RARE DISEASE
Oncogenic osteomalacia
Oncogenic osteomalacia
Oncogenic osteomalacia
Synonyms: Oncogenic hypophosphatemic osteomalacia, TIO, Tumor-induced osteomalacia
Synonyms: Oncogenic hypophosphatemic osteomalacia, TIO, Tumor-induced osteomalacia
Synonyms: Oncogenic hypophosphatemic osteomalacia, TIO, Tumor-induced osteomalacia
Drug discovery
2
drugs
With orphan designations
Overview
Oncogenic osteomalacia (OOM), also termed tumor-induced osteomalacia (TIO), is a rare paraneoplastic syndrome caused by phosphaturic mesenchymal tumors secreting fibroblast growth factor 23 (FGF23). This results in renal phosphate wasting, hypophosphatemia, and impaired bone mineralization, leading to osteomalacia (adults) or rickets (children). Key manifestations include progressive bone pain, fractures, muscle weakness, and fatigue. Diagnosis is often delayed due to tumor localization challenges [1][2][6][12].
Burden
Diagnosed 2.5–5 years after symptom onset, with frequent misdiagnoses (e.g., osteoporosis, rheumatologic disorders) [4][9][18].
Debilitating symptoms: chronic pain, fractures, mobility limitations, and reduced quality of life [4][9][12].
High healthcare utilization due to prolonged diagnostic workup and costly imaging (e.g., 68Ga-DOTATATE PET/CT) [6][9][18].
Categories: rare bone diseases, rare endocrine diseases, rare genetic diseases, rare renal diseases
Research Papers
511 drug discovery papers about Oncogenic osteomalacia, with 4 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
511 drug discovery papers about Oncogenic osteomalacia, with 4 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-08-01 | Successful Cryoablation of a Sacral Phosphaturic Mesenchymal Tumor Causing Tumor-Induced Osteomalacia
Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused by fibroblast growth factor 23 (FGF23)–secreting phosphaturic mesenchymal tumors. We report a 63-year-old man with TIO whose sacral tumor was identified after 2 years of nonlocalizing functional imaging. Owing to the surgically challenging location, computed tomography (CT)-guided cryoablation was performed. The patient's FGF23 level normalized 1 month postprocedure, and biochemical remission has been sustained for over 4 years. This case demonstrates that CT-guided cryoablation provides durable remission for sacral phosphaturic mesenchymal tumors not amenable to surgical resection, representing one of the longest reported follow-ups for cryoablation of sacral TIO.
2026-06-15 | Phosphaturic Mesenchymal Tumour of the Soft Tissue in the Finger Presenting without Tumour-Induced Osteomalacia: A Case Report.
Phosphaturic mesenchymal tumour (PMT) is a rare neoplasm that can occur with or without tumour-induced osteomalacia (TIO). While PMTs commonly arise in the lower extremities or head and neck, digital involvement is rare. A 70-year-old man presented with a 12-year history of an enlarging subcutaneous mass on the dorsal aspect of his left ring finger. Imaging studies suggested an organised thrombus within a venous malformation. Marginal excision was performed, and histopathological examination revealed a lesion composed of capillaries and small vessels surrounded by spindle cells with small ovoid nuclei, showing immunopositivity for somatostatin receptor 2, CD56, ERG and focally fibroblast growth factor-23 (FGF23). These findings were consistent with a diagnosis of PMT, mixed connective tissue and non-phosphaturic variant. No recurrence has been observed at 4 years and 6 months postoperatively. This report emphasises the diagnostic difficulty of PMTs in atypical locations and the utility of immunohistochemical profiling in confirming the diagnosis. Level of Evidence: Level V (Therapeutic).
