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

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。     

散发性低磷性骨软化症5例误诊临床分析

目的 通过对少见疾病散发性低磷性骨软化症(sporadic hypophosphatemic rickets)误诊原因分析,旨在提高临床对其诊治水平.方法 回顾性分析本院收治的5例散发性低磷性骨软化症的临床资料,包括临床表现、误诊情况、实验室检查以及诊治转归等情况.结果 5例患者中男4例、女1例,初诊分别误诊为原发性骨质疏松症、腰椎间盘突出症、强直性脊柱炎、无菌性股骨头坏死和肿瘤骨转移.临床表现主要为骨痛、骨折、行动困难等.5例患者显示低磷血症和高碱性磷酸酶水平.确诊散发性低磷性骨软化症前,治疗效果不佳,确诊后,经药物治疗病情显著改善.结论 临床上对散发性低磷性骨软化症容易误诊为原发性骨质疏松症等以骨痛、骨折为临床表现的疾病,结合其实验室生化检查及影像学特点,可与常见病相鉴别.     

阿德福韦酯致低血磷性骨软化症2例分析

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。     

肿瘤源性骨软化症与体内磷平衡的调节

肿瘤源性骨软化症(tumor～induced osteomalacia,TIO)是一种罕见的综合征,主要特征包括低磷血症,尿磷排出大量增加,血1,25(OH)_2D_3浓度降低,以及骨软化症。放射学及组织学检查可显示患者有骨软化症或佝偻病的表现。切除肿瘤后该病可得到治愈。磷自肾脏大量排出、丢失,肠道磷吸收降低,以及细胞内磷再分布等均可导致低磷血症。一些研究表明,肿瘤组织含有一种小于     

海绵状血管瘤诱发低磷性骨软化症1例并文献复习

<正>低磷性骨软化症是以低磷血症和活性维生素D合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、常染色体显性低磷性佝偻病、肿瘤相关性低磷性骨软化症(tumor induced osteomalacia,TIO)3型。肿瘤源性低磷骨软化症临床少见,2014年6月5日本院收治1例海绵状血管瘤所致TIO,经手术治疗症状明显好转,经文献检索,在     

肿瘤相关性成人低血磷骨软化症1例报道

目的报道一例肿瘤相关性低磷骨软化症(tumor-induced hypophosphorus osteomalacia,TIO),提高临床医师对本病的认识。方法对该TIO患者的临床表现、实验室检查、影像学、病理检查和治疗随访结果进行分析和总结。结果该病例支持成人低血磷骨软化症诊断,手术切除右下腹包块,病理符合良性磷酸盐尿性间叶肿瘤(PMT),进一步行FGF-23组化染色,显示FGF-23(+)。术后患者血磷快速恢复正常,尿磷降低;给予适当钙剂和维生素D制剂治疗,随访12周,患者全身疼痛完全缓解,步态恢复正常;随访至24周,患者的骨转换指标、血钙磷基本维持正常;随访36周时骨密度恢复正常,获得临床治愈。结论对于无家族史成人发病的低血磷骨软化症应考虑肿瘤相关性骨软化症的可能,手术切除肿瘤是治疗的关键,FGF-23染色阳性证实了对TIO的诊断。     

成纤维细胞生长因子-23与肿瘤源性骨软化症

肿瘤源性骨软化症是一种少见的副肿瘤综合征,其病理机制尚不清楚.近年研究发现,肿瘤源性骨软化症患者血磷水平降低而成纤维细胞生长因子(FGF)-23水平显著增高,两者呈负相关性.FGF-23既可抑制肾脏对磷的重吸收及维生素D3活化,又可负性调节成骨细胞分化和基质矿物化.肿瘤源性骨软化症患者肿瘤切除后血FGF-23水平可恢复正常,低磷血症即获纠正,表明FGF-23与肿瘤源性骨软化症的病理生成密切相关.该文就FGF-23表达特点及其在肿瘤源性骨软化症发病机制中的作用等方面的研究进展作一综述.     

