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Context Tumor-induced osteomalacia (TIO) is a rare condition with evidence mostly derived from case reports and case series. Objective We aimed to describe the clinical characteristics of a large cohort of patients diagnosed with TIO, with a focus on patients with nonlocalizing and malignant TIO. Methods This is a retrospective cohort of patients with TIO in an academic medical center, diagnosed between January 1998 and May 2023. We describe their demographics, biochemistries, tumor features, localization, treatment, and complications. Results Of 68 patients diagnosed with TIO, 49 (72%) were localizing and 5 (7.4%) were malignant. Of 50 patients who attempted localizing procedures, 29 (58%) achieved cure. Twenty (40%) had persistent disease due to the wrong tumor targeted, or refractory or recurrent tumors, despite up to 6 procedural attempts. There was no difference in demographics, phosphorus, or baseline fibroblast growth factor-23 (FGF23) levels between localizing vs nonlocalizing groups, and malignant vs nonmalignant groups. The lower extremity was the commonest site of localization (37%), with 47% in bone and 53% in soft tissue. Sixty percent of malignant cases were located in the trunk. Tumor size correlated with peak FGF23 (R = 0.566, P <.001) but was not associated with malignancy risk (P =.479). A cut-off FGF23 of >20 times upper limit of normal in the presence of normal renal function (P =.025) and recurrence after initial cure (P =.013) were factors significantly associated with malignancy. The nonlocalizing group had lower survival than the localizing group (P =.0097). Conclusion TIO is a condition with significant morbidity. Very high FGF23 levels and disease recurrence are associated with malignant disease. Reasons behind the observation of higher mortality in nonlocalizing TIO should be further explored. [ABSTRACT FROM AUTHOR]

Objective: We present a case of phosphaturic mesenchymal tumor (PMT) in the left ethmoid without any nasal symptoms in a 63-year-old woman. Initially diagnosed with postmenopausal osteoporosis, 2-year history of hypophosphatemia and a significantly higher uptake of Fluorine-18 (18F)-AlF-NOTA-octreotide (18F-OC) in the left ethmoid sinus, provided crucial information for accurate diagnosis. Methods: We presented a case with chart review and conducted review of the literature. Results: The patient endured 1-year history of weakness and bone pain but without any nasal symptoms before a tissue diagnosis was eventually reached. It is a challenging diagnosis to make-patients present with non-specific clinical symptoms and the culprit neoplasm is often tiny in size and difficult to detect. It emphasizes the importance of thorough patient history-taking and the whole-body functional imaging. Conclusions: Sinonasal PMTs are rare, and because of this most otolaryngologists are unfamiliar with its clinical presentation. This case highlights the importance of early diagnosis to enable prompt intervention and reduce the burden of associated symptoms. [ABSTRACT FROM AUTHOR]

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused by hypersecretion of fibroblast growth factor 23 (FGF23) by typically benign phosphaturic mesenchymal tumors (PMTs). FGF23 excess causes chronic hypophosphatemia through renal phosphate losses and decreased production of 1,25-dihydroxy-vitamin-D. TIO presents with symptoms of chronic hypophosphatemia including fatigue, bone pain, weakness, and fractures. Definitive treatment is surgical resection of the PMT with wide margins. Other therapeutic options are necessary when the tumor is unable to be localized, not amenable to complete resection, or when the patient is not a good surgical candidate. Alternative ablative approaches such as radiotherapy, radiofrequency ablation, and cryoablation, have been used with variable success and limited follow up. Medical management is warranted both prior to definitive therapy and in non-operable cases to improve symptoms and allow for bone remineralization. Oral phosphate and calcitriol were the mainstay of medical therapy, however, the development of burosumab, a monoclonal blocking antibody to FGF23, has introduced an approved therapy that improves hypophosphatemia and symptoms in patients with TIO. In select cases, cinacalcet can be an effective adjuvant to phosphate and calcitriol. Continued monitoring for tumor growth is necessary while on medical therapy. Infigratinib, a selective FGFR tyrosine-kinase inhibitor targeting a causative tumoral fusion protein, can reverse the biochemical findings of TIO and possibly reduce tumor mass; however, its use is constrained by serious side effects. Overall, innovations in medical and interventional treatments have broadened therapeutic options for patients with PMTs, particularly in cases where a curative surgical resection is not possible. [ABSTRACT FROM AUTHOR]

Context Tumor-induced osteomalacia (TIO) is an ultra-rare, paraneoplastic syndrome caused by tumors that secrete fibroblast growth factor 23 (FGF23). Initial signs and musculoskeletal symptoms can be nonspecific and unrecognized, leading to long delays in diagnosis and treatment, and resulting in severe and progressive disability in patients with TIO. Objective This review aimed to identify published evidence on healthcare resource use in TIO to better understand the burden of the disease. Evidence acquisition A targeted literature review was conducted to identify publications reporting on disease characteristics and healthcare resource use associated with TIO. Evidence synthesis In total, 414 publications were included in the review, of which 376 were case reports. From the case reports, data on 621 patients were extracted. These patients had a mean (SD) age of 46.3 (15.8) years; 57.6% were male. Mean time from first symptoms to diagnosis of TIO was 4.6 (4.7) years and, in cases where imaging tests were reported, patients underwent a mean of 4.1 (2.7) procedures. Tumor resection was attempted in 81.0% of patients and successful in 67.0%. Fracture was reported in 49.3% of patients. Results from association analyses demonstrated that longer time to diagnosis was associated with poorer tumor resection outcomes and a higher probability of tumor recurrence. Unfavorable tumor resection outcomes were associated with greater use of pharmacologic treatment and a greater likelihood of orthopedic surgery. Conclusion TIO is associated with a substantial healthcare resource burden. Improvements in the diagnostic process could lead to better management of TIO, thereby benefiting patients and reducing that burden. [ABSTRACT FROM AUTHOR]

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome characterized by hypophosphatemia caused by excessive secretion of fibroblast growth factor-23 (FGF-23) by tumors. This leads to impaired bone mineralization and, ultimately, osteomalacia. The most common underlying cause is a phosphaturic mesenchymal tumor (PMT). Due to its rarity, nonspecific clinical presentation, and limited clinician awareness, TIO is frequently underdiagnosed or misdiagnosed. A 42-year-old man presented with persistent pain in the chest, lower back, knees, and ankles for more than six months, which had worsened in the preceding week. Laboratory tests revealed hypophosphatemia and abnormalities in markers of bone metabolism. Symptomatic treatment provided minimal improvement. The whole-body PET/CT scan subsequently identified a cystic and solid mass in the popliteal fossa of the right knee, with high somatostatin receptor expression. The tumor was surgically removed, and histopathological examination confirmed PMT. The patient's blood phosphorus concentration returned to normal one week after surgery, and levels of other laboratory indicators gradually returned to normal. Although symptoms persisted during the first postoperative week, significant relief was noted by the second week. This case report highlighted the necessity of improving clinical recognition and management of TIO to ensure timely diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Objective: This study aims to report the application of 18F-AlF-NOTA-Octreotide PET/CT and 3D printing technology in the diagnosis and treatment of phosphaturic mesenchymal tumors (PMT) in patients with tumor-induced osteomalacia (TIO). Case presentation: A 68-year-old male patient (Case 1) was admitted to the Weifang People's Hospital in August 2022 with complaints of "persistent pain in the bilateral flank and lumbosacral region". 18F-AlF-NOTA-Octreotide PET/CT showed high octreotide expression in the left femoral region. A 48-year-old male patient (Case 2) was admitted to the Weifang People's Hospital in November 2022, complaining of "pain in the lumbar region and ribs". 18F-AlF-NOTA-Octreotide PET/CT showed high octreotide expression in the pancreatic uncinate process and the left acetabulum. They were diagnosed with hypophosphatemic osteomalacia, with a strong consideration of an underlying neuroendocrine tumor. Preoperative design of 3D virtual surgery, CAD/CAM, and 3D printing technology were used to customize the digital surgical guide plates, and the surgery was carried out. They were both finally confirmed as phosphateuric mesenchymal tumors (PMT) based on postoperative pathology and immunohistochemistry results. Both patients experienced substantial relief from their clinical manifestations after surgery. Conclusion: 18F-AlF-NOTA-Octreotide PET/CT may be a precise diagnostic method for TIO, while 3D printing technology may serve as an effective and dependable adjunct for the treatment of PMT in patients with TIO. [ABSTRACT FROM AUTHOR]

