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。     

鼻腔肿瘤相关低磷骨性软化症1例报告及文献复习

目的 了解肿瘤相关性低磷骨软化症(TIO)临床及病例特点,提高诊断治疗水平。方法 对1例TIO临床资料进行回顾性分析,并复习相关文献。结果 患者表现为进行性加重的全身骨痛、病理性骨折、血磷减少、尿磷增高,骨质疏松,人院后经鼻窦CT检查诊断左侧鼻腔内血管瘤可能性大,手术切除肿瘤病理报告证实为血管球周皮细胞瘤,术后3天复查血磷开始升高,尿磷下降,术后1个月血磷正常,患者全身疼痛改善,双下肢乏力缓解,活动恢复正常,术后6个月骨密度恢复正常。结论 对表现为乏力、骨痛、低血磷、高尿磷,骨质疏松或多发性骨折患者,体格检查或影像学检查提示有占位或肿瘤时,应首先考虑TIO。     

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.     

肿瘤源性骨软化症1例报道

目的熟悉肿瘤源性骨软化症(tumor induced osteomalacia,TIO)的特征。方法介绍1例低磷性骨软化症的临床表现、实验室检查、影像学和病理检查。结果患者,男,41岁,全身多关节疼痛伴跛行2年余。脊椎后突,肋外翻。血磷0.31mmol/L,血碱性磷酸酶255U/L;全身PET/CT:双侧多根肋骨、骶骨、双侧髋骨骨折;左侧股骨头低密度病灶,放射性摄取增高,肿瘤性病变可能。髋关节MRI:左侧股骨颈局限性骨质缺损,大小约1.0×1.5cm,为良性骨病,肿瘤样病变不除外。区域组织麻醉下行左股骨颈肿瘤切除术,病理报告:间叶源性肿瘤,联系临床考虑考虑为尿磷性间叶肿瘤(Phosphaturic mesenchymal tumor)。术后第7天复查血磷升至0.76mmol/L,碱性磷酸酶降至215U/L,24h尿磷降至8.4mmol/24h。术后一月随访骨痛症状及近端肌肉无力症状均有好转。本例最后诊断肿瘤源性骨软化(TIO)。结论成年发生的无家族史低磷性骨软化症应排除TIO,全身PET/CT功能显像和局部MRI解剖显像可确定肿瘤部位,手术切除肿瘤是治疗的关键。     

距骨肿瘤相关性低磷抗D骨软化症1例报道

肿瘤相关性低磷抗D骨软化症是由于新形成的骨基质不能正常矿化的一种代谢性骨病。该病病因之一是由肿瘤引起肾脏排磷增加而导致的获得性低血磷性骨软化症,由McCance于1947年首次描述。目前国内外文献对该病报道不足200例,发病部位主要集中在股骨和胫骨等负重部位,而未有距骨发生此病的文献报道,现有1例报道如下。     

阿德福韦酯治疗慢性乙型肝炎致低磷性骨软化症8例

目的：进一步探讨阿德福韦酯（ADV）所致低磷性骨软化症的临床特点。方法回顾性分析2010至2012年共收治的8例慢性乙型肝炎患者经ADV治疗所致低磷性骨软化症的临床表现、治疗和转归。结果8例患者均在服用ADV后出现低磷血症及骨质疏松，其主要临床表现为乏力、多发骨痛，进行加重至行走障碍；低血磷、低尿酸和高碱性磷酸酶血症、骨密度检查提示骨质疏松。经停用ADV、对症补钙、补磷治疗后患者的血磷恢复正常，疼痛缓解，骨质疏松改善。结论 ADV可引起低磷性骨软化症；补充磷、维生素D3及钙剂治疗可恢复。     

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.     

全髋关节置换术治疗肿瘤诱发低磷骨软化症:5～10年随访

背景:肿瘤诱发低磷骨软化症(tumor-induced osteomalacia,TIO)患者完全切除病因肿瘤后有较好的预后.但应用全髋关节置换术治疗位于股骨头颈部肿瘤的中长期临床效果还缺乏相关研究.目的:评估全髋关节置换术治疗TIO的中长期疗效.方法:回顾性分析在我院被诊断为TIO并于2004年12月至2015年12...     

