致Fanconi综合征和低磷性骨软化症并进行性肌无力1例

阿德福韦酯是一种常用的治疗慢性乙型病毒性肝炎的药物。阿德福韦酯的肾毒性具有剂量和时间相关性,多见于30 mg/d以上剂量以及有基础肾功能损害的患者。我们报道1例慢性乙肝患者,服用阿德福韦酯10 mg/d共4年,以腰骶部和膝、髋关节疼痛为主诉就诊,曾辗转多家医院均误诊为强直性脊柱炎或脊柱关节病,最终确诊为获得性Fanconi综合征和低磷性骨软化症伴进行性肌无力,查阅国内外文献,类似报道不足10例,阿德福韦酯的肾损害应引起临床医师的重视。     

低磷骨软化症11例分析

目的分析11例低磷骨软化症患者的临床表现、实验室检查及影像学表现,以提高对低磷性骨软化症的临床诊断水平。方法回顾性分析2012年6月—2013年5月解放军总医院内分泌科住院低磷骨软化症患者11例临床资料,其中男8例,女3例,年龄20⁶4岁,平均(40.5±15.0)岁,病程164岁,平均(40.5±15.0)岁,病程1¹0年,平均(3.6±2.6)年。结果双足跟疼痛3例,双下肢乏力3例,全身疼痛2例,腰部疼痛1例,髋关节疼痛1例。血磷均降低,血钾降低3例,正常8例,24h尿钾增多5例,甲状旁腺素升高8例,3例正常,1,25二羟维生素D_3均降低。X线检查均示长骨及扁骨普遍脱钙,骨密度减低,骨皮质变薄,骨小梁稀疏模糊。诱发疾病为:右股部肿瘤1例,左股骨内侧踝肿瘤1例,右股骨头肿瘤1例,甲状旁腺亢进1例,干燥综合征1例,肿瘤相关骨软化症可疑6例。结论低磷骨软化病患者起病隐匿,易误诊,以骨痛或乏力起病,进展迅速,血生化提示低磷血症,X线提示骨骼改变,应注意肿瘤性骨软化症.需行奥曲肽扫描,并结合CT或MR定位,手术切除后症状缓解。     

肿瘤相关低磷性骨软化症1例并文献复习

低血磷性骨软化症（hypophosphatemicosteoma—lacia,HO）（以往称为低磷维生素D-抵抗性软骨病）是由于低磷血症和活性维生素D产生不足造成的,以骨骼矿化不良、骨软化或佝偻病为主要特征的一组疾病,发病率约1：25000。     

家族性低血磷性骨软化症一例

低血磷性骨软化症有X性连锁显性遗传性低血磷性骨软化症（X-link,hypophosphatemia,XLH）、常染色体显性遗传低血磷性骨软化症（autosomal dominant hypophosphatemia osteomalacia,ADHO）、肿瘤相关性低血磷性骨软化症（tumor induced osteomalacia,TIO）3种病因。笔者在重庆医科大学附属第一医院进修期间收治1例XLH,报道如下。     

误诊为脊柱关节病的成人散发性低磷性骨软化症1例报告

脊柱关节病(spondyloarthropathy)即血清类风湿因子阴性脊柱关节病,是一组相互关联的多系统的炎性关节疾病[1],包括强直性脊柱炎、反应性关节炎、银屑病关节炎、炎性肠病性关节炎及未定型脊柱关节病等.慢性炎性腰背痛是脊柱关节病的主要临床特点.低磷性骨软化症是一种由于低磷血症造成的骨基质不能以正常方式进行矿化的代谢性骨病[2],该病临床少见,疾病初期易因腰背痛、非甾类抗炎药治疗有效等类似炎性腰背痛的临床表现而误诊为脊柱关节病.本文总结1例曾误诊为脊柱关节病的成人低磷性骨软化症患者的临床资料,并结合文献复习低磷性骨软化症与脊柱关节病的诊断及鉴别诊断方法,旨在提高临床的诊断水平.     