2026-05-22 | ORAL COMMUNICATION | A rare case of intracranial meningioma and tumour-induced osteomalacia
Introduction. Tumour-induced osteomalacia (TIO) is due to an overproduction of fibroblast growth factor 23 (FGF23) by mesenchymal tumours, causing hypophosphatemia, osteomalacia, and muscle weakness. TIO is cured by tumour resection, but neoplasms may be unidentifiable/ unresectable or the patient may refuse surgery. Description. We reported the case of a 64-year-old female with multiple non-traumatic fractures, low bone mineral density, pain, and reduced independence in activities of daily living. Biochemical evaluation showed hypophosphatemia, high alkaline phosphatase/C-terminal telopeptide, slightly high parathyroid hormone and normal albumin-corrected total calcium/vitamin D. Tubular phosphate reabsorption was slow (80%), whereas FGF23 was elevated. A ⁶⁸Ga-DOTATOC PET identified a lesion in the skull, compatible with a 27×18×28 mm meningioma. Total body computed tomography and cerebral magnetic resonance confirmed the meningioma. The neurosurgeon excluded intracranial surgery/biopsy, so medical treatment with oral phosphate and calcitriol was started, resulting in improvement in pain severity/fatigue and phosphate normalization. Neither adverse events nor tumour progression occurred during follow-up. Conclusions. Meningioma was identified as the cause of TIO, although there is limited knowledge about meningiomas causing TIO. This is the third case reported of TIO induced by an intracranial meningioma. However, an intracranial mass may hide a low-grade phosphaturic mesenchymal tumor, mixed connective tissue variant (PMTMCT).
2026-02-20 | Spinal decompression and radionuclide therapy for an unresectable FGF23 transmitted tumor causing cervical myelopathy: a case report and literature review.
Tumor-induced osteomalacia (TIO) is a rare disorder characterized by hypophosphatemic osteomalacia, mainly caused by benign tumors with excessive secretion of fibroblast growth factor 23 (FGF23) and somatostatin receptor expression. Although complete excision is recommended, reports on treatment strategies for anatomically challenging surgical cases are lacking. We report an unresectable case of FGF23 transmitted tumor in the cervical vertebrae causing myelopathy, which was treated with surgical decompression combined with radionuclide therapy. A 52-year-old woman presented to another hospital with complaints of knee pain. After confirming abnormal tracer uptake at the C7 vertebrae using somatostatin receptor scintigraphy and an elevated serum FGF23 level (>800 pg/mL), TIO was diagnosed 7 years after the initial presentation. Gait disturbance occurred 10 years after the initial presentation; therefore, the patient was referred to our department. Magnetic resonance imaging revealed a tumor with spinal cord compression and vertebral artery encasement, making complete resection impossible. Gait disturbance improved after spinal decompression with partial resection of the tumor. Peptide receptor radionuclide therapy targeting somatostatin receptors was initiated 2 years after surgery. Serum phosphate levels normalized, and the tumor size remained stable after the initiation of PRRT. Ambulation was maintained without joint pain recurrence at 3 years after surgery. The current literature on FGF23 transmitted tumors in the cervical spine includes six cases treated with definitive local therapy. This case suggests an alternative option for unresectable FGF23 transmitted tumor in the vertebrae, causing spinal myelopathy.
2026-02-03 | Phosphaturic mesenchymal tumour, connective tissue variant: a rare radiological presentation involving the radius mimicking fibrous dysplasia with oncogenic rickets.
Phosphaturic mesenchymal tumours (PMTs) are rare neoplasms that secrete fibroblast growth factor-23 (FGF-23), causing tumour-induced osteomalacia (TIO). Histological overlap with juvenile psammomatoid ossifying fibroma (JPOF) can lead to diagnostic difficulty, particularly outside the craniofacial skeleton. A 4-year-old girl presented with a painful forearm swelling. Radiographs demonstrated a fibro-osseous lesion in the radius and biopsy was initially non-diagnostic, leading to a presumptive diagnosis of fibrous dysplasia. Over the next 6 years, the lesion enlarged, and at age 10, the patient developed genu valgum with biochemical evidence of hypophosphataemic rickets (low phosphate, raised alkaline phosphatase, elevated FGF-23). Medical therapy corrected the rickets, though deformity required guided growth surgery. At age 13, a repeat biopsy of the enlarging lesion revealed a fibro-osseous tumour with spindle stroma and psammomatoid ossicles, negative for GNAS mutation, and consistent with a phosphaturic mesenchymal tumour, connective tissue variant. This case highlights a rare radiologic presentation of PMT involving a long bone, with imaging features closely mimicking fibrous dysplasia and histological overlap with JPOF. The rapid progression of imaging findings, discordant metabolic abnormalities and markedly elevated FGF-23 levels poses a diagnostic challenge. As such, fibrous dysplasia-like lesions of the extremities in the setting of hypophosphataemic rickets should prompt consideration of PMT.
antibodies
2026-09-27 | Burosumab-responsive micro tumor-induced osteomalacia caused by a 6-mm phosphaturic mesenchymal tumor of the femoral head: a case report with review of literature on small (≤10 mm) FGF23-producing tumors.
