Oncogenic osteomalacia associated with phosphaturic. Tumorinduced osteomalacia, or oncogenic osteomalacia, is a paraneoplastic syndrome of renal phosphate wasting. Table 1 from tumorinduced osteomalacia semantic scholar. Tumor induced osteomalacia tio is a paraneoplastic syndrome of hypophosphatemia, decreased renal phosphate reabsorption, normal or low serum 1,25dihydryxyvitamind concentration, myopathy, and.
Grand rounds clinicians corner at the johns hopkins bayview medical center tumorinduced osteomalacia suzanne m. Tumorinduced rickets in a child with a central giant cell. Available formats pdf please select a format to send. Tumorinduced osteomalacia with normal systemic fibroblast. Tumor induced osteomalacia tio, also known as oncogenic osteomalacia, is a rare paraneoplastic syndrome characterized by hypophosphatemia resulting from decreased tubular phosphate reabsorption. Tumor induced osteomalacia also known as oncogenic osteomalacia is a very rare acquired neoplasm of mesenchymal origin that causes a paraneoplastic syndrome of renal phosphorus loss through the secretion of phosphatonins.
Mohan t shenoy dm resident in endocrinology aimskochi 24. Tumor induced osteomalacia tio is a rare paraneoplastic syndrome, characterized by tumor secretion of fibroblast growth factor23 fgf23 causing hypophosphatemia due to renal phosphate wasting. This occurs when a tumor secretes a substance called fibroblast growth factor 23 fgf23. Tumorinduced osteomalacia is a rare disorder, with approximately 120 cases reported in the literature undoubtedly, there are many more cases that have not been reported,2 yet progress in understanding its pathogenesis is. Pdf tumorinduced osteomalacia tio is a rare and fascinating paraneoplastic syndrome in which patients present with bone pain, fractures. Intracranial phosphaturic mesenchymal tumor, mixed. Jul, 2017 tumour induced osteomalacia tio, also known as oncogenic osteomalacia, is a rare paraneoplastic disorder caused by tumours that secrete fibroblast growth factor 23 fgf23. Apr 27, 2018 tumor induced osteomalacia tio is a rare disorder in which fibroblast growth factor fgf23producing neoplasms cause renal phosphate wasting and skeletal disease. Tumor induced osteomalacia oncogenic osteomalacia is a clinicopathologic entity in which vitamin dresistant osteomalacia or rickets occurs in association with a bone or soft tissue tumor. Tio is a disease characterized by typically benign tumors that produce excess levels of fgf23, including its skin lesion variant, epidermal nevus. Tumorinduced osteomalacia caused by a phosphaturic. Its clinical expressions are hypo phosphatemia because of renal phosphate wasting, os.
Tumor induced osteomalacia rickets is a rare paraneoplastic disorder associated with a tumor producing fibroblast growth factor 23 fgf23. Tumor induced osteomalacia tio is an extremely rare paraneoplastic syndrome that is characterized by hypophosphatemia and hyperphosphaturia. Fgf23 inhibits the ability of the kidneys to absorb phosphate. Tumorinduced osteomalacia tio, also known oncogenic osteomalacia, is a rare paraneoplastic syndrome of abnormal phosphate and vitamin. Owing to the role of fgf23 in renal phosphate handling and vitamin d synthesis, tio is characterized by decreased renal tubular reabsorption of phosphate. The clinical presentation of tio includes bone fractures, bone and muscular pains, and sometimes height and weight loss. Clinical and bone density outcomes of tumorinduced.