阿德福韦酯导致胸痛、低磷血症2例报告

阿德福韦酯是一种单磷酸腺苷的无环核苷类似物,用于慢性乙型肝炎的抗病毒治疗。关于它引起低磷血症的报道较少,国内外也罕见以胸痛为首发症状和低磷血症的报道。本文报告2例患者服用阿德福韦酯后出现胸痛为首发症状和低磷血症。     

磷酸盐尿性间叶瘤继发低磷骨软化症1例

This case report concerns a 34-year-old woman who had been diagnosed with ankylosing spondylitis (AS), fibromyalgia syndrome (FMS), osteoarthritis (OA), lumbar disc herniation and the like in different hospitals during the past 18 months. She had progressive osteoarthrosis, significant muscle weakness, gait abnormalities in weight-bearing areas, however without typical inflammatory low back pain, while the treatment with non-steroidal anti-inflammatory drugs (NSAIDs) was invalid, with normal inflammation index, negative results for rheumatic factor (RF) and human leukocyte antigen (HLA)-B27, and normal erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). She had hyphosphatemia, normal serum calcium, 1, 25-(OH)2-D3 reduction, elevated alkaline phosphatase (ALP) and normal parathyroid hormone (PTH), however with elevated urinary phosphorus. Finally, the medial thigh nodule was found in the subcutaneous of her inner leg by careful examination and imaging scans including B-ultrasound and PET/CT. The final pathology confirmed that the nodule was phosphate urinary mesenchymal tumors. After the tumor was removed, the patient was treated with anti-osteoporosis and phosphorus supplementation. The symptoms of bone pain and muscle weakness were alleviated, and hypophosphatemia was corrected. It was confirmed that the patient had low-phosphorus osteomalacia due to tumor. Tumor-induced hypophosphatemia osteomalacia (TIO) was a rare paraneoplastic syndrome which was caused by excessive phosphorus excretion induced by the tumor, and was thus categorized as an acquired hypophosphatemic osteomalacia. TIO had an occult onset and was associated with a high rate of misdiagnosis, although TIO has some typical clinical features. Early diagnosis, correctly positioning of the tumor, and surgical resection can achieve good outcomes.     

低剂量阿德福韦酯致Fanconi综合征和低磷骨软化症1例及文献回顾

A young male patient with a clear diagnosis of chronic hepatitis B, had taken long-term adefovir dipivoxil and lamivudine antiviral therapy. Osteomalacia related symptoms, such as bone pain and walking difficulties appeared 10 months ago. Renal damage related symptoms, such as urine volume change and increased urinary foam appeared 7 months ago. The examination showed signs of osteomalacia after admission, such as duck step, osteoarticular tenderness, thoracic and pelvic compression sign positive. Relevant examinations showed that hypophosphatemic osteomalacia related signs, such as hypophosphatemia, normal blood calcium, elevated blood alkaline phosphatase, no significant decline in active vitamin D3 and intact parathyroid hormone (iPTH). In bone mineral density test, bone fracture line could be noted. Bone scan suggested multiple metabolic lesions. At the same time, there were Fanconi syndrome related performances, such as elevated serum creatinine, decreased blood uric acid, urine glucose positive, elevated urinary and uric acid, urinary protein positive with mainly small molecule proteins, increased renal tubular damage indicators, and the clearance test suggested a decrease in renal tubular reabsorption of phosphorus. Kidney stones could be seen in urinary ultrasound. Therefore, combined with the patient’s clinical manifestations, past history and examinations, we definitely considered his diagnosis was adefovir dipivoxil related renal injury. Adefovir has been widely used for the treatment of chronic hepatitis B. Some studies confirmed that the nephrotoxicity of adefovir, including Fanconi syndrome and hypophosphatemic osteomalacia, was dose-dependent. A daily high-dose of 60-120 mg/d adefovir was concluded in the treatment of human immunodeficiency virus (HIV) infection, inducing nearly 1/2 patients of renal injury. A daily moderate-dose of 30 mg/d adefovir was used for patients in chronic hepatitis B, with nearly 1/3 patients of renal injury. Long-term low-dose adefovir (10 mg/d) used for chronic hepatitis B patients was found to be responsible for renal injury, but the incidence was significantly reduced. We studied this patient and related literature to analyze the pathogenesis, clinical characteristics and treatment outcomes in low-dose adefovir-induced Fanconi syndrome and hypophosphatemic osteomalacia.     