Background: Acquired hypophosphatemic osteomalacia (AHO) is a rare metabolic bone disorder characterized by hypophosphatemia and impaired bone mineralization. Tumor-induced osteomalacia (TIO) is the most common cause of AHO, caused by phosphaturic tumors that overproduce fibroblast growth factor 23 (FGF-23). Objective: To present the clinical characteristics, diagnostic challenges, and outcomes of seven cases of AHO in Peruvian patients between 1999 and 2023. Methods: A retrospective review of seven patients diagnosed with AHO was conducted. Clinical data, including diagnostic procedures, treatments, and outcomes, were collected. Results: Seven cases of AHO were reviewed. In case one, osteomalacia did not improve despite supraphysiological doses of vitamin D (ergocalciferol/cholecalciferol), and no tumor was detected with available tests, resulting in the patient's death. Cases two and three involved tumors located in the right leg and right hemithorax, respectively, with symptom resolution following total resection. In cases four, five, and seven, exhaustive exams failed to locate tumors. Cases four, six, and seven showed elevated FGF-23 levels, while case five had inappropriately normal FGF-23 levels. Case seven was the first patient in Peru to receive burosumab treatment. In case six, a tumor in the head of the femur was identified, but the patient opted for nonsurgical management. Conclusion: The diagnosis of AHO is challenging, requiring a high index of clinical suspicion and biochemical confirmation. TIO is the most common cause of AHO, emphasizing the importance of locating the phosphaturic tumor. However, in some cases, the tumor remains elusive despite exhaustive diagnostic workups. This is particularly challenging in developing countries like Peru, where resources are limited. [ABSTRACT FROM AUTHOR]

Hypophosphatemic osteomalacia is a rare condition caused by different causes, all resulting in disturbances of calcium-phosphate management. One of the most common causes among adults is tumor-induced osteomalacia, which is characterized by increased secretion of fibroblast growth factor-23. Its symptoms are vague, tests necessary for diagnosis are not commonly used by clinicians and some of them are only available in highly specialized centers. Due to these reasons, patients often are misdiagnosed for more common conditions and are left without proper treatment for many years. We present a case of a patient suffering from multiple fractures, diffuse bone pain, and muscle weakness, who was previously misdiagnosed for osteoporosis, primary and secondary hyperparathyroidism. We discuss the pathophysiology of tumor-induced osteomalacia, diagnostic path, differential diagnosis, available forms of treatment and possible complications. [ABSTRACT FROM AUTHOR]

Excess fibroblast growth factor-23 (FGF23) causes renal phosphorous wasting and impaired activation of vitamin D leading to osteomalacia. Tumor-induced osteomalacia (TIO) is a rare cause of FGF23-mediated hypophosphatemia. We present 2 patients with FGF23-mediated hypophosphatemia who had low bone mineral density (BMD) at diagnosis and remarkable improvements in BMD with treatment. Patient 1 is a 43-year-old man who had years of progressive pain, difficulty ambulating, and multiple fractures. Patient 2 is a 48-year-old nonverbal man with autism and intellectual disability who had months of progressively declining mobility, presumed pain, and multiple fractures. Workup in both cases revealed hypophosphatemia, evidence of renal phosphorous wasting, and elevated FGF23. Patient 1 was diagnosed with TIO when imaging identified a subcutaneous left flank mass and excision resulted in rapid symptom improvement; he experienced a 96% increase in lumbar spine (LS) BMD after surgery. Patient 2 has had multiple scans over several years, but no FGF23-secreting tumor has been identified. He has been maintained on medical treatment with phosphorous and calcitriol with improvement in functioning and 48% increase in LS BMD. Both patients had improvements in BMD with treatment, with more pronounced improvement in the patient with TIO managed surgically. [ABSTRACT FROM AUTHOR]

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome characterized by hypophosphatemia caused by excessive secretion of fibroblast growth factor-23 (FGF-23) by tumors. This leads to impaired bone mineralization and, ultimately, osteomalacia. The most common underlying cause is a phosphaturic mesenchymal tumor (PMT). Due to its rarity, nonspecific clinical presentation, and limited clinician awareness, TIO is frequently underdiagnosed or misdiagnosed. A 42-year-old man presented with persistent pain in the chest, lower back, knees, and ankles for more than six months, which had worsened in the preceding week. Laboratory tests revealed hypophosphatemia and abnormalities in markers of bone metabolism. Symptomatic treatment provided minimal improvement. The whole-body PET/CT scan subsequently identified a cystic and solid mass in the popliteal fossa of the right knee, with high somatostatin receptor expression. The tumor was surgically removed, and histopathological examination confirmed PMT. The patient’s blood phosphorus concentration returned to normal one week after surgery, and levels of other laboratory indicators gradually returned to normal. Although symptoms persisted during the first postoperative week, significant relief was noted by the second week. This case report highlighted the necessity of improving clinical recognition and management of TIO to ensure timely diagnosis and treatment.

Aim. To present a clinical case of osteomalacia associated with fibroblast growth factor-23-secreting tumor under the mask of ankylosing spondylitis (AS).Materials and methods. Clinical observation of a 31-year-old patient with long-time diagnosis of AS is presented. Underestimation of back pain cause at the initial stage of diseaseled to an erroneous diagnosis of AS. A thorough assessment of the anamnesis, additional examination using modern imaging methods in combination with laboratory analysis (low blood phosphorus level, hyperphosphaturia, normal value of C-reactive protein, erythrocyte sedimentation rate, negative HLA-B27), made it possible to establish the correct diagnosis of “mesenchymal phosphaturic tumor of the left foot (surgical intervention dated 11.26.2020), secondary hypophosphatemic tumor-induced osteomalacia complicated by multiple bone fractures”, to carry out timely treatment with full recovery.Results. The literature data on epidemiology, pathogenetic mechanisms, clinical manifestations and management approaches of tumor induced phosphopenic osteomalacia are presented. An algorithm for examining patients with suspected of this disease is described, taking into account the expression of somatostatin transmembrane receptors on the surface of a mesenchymal phosphaturic tumor.Conclusion. One of the rarest causes of specific back pain is osteomalacia, which can be caused by various diseases, for example, a tumor secreting FGF23 The complexity of the diagnosis lies in the non-specificity of clinical manifestations – generalized myalgia and myopathy, ossalgia, pathological fractures, etc. Timely diagnosis and radical treatment makes it possible to achieve stable remission with complete leveling of symptoms, therefore surgical excision of the tumor is the “gold” standard of therapy.