Bgj398 for the treatment of tumorinduced osteomalacia full. Osteomalacia in children is known as rickets, and because of this, use of the term osteomalacia is often restricted to the milder, adult form of the disease. Slowgrowing benign mesenchymal or mixed connective tissue tumors are typically responsible for the syndrome, although other histologic types including carcinomas and sarcomas have. Tumourinduced osteomalacia tio, also known as oncogenic osteomalacia, is a rare paraneoplastic disorder caused by tumours that secrete fibroblast growth factor 23 fgf23. Tumorinduced osteomalacia tio, also known oncogenic osteomalacia, is a rare paraneoplastic syndrome of abnormal phosphate and vitamin metabolism caused by typically small endocrine tumors that secrete the phosphaturic hormone, fibro blast growth factor 23 fgf23. The tumorinduced osteomalacia is a paraneoplastic syndrome secondary in most cases to tumors of. Tumor induced osteomalacia is a paraneoplastic syndrome characterized by renal phosphate wasting that results in hypophosphatemia and osteomalacia. This report highlights the pitfalls and challenges in diagnosing and localizing tio in patients with refractory and resistant osteomalacia. Tumor induced osteomalacia is a paraneoplastic syndrome caused by a mesenchymal tumor elaborating a hormone that induces renalphosphate wasting. Sep 01, 2009 tumor induced osteomalacia tio is an acquired disorder of isolated renal phosphate wasting associated with tumors, typically of mesenchymal origin. Tumor induced osteomalacia tio are extremely rare paraneoplastic syndrome with less than 300 reported cases. Fractures of radius and ulna with rachitic changes of distal end of radius and ulna. Rare tumors identical to pmtmct occur without known tio. Tio is an acquired hypophosphatemic osteomalacia caused by decreased phosphorus reabsorption in the renal tubules and increased renal phosphorus.
Successful treatment of tumorinduced osteomalacia due to an. Oncogenic osteomalacia, or tumor induced osteomalacia tio, is an acquired paraneoplastic syndrome. Treatment and outcomes of tumorinduced osteomalacia. Tumorinduced osteomalacia orthopaedicsone articles. Since the initial observation by mccrance, 1 clinical and experimental studies implicate the humoral factors propagated by tumors in the profound biochemical and skeletal alterations observed in tio. Tumor induced osteomalacia tio is a rare and fascinating paraneoplastic syndrome in which patients present with bone pain, fractures, and muscle weakness. Mar 28, 2017 several diseases can result in disorders of bone mineralization in children, including rickets, renal diseases renal osteodystrophy, fanconi syndrome, tumor induced osteomalacia, hypophosphatasia, mccunealbright syndrome, and osteogenesis imperfecta with mineralization defect syndrome resembling osteogenesis imperfecta sroi. It is caused by mesenchymal tumors that produce the phosphate and vitamin dregulating hormone, fibroblast growth factor fgf.
Tumourinduced osteomalacia tio is a rare paraneoplastic syndrome clinical presentation of which includes bone fractures, bone and muscular pains, and sometimes loss of height and even weight. Oncogenic osteomalacia is characterized by the development of a tumor that causes the bones to be weakened. Tumorinduced osteomalacia robert f reilly, 2018 sage journals. Tumor induced osteomalacia tio is a paraneoplastic syndrome in which patients present with bone pain, fractures and muscle weakness. Signs and symptoms can include diffuse body pains, muscle weakness, and fragility of the bones. Tumorinduced osteomalacia tio is a rare disease, which causes hyperphosphaturia and hypophosphatemia with. Tumor induced osteomalacia tio is one of the hypophosphatemic diseases characterized by renal phosphate wasting. Cinacalcet in the management of tumor induced osteomalacia. Synonyms for tumor induced osteomalacia in free thesaurus. In cases of tio, identifying the responsible tumor is often difficult because they.
Tumor induced osteomalacia is curable if the tumors can be totally excised. Tumorinduced osteomalacia is caused by the development of a tumor that releases fibroblast growth factor 23 fgf23. The possibility of multifocal fgf23 production was considered, and the second, nonfdgavid lesion was resected, which resulted in complete cure. Nonspecific symptoms including fatigue, bone pain, and musculoskeletal weakness make the diagnosis elusive and. Patients with tio share similar biochemical and skeletal phenotypes with patients who have autosomal dominant hypophosphatemic rickets adhr and xlinked hypophosphatemia. Tumorinduced osteomalacia tio is a rare paraneoplasic syndrome with overproduction of fibroblast growth factor 23 as a phosphaturic agent, leading to.