A woman in her thirties presented with progressive bone pain, muscle weakness, recurrent stress fractures, and delayed fracture healing. Laboratory investigations demonstrated hypophosphatemia, renal phosphate wasting, elevated fibroblast growth factor 23 (FGF23), and inappropriately low 1,25-dihydroxyvitamin D, leading to a diagnosis of FGF23-mediated tumor-induced osteomalacia (TIO) approximately one year after symptom onset. Bone scintigraphy demonstrated multiple fractures involving the ribs and pubic bones. [18F]-fluorodeoxyglucose positron emission tomography/computed tomography ([18F]-FDG PET/CT) identified mild uptake in the left femoral head/femoral neck region, and targeted magnetic resonance imaging (MRI) confirmed a well-defined 6-mm lesion with low signal intensity on T1- and T2-weighted images and high signal intensity on short tau inversion recovery images. Somatostatin receptor scintigraphy (SRS) showed no abnormal uptake. Systemic venous sampling (SVS) demonstrated elevated FGF23 levels in the left pelvic venous drainage region. CT-guided biopsy revealed a phosphaturic mesenchymal tumor (PMT) with FGF23 immunohistochemical positivity. Complete resection would likely have required hemiarthroplasty or total hip arthroplasty because of the tumor location, and the patient declined surgery. Burosumab was therefore initiated. At 24 weeks, serum phosphate increased from 1.5 to 4.1 mg/dL, alkaline phosphatase decreased from 145 to 100 U/L, generalized bone pain and gait disturbance improved markedly, pseudofracture-related uptake disappeared on bone scintigraphy, and lumbar-spine and femoral-neck bone mineral density (BMD) improved. This case shows that multimodal localization can identify micro-TIO lesions that may escape conventional strategies, and that FGF23 blockade can be clinically effective in a localized FGF23-positive 6-mm PMT when surgery is anatomically challenging or declined.
2026-09-22 | Tumor-Induced Osteomalacia in a Patient with Metastatic Prostate Cancer Presenting with Refractory Hypophosphatemia
Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused by fibroblast growth factor 23 (FGF23) overproduction, which leads to renal phosphate wasting and hypophosphatemia. Herein, we present the case of an 81-year-old man with metastatic prostate adenocarcinoma who presented with fatigue, diffuse bone pain, paresthesia, carpopedal spasms, and muscle cramps. Laboratory tests revealed severe hypophosphatemia, 0.28 mmol/L (0.87 mg/dL; reference, 0.80–1.50 mmol/L [2.5–4.5 mg/dL]) and markedly elevated serum levels of alkaline phosphatase (786 U/L) and FGF23 (>1,525 RU/mL; reference, <100 RU/mL). Despite intensive oral and intravenous phosphate supplementation and cholecalciferol therapy, serum phosphate levels remained persistently low. Phosphate wasting was confirmed with a 24-hour urine phosphate excretion test. The patient had mildly elevated parathyroid hormone level with normal 25-hydroxyvitamin D level and preserved renal function, excluding common secondary causes. Therefore, TIO secondary to metastatic prostate cancer was established as the final diagnosis. This case underscores that TIO should be considered in patients with refractory hypophosphatemia and musculoskeletal symptoms. Urine phosphate excretion and serum FGF23 level measurement is essential for timely diagnosis. Burosumab, an anti-FGF23 monoclonal antibody, can be considered for treatment, although its use in malignancy-associated cases is often limited to off-label use.
2026-08-24 | Recurrent Tumor-Induced Osteomalacia After Surgical Resection: A Case Report Demonstrating Successful Treatment With Burosumab.
Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome in which a mesenchymal tumor secretes fibroblast growth factor 23 (FGF-23), causing renal phosphate wasting and osteomalacia. A 62-year-old woman was referred to our hospital with a two-year history of progressive muscle weakness and generalized bone pain. The patient was nonambulatory and required a wheelchair for mobility. Laboratory evaluation revealed hypophosphatemia and low serum 1,25-dihydroxyvitamin D levels. Further investigation of the hypophosphatemia demonstrated an elevated fractional excretion of phosphate (FeP) and increased serum FGF-23 levels. Genetic testing was negative. A 68Ga-DOTANOC PET/CT scan identified an infiltrative cervical lesion with increased somatostatin receptor expression. The tumor was surgically resected, after which the patient recovered functional ambulation, and serum phosphate normalized. One year later, the patient reported recurrence of musculoskeletal symptoms. Laboratory findings showed hypophosphatemia with an elevated FeP, raising suspicion of tumor recurrence. A repeat 68Ga-DOTANOC PET/CT scan demonstrated increased somatostatin receptor expression in a right parietal calvarial lesion that was not amenable to surgical resection or radiotherapy. Initiation of burosumab therapy led to the normalization of serum phosphate levels and complete resolution of symptoms. TIO is a rare disorder that is frequently misdiagnosed as osteoporosis, resulting in substantial diagnostic delay. A systematic evaluation of hypophosphatemia is essential for timely diagnosis and appropriate management. This case supports burosumab as an effective therapeutic option for achieving biochemical and clinical improvement in patients with unresectable TIO.
2026-08-11 | Real-world outcomes in patients with tumor-induced osteomalacia treated vs not treated with burosumab.
Tumor-induced osteomalacia (TIO) is an ultra-rare condition caused by tumors secreting fibroblast growth factor-23, leading to chronic hypophosphatemia, pain, muscle weakness, fractures, and impaired physical function. Burosumab is a monoclonal antibody indicated for treatment of TIO when tumors cannot be curatively resected. This study compares clinical and patient-reported outcomes in patients with TIO treated vs not treated with burosumab in a real-world setting. This interim analysis reports outcomes at enrollment in the prospective, observational Tumor-Induced Osteomalacia Disease Monitoring Program (NCT04783428), stratified by burosumab treatment status at enrollment. Tertiary care centers in the United States and Argentina. Patients with TIO from the Disease Monitoring Program. Burosumab treatment. Biochemistry measurements and patient-reported health-related quality of life (pain, fatigue, and physical function). 21 patients with TIO (61.9% female, median [Q1, Q3] age 49.7 years [41.6, 57.3]) were included. At enrollment, 11 (52.4%) patients were treated with burosumab, for a median (Q1, Q3) duration of 4.1 years (0.8, 7.0). Burosumab-treated patients had significantly higher serum phosphate and 1,25-dihydroxyvitamin D levels, and nonsignificantly lower alkaline phosphatase levels, compared with patients not treated with burosumab. Patients treated with burosumab reported significantly lower median Brief Pain Inventory scores, nonsignificantly lower Brief Fatigue Inventory scores, and nonsignificantly higher Patient-Reported Outcomes Measurement Information System Physical Function and Short-Form-36 scores, indicating lower symptom severity and better health-related quality of life. This study suggests favorable biochemical and patient-reported outcomes in patients with TIO treated with burosumab.
2026-04-20 | Burosumab an emerging therapy in TIO: a local clinical survey and a systematic review with individual patient data analysis.
Burosumab, a recombinant antibody against fibroblast growth factor 23 (FGF23), is a new therapeutical option for Tumor induced osteomalacia (TIO). To estimate the clinical need and to evaluate the efficacy and safety of burosumab, we conducted a hybrid study composed by a clinical survey and a systematic review. All patients referring for TIO to the Federico II University were enrolled in our clinical survey. A comprehensive literature search on a Medline, Google Scholar, Google Books, and the Cochrane Library was conducted for the Systematic Review. Data were extracted on 12/31/2025. For the local survey, we collected 10 patients affected by TIO [M: F = 5 (50.0%): 5 (50.0%); mean age at symptom onset 57.6 ± 14.3 years]. Two (20.0%) patients received burosumab, obtaining clinical and biochemical improvement. Two who didn't receive the treatment died. For the systematic review, we collected 42 studies and 49 cases [M: F = 19 (44.2%): 24 (55.8%); mean age at onset 36.8 ± 21.3 years; mean age at diagnosis 44.5 ± 22.9 years]. Burosumab reduced clinical symptoms and ameliorates biochemical investigations by normalizing phosphate serum levels. It is also safe and well tolerated. Burosumab represents a safe and efficient treatment in TIO patients, to be administered in case of tumor identification while waiting for surgery, and in case of surgical inoperability to manage hormonal FGF23 effect.
