Tumor-induced Osteomalacia Research Articles

Approach to Determining Etiology of Hypophosphatemia in a Patient with Coexisting Phosphaturic Mesenchymal Tumor and Fibrous Dysplasia

Abstract Dysregulated fibroblast growth factor-23 (FGF23) production is a demonstrated cause of hypophosphatemia and osteomalacia. Diseases associated with these conditions include phosphaturic mesenchymal tumor (PMT) causing tumor induced osteomalacia (TIO), various forms of rickets, and fibrous dysplasia (FD). Coexistence of two conditions that can increase FGF23 concentrations is rare. We report a case of a 79-year-old man who presented with rib and right flank pain. Imaging revealed bone lesions in the right iliac wing, left supra-acetabular area, and L4 vertebral body. Biopsies showed a right iliac PMT and left supra-acetabular FD. Cryoablation of both lesions resolved the phosphaturia with normalization of phosphorus level. Coexistence of PMT and FD in this patient with hypophosphatemia raised questions about the source of the FGF23, meaning of co-existence of PMT and FD in the same patient and, about the nature of the third lesion in the L4 vertebral body. Using FGF23 mRNA chromogenic in situ hybridization, we identified the PMT, rather than the FD, as the source of FGF23. Lack of GNAS mutation in the PMT suggested it being independent of FD. Assessment by the intact FGF23: total FGF23 ratio as well as gallium-DOTATATE scan suggested that the vertebral body lesion could represent FD. Other than understanding difference in underlying molecular processing of FGF23 in PMT and FD, testing for mutations, imaging studies as well as in situ hybridization helped solve the questions arising from this unique case of coexistence of PMT and FD.

Phosphaturic Mesenchymal Tumor and Tumor-Induced Osteomalacia: A Report of 5 Cases, Including 2 Skull Base Cases With Arterial Spin Label Perfusion.

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome characterized by renal phosphate wasting and impaired bone mineralization secondary to secretion of fibroblast growth factor 23 (FGF23) from mesenchymal tumors (phosphaturic mesenchymal tumors, PMTs). PMTs have wide anatomical distribution but typically affect extremities and craniofacial bones. Diagnosis of TIO/PMT is often delayed, and a high index of suspicion is essential in patients with unexplained fractures, but many physicians lack familiarity with TIO/PMT and simply attribute fractures to the more common diagnosis of osteoporosis. We present 5 cases of TIO, with 4 having long histories of multiple insufficiency fractures prior to recognition of TIO and localization of a PMT. Four patients were treated surgically, while 1 preferred medical management. Two patients had lesions localized to the skull base, both of which showed marked hypervascularity on arterial spin label perfusion imaging. Thus, arterial spin label may not only help to localize these tumors, but may also be a helpful supplemental imaging finding in supporting this diagnosis. PMT should be considered in the differential diagnosis for hypervascular skull base masses, especially if the patient has any history of insufficiency fracture or imaging evidence of osteopenia, as early diagnosis of TIO can help prevent disabling complications.

Model-Informed Approach to Recommend Burosumab Dosing Regimens for Pediatric and Adult Patients With the Ultrarare Disease Tumor-Induced Osteomalacia.