We report a case of breast cancer induced oncogenic osteomalacia and discuss its diagnosis and management. Recent studies have shown that chromosomal translocations causing a fibronectinfgfr1 fn1fgfr1 fusion gene have been identified in 4060% of these tumors. Symptoms include chronic muscle and bone pain, weakness, and fatigue in association with a high risk of fragility fractures due to osteomalacia. Tumorinduced osteomalacia with normal systemic fibroblast growth. In this first series of south american patients, we show that the clinical presentation and sensitivity of plasmatic fibroblast growth factor 23 and somatostatin analogbased imaging are similar to those described in other populations. Gradually, his sternum protruded whenever he rose from bed. The majority of tumor induced osteomalacia cases have been reported in the northern hemisphere and asia. A 25yearold law graduate from indonesia was referred by his rheumatologist in june, 2012, to our hospital in singapore. The culprit tumors of tio could produce fibroblast growth factor 23 which plays a role in. A patient with classic clinical and biochemical features of tumor induced osteomalacia hypophosphatemia, phosphaturia, and undetectable serum concentrations of 1,25dihydroxyvitamin d 1,25oh 2 d was studied before and after resection of a benign extraskeletal chondroma from the plantar surface of the foot.
Clinical manifestations include hypophosphatemia, muscle weakness, bone pain, osteomalacia, and fractures. Tumorinduced osteomalacia localization by wholebody sestam. Article tumorinduced osteomalacia tio also known as. Oncogenic osteomalacia presenting as a crippling illness. Tumorinduced osteomalacia is usually referred to as a paraneoplastic phenomenon, however, the tumors are usually benign and the symptomatology is due to osteomalacia or rickets. Tumor induced osteomalacia is typically associated with benign mesenchymal tumors arising in the bone and soft tissue. The resection of the tumor cured her osseous abnormalities. The clinical presentation of tio includes bone fractures, bone and muscular pains, and. Wbmri is now developing remarkably and widely used in oncologic field. Worsening of unrecognized tumourinduced osteomalacia with.
Weight loss is unusual, but sometimes observed, and could be explained by general debilitated state of the patient with consequent poor nutrient intake and loss of muscle mass 1, 2. Soon after surgery, she recovered, resumed her normal life, and went back to jogging. Phosphaturic mesenchymal tumor of the brain without tumor. This is an open access article distributed under the terms of the creative commons attributionnoncommercialsharealike 3. Several different disorders cause osteomalacia via mechanisms that result in hypocalcemia, hypophosphatemia, or direct inhibition of the mineralization process. We present the case of a tumor induced osteomalacia whose biochemical parameters did not improve after removal of the fdgavid tumor initially. Tumors that can lead to this syndrome are classified histologically as phosphaturic mesenchymal tumors with mixed connective tissue, osteoblastomalike tumors, ossifying fibrouslike tumors, or nonossifying fibrouslike tumors 1, 2. Tumor induced osteomalacia tio is a rare disease, which causes hyperphosphaturia and hypophosphatemia with inappropriately normal or low 1,25dihydroxyvitamin d. Cloning and characterization of fgf23 as a causative.
Oncogenic osteomalacia associated with an occult phosphaturic. Tumorinduced osteomalacia and rickets clinical gate. Since tio was first described in 1947, more than 500 cases have been reported worldwide. Tumorinduced osteomalacia is a rare paraneoplastic syndrome with.
Biochemical hallmarks of the disorder are hypophosphatemia due to renal. Catheterization to locate mesenchymal tumors in patients with. Mar 25, 2017 the majority of tumor induced osteomalacia cases have been reported in the northern hemisphere and asia. Sep 21, 2017 tumor induced osteomalacia tio is a rare paraneoplastic syndrome characterized by severe hypophosphatemia and osteomalacia related to abnormal tumor production of fibroblast growth factor 23 fgf23 1, 2.