small molecules
2026-08-01 | Successful Cryoablation of a Sacral Phosphaturic Mesenchymal Tumor Causing Tumor-Induced Osteomalacia
Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused by fibroblast growth factor 23 (FGF23)–secreting phosphaturic mesenchymal tumors. We report a 63-year-old man with TIO whose sacral tumor was identified after 2 years of nonlocalizing functional imaging. Owing to the surgically challenging location, computed tomography (CT)-guided cryoablation was performed. The patient's FGF23 level normalized 1 month postprocedure, and biochemical remission has been sustained for over 4 years. This case demonstrates that CT-guided cryoablation provides durable remission for sacral phosphaturic mesenchymal tumors not amenable to surgical resection, representing one of the longest reported follow-ups for cryoablation of sacral TIO.
2026-06-15 | Phosphaturic Mesenchymal Tumour of the Soft Tissue in the Finger Presenting without Tumour-Induced Osteomalacia: A Case Report.
Phosphaturic mesenchymal tumour (PMT) is a rare neoplasm that can occur with or without tumour-induced osteomalacia (TIO). While PMTs commonly arise in the lower extremities or head and neck, digital involvement is rare. A 70-year-old man presented with a 12-year history of an enlarging subcutaneous mass on the dorsal aspect of his left ring finger. Imaging studies suggested an organised thrombus within a venous malformation. Marginal excision was performed, and histopathological examination revealed a lesion composed of capillaries and small vessels surrounded by spindle cells with small ovoid nuclei, showing immunopositivity for somatostatin receptor 2, CD56, ERG and focally fibroblast growth factor-23 (FGF23). These findings were consistent with a diagnosis of PMT, mixed connective tissue and non-phosphaturic variant. No recurrence has been observed at 4 years and 6 months postoperatively. This report emphasises the diagnostic difficulty of PMTs in atypical locations and the utility of immunohistochemical profiling in confirming the diagnosis. Level of Evidence: Level V (Therapeutic).
2026-05-22 | ORAL COMMUNICATION | A rare case of intracranial meningioma and tumour-induced osteomalacia
Introduction. Tumour-induced osteomalacia (TIO) is due to an overproduction of fibroblast growth factor 23 (FGF23) by mesenchymal tumours, causing hypophosphatemia, osteomalacia, and muscle weakness. TIO is cured by tumour resection, but neoplasms may be unidentifiable/ unresectable or the patient may refuse surgery. Description. We reported the case of a 64-year-old female with multiple non-traumatic fractures, low bone mineral density, pain, and reduced independence in activities of daily living. Biochemical evaluation showed hypophosphatemia, high alkaline phosphatase/C-terminal telopeptide, slightly high parathyroid hormone and normal albumin-corrected total calcium/vitamin D. Tubular phosphate reabsorption was slow (80%), whereas FGF23 was elevated. A ⁶⁸Ga-DOTATOC PET identified a lesion in the skull, compatible with a 27×18×28 mm meningioma. Total body computed tomography and cerebral magnetic resonance confirmed the meningioma. The neurosurgeon excluded intracranial surgery/biopsy, so medical treatment with oral phosphate and calcitriol was started, resulting in improvement in pain severity/fatigue and phosphate normalization. Neither adverse events nor tumour progression occurred during follow-up. Conclusions. Meningioma was identified as the cause of TIO, although there is limited knowledge about meningiomas causing TIO. This is the third case reported of TIO induced by an intracranial meningioma. However, an intracranial mass may hide a low-grade phosphaturic mesenchymal tumor, mixed connective tissue variant (PMTMCT).