低磷抗维生素D骨软化症2例报道

通过低磷抗维生素D骨软化症2例分析,了解其相关发病机理和临床表现,以及实验室相关异常指标和治疗体会。     

Tumor-Induced Osteomalacia Caused by a Phosphaturic Mesenchymal Tumor of the Sole Presenting as a Crippling Illness in a Postmenopausal Woman

Tumor-induced osteomalacia, a rare and intriguing paraneoplastic syndrome that is usually caused by a phosphaturic mesenchymal tumor, leads to severe pain and hypophosphatemia. However, during clinical practice, most patients suffer from significant delay of diagnosis and treatment because the symptoms are similar to those of some very common diseases, such as osteoporosis and osteoarthritis. Moreover, physical complaints from postmenopausal women usually exacerbate the possibility of such delays. We describe a case of a postmenopausal woman with crippling bone pain and weakness, who had been diagnosed with a case of simple osteoporosis and osteoarthritis for 3 years, even with fine-needle aspiration biopsy of the offending phosphaturic mesenchymal tumor. After surgical removal of the 2 × 3-cm² tumor in her sole, we observed immediate relief of her systemic symptoms, with visual analogue scale improvement from 5 of 10 preoperatively to 2 of 10 5 days after surgery. There were no signs of recurrence during 2-year follow-up. This case highlights the significance of thorough history-taking as a fundamental tool for diagnosis even in the era of advanced technology, and that the awareness of tumor-induced osteomalacia should be raised. Otherwise, such a small localized soft tissue mass would seldom be associated with the severe systemic symptoms.     

Infiltrative nature of tumor-induced osteomalacia lesions in bone: Correlation between radiological and histopathological features

ObjectiveTumor-induced osteomalacia is a rare paraneoplastic syndrome usually caused by phosphaturic mesenchymal tumors, which commonly occur in bone. This study aimed to investigate the radiological features of tumor-induced osteomalacia lesions in bone, and their correlation with its histopathology.Materials and methodsThis study included 13 patients with tumor-induced osteomalacia treated between January 2000 and April 2018 at our hospital. All patients were surveyed to detect the tumor causing the condition. Diagnostic imaging studies of the suspected tumors were obtained before tumor removal. We evaluated the radiological features of all tumors, investigated histopathological findings in 10 cases that underwent surgery, and obtained evaluable tumor specimens.ResultsThe tumors were classified into the following three types by CT: sclerotic (n = 4), lytic (n = 7), and mixed (n = 2). In two cases, lytic lesions focally invaded the surrounding cancellous bone, detected by the soft tissue-window of CT, not the bone-window. Histopathology revealed inter-trabecular invasion in all cases, regardless of radiological features. Osteoclasts were seen in lytic types, and creeping substitution-like thickened trabecular bone and calcification were observed in sclerotic types. In all cases, focal invasion of the tumor into cortical bone was seen.ConclusionsTumor-induced osteomalacia lesions in bone showed a wide variety of radiological features, and tended to invade into cancellous and cortical bone. These findings suggest that extended curettage or resection of thinned cortical bone may be necessary. This might improve the cure rate of surgeries for tumor-induced osteomalacia lesions in bones.     