Burosumab is approved for the treatment of hypophosphatemia in persistent tumor-induced osteomalacia. This work exemplifies a model-informed drug development approach that evaluated burosumab pharmacokinetics and pharmacokinetic/pharmacodynamics in the ultrarare tumor-induced osteomalacia population to support adult and pediatric dosing. Data from tumor-induced osteomalacia participants were combined with data from X-linked hypophosphatemia to understand pharmacokinetic and pharmacokinetic/pharmacodynamic characteristics and covariates specific to tumor-induced osteomalacia. Pharmacokinetic and pharmacokinetic/pharmacodynamic simulations were performed using final models to support dosing recommendations for adults and extrapolation to pediatric patients. Burosumab pharmacokinetics were described using a one-compartment model with first-order absorption and body weight as a significant covariate. Pharmacokinetic/pharmacodynamic relationships were described using a sigmoidal Emax model with significant covariates of baseline fibroblast growth factor 23 on baseline fasting serum phosphate and potency of burosumab response and tumor-induced osteomalacia disease state resulting in a steep slope of response; however, the covariates are not clinically meaningful. Simulations demonstrated that, in pediatric patients, starting doses of burosumab 0.3 and 0.4 mg/kg every 2 weeks at steady state would achieve normal serum phosphate levels in ≥ 30% of patients with relatively low risk of hyperphosphatemia (< 3%). In adults, burosumab 0.3 and 0.5 mg/kg every 4 weeks achieves similar percentages of responders and a relative low risk of hyperphosphatemia (< 7%). Serum phosphate titration-based burosumab dosing increased the probability of achieving normal serum phosphate levels. The models supported a model-informed drug development approach for global approvals of titration-based burosumab dosing, guided by monitoring fasting serum phosphate levels.

Advanced tumour-induced osteomalacia secondary to sinonasal phosphaturic mesenchymal tumour.

A rare case of sinonasal PMT is presented, with a focus on the imaging findings and role of the radiologist and nuclear physician.

A Rare Case of Tumor-Induced Osteomalacia Due to Mesenchymal Tumor at Foramen Magnum Diagnosed Preoperatively on 68Ga DOTATATE PET/CT.

A 42-year-old man, a known case of FGF23-dependent hypophosphatemia, underwent 68Ga- DOTATATE PET-CT, which showed a somatostatin receptor-expressing lesion in the left arch of foramen magnum that was correlated on MRI as a soft tissue lesion measuring 2.2 × 1.3 cm. It was excised and histopathologically confirmed as phosphaturic mesenchymal tumor. Postoperatively, patient improved clinically and recovered from hypophosphatemia completely. A distinct focal uptake in a 68Ga- DOTATATE PET-CT in a patient with tumor-induced osteomalacia needs extensive workup and high degree of suspicion to rule out mesenchymal tumor at nonconventional location as seen in the present case.

Sinonasal Phosphaturic Mesenchymal Tumors Without Any Nasal Symptoms: A Case Report and Literature Review.

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. We presented a case with chart review and conducted review of the literature. 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. 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.

7999 Tumor Induced Osteomalacia Caused By Glomangiopericytoma

Abstract Disclosure: N. Kabir: None. E. Campbell: None. S. Singh: None. Introduction: Tumor induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused primarily by FGF-23 secreting tumors. Excessive production of FGF23 causes hypophosphatemia, decreased phosphate resorption in the gut, increased renal phosphate wasting, and decreased activation of Vitamin D. This leads to decreased bone density, bone pain, proximal muscle weakness, impaired gait, and recurrent fractures. Case Presentation: 44 year old male with a history of recurrent insufficiency fractures and weakness. At the time of evaluation, he reported fracture of tibial growth plate, sacral fracture, and metatarsal stress fracture. Other symptoms included bone pain, fatigue, muscle weakness, and intercostal muscle spasms with exertion. His pain was debilitating, requiring crutches to ambulate. Available labs at that time were significant for hypophosphatemia (1.3 mg/dL), elevated ALP (160 U/L), low 25OH-vitamin D (26 ng/mL), and normal calcium (8.7 mg/dL). Urine studies demonstrated phosphaturia (fractional excretion of phosphate, 62.4%). FGF23 level resulted at the upper limit of normal (210 RU/mL). Pending further evaluation, burosumab was started. Further work up included a 68Ga-PET-DOTATATE scan revealing a somatostatin receptor expressing soft tissue mass in the left sphenoid sinus and posterior left ethmoid sinus. The scan also demonstrated impending bilateral femur fractures, prior rib fractures, and sacral insufficiency fractures. Based on these findings, he was admitted to the hospital and underwent prophylactic, intramedullary nail fixation of his bilateral femur fractures. He underwent resection of skull base tumor with the final pathology revealing a sinonasal glomangiopericytoma. Immunohistochemical stain was positive for CD99 and cyclin D1, and focally positive for SMA, consistent with histopathologic diagnosis. Patient required prolonged inpatient rehabilitation to recover independent ambulation. Discussion: Sinonasal glomangiopericytoma (SNGP) is a mesenchymal tumor that accounts for &amp;lt;0.5% of all nasal and sinus tumors. TIO due to SNGP is extremely rare, with only a few cases reported since the 1990s. As seen with our patient, TIO from SNGP rarely presents with sinonasal symptoms, and can often be overlooked. Our patient hadb significant progression of disease and disability due to numerous delays in diagnosis and management. Definitive cure for TIO can be achieved with complete surgical resection of the tumor, but failure to diagnose in a timely manner can result in decline in quality of life. Our takeaway from this case is that providers should obtain FGF23 levels, especially in the setting of hypophosphatemia and phosphaturia, to complete the work up for osteomalacia. Presentation: 6/1/2024