2026-02-20 | Spinal decompression and radionuclide therapy for an unresectable FGF23 transmitted tumor causing cervical myelopathy: a case report and literature review.
Tumor-induced osteomalacia (TIO) is a rare disorder characterized by hypophosphatemic osteomalacia, mainly caused by benign tumors with excessive secretion of fibroblast growth factor 23 (FGF23) and somatostatin receptor expression. Although complete excision is recommended, reports on treatment strategies for anatomically challenging surgical cases are lacking. We report an unresectable case of FGF23 transmitted tumor in the cervical vertebrae causing myelopathy, which was treated with surgical decompression combined with radionuclide therapy. A 52-year-old woman presented to another hospital with complaints of knee pain. After confirming abnormal tracer uptake at the C7 vertebrae using somatostatin receptor scintigraphy and an elevated serum FGF23 level (>800 pg/mL), TIO was diagnosed 7 years after the initial presentation. Gait disturbance occurred 10 years after the initial presentation; therefore, the patient was referred to our department. Magnetic resonance imaging revealed a tumor with spinal cord compression and vertebral artery encasement, making complete resection impossible. Gait disturbance improved after spinal decompression with partial resection of the tumor. Peptide receptor radionuclide therapy targeting somatostatin receptors was initiated 2 years after surgery. Serum phosphate levels normalized, and the tumor size remained stable after the initiation of PRRT. Ambulation was maintained without joint pain recurrence at 3 years after surgery. The current literature on FGF23 transmitted tumors in the cervical spine includes six cases treated with definitive local therapy. This case suggests an alternative option for unresectable FGF23 transmitted tumor in the vertebrae, causing spinal myelopathy.
2026-02-03 | Phosphaturic mesenchymal tumour, connective tissue variant: a rare radiological presentation involving the radius mimicking fibrous dysplasia with oncogenic rickets.
Phosphaturic mesenchymal tumours (PMTs) are rare neoplasms that secrete fibroblast growth factor-23 (FGF-23), causing tumour-induced osteomalacia (TIO). Histological overlap with juvenile psammomatoid ossifying fibroma (JPOF) can lead to diagnostic difficulty, particularly outside the craniofacial skeleton. A 4-year-old girl presented with a painful forearm swelling. Radiographs demonstrated a fibro-osseous lesion in the radius and biopsy was initially non-diagnostic, leading to a presumptive diagnosis of fibrous dysplasia. Over the next 6 years, the lesion enlarged, and at age 10, the patient developed genu valgum with biochemical evidence of hypophosphataemic rickets (low phosphate, raised alkaline phosphatase, elevated FGF-23). Medical therapy corrected the rickets, though deformity required guided growth surgery. At age 13, a repeat biopsy of the enlarging lesion revealed a fibro-osseous tumour with spindle stroma and psammomatoid ossicles, negative for GNAS mutation, and consistent with a phosphaturic mesenchymal tumour, connective tissue variant. This case highlights a rare radiologic presentation of PMT involving a long bone, with imaging features closely mimicking fibrous dysplasia and histological overlap with JPOF. The rapid progression of imaging findings, discordant metabolic abnormalities and markedly elevated FGF-23 levels poses a diagnostic challenge. As such, fibrous dysplasia-like lesions of the extremities in the setting of hypophosphataemic rickets should prompt consideration of PMT.
antibodies
2026-09-27 | Burosumab-responsive micro tumor-induced osteomalacia caused by a 6-mm phosphaturic mesenchymal tumor of the femoral head: a case report with review of literature on small (≤10 mm) FGF23-producing tumors.