Objective The orthopedic surgical treatment strategies for patients with tumor‐induced osteomalacia (TIO) require improvement, especially for patients where the causative tumors are located in surgically challenging areas, requiring a greater degree of in‐depth investigation. This work aims to summarize and investigate clinical features and orthopedic surgical treatment effects of patients with tumor‐induced osteomalacia (TIO), whose causative tumors are located in the hip bones. Methods A retrospective analysis was conducted on the clinical data of all patients diagnosed with culprit tumors located in the hip bones who underwent surgical treatment at the orthopedic bone and soft tissue tumor sub‐professional group of Peking Union Medical College Hospital from January 2013 to January 2023. This retrospective study summarized the clinical data, preoperative laboratory test results, imaging findings, surgery‐related data, perioperative changes in blood phosphorus levels, and postoperative follow‐up data of all patients who met the inclusion criteria. Normally distributed data are presented as mean and standard deviation, while non‐normally distributed data are shown as the means and 25th and 75th interquartile ranges. Results The clinical diagnostic criteria for TIO were met by all 16 patients, as confirmed by pathology after surgery. Among the 16 patients, we obtained varying degrees of bone pain and limited mobility (16/16), often accompanied by difficulties in sitting up, walking, and fatigue. An estimated 62.5% (10/16) of patients had significantly shorter heights during the disease stages. All 16 patients underwent surgical treatment for tumors in the hip bones, totaling 21 surgeries. In the pathogenic tumor, there were 16 cases of skeletal involvement and none of pure soft tissue involvement. Out of the 16 patients, 13 cases had a gradual increase in blood phosphorus levels following the latest orthopedic surgery, which was followed up for 12 months to 10 years. Due to unresolved conditions after the original surgery, four patients received reoperation intervention. Two cases of refractory TIO did not improve in their disease course. Conclusion In summary, the location of the causative tumor in the hip bone is hidden and diverse, and there is no defined orthopedic surgical intervention method for this case in clinical practice. For patients with TIO where the tumors are located in the hip bones, surgical treatment is difficult and the risk of postoperative recurrence is high. Careful identification of the tumor edge using precise preoperative positioning and qualitative diagnosis is crucial to ensure adequate boundaries for surgical resection to reduce the likelihood of disease recurrence and improve prognosis.

Phosphaturic mesenchymal tumor (PMT) is a rare benign mesenchymal tumor characterized by excessive secretion of fibroblast growth factor 23 (FGF23), leading to phosphate loss and systemic osteomalacia. Despite recent progress in PMT research, no consensus on diagnosis and treatment guidelines has been established. This case series describes the clinical and pathological features of six pathologically confirmed PMT patients treated at the Third Affiliated Hospital of Sun Yat-sen University from 2010 to 2024, aiming to provide new insights for the management of this condition. The patients, consisting of three males and three females with an average age of 44 years and follow-up periods of 0.5 to 4.5 years, presented primarily with muscle pain and lower limb weakness. One patient experienced loose teeth, and two had palpable, painless masses. One case developed hyperphosphatemia, tertiary hyperparathyroidism, and renal impairment after prolonged phosphate supplementation. Tumor localization was achieved using 18F-FDG or 68Ga-DOTATATE Positron Emission Tomography-Computed Tomography(PET/CT) and MRI, followed by complete surgical resection. Pathological examination confirmed PMT, and postoperative recovery was marked by significant symptom relief and normalization of serum phosphate levels. Two patients experienced recurrence within three years but showed no further recurrence following repeat surgery by the last follow-up. The diagnosis of PMT is challenging and may take years, potentially leading to complications due to inadequate treatment. Complete tumor resection remains the primary treatment, generally resulting in a favorable prognosis; however, long-term monitoring is essential to detect potential recurrences and initiate timely interventions.

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome characterized by hypophosphatemia, bone mineralization disorders with increased risk of fragility fractures, muscle pain, and progressive weakness. TIO has been associated with increased production of the phosphaturic hormone Fibroblast Growth Factor 23 (FGF23) usually by mesenchymal tumors of soft tissue or bone (Phosphaturic Mesenchymal Tumors—PMTs). In rare cases TIO may be observed in association with other malignancies. We report the case of a 66-year-old woman with an occasional diagnosis of both a PMT and an ovarian cancer during the evaluation of TIO. We also systematically review the literature to discover possible correlations between osteomalacia, FGF23 production, and ovarian cancer. Four studies were eligible for the analysis. Two case reports described an association between TIO development and ovarian cancer, whereas the two case-control studies hypothesized a possible correlation between FGF/FGF receptor axis and cancer development. Although it does not provide conclusive evidence regarding the association between TIO and ovarian cancer, this case report highlights the possibility that in the diagnostic workup of suspected TIO, both FGF23-secreting tumors distinct from PMT and tumors unrelated to the clinical presentation of TIO could be identified. This information is important for guiding successful tumor staging and determining the necessity for surgical intervention and/or eventual adjuvant therapy. [ABSTRACT FROM AUTHOR]

Objective: The orthopedic surgical treatment strategies for patients with tumor‐induced osteomalacia (TIO) require improvement, especially for patients where the causative tumors are located in surgically challenging areas, requiring a greater degree of in‐depth investigation. This work aims to summarize and investigate clinical features and orthopedic surgical treatment effects of patients with tumor‐induced osteomalacia (TIO), whose causative tumors are located in the hip bones. Methods: A retrospective analysis was conducted on the clinical data of all patients diagnosed with culprit tumors located in the hip bones who underwent surgical treatment at the orthopedic bone and soft tissue tumor sub‐professional group of Peking Union Medical College Hospital from January 2013 to January 2023. This retrospective study summarized the clinical data, preoperative laboratory test results, imaging findings, surgery‐related data, perioperative changes in blood phosphorus levels, and postoperative follow‐up data of all patients who met the inclusion criteria. Normally distributed data are presented as mean and standard deviation, while non‐normally distributed data are shown as the means and 25th and 75th interquartile ranges. Results: The clinical diagnostic criteria for TIO were met by all 16 patients, as confirmed by pathology after surgery. Among the 16 patients, we obtained varying degrees of bone pain and limited mobility (16/16), often accompanied by difficulties in sitting up, walking, and fatigue. An estimated 62.5% (10/16) of patients had significantly shorter heights during the disease stages. All 16 patients underwent surgical treatment for tumors in the hip bones, totaling 21 surgeries. In the pathogenic tumor, there were 16 cases of skeletal involvement and none of pure soft tissue involvement. Out of the 16 patients, 13 cases had a gradual increase in blood phosphorus levels following the latest orthopedic surgery, which was followed up for 12 months to 10 years. Due to unresolved conditions after the original surgery, four patients received reoperation intervention. Two cases of refractory TIO did not improve in their disease course. Conclusion: In summary, the location of the causative tumor in the hip bone is hidden and diverse, and there is no defined orthopedic surgical intervention method for this case in clinical practice. For patients with TIO where the tumors are located in the hip bones, surgical treatment is difficult and the risk of postoperative recurrence is high. Careful identification of the tumor edge using precise preoperative positioning and qualitative diagnosis is crucial to ensure adequate boundaries for surgical resection to reduce the likelihood of disease recurrence and improve prognosis. [ABSTRACT FROM AUTHOR]

Tumor-induced osteomalacia (TIO) is an exceedingly rare paraneoplastic condition characterized by hypophosphatemia, osteomalacia, fragility fractures, and fatigue. A 39-year-old man was assessed for hemoptysis, pathological rib fractures, and fatigue, and was found to have a chest mass with lung metastasis. Biopsy of the mass suggested high-grade epithelioid and spindle cell neoplasm. He was initially treated for soft tissue sarcoma with an ifosfamide-based regimen and developed Fanconi syndrome that resolved on cessation of ifosfamide. Serum phosphate remained low. A low tubular maximum reabsorption of phosphate to glomerular filtration rate ratio (TmP/GFR) indicated disproportionate phosphaturia, while a severely elevated fibroblast growth factor-23 (FGF23) level enabled a diagnosis of TIO. He was started on phosphate and calcitriol supplementation. Subsequent next-generation sequencing demonstrated a RET -fusion mutation, leading to reclassification of his malignancy to a sarcomatoid non–small cell lung carcinoma. He was switched to selpercatinib, a targeted RET -kinase inhibitor approved for locally advanced or metastatic RET -fusion–positive solid tumors. This induced tumor remission with subsequent normalization of his FGF23 levels and hypophosphatemia. Despite the presence of a confounding etiology like drug-induced Fanconi syndrome, persistence of hypophosphatemia should prompt a workup of TIO, especially in the presence of a tumor. [ABSTRACT FROM AUTHOR]