6463 A Case of Tumour-Induced Osteomalacia Which Remitted After Treatment of Metastatic Prostate Cancer

Abstract Disclosure: J. Chua: None. M. Chuah: None. A case Tumour-induced osteomalacia (TIO) which remitted after treatment of metastatic prostate cancer. Dr Chua Jia Min, Dr Matthew Chuah Bingfeng Abstract Case report: A 69-year-old gentleman with a known history of bladder cancer presented to the emergency department with fatigue, lower back pain and bilateral lower limb weakness worsening over the past one month. MRI and bone scan revealed extensive osteoblastic bone metastases across the skeletal system. This gentleman was referred to the Endocrinology service for the evaluation of high PTH. His corrected calcium was normal at 2.17mmol/L (2.09-2.46mmol/L) and iPTH was raised at 8.74pmol/L (1.60-6.90pmol/L). He was noted to have severe hypophosphatemia 0.34mmol/L (0.94-1.50mmol/L). Bicarbonate levels were normal, there was no glycosuria or proteinuria. There was no history of IV ferrous carboxymaltose use. Further investigations were consistent with urinary phosphate loss - TRP was 0.398 and TMP-GFR was 0.199. ALP was elevated at 282ug/L (39-99ug/L). 25-hydroxyvitamin D was low at 12 ug/L, which accounted for the high PTH levels (secondary hyperparathyroidism). FGF-23 levels returned high at 1293 RU/ml (&amp;lt;180 RU/ml). BMD showed osteoporosis with T-score of -2.6 at the left femoral neck. He was subsequently diagnosed with metastatic prostate adenocarcinoma, based on histology from a bone biopsy of an affected vertebrae. PSA was markedly raised at 606ug/L. A diagnosis of TIO secondary to metastatic prostate cancer was made. The patient was started on PO sodium-phosphate solution 4ml TDS (approximately 3mmol/kg/day of elemental phosphorus), calcitriol 0.25mcg BD and vitamin D was replaced. After phosphate was replete, the patient's weakness and fatigue improved. He was subsequently started on androgen deprivation therapy with leuprorelin acetate injection once every 3 months and apalutamide daily. SC denosumab 60mg Q6monthly was also commenced in view of extensive bone metastases. Repeat imaging showed response to treatment with decrease in the size of the prostate and bone lesions. His PSA levels are now undetectable and TMP-GFR has normalised. His oral phosphate and calcitriol doses were gradually reduced and subsequently stopped. His calcium and phosphate levels remain within normal limits on no supplementation, suggesting remission of his TIO. PTH levels normalised after vitamin D repletion. Learning points TIO is a rare paraneoplastic syndrome usually associated with mesenchymal tumours, and treatment involves resection of the causative tumour. Cases of TIO secondary to prostate cancer (an epithelial cancer) are exceedingly rare. Despite metastatic disease, this patient responded exceedingly well to his cancer therapy. Suppression of the tumour cells with androgen deprivation therapy resulted in the lack of phosphotonin production and remission of his TIO. Presentation: 6/1/2024