A woman in her thirties presented with progressive bone pain, muscle weakness, recurrent stress fractures, and delayed fracture healing. Laboratory investigations demonstrated hypophosphatemia, renal phosphate wasting, elevated fibroblast growth factor 23 (FGF23), and inappropriately low 1,25-dihydroxyvitamin D, leading to a diagnosis of FGF23-mediated tumor-induced osteomalacia (TIO) approximately one year after symptom onset. Bone scintigraphy demonstrated multiple fractures involving the ribs and pubic bones. [18F]-fluorodeoxyglucose positron emission tomography/computed tomography ([18F]-FDG PET/CT) identified mild uptake in the left femoral head/femoral neck region, and targeted magnetic resonance imaging (MRI) confirmed a well-defined 6-mm lesion with low signal intensity on T1- and T2-weighted images and high signal intensity on short tau inversion recovery images. Somatostatin receptor scintigraphy (SRS) showed no abnormal uptake. Systemic venous sampling (SVS) demonstrated elevated FGF23 levels in the left pelvic venous drainage region. CT-guided biopsy revealed a phosphaturic mesenchymal tumor (PMT) with FGF23 immunohistochemical positivity. Complete resection would likely have required hemiarthroplasty or total hip arthroplasty because of the tumor location, and the patient declined surgery. Burosumab was therefore initiated. At 24 weeks, serum phosphate increased from 1.5 to 4.1 mg/dL, alkaline phosphatase decreased from 145 to 100 U/L, generalized bone pain and gait disturbance improved markedly, pseudofracture-related uptake disappeared on bone scintigraphy, and lumbar-spine and femoral-neck bone mineral density (BMD) improved. This case shows that multimodal localization can identify micro-TIO lesions that may escape conventional strategies, and that FGF23 blockade can be clinically effective in a localized FGF23-positive 6-mm PMT when surgery is anatomically challenging or declined.
2026-09-22 | Tumor-Induced Osteomalacia in a Patient with Metastatic Prostate Cancer Presenting with Refractory Hypophosphatemia
Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused by fibroblast growth factor 23 (FGF23) overproduction, which leads to renal phosphate wasting and hypophosphatemia. Herein, we present the case of an 81-year-old man with metastatic prostate adenocarcinoma who presented with fatigue, diffuse bone pain, paresthesia, carpopedal spasms, and muscle cramps. Laboratory tests revealed severe hypophosphatemia, 0.28 mmol/L (0.87 mg/dL; reference, 0.80–1.50 mmol/L [2.5–4.5 mg/dL]) and markedly elevated serum levels of alkaline phosphatase (786 U/L) and FGF23 (>1,525 RU/mL; reference, <100 RU/mL). Despite intensive oral and intravenous phosphate supplementation and cholecalciferol therapy, serum phosphate levels remained persistently low. Phosphate wasting was confirmed with a 24-hour urine phosphate excretion test. The patient had mildly elevated parathyroid hormone level with normal 25-hydroxyvitamin D level and preserved renal function, excluding common secondary causes. Therefore, TIO secondary to metastatic prostate cancer was established as the final diagnosis. This case underscores that TIO should be considered in patients with refractory hypophosphatemia and musculoskeletal symptoms. Urine phosphate excretion and serum FGF23 level measurement is essential for timely diagnosis. Burosumab, an anti-FGF23 monoclonal antibody, can be considered for treatment, although its use in malignancy-associated cases is often limited to off-label use.
2026-08-24 | Recurrent Tumor-Induced Osteomalacia After Surgical Resection: A Case Report Demonstrating Successful Treatment With Burosumab.
Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome in which a mesenchymal tumor secretes fibroblast growth factor 23 (FGF-23), causing renal phosphate wasting and osteomalacia. A 62-year-old woman was referred to our hospital with a two-year history of progressive muscle weakness and generalized bone pain. The patient was nonambulatory and required a wheelchair for mobility. Laboratory evaluation revealed hypophosphatemia and low serum 1,25-dihydroxyvitamin D levels. Further investigation of the hypophosphatemia demonstrated an elevated fractional excretion of phosphate (FeP) and increased serum FGF-23 levels. Genetic testing was negative. A 68Ga-DOTANOC PET/CT scan identified an infiltrative cervical lesion with increased somatostatin receptor expression. The tumor was surgically resected, after which the patient recovered functional ambulation, and serum phosphate normalized. One year later, the patient reported recurrence of musculoskeletal symptoms. Laboratory findings showed hypophosphatemia with an elevated FeP, raising suspicion of tumor recurrence. A repeat 68Ga-DOTANOC PET/CT scan demonstrated increased somatostatin receptor expression in a right parietal calvarial lesion that was not amenable to surgical resection or radiotherapy. Initiation of burosumab therapy led to the normalization of serum phosphate levels and complete resolution of symptoms. TIO is a rare disorder that is frequently misdiagnosed as osteoporosis, resulting in substantial diagnostic delay. A systematic evaluation of hypophosphatemia is essential for timely diagnosis and appropriate management. This case supports burosumab as an effective therapeutic option for achieving biochemical and clinical improvement in patients with unresectable TIO.