ObjectiveThis study aims to report the application of 18F-AlF-NOTA-Octreotide PET/CT and 3D printing technology in the diagnosis and treatment of phosphaturic mesenchymal tumors (PMT) in patients with tumor-induced osteomalacia (TIO).Case presentationA 68-year-old male patient (Case 1) was admitted to the Weifang People’s Hospital in August 2022 with complaints of “persistent pain in the bilateral flank and lumbosacral region”. 18F-AlF-NOTA-Octreotide PET/CT showed high octreotide expression in the left femoral region. A 48-year-old male patient (Case 2) was admitted to the Weifang People’s Hospital in November 2022, complaining of “pain in the lumbar region and ribs”. 18F-AlF-NOTA-Octreotide PET/CT showed high octreotide expression in the pancreatic uncinate process and the left acetabulum. They were diagnosed with hypophosphatemic osteomalacia, with a strong consideration of an underlying neuroendocrine tumor. Preoperative design of 3D virtual surgery, CAD/CAM, and 3D printing technology were used to customize the digital surgical guide plates, and the surgery was carried out. They were both finally confirmed as phosphateuric mesenchymal tumors (PMT) based on postoperative pathology and immunohistochemistry results. Both patients experienced substantial relief from their clinical manifestations after surgery.Conclusion18F-AlF-NOTA-Octreotide PET/CT may be a precise diagnostic method for TIO, while 3D printing technology may serve as an effective and dependable adjunct for the treatment of PMT in patients with TIO.

Fibroblast growth factor 23 (FGF23) is a pivotal humoral factor for the regulation of serum phosphate levels and was first identified in patients with autosomal dominant hypophosphatemic rickets and tumor-induced osteomalacia (TIO), the most common form of acquired FGF23-related hypophosphatemic rickets/osteomalacia (FGF23rHR). After the identification of FGF23, many other inherited and acquired forms of FGF23rHR were reported. In this review article, the detailed features of each acquired FGF23rHR are discussed, including TIO, ectopic FGF23 syndrome with malignancy, fibrous dysplasia/McCune-Albright syndrome, Schimmelpenning-Feuerstein-Mims syndrome/cutaneous skeletal hypophosphatemia syndrome, intravenous iron preparation-induced FGF23rHR, alcohol consumption-induced FGF23rHR, and post-kidney transplantation hypophosphatemia. Then, an approach for the differential diagnosis and therapeutic options for each disorder are concisely introduced. Currently, the majority of endocrinologists might only consider TIO when encountering patients with acquired FGF23rHR; an adequate differential diagnosis can reduce medical costs and invasive procedures such as positron emission tomography/computed tomography and venous sampling to identify FGF23-producing tumors. Furthermore, some acquired FGF23rHRs, such as intravenous iron preparation/alcohol consumption-induced FGF23rHR, require only cessation of drugs or alcohol to achieve full recovery from osteomalacia.

Purpose: This article aims to provide a comprehensive review of the management challenges associated with Spinal Phosphaturic Mesenchymal tumors (PMTs) and evaluates the surgical management outcomes for this rare entity linked to Tumor-induced osteolysis. The primary objective of this study is to enhance the familiarity of treating physicians with the clinical features, diagnosis, and treatment options for Spinal PMTs. Methods: A retrospective analysis was conducted, reviewing electronic medical records of patients diagnosed with spinal PMTs at our hospital between January 2019 and December 2022. The data collected included demographic information, clinical presentation, radiological findings, surgical details, and follow-up outcomes. Results: A total of three cases of Spinal PMTs causing Tumor-induced osteomalacia were identified. The diagnosis of Spinal PMTs presented challenges, with incidental detection often occurring during routine imaging. Surgical management was undertaken, resulting in successful symptom resolution and normalization of phosphate levels. The application of 68 Ga-DOTA-TATE PET/CT scans facilitated tumor localization, aiding in surgical planning. Spinal PMTs demonstrated a favorable response to surgical intervention. Conclusion: Spinal PMTs play a significant role in Tumor-induced osteolysis, warranting timely and accurate diagnosis. Although diagnosing Spinal PMTs presents challenges, surgical management has proven to yield favorable outcomes, effectively alleviating symptoms and restoring phosphate levels. A multidisciplinary approach and continued vigilance are essential in ensuring early diagnosis, effective treatment, and long-term monitoring for patients affected by spinal PMTs. [ABSTRACT FROM AUTHOR]

Phosphaturic mesenchymal tumors are rare, usually benign neoplasms that occur in the soft tissue or bone and are the cause of nearly all cases of tumor-induced osteomalacia. Tumor-induced osteomalacia due to phosphaturic mesenchymal tumor is a challenging diagnosis to make—patients present with variable clinical and radiologic findings and the culprit neoplasm is often small and can occur anywhere head to toe. We present two cases of phosphaturic mesenchymal tumor in the scapular body and plantar foot. In both cases, the patient endured years of debilitating symptoms before a tissue diagnosis was eventually reached. Descriptions of clinical presentation, laboratory workup, surgical resection, and imaging characteristics, with a focus on CT, MRI, and functional imaging, are provided to assist with the diagnosis and management of this rare entity. A brief review of current literature and discussion of the differential diagnoses of phosphaturic mesenchymal tumor is also provided. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Tumor‐induced osteomalacia is a rare but potentially serious disease with nonspecific misguiding manifestations that can result in a wrong diagnosis and being treated for rheumatologic or other similar diseases. In patients with unexpected fractures, resistant musculoskeletal pains, and hypophosphatemia, this diagnosis should be considered by the physicians and approached through a complete history taking, physical exam laboratory, and radiologic evaluation to give the opportunity of on‐time treatment to the patient. Tumor‐induced osteomalacia (TIO) is an uncommon mesenchymal tumor that results in disproportionate phosphorus excretion, primarily leading to bone‐related symptoms. Laboratory, imaging, and histopathological evaluation can confirm this pathologic condition. In this case, we present the history and subsequent clinical parts of a 50‐year‐old woman who presented with an unusual presentation of generalized musculoskeletal pains and a right ankle mass. Her disease was diagnosed with multidisciplinary evaluation and was approached by a surgical treatment. The patient was treated with total resection of the tumor, which led to complete resolution of musculoskeletal and metabolic abnormalities, which were resolved following total tumor resection. TIO is a paraneoplastic disease that results in abnormal secretion of phosphatonins, particularly fibroblast growth factor 23 (FGF23). This can cause hypophosphatemia, hyperparathyroidism, lower bone density, and increased risk of pathologic fractures. These tumors are mostly cured by surgical ± radiotherapy. The present study aims to provide insight into the fact that a TIO diagnosis is not always straightforward. However, in suspicious cases such as unexplained hypophosphatemia, it should be considered to prevent delayed diagnosis of the progressive pathology. The earlier treatment can prevent several complications and reduce the risk of mortality. [ABSTRACT FROM AUTHOR]

Tumor-induced osteomalacia (TIO) is a rare acquired form of hypophosphatemia that can be cured when the tumor responsible is completely removed. These tumors can be small and located in anatomically challenging areas, rendering surgery both risky and extensive. Radiofrequency ablation (RFA) has been explored as an effective treatment option for such tumors. We present a case of a 35-year-old man exhibiting clinical and biochemical features consistent with TIO. The culprit lesion was not detectable on the whole-body computed tomography (CT) scan. Gallium (Ga-68) DOTANOC positron emission tomography (PET)/CT showed increased uptake in the left acetabulum and magnetic resonance imaging (MRI) confirmed the location of the tumor. Given the risky anatomical location, we opted for less-invasive RFA. Following an unsuccessful attempt at CT-guided RFA of the lesion, we used real-time Ga-68 DOTANOC PET/CT guidance for precise imaging during the ablation procedure. Our patient achieved complete remission both clinically and biochemically after RFA. This response was also evident by the absence of tracer uptake in follow-up imaging. In conclusion, DOTANOC PET/CT–guided RFA can serve as a safe and effective treatment for patients with tumors causing TIO. This modality proves valuable when surgical resection is not a viable option. [ABSTRACT FROM AUTHOR]