7582 Genetic Profiling of Phosphaturic Mesenchymal Tumors Unravels Osterix's Significance in Tumor-Induced Osteomalacia

Abstract Disclosure: Y. Imanishi: None. Y. Nagata: None. M. Ohara: None. T. Maeda-Tateishi: None. T. Shoji: None. M. Emoto: None. Background &amp; Purpose: Tumor-induced osteomalacia (TIO) is a rare condition caused by tumors releasing too much fibroblast growth factor 23 (FGF23). These tumors, specifically called phosphaturic mesenchymal tumors, mixed connective tissue variant (PMTMCT), lead to osteomalacia due to low serum phosphate levels. However, a detailed study regarding the genetic makeup of these tumors and their similarity to bone cells (osteoblasts/osteocytes) has been lacking. Methods: Nineteen PMTMCTs were analyzed and compared their gene expressions to 6 non-TIO tumors. Our focus was on genes usually found in bone cells. Additionally, we examined the relationship between FGF23 and these genes in PMTMCTs. One gene, Osterix, showing significant correlation was further studied using UMR106 osteoblast cells. Results: Fourteen genes related to bone cells expressed significantly higher in PMTMCTs compared to non-TIO tumors. Immunoblotting and Immunohistochemical examinations confirmed the presence of FGF23, Runx2, and Osterix in PMTMCTs. Particularly, Osterix showed the strongest link with FGF23 in PMTMCTs. Immunohistochemical tests revealed similar patterns of distribution for Osterix and FGF23, even co-localizing in some instances. However, the distribution of another gene, DMP1, differed from that of FGF23. In UMR106 cells, silencing Osterix expression led to decreased FGF23 expression, irrespective of DMP1 levels. Conclusions: PMTMCTs exhibit higher levels of genes associated with bone cell functions compared to other tumors. These tumors likely originated from mesenchymal stem cells and transformed into bone cells. Furthermore, Osterix might play a crucial role in the excessive release of FGF23 in PMTMCTs. Presentation: 6/1/2024

Progressive bone pain caused by a phosphaturic mesenchymal tumor in the left femur: a case report and literature review.

Phosphaturic mesenchymal tumors (PMTs) are extremely rare mesenchymal tumors of soft tissue and bone that cause tumor-induced osteomalacia (TIO). Some of these tumors are completely asymptomatic and may grow undetected unless they become large enough to cause pain or discomfort. This type of tumor is crucial to diagnose in patients being treated for phosphate metabolism disorders and are a rare reason why patients seek medical help owing to pain. Here, we report the details of a patient with progressive bone pain caused by a PMT originating in the left femur.

Atypical Location of Tumor-Induced Osteomalacia (TIO) and Its Clinical Implications

Atypical Location of Tumor-Induced Osteomalacia (TIO) and Its Clinical Implications

7149 Asymptomatic Tumor-Induced Osteomalacia: Reverse Diagnosis Of Hypophosphatemia Based On Pathologic Findings In A Tumor

7149 Asymptomatic Tumor-Induced Osteomalacia: Reverse Diagnosis Of Hypophosphatemia Based On Pathologic Findings In A Tumor

Phosphaturic mesenchymal tumor demonstrated by 68Ga-DOTATATE PET/CT in a patient: a case report

Tumor-induced osteomalacia (TIO) is a paraneoplastic syndrome caused by abnormally high levels of fibroblast growth factor 23 (FGF-23), most commonly produced and secreted by small phosphaturic mesenchymal tumors (PMT). These tumors can show various anatomic locations throughout soft tissue and bone. The presence of the tumor itself rarely causes symptoms. Nonspecific symptoms such as muscle weakness and musculoskeletal pain are related to the developing hypophosphatemia and osteomalacia as a secondary effect of the increased circulating levels of FGF-23. Therefore, as the initial presentation can mimic a wide range of metabolic or inflammatory diseases, proper diagnosis is often delayed. Localization of the tumor is crucial, as its complete surgical resection is the only curative treatment. Whole-body functional imaging targeting the overexpression of somatostatin receptors (SSTR) on the surface of the PMT cells, is a highly specific and sensitive imaging method to detect the primary tumor site. Here, we discuss a case of TIO in a patient initially presenting with symptoms of inflammatory spondyloarthritis. SSTR positron emission imaging using 68Ga-DOTATATE was central in diagnosing and localizing the primary tumor.