低剂量阿德福韦酯致Fanconi综合征和低磷骨软化症1例及文献回顾

A young male patient with a clear diagnosis of chronic hepatitis B, had taken long-term adefovir dipivoxil and lamivudine antiviral therapy. Osteomalacia related symptoms, such as bone pain and walking difficulties appeared 10 months ago. Renal damage related symptoms, such as urine volume change and increased urinary foam appeared 7 months ago. The examination showed signs of osteomalacia after admission, such as duck step, osteoarticular tenderness, thoracic and pelvic compression sign positive. Relevant examinations showed that hypophosphatemic osteomalacia related signs, such as hypophosphatemia, normal blood calcium, elevated blood alkaline phosphatase, no significant decline in active vitamin D3 and intact parathyroid hormone (iPTH). In bone mineral density test, bone fracture line could be noted. Bone scan suggested multiple metabolic lesions. At the same time, there were Fanconi syndrome related performances, such as elevated serum creatinine, decreased blood uric acid, urine glucose positive, elevated urinary and uric acid, urinary protein positive with mainly small molecule proteins, increased renal tubular damage indicators, and the clearance test suggested a decrease in renal tubular reabsorption of phosphorus. Kidney stones could be seen in urinary ultrasound. Therefore, combined with the patient’s clinical manifestations, past history and examinations, we definitely considered his diagnosis was adefovir dipivoxil related renal injury. Adefovir has been widely used for the treatment of chronic hepatitis B. Some studies confirmed that the nephrotoxicity of adefovir, including Fanconi syndrome and hypophosphatemic osteomalacia, was dose-dependent. A daily high-dose of 60-120 mg/d adefovir was concluded in the treatment of human immunodeficiency virus (HIV) infection, inducing nearly 1/2 patients of renal injury. A daily moderate-dose of 30 mg/d adefovir was used for patients in chronic hepatitis B, with nearly 1/3 patients of renal injury. Long-term low-dose adefovir (10 mg/d) used for chronic hepatitis B patients was found to be responsible for renal injury, but the incidence was significantly reduced. We studied this patient and related literature to analyze the pathogenesis, clinical characteristics and treatment outcomes in low-dose adefovir-induced Fanconi syndrome and hypophosphatemic osteomalacia.     

低磷性骨软化症一例报道

低磷性骨软化症（hypophosphatemic osteomalacia,HO）是由于低血磷、维生素D缺乏所致的,以骨骼矿化不良、骨软化或佝偻病为主要特征的一组疾病.临床分为X连锁显性遗传性低血磷性骨软化症（X-linked hypophosphatemia,XLH）、常染色体显性遗传性低血磷性骨软化症（autosomal dominant hypophosphatemic rickets,ADHR）、肿瘤相关性低血磷性骨软化症（tumor induced osteomalacia,TIO）[1].现将重庆医科大学附属第一医院内分泌科收治的1例低磷性骨软化症报道如下.     

肿瘤性低磷骨软化症一例报道并文献复习

肿瘤性低磷骨软化症（TIO）是临床上一种罕见的伴瘤综合征,由肿瘤导致肾脏排磷增加,造成的获得性低血磷骨软化症。TIO起病隐匿,临床误诊率较高,但仍具有典型的临床特点,如肌无力、进行性骨痛、身高变矮等。临床中应提高对该病的认识,早期诊断,明确肿瘤位置,手术切除一般可达到较好的治疗效果。对于疑似TIO患者,仔细的体格检查,并结合实验室检查、影像学检查等手段对肿瘤的发现和定位具有重要意义。本文回顾性报道了被诊断为TIO且得到成功诊治的患者1例,并对相关文献进行了复习,以提高临床医生对本病的认识,为临床工作提供借鉴。     