Phosphaturic mesenchymal tumors (PMT) are rare and distinctive tumors that typically result in paraneoplastic syndrome known as tumor-induced osteomalacia (TIO). We report a case of bilateral osteoporotic femoral neck fracture caused by PMT. PMT was surgically resected, followed by sequential treatment of bilateral femoral neck fractures with total hip arthroplasty (THA). A 49-year-old perimenopausal woman experienced consistent bone pain with limb weakness persisting for over 2 years. Initially, she was diagnosed with early osteonecrosis of the femoral head and received nonsurgical treatment. However, from 2020 to 2022, her pain extended to the bilateral shoulders and knees with increased intensity. She had no positive family history or any other genetic diseases, and her menstrual cycles were regular. Physical examination revealed tenderness at the midpoints of the bilateral groin and restricted bilateral hip range of motion, with grade 3/5 muscle strength in both lower extremities. Laboratory findings revealed moderate anemia (hemoglobin 66 g/L), leukopenia (2.70 × 109 /L), neutropenia (1.28 × 109 /L), hypophosphatemia (0.36 mmol/L), high alkaline phosphatase activity (308.00 U/L), and normal serum calcium (2.22 mmol/L). After surgery, additional examinations were performed to explore the cause of hypophosphatemic osteomalacia. After definitive diagnosis, the patient underwent tumor resection via T11 laminectomy on August 6, 2022. Six months after the second THA, the patient regained normal gait with satisfactory hip movement function without recurrence of PMT-associated osteomalacia or prosthesis loosening. By providing detailed clinical data and a diagnostic and treatment approach, we aimed to improve the clinical understanding of femoral neck fractures caused by TIO. [ABSTRACT FROM AUTHOR]

Spinal phosphaturic mesenchymal tumor (PMT) is a rare disorder but can be cured once the diagnosis is clear and a complete removal by surgery is performed. To the best of our knowledge, only 22 cases in the spine have been described, and we report a case with the largest number of spinal segments (T12-L5) affected among spine PMT cases. A comprehensive literature search was performed until May 23, 2023, following the Preferred Reporting Items for Systematic Reviews guidelines. Studies were chosen through relevant PubMed, Web of Science, and EMBASE searches to prioritize obtaining the largest studies. The Medical Subject Headings and Boolean operators employed for this search were ("PMT" or "TIO" or "Tumor-induced osteomalacia" or "phosphaturic mesenchymal tumor") and ("spine" or "spinal"). Two researchers (L.S.Z. and D.B.C) independently reviewed and evaluated the included articles. Any differing opinions were discussed until a consensus was reached. A total of 18 studies were included. A case report is also presented. We report a case of spinal PMT. The full text of the relevant articles was construed. A total of 18 studies were reviewed and consolidated. These articles are roughly divided into the following 5 subcategories: 1) clinical features and baseline distribution, 2) laboratory and imaging findings, 3) pathological manifestations, and 4) surgical methods and treatment options. Spinal PMT is very rare with a high rate of misdiagnosis and debilitating complications, so it is of significance to increase awareness of the disease among spine surgeons consulted by patients with spinal PMT. 68Ga-DOTATOC-PET/CT shows very high sensitivity to the spinal PMT but there is no way to exactly determine the location of the tumor. PMT has unique immunohistochemical characteristics and malignant PMT is rare. Once diagnosed, complete surgical excision is the recommended treatment. Burosumab is one of the available options, especially in cases that are recurrent and difficult to surgically resect. [ABSTRACT FROM AUTHOR]

Context: Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome usually caused by oversecretion of fibroblast growth factor 23 (FGF23) from a phosphaturic mesenchymal tumor (PMT). PMTs are usually benign neoplasms but some of them show malignant characteristics. Objective: The aim of this study was to compare the clinical characteristics of benign and malignant PMTs inducing TIO. Methods: On March 31, 2023, we performed a systematic review of individual patient data analysis in Medline, Google Scholar, Google book, and Cochrane Library using the terms “tumor induced osteomalacia,” “oncogenic osteomalacia,” “hypophosphatemia,” with no language restrictions and according to Preferred Reporting Items for Systematic reviews and Meta-Analyses criteria. Results: Overall, we collected data from 837 patients with TIO in which the diagnosis of benign and malignant PMT was specified. Of them, 89 were affected by malignant PMT and 748 by benign PMT. Patients with malignant PMTs were younger and presented bone pain, functional impairment, and bone deformities more frequently. Malignant PMTs showed higher values of intact FGF23 and a higher mortality rate. Conclusion: The study results identify the clinical characteristics of patients with malignant TIO, permitting the early identification of patients with PMT at increased risk of malignancy. This may significantly improve the diagnostic approach to disease. Further experimental studies are mandatory to clarify the role of FGF23 in the pathogenesis of malignancy in PMTs. [ABSTRACT FROM AUTHOR]

Tumor-induced osteomalacia is caused by excessive fibroblast growth factor 23 production mainly from phosphaturic mesenchymal tumors. Surgical excision or tumor ablation are the preferred treatment. Information on bone microarchitecture parameters assessed by high-resolution peripheral quantitative computed tomography is limited. We report a woman with hypophosphatemic osteomalacia with generalized pain, weakness and recurrent fractures, and a large thoracic vertebral mass extending to the posterior mediastinum. Detailed radiologic and histopathologic evaluation revealed a phosphaturic mesenchymal tumor. Two surgeries were necessary for complete removal of the mass. Clinical symptoms improved after attaining normophosphatemia. Four-year post-surgical HR-pQCT parameters, compared to baseline, showed in the left distal radius, stable trabecular and cortical volumetric bone mineral density although below reference range. There was stability of trabecular number and thickness. Both stiffness and failure load decreased. A shift in cortical parameters was noted in year 2. In the left distal tibia, trabecular volumetric bone mineral density decreased whereas cortical volumetric bone mineral density markedly increased, as did cortical area. There was stability in the trabecular number and thickness. Both stiffness and failure load improved. Findings from HR-pQCT measurements in this patient disclosed that the healing of osteomalacia is not similar across the peripheral skeletal sites in the first years following tumor removal. Results contrasted low but stable volumetric bone mineral density in the distal radius with increase in the distal tibia at the expense of cortical bone. Our report helps further delineate the pattern of bone healing after treatment of this rare bone disorder.

Tumor-induced osteomalacia (TIO) is a rare, paraneoplastic disorder of hypophosphatemia associated with elevated tumor-produced fibroblast growth factor 23 (FGF23). Maxillofacial tumors are rarely involved in TIO, especially maxillary TIO in children. We present a 14-year-old boy with osteomalacia and high serum levels of FGF23, a hormone associated with decreased phosphate resorption, due to a maxillary tumor. The patient was treated with oral phosphorus and calcitriol, and surgical removal of the tumor was performed. After 21 months follow-up, he was pain free and had returned to full activity. We review the reported pediatric cases of TIO in the maxillofacial and oral region and discuss the management of these patients considering the published evidence.