Phosphopenic osteomalacia of tumor genesis under mask of ankylosing spondylitis

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.

Clinical characteristics and surgical outcomes of vertebral lesions associated with tumor-induced osteomalacia: report of 16 patients and review of the literature

SummaryVertebral tumors in patients with tumor-induced osteomalacia (TIO) have a low diagnostic rate and poor postoperative outcomes. The application of 68 Ga-DOTATATE-PET/CT significantly increased the detection rate. Compared with tumor curettage, segmental resection was recommended as the preferred surgical type due to its high recovery rate.PurposeTumor-induced osteomalacia (TIO) is an acquired hypophosphatemic osteomalacia, and surgery is the first-line therapy. Most TIO tumors are found in the bones of the appendicular skeleton, cranium, and paranasal sinuses but rarely in the vertebrae. Tumor curettage and segmental resection are the two main surgical options for vertebral TIO patients. However, research on the clinical characteristics and surgical prognosis of vertebral TIO patients is rare. In the present study, for the first time, we investigated the clinical characteristics of 16 vertebral TIO patients and compared the surgical outcomes of patients who underwent surgery via two different surgical methods.MethodsThis was a retrospective cohort study. In this study, we included 16 adult TIO patients with lesions in vertebrae from Peking Union Medical College Hospital (PUMCH), all of whom underwent surgery. Baseline laboratory data were collected through medical records review. Technetium-99 m octreotide scintigraphy (99Tcm-OCT) and 68gallium-DOTA-TATE-positron emission tomography/computed tomography (68 Ga-DOTATATE-PET/CT) were conducted at the Department of Nuclear Medicine of PUMCH. The tumor histopathology was confirmed by a senior pathologist at our center.ResultsVertebral TIO patients had lower serum phosphorus and TmP/GFR and higher serum alkaline phosphatase (ALP), serum parathyroid hormone (PTH), and serum C-terminal cross-linked telopeptide of type I collagen (β-CTX) levels than the normal range. The sensitivity of 68 Ga‒DOTATATE PET/CT was 100%, significantly greater than that of 99Tcm-OCT (40%). After comparing the outcomes between the two surgical methods, we found that the recovery rate after segmental resection (62.5%) was greater than that after tumor curettage (12.5%). In the thoracic and sacral vertebrae, segmental resection surgery had a good prognosis.Conclusion68 Ga-DOTATATE PET/CT could serve as the first diagnostic tool in patients with vertebral TIO, and segmental resection could be used as the preferred surgery. This study would raise awareness of the clinical features and management of these rare vertebral TIO patients.

Comprehensive Molecular Characterization of a Large Series of Calcified Chondroid Mesenchymal Neoplasms Widening Their Morphologic Spectrum.

Recently, FN1 fusions to receptor tyrosine kinase genes have been identified in soft tissue tumors with calcified chondroid matrix named calcifying chondroid mesenchymal neoplasms (CCMNs). We collected 33 cases of CCMN from the French network for soft tissue and bone tumors. We performed whole-exome RNA sequencing, expression analysis, and genome-wide DNA methylation profiling in 33, 30, and 20 cases of CCMN compared with a control group of tumors, including noncalcified tenosynovial giant cell tumor (TGCT). Among them, 15 cases showed morphologic overlap with soft tissue chondroma, 8 cases with tophaceous pseudogout, and 10 cases with chondroid TGCT. RNA-sequencing revealed a fusion of FN1 in 76% of cases (25/33) with different 5' partners, including most frequently FGFR2 (14 cases), TEK or FGFR1. Among CCMN associated with FGFR1 fusions, 2 cases had overexpression of FGF23 without tumor-induced osteomalacia. Four CCMN had PDGFRA::USP8 fusions; 3 of which had histologic features of TGCT and were located in the hip, foot, and temporomandibular joint (TMJ). All cases with FN1::TEK fusion were located at TMJ and had histologic features of TGCT with or without chondroid matrix. They formed a distinct cluster on unsupervised clustering analyses based on whole transcriptome and genome-wide methylome data. Our study confirms the high prevalence of FN1 fusions in CCMN. In addition, through transcriptome and methylome analyses, we have identified a novel subgroup of tumors located at the TMJ, exhibiting TGCT-like features and FN1::TEK fusions.

