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。     

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.     

肿瘤相关性骨软化症1例报告并文献回顾

正肿瘤相关性骨软化症(tumor-induced osteomalacia,TIO)是临床上一种罕见的副瘤综合征,主要由于磷酸盐尿性间叶肿瘤(phosphaturic mesenchymal tumor,PMT)分泌的成纤维生长因子-23(fibroblast growth factor-23,FGF-23)导致肾磷排出显著增加,进而引起血磷降低,骨矿化不全[1]。TIO患者临床表现以不明原因的进行性骨痛、肌无力、病理性骨折、     

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。     

肿瘤相关性低磷抗D骨软化症的外科干预治疗

目的观察分析采用外科手术方法治疗肿瘤相关性低磷抗D骨软化症的早期疗效及此类肿瘤的外科学特点.方法从2004年2月至2005年3月,对7例诊断为肿瘤相关性低磷抗D骨软化症的患者进行手术治疗,完整切除软组织肿瘤5例,骨肿瘤2例.术后平均随访4个月（2周～12月）.结果6例患者术后临床症状明显改善,血磷恢复正常,1例未见明显改善.结论肿瘤低磷抗D骨软化症是一种罕见病例,5例软组织肿瘤临床症状少,常规体检不易发现;2例骨肿瘤在X线片上仅表现为骨密度增高区,无明显溶骨及破坏,易被误诊.一经确诊,手术治疗效果良好.     

肿瘤相关性低磷骨软化病的诊断和治疗

目的分析、探讨肿瘤相关性低磷骨软化病(tumor induced osteomalacia,TIO)患者的临床特点、诊断及外科治疗,提高对该病的认识。方法分析8例TIO患者的临床资料和实验室及影像学检查特点,其中男5例,女3例,年龄32~54岁,平均(43±7)岁,病程(115±85)个月。结果 8例患者均符合低磷骨软化的临床诊断,均成年起病;低血磷,尿磷水平高,血钙正常偏低水平,碱性磷酸酶升高,甲状旁腺激素基本正常。奥曲肽显像有1例阴性,7例提示生长抑素受体高表达。2例行CT检查,6例行MRI检查,2例行彩超检查,2例行全身骨扫描检查,4例行PETCT检查。明确定位后行手术治疗,术后病理明确诊断。结论 TIO有典型的临床特点,明确TIO肿瘤部位是外科治疗的前提,奥曲肽显像结合超声、CT及MRI有助于肿瘤的发现和定位,完整手术切除肿瘤是治疗的关键。     

腰椎管内间叶性肿瘤致低血磷骨软化症1例报道

<正>肿瘤相关性低血磷性骨软化症(tumor induced osteomalacia,TIO)是一种由肿瘤引起肾脏排磷增加造成的获得性低血磷性骨软化症,临床表现为肌无力、骨痛,严重者出现骨骼畸形、骨折、活动障碍,显著影响生活质量,切除肿瘤后,病情可以获得明显缓解[1]。TIO肿瘤大多为来源于间叶组织的良性肿瘤,最好发于四肢、头颈颌面部[2],椎管内肿瘤导致的低血磷骨软化症尚未见报道。现将北京协     

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     

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...     

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.     

Cinacalcet in the management of tumor-induced osteomalacia.

Both FGF-23 and PTH inhibit renal phosphate reabsorption. We treated two patients with TIO and FGF-23-mediated hypophosphatemia with cinacalcet to test the hypothesis that medicinally induced hypoparathyroidism would decrease renal phosphate wasting. Cinacalcet treatment resulted in increased renal phosphate reabsorption, allowed for a decrease in phosphate supplementation, and showed evidence of bone healing in one of the two patients. INTRODUCTION: Tumor-induced osteomalacia (TIO) is a rare, acquired disease of renal phosphate wasting, which results in hypophosphatemia and osteomalacia. It is caused by mesenchymal tumors that produce the phosphate and vitamin D-regulating hormone, fibroblast growth factor (FGF)-23. Removal of the tumor is curative, but the tumors are often difficult to locate. Medical treatment involves high doses of oral phosphate and calcitriol, but the phosphate is often poorly tolerated and leads to diarrhea. Because PTH also promotes phosphaturia, and patients with hypoparathyroidism are hyperphosphatemic in the setting of elevated serum FGF-23, we postulated that the calcium-sensing receptor agonist, cinacalcet, which can induce hypoparathyroidism, would be an effective adjuvant in the treatment of TIO. MATERIALS AND METHODS: Two subjects with presumed TIO in whom the tumor was not located after extensive testing and who did not tolerate medical therapy with phosphorus and calcitriol were treated with cinacalcet. RESULTS: Neither treatment with phosphorus nor combined treatment with phosphorus and calcitriol had an effect on serum FGF-23 levels. Treatment with cinacalcet resulted in increased renal phosphate reabsorption and serum phosphorus and allowed for a decrease in phosphate supplementation to a dose that was tolerated. On this regimen, one patient showed significant bone healing as shown by resolution of activity on bone scan and lack of osteomalacia as assessed by histomorphometry. CONCLUSIONS: These data show that medically induced hypoparathyroidism with cinacalcet is a therapeutic option for disorders of FGF-23-mediated hypophosphatemia and that, in the absence of PTH, the phosphaturic effect of FGF-23 is decreased.     