Tumor-induced osteomalacia (TIO), a rare paraneoplastic syndrome is seen in association with the overproduction of fibroblast growth factor-23 (FGF-23) by certain mesenchymal tumors in adults. In children, these phosphaturic mesenchymal tumors produce features of rickets similar to TIO. This condition is characterized by elevated blood levels of FGF-23, low phosphate, low or normal active vitamin D, and high alkaline phosphatase. Though the removal of the tumor is curative; in cases where surgical resection is not possible, medical treatment is successful with phosphate and active vitamin D in the improvement of symptoms. The case of a child with features of rickets is presented here to illustrate the importance of identifying this rare condition and instituting appropriate intervention. [ABSTRACT FROM AUTHOR]

Background: Phosphaturic mesenchymal tumors (PMTs) are rare mesenchymal tumors, associated with long-standing, non-specific but often debilitating symptoms in the affected patients. These tumors display characteristic histopathological features and in case, identified timely, can be a boon for patients, given an excision is completely curative. Aims: To evaluate the clinical and histopathological features of 10 PMTs, diagnosed at our institution, along with clinical outcomes in those patients. Materials and Methods: This was a retrospective study, wherein 10 PMTs, diagnosed from January 2013 to July 2022, were included. Results: The average age at the time of diagnosis was 40 years with an M:F ratio of 4:1. Clinical features included lumps, weakness, bone pain, difficulty in moving and walking, and pathologic fractures. The biochemical analysis showed normal serum calcium levels (average = 9.5 mg/dL), with low serum phosphorus (average = 2.2 mg/dL) and raised serum fibroblast growth factor 23 (FGF23) levels, in all the cases, wherever available. On histopathology, all tumors showed cells arranged in a hemangiopericytomatous pattern, including oval to short spindle forms. Multinucleate giant cells were present in nine tumors, and characteristic “grungy calcifications” was observed in eight tumors. Prominent pseudo cystic spaces were seen in eight tumors. A significant number of mitotic figures and tumor necrosis were not seen in any tumor. In five cases where follow-up was available, there was complete resolution of symptoms post-resection with no recurrence or metastasis. All those patients were free of disease until the last follow-up. Conclusion: This constitutes the first largest comprehensive study on these rare tumors from our country. PMTs can be diagnosed based on certain histopathological features and correlation with clinicoradiological and biochemical findings. These are invariably benign neoplasms. Patients are relieved of their debilitating symptoms after adequate surgical tumor resection. Therefore, their correct and timely diagnosis is crucial.

Hypophosphatemic osteomalacia is a rare condition caused by different causes, all resulting in disturbances of calcium-phosphate management. One of the most common causes among adults is tumor-induced osteomalacia, which is characterized by increased secretion of fibroblast growth factor-23. Its symptoms are vague, tests necessary for diagnosis are not commonly used by clinicians and some of them are only available in highly specialized centers. Due to these reasons, patients often are misdiagnosed for more common conditions and are left without proper treatment for many years. We present a case of a patient suffering from multiple fractures, diffuse bone pain, and muscle weakness, who was previously misdiagnosed for osteoporosis, primary and secondary hyperparathyroidism. We discuss the pathophysiology of tumor-induced osteomalacia, diagnostic path, differential diagnosis, available forms of treatment and possible complications.

Tumor-induced osteomalacia (TIO), also known as oncogenic osteomalacia, is very rare, with about 1000 reported cases globally. Removing most TIO culprit tumors requires the evaluation and intervention of orthopedic doctors. However, orthopedic doctors often have a poor understanding of the optical treatment of TIO due to its rarity. In addition, most TIO patients lack specific clinical manifestations. Also, the clinical localization and qualitative diagnosis of TIO are difficult and thus can easily be misdiagnosed and mistreated. Furthermore, the true incidence rate of TIO may be underestimated. Although many breakthroughs have been made in exploring the pathogenesis, clinical diagnosis, and treatment of TIO, rational and standardized orthopedic surgical treatment experience summary and sorting for TIO patients are lacking. In this article, the recent experience and progress in the field of orthopedic surgical treatment for TIO globally have been summarized, providing a theoretical basis and new clinical practice guidance for the rational treatment of TIO patients.

Key Clinical Message: Phosphaturic mesenchymal tumor (PMT) is a rare disorder primarily affecting the extremities. It is notable for its correlation with hypophosphatemic osteomalacia and high FGF23 serum levels, which results in renal phosphate wasting and clinical symptoms associated with low serum phosphorus. We presented a patient with a 5‐year history of progressive osteomalacia who recently experienced a major pathological bone fracture. Laboratory findings showed a persistent low serum phosphate, normal calcium, elevated alkaline phosphatase activity, high parathyroid hormone levels, and increased renal excretion of phosphate. According to ultrasonography and nuclear imaging, there was no evidence of parathyroid adenoma. During further diagnostic assessment, a sinonasal cavity tumor was found and resected. Histologically, the tumor was composed of bland spindle cell proliferation in the background of a calcified matrix with foci of osteoid formation, hemangiopericytoma‐like (HPC‐like) vasculature, and osteoclast‐like giant cells. Tumor cells showed variable positivity for SMA, but CD34, S100, CD99, Melan‐A, p63, and desmin were all nonreactive. Regarding the clinical context, histological and immunohistological findings, a final diagnosis of tumor‐induced osteomalacia (TIO) secondary to a PMT was made. After surgery, laboratory results returned to normal, clinical symptoms disappeared, and the patient did not experience a recurrence during a six‐month follow‐up. [ABSTRACT FROM AUTHOR]

Background/Aim: X-linked hypophosphatemia (XLH), the most common form of hereditary rickets, results from loss-of-function mutations in the phosphate-regulating PHEX gene. Elevated fibroblast growth factor 23 (FGF23) contributes to hypophosphatemia in XLH. This study aimed to characterize PHEX variants and serum FGF23 profiles in Taiwanese patients with XLH. Patients and Methods: We retrospectively reviewed the records of 102 patients clinically suspected of having hypophosphatemic rickets from 2006 to 2022. Serum intact Fibroblast growth factor-23 (iFGF23) levels were measured on clinic visit days. PHEX mutations were identified using Sanger sequencing, and negative cases were analyzed using whole-exome sequencing. Results: The majority (92.1%) of patients exhibited elevated FGF23 compared with normal individuals. Among 102 patients, 44 distinct PHEX mutations were identified. Several mutations recurred in multiple unrelated Taiwanese families. We discovered a high frequency of novel PHEX mutations and identified variants associated with extreme FGF23 elevation and tumorigenesis. Conclusion: Our findings revealed the PHEX genotypic variants and FGF23 levels in Taiwanese patients with XLH. These results are crucial given the recent approval of burosumab, a monoclonal FGF23 antibody, for XLH therapy. This study provides key insights into the clinical management of XLH in Taiwan. [ABSTRACT FROM AUTHOR]

Phosphaturic mesenchymal tumor is a rare tumor characterized by paraneoplastic osteomalacia. The diagnosis is often delayed because of nonspecific symptoms and difficulty to localize the tumor. In this study we report a case of PMT of the left femur detected by Ga-68-DOTATATE PET-CT with radiological features mimicking osteoid osteoma. We report a 31-year-old female patient who presented to our hospital for evaluation due to progressive bone pain and muscle weakness. Her laboratory data showed hypophosphatemia and increased fibroblast growth factor 23 (FGF-23) together with reduced bone mineral density on bone densitometry. The diagnosis of PMT was suspected and the tumor was identified on Ga-68-DOTATATE PET-CT as a focal uptake in a lucent lesion of the left femoral head with a central sclerotic dot mimicking a nidus as seen in osteoid osteoma. The lesion was treated with percutaneous radiofrequency ablation. Laboratory tests and bone densitometry rapidly improved post-treatment. The present case emphasizes the difficulty to diagnose PMT due to its nonspecific biochemical and clinical presentation and the relevance of functional imaging for locating these tumors despite different radiological presentation.

Phosphaturic mesenchymal tumors (PMT) are rare neoplasms, which can give rise to a multifaceted syndrome, otherwise called tumor-induced osteomalacia (TIO). Localizing these tumors is crucial to obtain a cure for the phosphate metabolism derangement, which is often the main cause leading the patient to seek medical help, because of invalidating physical and neuromuscular symptoms. A proportion of these tumors is completely silent and may grow unnoticed, unless they become large enough to produce pain or discomfort. FGF-23 can be produced by several benign or malignant PMTs. The phosphate metabolism, radiology and histology of these rare tumors must be collectively assessed by a multidisciplinary team aimed at curing the disease locally and improving patients’ quality of life. This narrative review, authored by multiple specialists of a tertiary care hospital center, will describe endocrine, radiological and histological features of these tumors, as well as present surgical and interventional strategies to manage PMTs.