PTH like substance secreting mesenchymal tumor causing oncogenic osteomalacia; unravelling the difficulties in localization – A report of 2 cases

BackgroundOncogenic osteomalacia is a rare paraneoplastic association of Phosphaturic mesenchymal tumor (PMT) secreting excessive levels of a PTH like substance. They usually remain undiagnosed and patients suffer for years. The rarity of this tumor and its non-specific clinical presentations poses great challenge to the treating surgeons. Its management is poorly described in literature. We report two of such rare cases without much diagnostic delay. Case reportWe had 2 cases; A 53-year-old south east Asian male with 6 months of debilitating pain over multiple sites, and another 44-year-old male patient with complaints of low back ache, and pain over both lower and upper limbs for 1.5 years. Both had low serum phosphorus and elevated FGF-23 values, but all other parameters were normal. A PMT was suspected and confirmed on a Ga68- DOTATOC scan in both cases, and on complete excision, their symptoms and the altered blood parameters got normalized. Histology was consistent with PMT. ConclusionAccurate and timely diagnosis of a PMT with non-specific features are extremely challenging, but not without solutions. Even though a tumor of rarity, with the appropriate imaging modalities like Ga68- DOTATOC scan, and estimation of FGF-23 and serum phosphorus levels, they can be diagnosed. Once identified, complete removal is often curative within a few months.

Long-Term Follow-Up Data of Tumor-Induced Osteomalacia Managed with Surgery and/or Radiofrequency Ablation from a Single Center.

Data on radiofrequency ablation (RFA) in tumor-induced osteomalacia (TIO) are restricted to case reports (~ 11 patients) and long-term follow-up data are further scarce. We describe our experience on managing TIO from a tertiary care center in India. Retrospective study of patients with localized TIO was performed and clinical, biochemical, treatment and follow-up details were retrieved. Normalization of serum phosphorus in absence of phosphate supplementation was defined as remission. Of 33 patients (23 males), 24 patients underwent surgery as first-line treatment, and early remission, delayed remission (> 1month for phosphorus normalization) and persistence were observed 12, 3, and 9 patients at a median follow-up of 5 (4-9) years. The gender, age, tumor size, location of tumors and FGF23 levels were not statistically different in patients who were in remission after surgery versus those with persistent disease. Second/third line treatment included conventional medical treatment and/or repeat surgery (n = 3), radiotherapy (n = 3), peptide receptor radionuclide therapy (n = 1), RFA (n = 1). Two patients had transient worsening (weeks) of weakness post-surgery. 10 patients underwent RFA (first-line n = 9); at the last follow-up 5 (4-10) years, 7 are in remission. Two of three persistent disease patients had large tumors (5.6 and 3.6cm). There were no RFA-related complications except local ulcer in one. Although persistent disease was present in a few patients in both arms, there was no recurrence in either RFA or surgical cohort. RFA provide durable response similar to surgery, persistence requires multi-modality treatment.

Healthcare resource use associated with tumor-induced osteomalacia: a literature review.

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 non-specific and unrecognized, leading to long delays in diagnosis and treatment, which results in severe and progressive disability in patients with TIO. This review aimed to identify published evidence on healthcare resource use in TIO to better understand the burden of the disease. A targeted literature review was conducted to identify publications reporting on disease characteristics and healthcare resource use associated with TIO. 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 (standard deviation) 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. 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.

Orthopedic Surgical Treatment of Patients with Tumor-induced Osteomalacia Located in the Hip Bones: A Retrospective Analysis of 10 Years in a Single Center.

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. 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. 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. 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.