2026-08-11 | Real-world outcomes in patients with tumor-induced osteomalacia treated vs not treated with burosumab.
Tumor-induced osteomalacia (TIO) is an ultra-rare condition caused by tumors secreting fibroblast growth factor-23, leading to chronic hypophosphatemia, pain, muscle weakness, fractures, and impaired physical function. Burosumab is a monoclonal antibody indicated for treatment of TIO when tumors cannot be curatively resected. This study compares clinical and patient-reported outcomes in patients with TIO treated vs not treated with burosumab in a real-world setting. This interim analysis reports outcomes at enrollment in the prospective, observational Tumor-Induced Osteomalacia Disease Monitoring Program (NCT04783428), stratified by burosumab treatment status at enrollment. Tertiary care centers in the United States and Argentina. Patients with TIO from the Disease Monitoring Program. Burosumab treatment. Biochemistry measurements and patient-reported health-related quality of life (pain, fatigue, and physical function). 21 patients with TIO (61.9% female, median [Q1, Q3] age 49.7 years [41.6, 57.3]) were included. At enrollment, 11 (52.4%) patients were treated with burosumab, for a median (Q1, Q3) duration of 4.1 years (0.8, 7.0). Burosumab-treated patients had significantly higher serum phosphate and 1,25-dihydroxyvitamin D levels, and nonsignificantly lower alkaline phosphatase levels, compared with patients not treated with burosumab. Patients treated with burosumab reported significantly lower median Brief Pain Inventory scores, nonsignificantly lower Brief Fatigue Inventory scores, and nonsignificantly higher Patient-Reported Outcomes Measurement Information System Physical Function and Short-Form-36 scores, indicating lower symptom severity and better health-related quality of life. This study suggests favorable biochemical and patient-reported outcomes in patients with TIO treated with burosumab.
2026-04-20 | Burosumab an emerging therapy in TIO: a local clinical survey and a systematic review with individual patient data analysis.
Burosumab, a recombinant antibody against fibroblast growth factor 23 (FGF23), is a new therapeutical option for Tumor induced osteomalacia (TIO). To estimate the clinical need and to evaluate the efficacy and safety of burosumab, we conducted a hybrid study composed by a clinical survey and a systematic review. All patients referring for TIO to the Federico II University were enrolled in our clinical survey. A comprehensive literature search on a Medline, Google Scholar, Google Books, and the Cochrane Library was conducted for the Systematic Review. Data were extracted on 12/31/2025. For the local survey, we collected 10 patients affected by TIO [M: F = 5 (50.0%): 5 (50.0%); mean age at symptom onset 57.6 ± 14.3 years]. Two (20.0%) patients received burosumab, obtaining clinical and biochemical improvement. Two who didn't receive the treatment died. For the systematic review, we collected 42 studies and 49 cases [M: F = 19 (44.2%): 24 (55.8%); mean age at onset 36.8 ± 21.3 years; mean age at diagnosis 44.5 ± 22.9 years]. Burosumab reduced clinical symptoms and ameliorates biochemical investigations by normalizing phosphate serum levels. It is also safe and well tolerated. Burosumab represents a safe and efficient treatment in TIO patients, to be administered in case of tumor identification while waiting for surgery, and in case of surgical inoperability to manage hormonal FGF23 effect.
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Drug Discovery Landscape
2 orphan drug designations for Oncogenic osteomalacia, including 2 approved therapies.
2 orphan drug designations for Oncogenic osteomalacia, including 2 approved therapies.
Drug | Therapy type | Orphan designation | Clinical trial status | Sponsor |
|---|---|---|---|---|
Burosumab [CRYSVITA] | antibodies | EMA | Approved | Kyowa Kirin Holdings B.V. |
burosumab-twza [Crysvita] | antibodies | FDA | Approved | Kyowa Kirin, Inc. |
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