成人低血磷性骨软化病1例并文献复习

目的 分析低血磷性骨软化症的病因、发病机制、诊断标准与治疗.方法 采用病例回顾的方式,讨论低血磷性骨软化症临床和影像学特征.结果 该患者经过详细检查,并未发现肿瘤.该低血磷性骨软化症患者的临床和影像学特征:(1)骨痛、骨畸形、多发骨折、肌无力;(2)显著低血磷、高尿磷,碱性磷酸酶明显增高,血钙正常或偏低;(3)X线表现为全身普遍性骨密度降低、骨畸形和假骨折.(4)中性磷合剂及活性D治疗效果显著,常规剂量维生素D无效.结论 成人发作的低血磷性骨软化症是罕见代谢性骨病,该病容易被误诊且致残率高,临床医生应进一步提高对该疾病的认识.     

外科患者术后血磷浓度变化的临床观察

作者用钼兰显色法检测２５７例外科术后重症监护患者的血磷浓度。结果有１３６例血磷浓度〈０．８ｍｍｏｌ／Ｌ，称为低磷血症，发生率为５２．９％。低磷血症的发生与患者年龄、原发疾病以及术后静脉输流高渗葡萄糖溶液有关，同时可合并低血钙、低血钠、低血钾等。并且与脏器功能的受损或衰竭有关。本组４０例死亡患者中，低磷血症的有３１例。作者认为为提高外科危重患者的治疗愈率，低磷血症的及时诊和积极预防治疗是十分重要的环     

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[1].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.     

Hypophosphatemic osteomalacia induced by low-dose adefovir therapy: focus on manifestations in the skeletal system and literature review

Osteomalacia is a metabolic bone disease that leads to softening of the bones and can be caused by hypophosphatemia. Large clinical studies of low-dose adefovir dipivoxil (adefovir) have found no evidence of renal tubular dysfunction leading to hypophosphatemia after 48 weeks of treatment. We report two cases of low-dose adefovir-induced hypophosphatemic osteomalacia that initially presented with diffuse musculoskeletal pain. The first patient was a 62-year-old man with a 2-year history of bone pain involving the dorsal mid-thorax, lower anterior chest wall, right sacroiliac joint area, and both knees. The patient had been receiving adefovir for 5 years before confirmation of hypophosphatemia and urinary phosphate wasting. Bone scintigraphy revealed multifocal lesions including multiple ribs, costochondral junctions, costovertebral junctions, sacrum, both posterior iliac bones, both proximal tibia, right calcaneus, and the left second metatarsophalangeal joint area, which were suggestive of metabolic bone disorder. Bone pain was significantly reduced within 3 months after supplementation with phosphate and calcitriol. The second patient was a 54-year-old male who presented with an 18-month history of severe bone pain of the right medial knee and low back. The patient had been taking adefovir for approximately 40 months before the development of bone pain. Laboratory data revealed hypophosphatemia and vitamin D deficiency. Bone scintigraphy showed increased uptake in bilateral ribs, sternum, both scapulae, both costovertebral junctions, both pelvic bones, medial cortex of the right proximal femur, right proximal tibia, and the left lateral tarsal bone. The symptoms improved by changing the antiviral agent from adefovir to entecavir. Because osteomalacia often presents with diffuse bone pain, non-specific radiologic findings and non-characteristic routine serum biochemical changes, the disease can be confused with various musculoskeletal diseases and a high index of suspicion is necessary for an early diagnosis in patients receiving adefovir therapy.     

Diagnostic utility of magnetic resonance imaging skeletal survey in a patient with oncogenic osteomalacia.