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused by tumors secreting fibroblast growth factor 23 (FGF23) that promotes urinary phosphorus excretion. Thus, TIO is typically characterized by phosphoruria, hypophosphatemia, and osteomalacia. Diagnosis and localization of the tumor is often difficult due to its small size, slow growth and concealed location. Due to the high expression of somatostatin receptors in pathogenic tumors, nuclear medicine functional imaging, particularly somatostatin receptor imaging, is used for diagnosis and localization of culprit tumors with high sensitivity and specificity. Here we retrospectively analyze 25 cases in which 68Ga-DOTATATE PET/CT successfully localized and diagnosed TIO culprit tumors. The clinical features, pathological results and image characteristics of 68Ga-DOTATATE PET/CT imaging were analyzed and compared with other imaging diagnostic techniques. It was confirmed that 68Ga-DOTATATE PET/CT imaging was the preferred imaging technique for successful diagnosis and localization of TIO pathogenic tumors.

Objectives: We aimed to report the surgical outcomes of phosphaturic mesenchymal tumors causing tumor-induced osteomalacia in the head and neck. Methods: This study analyzed nine patients who underwent surgical excision of phosphaturic mesenchymal tumors in the head and neck region. The primary sites were two in the maxilla and ethmoid sinus, and one in the intracranial, skull, parotid gland, maxillary sinus, and nasal cavity in each patient. Outcomes were compared with those in the extremities and trunk (n = 32). Results: Five of nine patients (56%) developed residual disease/local recurrence associated with low serum phosphate level after initial surgical excision. At the last follow-up, the biochemical parameters were normalized in four of the five patients after re-excision without any medication. The local recurrence/residual disease risk was significantly higher for the head and neck compared with the extremities and trunk (56% vs. 25%, p = 0.048). The rate of remission (normalized serum phosphate without medication) at final follow-up was similar in both groups after re-excision (head and neck vs. extremities and trunk, 86% vs. 73%, p = 0.827). Conclusions: Phosphaturic mesenchymal tumor resection in the head and neck region was challenging because of its complex anatomy and proximity to the brain or other crucial organs, which was associated with high local recurrence/residual disease rate. However, biological remission was achieved in the majority of the patients after re-excision.

Context: Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused by excessive production of fibroblast growth factor 23 (FGF23) by a tumor. After successful tumor resection, patients can recover from hypophosphatemia quicky. However, data on the changes in bone mineral density (BMD) and microstructure in the short term after surgery remained unclear. Objective: This work aimed to investigate the postoperative changes in BMD and microstructure both in peripheral and axial bone in TIO patients. Methods: We evaluated BMD and microarchitecture in 22 TIO patients using high-resolution peripheral quantitative computed tomography (HRpQCT) and dual-energy x-ray absorptiometry (DXA) before and 3 months after surgery in this retrospective study. Results: In this study, a total of 22 TIO patients who had recovered serum phosphate levels postoperatively were enrolled. After surgery, areal BMD (aBMD) increased by 21.6% in the femoral neck, by 18.9% in the total hip, and by 29.5% in the lumbar spine. Moreover, TBS increased by 14.1% (all P < .001). In contrast, trabecular or cortical volumetric BMD (vBMD), and microstructure of trabecular bone (trabecular number, separation and bone volume ratio) and cortical bone (cortical thickness and porosity) at the distal radius or tibia were further deteriorated. Correlation analyses found that changes in femoral neck and total hip aBMD were both conversely associated with changes in trabecular vBMD and bone volume ratio, while positively correlated with change in trabecular separation at the distal radius. Conclusion: Although aBMD and microstructure in the axial bone were improved, vBMD and microstructure in the peripheral bone were further impaired shortly after surgery. Correlation of improvement of aBMD in the total hip and femoral neck with deterioration of vBMD and microstructure at the distal radius indicated a shift in calcium from the peripheral bone to the axial bone in the short term after tumor resection in TIO patients. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study is to review the clinical and laboratory characteristics, diagnostic and treatment modalities of tumor-induced osteomalacia (TIO) cases managed in a single center. Material methods: Demographic and clinical features, biochemical findings, diagnostic procedures, treatment modalities, and outcomes of nine patients who had the diagnosis of TIO were reviewed retrospectively. Results: Mean age of the study group (F/M: 4/5) was 45.8 ± 10.8 years, and mean time from the onset of symptoms to diagnosis was 4.7 ± 2.8 years. The clinical manifestations were muscle weakness and difficulty in walking (8/9), hip pain (3/9), multiple fractures (2/9), stress fracture (2/9). Mean plasma phosphorus concentration was 1.28 ± 0.4 mg/dl at presentation. We performed radionuclide imaging modalities (18F-FDG PET/CT, Ga68-DOTATATE PET/CT, octreotide scintigraphy) in seven of nine patients, and tumor was detected in all. Lower extremity (n = 6; %67), head region (n = 2; %22) and thorax (n = 1; %11) were the tumor locations of our cases. Eight patients underwent surgery and remission was achieved postoperatively in all of the operated patients and plasma phosphorus level normalized in 4 ± 2 days. Pathological examination revealed mesenchymal tumors with different subtypes. Recurrence occurred in three patients at 13 ± 10.5 months after the first surgery. Two patients were reoperated and radiotherapy was also performed in one of them. Conclusion: Hypophosphatemia necessitates careful evaluation for the etiology. TIO is one of the important causes of adult-onset hypophosphatemic osteomalacia. Diagnosis of TIO is essential because the laboratory and clinical findings resolve after appropriate treatment. [ABSTRACT FROM AUTHOR]

Objectives: Tumor-induced osteomalacia (TIO) is a rare acquired paraneoplastic disorder characterized by hypophosphatemia resulting from tumor-secreted fibroblast growth factor-23 (FGF23). Surgical resection of the culprit TIO is the first choice of treatment. However, TIO is difficult to detect with conventional diagnostic tools due to its small size and variable location in the body. Somatostatin receptor scintigraphy (SSR) has recently emerged as a functional molecular imaging choice for TIO detection and localization. This research was undertaken to evaluate the efficacy of 99mTc-labeled hydrazinonicotinyl-Tyr3-octreotide (99mTc-HYNIC-TOC) SPECT/CT in detecting TIO. Methods: 99mTc-HYNIC-TOC SPECT/CT and the available clinical data of 25 patients with suspected TIO were analyzed retrospectively. The 99mTc-HYNICTOC SPECT/CT findings were compared with the post-surgical pathology diagnosis and clinical follow-up results. Results: Using 99mTc-HYNIC-TOCSPECT/CT, suspicious tumorswere found in 18 of the 25 patients, and 15 of them underwent surgical resection. The postoperative pathology confirmed a TIO in those 13 patients whose symptoms and biochemical anomalies gradually resolved after the surgery. The remaining five patients were finally considered false positives. Moreover, the 99mTc-HYNIC-TOC SPECT/CT results were negative in seven patients, with six patients being true negative (4 patients were diagnosed with acquired Fanconi syndrome and 2 patients responded well to conservative therapy) and one being false negative. Therefore, the sensitivity and specificity values of 99mTc-HYNIC-TOC SPECT/CT in the evaluation of TIO were 92.9% (13/14) and 54.5% (6/11), respectively. The overall accuracy of 99mTc-HYNIC-TOC SPECT/CT for detecting TIO was 76.0% (19/25). Conclusions: The 99mTc-HYNIC-TOC SPECT/CT is an accurate imaging modality for locating culprit tumors in TIO. [ABSTRACT FROM AUTHOR]