Comparison of two assays for fibroblast growth factor (FGF)-23

FGF-23 was recently shown to be involved in the development of several hypophosphatemic diseases, including X-linked hypophosphatemic rickets/osteomalacia (XLH) and tumor-induced rickets/osteomalacia (TIO). FGF-23 is processed between Arg¹⁷⁹ and Ser¹⁸⁰, and only full-length FGF-23 was shown to cause hypophosphatemia. Two assays for FGF-23 have been reported. One assay detects only full-length FGF-23. In contrast, the C-terminal assay recognizes both full-length and processed C-terminal fragment of FGF-23. However, discrepant results concerning circulatory levels of FGF-23 in patients with TIO and XLH have been reported using these two assays. We simultaneously measured FGF-23 levels in 13 patients with adult-onset hypophosphatemic osteomalacia and 29 patients with XLH by these two assays. The full-length assay indicated that FGF-23 was above the upper limit of the reference range in all patients with osteomalacia and in 24 of 29 patients with XLH. However, the C-terminal assay in dicated that FGF-23 was within the reference range in 3 of 13 patients with osteomalacia and 16 of 29 patients with XLH. In addition, there was no correlation between FGF-23 levels measured by these assays in patients with XLH whose FGF-23 was within the reference range by C-terminal assay. These results indicate that FGF-23 within the reference range by C-terminal assay does not rule out an increase in full-length FGF-23. In addition, because FGF-23 was high in most of these hypophosphatemic patients, these results support the notion that FGF-23 plays a major role in the development of hypophosphatemia in patients with TIO and XLH.     

Tumor-related osteomalacia followed after treatment by hyperparathyroidism

Tumor-induced osteomalacia is due to renal phosphate wasting in response to a humoral factor produced by a tumor, usually a benign mesenchymal tumor. Removal of the tumor is followed by resolution of the metabolic disorder. Physicians should be aware that sporadic renal phosphate wasting in an adult should prompt a search for a tumor. A case of tumor-induced osteomalacia due to a nonossifying fibroma of the radius is reported. After removal of the tumor, renal phosphate excretion returned to normal, but the patient developed tertiary hyperparathyroidism. Eight years elapsed between symptom onset and the diagnosis of the tumor. The pathogenesis of tumor-induced osteomalacia and the role of treatment for renal phosphate wasting on the subsequent development of hyperthyroidism are discussed.     

Tumor-induced osteomalacia—a diagnostic dilemma for an orthopedic surgeon

Tumor-induced osteomalacia is a rare condition caused by excess production of phosphatonins most notably fibroblast growth factor?23 (FGF-23), by the tumor cells, leading to phosphate wasting and consecutive severe hypophosphatemia. This results in patient developing gradually progressive muscle weakness and bone loss resulting in severe osteomalacia, making the patient bedbound. These tumors are mostly benign mesenchymal tumors, which remain hidden in soft tissues or bone and thus are difficult to diagnose. And in the presence of normal serum calcium and parathyroid levels with only mild alteration of vitamin D levels, the diagnosis gets further delayed causing a lot of apathy to the patient. We hereby present a thorough review of this condition along with our experience in diagnosing and treating this patient. This underlines the fact that a high index of suspicion is required for diagnosing this condition in a patient with persistent complains of fatigue and bone pains. Appropriate investigations done at an early stage can help one in identifying and excising these tumors, bringing about a rapid relief of symptoms and saving the patient from a lot of distress.