成人低血磷性抗维生素D骨软化症长期误诊1例

成人低血磷性抗维生素D骨软化症是一综合病症,主要缺陷在细胞的1,25(OH)_2D_3受体或受体后,由近曲小管重吸收磷酸盐障碍,肠道吸收磷亦减低,致磷的转运系统发生障碍。属性染色体连锁显性遗传性疾病。现将1例被长期误诊的病例报道如下。     

肿瘤相关性低磷性骨软化症的研究进展

摘要 肿瘤相关性低磷性骨软化症,又称为瘤源性骨软化症,是由于肿瘤分泌成纤维细胞生长因子-23等调磷因子使肾脏磷丢失增多,导致低磷血症,引起骨基质矿化障碍的获得性代谢性疾病,是一种少见的副瘤综合征。该病发病率低,且临床表现不典型,易漏诊及误诊。该文通过对肿瘤特征、发病机制、临床表现、实验室检查、肿瘤定位、治疗方法以及难治结局的危险因素等方面进行综述,旨在提高临床医生对该病的认识。     

成人低血磷性抗维生素D骨软化症1例并文献复习

低磷性佝偻病/骨软化症（以往称为低磷维生素D-抵抗性软骨病/佝偻病）是一种肾小管遗传缺陷性疾病,发病率约1∶25 000.有低血磷性和低血钙性两种.比较多见的是低血磷性抗维生素D骨软化症,又称家族性低磷血症或肾性低血磷性骨软化症[1].现对1例低血磷性抗维生素D骨软化症患者进行报道并结合文献进行复习,旨在提高临床上对该病的认识.     

PHEX基因新发突变致低磷性佝偻病/骨软化症1例并文献复习

<正>低磷性佝偻病/骨软化症(hypophosphatemic rickets/osteomalacia, HO)是一组由于遗传性或获得性原因导致以低磷血症为主要特征的骨骼矿化障碍性疾病,该类疾病相对罕见,导致公众甚至专科医师对该疾病的认识和重视程度不高,从而易漏诊、误诊。现就我院收治的1例低磷性佝偻病/骨软化症报道如下,以期加强临床医生对该病的认识,提高临床诊治能力。     

肿瘤相关性低磷性骨软化症(TIO) 1例

低磷性骨软化症是由于低磷血症和活性维生素D生成不足造成的以骨骼矿化不良为特征的一种疾病,主要包括X连锁低磷性佝偻病(X-linked hypophosphatemic rickets,XLH)、常染色体显性低磷     

阿德福韦酯治疗慢性乙型肝炎的不良反应分析

目的 研究阿德福韦酯治疗慢性乙型肝炎的不良反应.方法 方便收集广东省兴宁市人民医院感染性疾病科2014年1月—2016年1月慢性乙型肝炎患者140例分两组,每组70例.拉米夫定组采用拉米夫定进行治疗;阿德福韦酯组采用阿德福韦酯治疗.就两组患者治疗前后肝功能有关指标的差异和慢性乙型肝炎治疗总有效率、药物不良反应发生率进行比较.结果 阿德福韦酯组慢性乙型肝炎治疗总有效率88.57%稍微高于拉米夫定组85.71%,但组间差异无统计学意义(P>0.05).仅有个别出现镜下血尿、一过性尿蛋白阳性、一过性尿素氮升高现象,所有患者无其他不良反应,淀粉酶、血肌酸激酶以及血常规等均正常,无出现血磷降低或血清肌酐上升现象,发生率均为2.86%.在治疗前两组患者肝功能有关指标相似,组间差异无统计学意义(P>0.05).治疗后两组患者肝功能有关指标均显著改善,跟治疗前比较差异有统计学意义(P<0.05).结论 阿德福韦酯治疗慢性乙型肝炎的效果确切,可有效改善患者肝功能,但需注意监测血清肾功能和尿常规.