Context: Nearly 20% patients with tumor-induced osteomalacia (TIO) experienced recurrence or nonrecovery after surgery. Serum fibroblast growth factor 23 and phosphate concentrations are not sufficient for prognosis in such cases. Despite its importance for understanding of prognosis and underlying pathogenesis, the alteration of systemic metabolism in refractory TIO remains unclear. Objective: We aimed to find the metabolomic characteristics of refractory TIO and establish a novel predictive model for early discriminating refractory TIO based on their serum metabolomics. Design and setting: Cross-section study for comparison of metabolomic profile between TIO and normal control and longitudinal study for identifying prognostic model. Methods: Based on liquid chromatography-tandem mass spectrometry, we analyzed the global metabolomes of preoperative sera from 86 samples (32 TIO recovery patients, 11 nonremission patients, and 43 matched controls). Statistical analyses, pathway enrichment, and receiver operating characteristic analysis were performed to identified and evaluate potential markers. Results: Sparse partial least squares discriminant analysis indicated a clear separation of metabolomic profiles between healthy controls (HC) and TIO patients. The serum metabolites altered in different prognostic groups. L-pipecolic acid, 2-dodecylbenzenesulfonic acid, and 2- deoxygalactopyranose were the top 3 metabolites that were significantly perturbed. A combination of L-pipecolic acid and 2- dodecylbenzenesulfonic acid demonstrated a high-performance panel for TIO prognosis evaluated by random forest algorithm (area under the curve= 0.921, 95% CI, 0.787-0.995). Conclusions: We investigate the global metabolomes of refractory TIO and identify potential prognostic biomarkers preliminarily. A high sensitivity and specificity panel were identified as promising discriminating predictors, which need to be verified in more patients. This work may demonstrate novel insights into TIO prognosis and pathogenesis. [ABSTRACT FROM AUTHOR]

Phosphaturic mesenchymal tumors (PMT) are rare neoplasms, which can give rise to a multifaceted syndrome, otherwise called tumor-induced osteomalacia (TIO). Localizing these tumors is crucial to obtain a cure for the phosphate metabolism derangement, which is often the main cause leading the patient to seek medical help, because of invalidating physical and neuromuscular symptoms. A proportion of these tumors is completely silent and may grow unnoticed, unless they become large enough to produce pain or discomfort. FGF-23 can be produced by several benign or malignant PMTs. The phosphate metabolism, radiology and histology of these rare tumors must be collectively assessed by a multidisciplinary team aimed at curing the disease locally and improving patients' quality of life. This narrative review, authored by multiple specialists of a tertiary care hospital center, will describe endocrine, radiological and histological features of these tumors, as well as present surgical and interventional strategies to manage PMTs. [ABSTRACT FROM AUTHOR]

Introduction: Tumor-induced osteomalacia (TIO) is an uncommon paraneoplastic syndrome due to the overproduction of fibroblast growth factor 23 (FGF23). It is predominantly caused by mesenchymal tumors and cured upon their complete removal. Non-surgical treatment is an alternative option but limited to specific clinical conditions. Methods: We report a challenging case of TIO caused by a tumor involving the occipital bone. We also performed a literature review of TIO caused by tumors localized at this site, focusing on clinical findings, treatment, and outcomes. Results: The patient, a 62-year-old male, presented with a long-lasting history of progressive weakness. Biochemical evaluation revealed severe hypophosphatemia due to low renal tubular reabsorption of phosphate with raised intact FGF23 values. A 68 Ga-DOTATATE PET/TC imaging showed a suspicious lesion located in the left occipital bone that MRI and selective venous catheterization confirmed to be the cause of TIO. Stereotactic gamma knife radiosurgery was carried out, but unfortunately, the patient died of acute respiratory failure. To date, only seven additional cases of TIO have been associated to tumors located in the occipital bone. Furthermore, the tumor involved the left side of the occipital bone in all these patients. Conclusion: The occipital region is a difficult area to access so a multidisciplinary approach for their treatment is required. If anatomical differences could be the basis for the predilection of the left side of the occipital bone, it remains to be clarified. [ABSTRACT FROM AUTHOR]

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome associated with tumors secreting fibroblast growth factor 23 that can be cured with complete surgical resection of the tumor. However, when these tumors are at difficult locations, less invasive modalities such as thermal ablation (TA) might be a good alternative. A 40-year-old woman was seen for a second opinion because of severe hypophosphatemia with complaints of fatigue, myalgia, and muscle weakness for which she needed IV phosphate for 15 to 18 hours per day in addition to oral alfacalcidol and phosphate. Initial laboratory results revealed hypophosphatemia (0.59 mmol/L [1.83 mg/dL]; reference range, 0.90-1.50 mmol/L [8.40-10.2 mg/dL]), increased fibroblast growth factor 23 levels (137 RU/mL; reference range, <125 RU/mL), and a reduced TmP-GFR (0.47 mmol/L; reference range, 0.8-1.4 mmol/L). Gallium-positron emission tomography/computed tomography (CT) showed moderately increased uptake at thoracic vertebra (Th) 8 and mildly increased uptake at Th7, suggestive of TIO. Complete tumor removal would have required resection of at least 1 vertebral body. Therefore, CT-guided TA was performed at Th8. No complications were observed, and in the months after, treatment with IV phosphate could be discontinued, indicating a satisfying result from the procedure. This extreme TIO case demonstrates that CT-guided TA can be an alternative to extensive or risky classical surgery. [ABSTRACT FROM AUTHOR]

ObjectivesTumor-induced osteomalacia (TIO) is a rare acquired paraneoplastic disorder characterized by hypophosphatemia resulting from tumor-secreted fibroblast growth factor-23 (FGF23). Surgical resection of the culprit TIO is the first choice of treatment. However, TIO is difficult to detect with conventional diagnostic tools due to its small size and variable location in the body. Somatostatin receptor scintigraphy (SSR) has recently emerged as a functional molecular imaging choice for TIO detection and localization. This research was undertaken to evaluate the efficacy of 99mTc-labeled hydrazinonicotinyl-Tyr3-octreotide (99mTc-HYNIC-TOC) SPECT/CT in detecting TIO.Methods99mTc-HYNIC-TOC SPECT/CT and the available clinical data of 25 patients with suspected TIO were analyzed retrospectively. The 99mTc-HYNIC-TOC SPECT/CT findings were compared with the post-surgical pathology diagnosis and clinical follow-up results.ResultsUsing 99mTc-HYNIC-TOC SPECT/CT, suspicious tumors were found in 18 of the 25 patients, and 15 of them underwent surgical resection. The post-operative pathology confirmed a TIO in those 13 patients whose symptoms and biochemical anomalies gradually resolved after the surgery. The remaining five patients were finally considered false positives. Moreover, the 99mTc-HYNIC-TOC SPECT/CT results were negative in seven patients, with six patients being true negative (4 patients were diagnosed with acquired Fanconi syndrome and 2 patients responded well to conservative therapy) and one being false negative. Therefore, the sensitivity and specificity values of 99mTc-HYNIC-TOC SPECT/CT in the evaluation of TIO were 92.9% (13/14) and 54.5% (6/11), respectively. The overall accuracy of 99mTc-HYNIC-TOC SPECT/CT for detecting TIO was 76.0% (19/25).ConclusionsThe 99mTc-HYNIC-TOC SPECT/CT is an accurate imaging modality for locating culprit tumors in TIO.

Abstract Shivam Bansal Mohit Dhingra Background Oncogenic osteomalacia term used for tumor-induced osteomalacia (TIO) is a paraneoplastic syndrome of abnormal phosphate metabolism secondary to ectopic endocrine tumors. The diagnosis often becomes difficult due to rarity of occurrence and deficient literature. The reconstruction following resection has its own technical difficulties, which are addressed in this article. Presentation of Case A 39-year-old female presented with pain in bilateral lower limbs and difficulty in mobilizing. The patient had unexplained hypophosphatemia which was diagnosed due to tumor (arising ectopically in greater trochanter), inducing osteomalacia. She was managed successfully with excision of tumor and reconstruction. The biochemical parameters improved drastically within 5 days and fracture healed in 6 weeks' time. Conclusion TIO is a debilitating disease with significant morbidity due to prolonged onset to diagnosis interval and difficulty in localizing the causative tumor. So thorough clinico-radiological and laboratory parameter correlation is a necessity. A rapid diagnosis followed by complete surgical excision, which remains the gold standard treatment modality that confers favorable prognosis in most patients, with strict vigilance for recurrence is required.