Oncogenic osteomalacia is a rare paraneoplastic syndrome characterized by hypophosphatemic osteomalacia due to renal phosphate wasting. The same biochemical features are found in patients with X-linked hypophosphatemic rickets/osteomalacia and sporadic hypophosphatemic osteomalacia with unknown etiology. Oncogenic osteomalacia is cured by resection of the responsible tumor. In contrast, patients with other types of hypophosphatemic rickets/osteomalacia need long-term treatment with large doses of active vitamin D3. Therefore, detection of the responsible tumor for oncogenic osteomalacia has great clinical importance. However, there is no standard method for detecting the tumor for oncogenic osteomalacia, and the responsible tumor is often very difficult to be found. We describe a patient with adult-onset osteomalacia due to renal phosphate wasting. Although oncogenic osteomalacia was suspected, cranial, chest, and abdominal computed tomography scanning, urological and otolaryngological examinations, and detailed palpation for soft tissue mass failed to detect the responsible tumor. However, magnetic resonance imaging skeletal survey revealed a tumor in the right femoral bone. Resection of the tumor resulted in normalization of serum phosphate and renal phosphate handling. Because the most frequent causes for oncogenic osteomalacia are tumors in bone or soft tissue, magnetic resonance imaging skeletal survey is a very powerful method for detecting the responsible tumor. Vigorous search for tumors with this method in patients with hypophosphatemic osteomalacia would be helpful not only for proper management of patients, but also for clarifying the identity of sporadic hypophosphatemic osteomalacia.     

Use of adefovir in the treatment of the chronic hepatitis B virus infection with resistance to lamivudine

Current therapies for the treatment of chronic hepatitis B virus (HBV) infection do not eliminate viral replication once therapy is stopped, resulting in a rapid rebound of viremia in a majority of patients. Prolonged therapy results in emergence of resistant virus, which is a major clinical concern. The appearance of resistant HBV is associated with decreased seroconversion rates as well as worse liver histology. Adefovir dipivoxil, a nucleotide analogue with potent antiviral activity against HBV and human immunodeficiency virus (HIV), has shown in vivo and in vitro to have activity against lamivudine-resistant HBV. We present a series of 6 patients with chronic HBV infection and lamivudine-resistant HBV treated with adefovir dipivoxil. The viremia decreased in all patients; in 4 of them, serum HBV DNA was negative by chain reaction (PCR) in a mean period of 10 months from beginning of treatment. Resistance to adefovir after 12 months of treatment has not been detected. Alanine aminotransferase (ALT) levels decreased in all patients and, at this moment, 5 of 6 patients present normal levels. There were no toxic side effects due to adefovir treatment. The data confirm that adefovir treatment has efficacy against HBV lamivudine-resistant forms.     

阿德福韦酯致低磷性骨软化临床诊治应对

阿德福韦酯(adefovir dipivoxil,ADV)是单磷酸腺苷核苷酸类似物,是阿德福韦的前体,具有抗病毒的作用,最早用于艾滋病的治疗。近年发现小剂量阿德福韦酯(10mg/d)可导致肾脏的损害,临床属少见病例,容易误诊,本文通过1例长期口服阿德福韦酯所致低血磷性骨软化诊治分析,以提高临床诊断治疗水平。     

阿德福韦酯联合拉米夫定治疗乙型肝炎肝硬化失代偿期的临床体会

目的对阿德福韦酯联合拉米夫定治疗乙型肝炎肝硬化失代偿期的临床疗效和药物安全性进行观察和探讨。方法将102例乙型肝炎肝硬化失代偿期患者随机分成两组：每组各51例。对两组都进行常规护肝及抗纤维化对症治疗,观察组在常规的基础上对其进行阿德福韦酯10mg/d和拉米夫定100mg/d的联合治疗,对照组在常规的基础上对其进行阿德福韦酯10mg/d的治疗,并对两组患者治疗后的各项疗效指标进行比较和观察。结果治疗48周时观察组的各项指标在改善程度上都比对照组组高,两组数据差异具有统计学意义（P〈0.05）。结论阿德福韦酯联合拉米夫定治疗乙型肝炎肝硬化失代偿期疗效显著,是理想的抗乙肝病毒药物,两种药物的联合使用可以增加抗毒效果,对患者预后能明显改善。     