Occult phosphaturic mesenchymal tumour of femur cortex. Because removal of responsible tumors normalizes phosphate metabolism, an unknown phosphaturic factor sometimes called phosphatonin is believed to be responsible for this paraneoplastic syndrome 1, 2. Bgj398 for the treatment of tumorinduced osteomalacia. Tumors induced osteomalaciaa curious case of double. Phosphaturic mesenchymal tumor mixed connective tissue variant pmtmct are tumors that may cause tumor induced osteomalacia and rarely appear intracranially.
Tumorinduced osteomalacia tio is a rare and fascinating paraneoplastic syndrome in which patients present with bone pain, fractures, and muscle weakness. Tio is usually induced by small, slowly growing tumors of mesenchymal origin phosphaturic mesenchymal tumor mixed connective tissue variant pmtmct. The excessive aminoaciduria and glucosuria of the first patient also remitted. Tumor induced osteomalacia is usually referred to as a paraneoplastic phenomenon, however, the tumors are usually benign and the symptomatology is due to osteomalacia or rickets. Phosphaturic mesenchymal tumor of the brain without tumor induced osteomalacia in an 8yearold girl. Tumor induced osteomalacia is a renal phosphatewasting disorder resulting in low serum phosphorus concentration and osteomalacia. A benign mesenchymal or mixed connective tissue tumor usually phosphaturic mesenchymal tumor and hemangiopericytoma are the most common associated tumors. Fgf23 levels were significantly increased, and total body magnetic resonance imaging mri revealed a tumor mass located at the distal tibia leading to the diagnosis of tumor induced osteomalacia tio. Tumorinduced osteomalacia tio is a paraneoplastic syndrome characterized by bone pain, fractures and muscle weakness. Tumour induced osteomalacia tio is a rare paraneoplastic syndrome characterised by severe hypophosphataemia and osteomalacia, with renal phosphate wasting that occurs in association with tumour. Tumor induced osteomalacia tio is a rare, paraneoplastic disease that can be difficult to distinguish from genetic forms of hypophosphatemia and severe osteomalacia. Tumour induced osteomalacia tio, is a rare paraneoplasatic syndrome found in 95% of benign tumours that secrete fibroblast growth factor 23 a phosphaturic circulating hormone. Oncogenic osteomalacia presenting as a crippling illness in a.
Tumour induced osteomalacia tio, also known as oncogenic osteomalacia, is a rare paraneoplastic disorder caused by tumours that secrete fibroblast growth factor 23 fgf23. The authors describe the case of an 8yearold girl who was found to have pmtmct with involvement of the cerebellar hemisphere and a small tumor pedicle breaching the dura mater and. Tumorinduced osteomalacia tio, also known as oncogenic osteomalacia, is a rare paraneoplastic syndrome characterized by persistent hypophosphatemia. Most of the tumors are phosphaturic mesenchymal tumors pmts, which are small and difficult to detect. Apr 23, 2015 tumor induced osteomalacia tio is a paraneoplastic syndrome resulting in renal phosphate wasting and decreased bone mineralization. Tumorinduced osteomalacia tio, also known as oncogenic osteomalacia, is a rare paraneoplastic syndrome characterized by. Tumorinduced osteomalacia tio is a rare paraneoplastic syndrome clinically characterized by bone pain, fractures and muscle weakness.
Dec 20, 2004 catheterization to locate mesenchymal tumors in patients with tumor induced osteomalacia or oncogenic osteomalacia the safety and scientific validity of this study is the responsibility of the study sponsor and investigators. It is caused by tumoral overproduction of fibroblast growth factor 23 fgf23 producing hypophosphatemia and osteomalacia. The histopathologic analysis revealed that the metatarsal lesion was a mesenchymal tumor. Phosphate is important for keeping bones strong and healthy. Rickets and osteomalacia the distal ends of the radius and ulna display extensive cupping, fraying, and splaying of the diaphysis, with widening of the metaphysis. Dementia, using desferrioxamine infusions and oral 1alpha.
