| OBJECTIVESTumor-induced osteomalacia(TIO) is an acquired form of hypophosphatemia,and commonly associated with benign mesenchymal tumors.The tumors are usually small,slow growing,and difficult to find.Probably as this result,TIO is rare reported.Nevertheless,resections of the tumors lead to complete cure of osteomalacia.In this study,we study the detection methods and therapy of TIO.METHODSFrom Jan 2004 to Jul 2007,we collected 52 patients of after puberty onset hypophosphatemic osteomalacia without family history of hypophosphatemia.Physical examination and detection by technetium-99 octreotide scintigraphy(99Tcm-OCT) were performed on every patient.If the tumor was suspected,ultrasound,CT and MRI would be done on the patient.Resection would be performed when the tumor was determined.RESULTSWithin 52 patients,21 patients were detected of abnormally high uptakes by 99Tcm-OCT,then, 18 of them accepted the operations and 17 were diagnosed as TIOs.1 patient(T19) had the history of mandible tumor resection with symptoms relieved,but recurred for 2 years,99Tcm-OCT,PET and CT showed a mass in soft tissue within scapular bone,she refused operation.1 patient(T18) with negtive 99Tcm-OCT result also had the operation on tumor of gum and obtained symptoms relieved.Therefore,19 TIOs were diagnosed in our hospital.19 TIO patients(M/F=9/10) aged 43.1±13.5 years(21-69 years old) with the history of 8.8±8.1 years(2-28 years),suffered from fatigue(100%),bone pain(100%),movement disorder (100%),shorten of stature(63.2%) and pathological fractures(63.2%).X ray showed pelvis deformity(57.9%),pseudofractures(26.3%) and vertebral fractures(73.7%).Their serum calcium 2.27±0.10mmol/L,phosphate 0.41±0.10mmol/L,ALP 293±143U/L,PTH 91.3±83.6pg/ml,24 hours urine calcium 2.12±1.29mmol,24 hours urine phosphate 17.01±6.98mmol,TMP/GFR 0.43±0.15mmol/L,serum 1,25(OH)2D3 15.4±8.9pg/ml.Only 6 of them(6/19,31.5%) could be detected of masses by physical examinations.After ultrasound(9/13,69.2%),CT(11/11,100%) and MRI(7/7,100%),18 patients accepted tumor resections,and 15 of them(83.3%) had the rise in serum phosphate 4.9±2.1days after the operations(P＜0.001).During the followup,3 patients' serum phosphate(3/15,20%) dropped down again in 8-28 months.CONCLUSION1.19/52(36.5%) TIO patients were found in in after puberty onset hypophosphatemic osteomalacia.So,TIO is probably not rare hypophosphatemic osteomalacia.2.18/19 TIO patients(94.7%) had the postive results in 99Tcm-OCT examination. Therefore,99Tcm-OCT is a effective method to detect the tumor of TIO.Ultrasound,CT and MRI are helpful to locate the TIO tumors.3.Pathologic results of TIO were mesenchymal tumors including PMT and PMTMCT.Most of the TIO patients(15/18,83.3%) were recovered after tumor resections,4.Hypophosphatemia recurred in some TIO patients(3/15,20%) even after operation.It is necessary to follow the TIO patients for a long time. OBJECTIVESTumor induced osteomalacia (TIO) is an acquired hypophosphatemic syndrome characterized by impaired renal tubular reabsorption of phosphate, low serum concentrations of phophate and calciriol(l,25-dihydroxyvitamin D3), and defective bone mineralization. Experimental evidence suggests that the biochemical and skeletal defects are caused by humoral factors (phosphatonins). Fibroblast growth factor 23 (FGF-23), matrix extracellular phosphoglycoprotein (MEPE) and secreted Frizzled related protein 4 (sFRP4) are potential candidates for phosphatonins. This aim of the study was to evaluate the role of FGF23, MEPE and sFRP4 in pathogenesis of TIO.METHODSThe mRNA expressions of FGF23, MEPE and sFRP4 were detected in 8 TIO tumors (T1-8), 5 other mesenchymal tumors(C1-5), 2 normal bone tissues(B1-2), 2 normal muscle tissues(M1-2), 1 patients of hypophospatemic osteomalacia but not TIO (P1) using RT-PCR. The FGF23 protein expressions were analysed in 8 TIO tumors using Western blot.Serum FGF23 and phosphate were measured before and after operation in 6 TIO patients (T1,3,4,7,11,13) and 1 patients of hypophospatemic osteomalacia but not TIO (P1).RESULTS1. The mRNA of FGF23 and MEPE were expressed in TIO tumors abundantly. Some TIO tumors expressed sRP4 mRNA. There were varible FGF23 expressions in bone tissues, osteosarcoma and bone giant cell tumor. In blood clotting and necrostic tissue of bone, lipoma, and bone giant cell tumor, there were varible expressions of MEPE. Bone tissue and neurofibroma had some sFRP4 expressions.2. 7/8 TIO tumors expressed varible FGF23 protein in Western blot. 3. 22 normal patients were measured of their serum FGF23 in ELISA. The average was 20.7±7.0pg/ml (rangell.4-33.3pg/ml) . Serum FGF23 in TIO patients were elevated, but went down rapidly (in 2-6 hrs) after tumor resections. The decrease of serum phosphate were slower than FGF23 (in 3-10 days). The serum FGF23 were stably high in patients without serum phosphate elevation.4. The expressions of FGF23 and MEPE mRNA were related (r=0.884, P=0.047). MEPE mRNA was inversely correlated with serum calcium (r=—0.927, P = 0.023). There was a positive relationship between FGF23 mRNA and protein expression (r=0.921, P = 0.026). We could find a trend that the more expression of FGF23 in TIO rumors, the more FGF23 detected in circulation.CONCLUSIONSTIO rumors expressed high level of FGF23 mRNA and protein. Serum FGF23 levels were elevated in TIO patients, and went down rapidly after tumor resections. The decrease of serum phosphate was slower than FGF23. The serum FGF23 levels were stably high in patients without serum phosphate elevations. These suggest that FGF23 may play a important role in pathogenesis ofTIO.TIO tumors expressed high level of MEPE mRNA. The expressions of FGF23 and MEPE were related. Therefore, MEPE may be involved in pathogenesis of TIO.sFRP4 were expressed in some TIO tumors, other mesenchymal rumors and bone. There was no relationship between sFRP4 with FGF23 or MEPE. The role of sFRP4 in pathogenesis of TIO is still need to be explored. |
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