Oncogenic osteomalacia: two case reports with surprisingly different outcomes

Oncogenic osteomalacia is a rare paraneoplastic syndrome of acquired hypophosphatemic osteomalacia, resulting from a deficit in renal tubular phosphate reabsorption, in which fibroblast growth factor 23 (FGF23) seems to be implicated. This condition is usually associated with a phosphaturic mesenchymal tumor of mixed connective tissue located in the bone or soft tissue. The clinical and the radiologic findings are the same as those seen in osteomalacia, and the biochemical features include renal phosphate loss, low serum phosphate and 1,25-(OH)₂ vitD₃ levels, increased alkaline phosphatase, and normal calcium, PTH, calcitonin, 25-OH-vitD₃ and 25,25-(OH)₂ vitD₃. We present two cases of oncogenic osteomalacia associated with phosphaturic mesenchymal tumors, which were histologically similar, but presented a completely different evolution. In the first patient, the tumor developed on the sole of the foot. Following removal of the mass, the symptoms resolved and biochemical and radiological parameters returned to normal. However, in the second patient, a liver tumor developed and resection did not resolve the disease. Multiple lesions appeared in several locations during follow-up. This disease usually remits with complete tumor resection. Nevertheless, if this is not possible, oral treatment with phosphate, calcium and calcitriol can improve the symptoms. If scintigraphy of the tumor shows octreotide receptors, patients may respond partially to therapy with somatostatin analogs, with stabilization of the lesion.     

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.     

Burosumab in tumor-induced osteomalacia: A case report

Tumor-induced osteomalacia is a rare cause of acquired hypophosphatemia due to the paraneoplastic overproduction of fibroblast growth factor-23. Unlike many causes of osteomalacia, tumor-induced osteomalacia is curable by resection of the offending tumor. If a patient has a tumor that is unidentifiable, unresectable, or makes the decision to forgo surgery, medical treatment is recommended. Burosumab (KRN23) is a fully human monoclonal antibody against fibroblast growth factor-23 that was recently approved for the treatment of X-linked hypophosphatemia. We present a case of tumor-induced osteomalacia due to two somatostatin receptor avid meningiomas. The patient initially was wheelchair bound due to symptoms of diffuse bone and muscle pain with recurrent traumatic and nontraumatic fractures. Serum phosphate was 1.8 mg/dL (reference range: 2.4–5.0 mg/dL) with no other laboratory or historical cause. Workup revealed two widely separated intracranial meningiomas with typical magnetic resonance imaging characteristics. The duplicity of tumors precluded safe surgery and the potential delay in, or lack of, efficacy using radiosurgery prompted the treatment team to opt for medical treatment. Burosumab was initiated resulting in improvement in pain symptoms and mobility. Serum phosphate normalized. Trials are ongoing to assess the utility of burosumab in the treatment of tumor-induced osteomalacia.     

Bone Turnover and the Osteoprotegerin–RANKL Pathway in Tumor-Induced Osteomalacia: A Longitudinal Study of Five Cases

To evaluate serum levels of osteoprotegerin (OPG), soluble receptor activator of the nuclear factor-κB (RANKL), and their relationship with FGF-23, lumbar bone mineral density (BMD), and bone turnover markers, five patients with tumor-induced osteomalacia (TIO) and 40 healthy controls were studied. TIO patients were followed for 360 days after surgical removal of underlying tumor (n = 2) or beginning of therapy with phosphate and calcitriol when surgical treatment was impossible (n = 3). At diagnosis, TIO patients had higher levels of FGF-23 and bone-specific alkaline phosphatase (bALP) and lower levels of cathepsin K (CathK), RANKL, and RANKL/OPG ratio compared to controls. During the follow-up, FGF-23 decreased significantly only in patients who underwent a surgical excision, while phosphate and BMD increased in all patients. The increases in BMD, phosphate, and renal phosphate reabsorption rate were directly related. In the first 60 days of follow-up, we observed a prolonged inhibition of RANKL, CathK, and bone resorption markers associated with a persistence of TIO symptoms and an increase in bALP. From day 60, levels of bone turnover markers returned progressively within the normal range and a clinical remission was observed. The inhibition of the RANKL/OPG pathway and the uncoupling of bone formation and resorption observed in patients with active TIO may be a compensatory mechanism, attempting to reduce worsening of osteomalacia. The BMD increase during TIO treatment is related to the improvement of phosphate rather than FGF-23 levels. A “hungry bone”-like syndrome was observed after surgical or pharmacological treatment.