The world health organization def ines osteoporosis as a tscore. A 71yearold woman with advanced breast cancer developed symptomatic oncogenic osteomalacia with raised fgf23, severe hypophosphataemia and hypocalcaemia. Tumorinduced osteomalacia current imaging modalities. Oncogenic osteomalacia and metastatic breast cancer. Tumor induced osteomalacia, also known as oncogenic osteomalacia oom, is an acquired disorder character ized by marked mineral derange and adjustment of ske letal metabolism 1,2. Krn23 is an investigational recombinant fully human monoclonal igg1 antibody against the phosphaturic hormone fibroblast growth factor 23 fgf23 in development for tumor induced osteomalacia tio. A sherlock holmes approach to diagnosis and management. Tumorinduced osteomalacia geriatrics jama jama network. Tumor induced osteomalacia is a paraneoplastic syndrome, the diagnosis of which is often challenging. Burosumab improved serum phosphorus, osteomalacia, mobility, and fatigue in the 48week, phase 2 study in adults with tumor induced osteomalacia syndrome. He had no fever, morning stiffness, or joint inflammation. Successful treatment of dialysis osteomalacia oop concepts pdf and. Since her initial diagnosis, msrreceivesmedicaltherapythathas improvedhersymptoms.
As heparan sulfate or heparin was reported to modulate the activity of several fgfs 1216we examined the inhibitory activity of fgf in the presence of heparin. Oct 19, 2017 tumor induced osteomalacia is caused by the development of a tumor that releases fibroblast growth factor 23 fgf23. Tumor induced osteomalacia tio also known as oncogenic osteomalacia case followup. Phosphaturic mesenchymal tumor, mixed connective tissue variant pmtmct is a rare tumor typically occurring in soft tissues and bone, causing oncogenic tumor induced osteomalacia tio through secretion of the phosphaturic hormone, fibroblast growth factor23 fgf23. Effects of krn23, an antifgf23 antibody in patients with. Tumorinduced osteomalacia tio, also known as oncogenic osteomalacia, is a rare paraneoplastic syndrome characterized by hypophosphatemia resulting from decreased tubular phosphate reabsorption, with a low or inappropriately normal level of active vitamin d.
Patients present with bone pain at multiple sites due to hypophosphataemic osteomalacia induced by a. The purpose of this page is to hopefully communicate with other people that have the same bone disease my husband has and gain some more knowledge on it. We present a child with symptoms of rickets as the first clinical sign of a central giant cell granuloma cgcg with high serum levels of fgf23, a hormone associated with decreased phosphate resorption. It is caused by tumoral overproduction of fibroblast growth factor 23 fgf23 that acts primarily at the proximal renal tubule, decreasing phosphate reabsorption and 1. Sep 27, 2014 a 25yearold law graduate from indonesia was referred by his rheumatologist in june, 2012, to our hospital in singapore. Tumor induced osteomalacia tio and epidermal nevus syndrome ens are rare diseases of excess fibroblast growth factor 23 fgf23 that are characterized by hypophosphatemia secondary to phosphaturia and impaired active vitamin d synthesis that results in bone pain, osteomalacia, fractures, and muscle weakness. Tio is usually caused by small, benign, difficulttolocalize, mesenchymal tumors. Successful treatment of tumorinduced osteomalacia due to. Oncogenic osteomalacia is a rare paraneoplastic syndrome that is usually induced by bone or soft tissue tumours. Definitive therapy, it can be associated with considerable morbidity depending on the. Conventional imaging and new nuclear medicine imaging modalities play an important role in tumor. Tumor induced osteomalacia tio is a rare paraneoplastic syndrome characterized by severe hypophosphatemia and osteomalacia related to abnormal tumor production of fibroblast growth factor 23 fgf23 1, 2.
Fgf23 is responsible for regulating levels of phosphate and vitamin d in the body by telling the kidneys how much phosphate to absorb and how much phosphate to release from the body in the urine. The cause is high blood levels of the recently identified phosphate and vitamin dregulating hormone, fibroblast growth factor 23 fgf23. Among the soft tissue tumours, phosphaturic mesenchymal tumours form the major group. Pdf tumorinduced osteomalacia tio is a rare paraneoplastic syndrome clinically characterized by bone pain, fractures and muscle weakness. To report the outcomes of tumor induced osteomalacia after treatment, particularly related to recovery of bone mass.