Nonosteomalacic osteopathy associated with chronic hypophosphatemia

Summary We studied bone histomorphometry in 19 patients with chronic hypophosphatemia related to an idiopathic renal phosphate wasting and without histological osteomalacia. Nine patients had renal lithiasis (group 1), three had radiological osteoporosis (group 2), and seven had lumbar pain (group 3). In the whole group of 19 patients, serum phosphate levels were low (24.9±2.1 mg/l), calcium in blood was normal, calcium in urine was increased, and iPTH was low. Histomorphometric data showed decreased osteoblastic surfaces with normal resorption surfaces, normal osteoid volume and calcification front. There was no correlation between serum phosphate level and histomorphometric parameters. There was no statistical difference between the data of the 3 groups of hypophosphatemic patients. We concluded that chronic hypophosphatemia in the adult doses not always lead to osteomalacia but to an unusual osteopathy characterized by an osteopenia due to an isolated decrease in bone formation. The respective importance of phosphate deficiency and of decreased iPTH level in the pathogenesis of this osteopathy is uncertain.     

乙型肝炎肝硬化并脾亢脾部分栓塞术后阿德福韦酯疗效分析

目的观察乙型肝炎肝硬化并脾功能亢进患者行脾部分栓塞术后阿德福韦酯疗效。方法41例乙型肝炎肝硬化并脾功能亢进患者行脾部分栓塞术治疗后,21例口服阿德福韦酯10mg／d,疗程1年,对照组20例常规护肝、降酶等对症治疗。观察两组患者肝功能、血清肝纤维化指标、HBVDNA、HBeAg／抗．HBe血清学变化、Child-Pugh分级比较和不良反应。结果治疗组ALT、AST、TBil、ALB各项指标优于对照组,血清肝纤维化HA、PC-Ⅲ、Ⅳ—C各项优于对照组,治疗组HBVDNA转阴11例,对照组转阴1例,差异有统计学意义（Χ^2=8．5,P〈0．05）。治疗组发生HBeAg／抗．HBe血清转换者4例,对照组1例,差异有统计学意义（Χ^2=3．2,P〈0．05）。治疗组Child．Pugh分级为A级者9例,B级10例,C级2例;对照组A级6例,B级7例,C级7例,差异有统计学意义（Χ^2=5．9,P〈0．05）。阿德福韦酯治疗组未发现相关的肾功能损害和其他不良反应。结论乙型肝炎肝硬化并脾功能亢进患者行脾部分栓塞术治疗,脾功能亢进可获得明显改善,但不能阻止乙型肝炎肝硬化病情进展,脾栓塞术后采用阿德福韦酯是较理想的长期抗病毒药物。     

Nonosteomalacic osteopathy associated with chronic hypophosphatemia

We studied bone histomorphometry in 19 patients with chronic hypophosphatemia related to an idiopathic renal phosphate wasting and without histological osteomalacia. Nine patients had renal lithiasis (group 1), three had radiological osteoporosis (group 2), and seven had lumbar pain (group 3). In the whole group of 19 patients, serum phosphate levels were low (24.9 +/- 2.1 mg/l), calcium in blood was normal, calcium in urine was increased, and iPTH was low. Histomorphometric data showed decreased osteoblastic surfaces with normal resorption surfaces, normal osteoid volume and calcification front. There was no correlation between serum phosphate level and histomorphometric parameters. There was no statistical difference between the data of the 3 groups of hypophosphatemic patients. We concluded that chronic hypophosphatemia in the adult doses not always lead to osteomalacia but to an unusual osteopathy characterized by an osteopenia due to an isolated decrease in bone formation. The respective importance of phosphate deficiency and of decreased iPTH level in the pathogenesis of this osteopathy is uncertain.