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AJNR. American Journal of Neuroradiology Jun 2022Phosphaturic mesenchymal tumors (PMTs) are neoplasms associated with tumor-induced osteomalacia. Patients typically present with pathologic fractures in the setting of...
Phosphaturic mesenchymal tumors (PMTs) are neoplasms associated with tumor-induced osteomalacia. Patients typically present with pathologic fractures in the setting of chronic hypophosphatemic hyperphosphaturic osteomalacia, as well as gradual muscle weakness, bone pain, and difficulty walking. Because of their rarity and nonspecific symptomatology, phosphaturic mesenchymal tumors often go undiagnosed for years. Even when discovered on imaging, the tumors can be diagnostically challenging for radiologists. Phosphaturic mesenchymal tumors often tend to be small and can be located nearly anywhere in the body, and, therefore, can mimic many other tumors. This case highlights the imaging and pathologic markers of a phosphaturic mesenchymal tumor, often found in a patient with tumor-induced osteomalacia.
Topics: Humans; Mesenchymoma; Neoplasms, Connective Tissue; Osteomalacia; Paraneoplastic Syndromes
PubMed: 35589138
DOI: 10.3174/ajnr.A7513 -
Rhode Island Medical Journal (2013) Oct 2022Osteomalacia is defined by the undermineralization of newly formed bone due to a lack of available calcium, phosphorus, or vitamin D. Causative factors of osteomalacia...
Osteomalacia is defined by the undermineralization of newly formed bone due to a lack of available calcium, phosphorus, or vitamin D. Causative factors of osteomalacia include nutritional deficiency, diminished absorptive capabilities (often due to gastrointestinal disorders), and renal insufficiency. Renal osteodystrophy is a specific form of metabolic bone disease defined by the presence of osteomalacia and associated hyperparathyroidism secondary to a malfunction in, or absence of, renal parenchyma. This reduces the conversion of vitamin D to its active form, thus leading to a cascade of effects that negatively impact the stability of the skeleton. Osteomalacia occurs across a spectrum of severity and can produce severe consequences for specific populations, including patients with dietary, nutritional, and absorptive deficiencies. Renal osteodystrophy affects patients with chronic kidney disease, those undergoing dialysis, and renal transplant patients. Special considerations must be taken into account when assessing the bone health of patients fitting these criteria.
Topics: Calcium; Chronic Kidney Disease-Mineral and Bone Disorder; Humans; Osteomalacia; Renal Dialysis; Vitamin D
PubMed: 36173905
DOI: No ID Found -
Endocrine Practice : Official Journal... Jan 2023Phosphate is crucial for cell signaling, energy metabolism, nucleotide synthesis, and bone mineralization. The gut-bone-parathyroid-kidney axis is influenced by... (Review)
Review
OBJECTIVE
Phosphate is crucial for cell signaling, energy metabolism, nucleotide synthesis, and bone mineralization. The gut-bone-parathyroid-kidney axis is influenced by parathyroid hormone, 1,25-dihydroxyvitamin D, and phosphatonins, especially fibroblast growth factor 23 (FGF23). These hormones facilitate maintenance of phosphate homeostasis. This review summarizes current knowledge regarding the phosphate homeostasis, phosphatonin pathophysiology, and clinical implications of FGF23-related hypophosphatemic disorders, with specific focus on burosumab treatment.
METHOD
A focused literature search of PubMed was conducted.
RESULTS
Phosphatonins including FGF23, secreted frizzled-related protein 4, matrix extracellular phosphoglycoprotein, and fibroblast growth factor 7 play a pathogenic role in several hypophosphatemic disorders. Excess FGF23 inhibits sodium-dependent phosphate cotransporters (NaPi-2a and NaPi-2c), resulting in hyperphosphaturia and hypophosphatemia. Additionally, FGF23 suppresses 1,25-dihydroxyvitamin D synthesis in the proximal renal tubule, and thus, it indirectly inhibits intestinal phosphate absorption. Disorders of FGF23-related hypophosphatemia include X-linked hypophosphatemia (XLH), autosomal dominant hypophosphatemic rickets, autosomal recessive hypophosphatemic rickets, fibrous dysplasia/McCune-Albright syndrome, and tumor-induced osteomalacia (TIO). Complications of conventional therapy with oral phosphate and vitamin D analogs comprise gastrointestinal distress, hypercalcemia, nephrocalcinosis, and secondary/tertiary hyperparathyroidism. In both children and adults with XLH and TIO, the anti-FGF23 antibody burosumab exhibits a favorable safety profile and is associated with healing of rickets in affected children and improvement of osteomalacia in both children and adults.
CONCLUSION
The treatment paradigm for XLH and TIO is changing based on data from recent clinical trials. Research suggest that burosumab is effective and safe for pediatric and adult patients with XLH or TIO.
Topics: Adult; Humans; Child; Fibroblast Growth Factors; Familial Hypophosphatemic Rickets; Phosphates; Hypophosphatemia; Kidney; Bone and Bones; Osteomalacia
PubMed: 36210014
DOI: 10.1016/j.eprac.2022.09.007 -
Calcified Tissue International Jan 2021Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused by tumoral production of fibroblast growth factor 23 (FGF23). The hallmark biochemical features... (Review)
Review
Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused by tumoral production of fibroblast growth factor 23 (FGF23). The hallmark biochemical features include hypophosphatemia due to renal phosphate wasting, inappropriately normal or frankly low 1,25-dihydroxy-vitamin D, and inappropriately normal or elevated FGF23. TIO is caused by typically small, slow growing, benign phosphaturic mesenchymal tumors (PMTs) that are located almost anywhere in the body from the skull to the feet, in soft tissue or bone. The recent identification of fusion genes in a significant subset of PMTs has provided important insights into PMT tumorigenesis. Although management of this disease may seem straightforward, considering that complete resection of the tumor leads to its cure, locating these often-tiny tumors is frequently a challenge. For this purpose, a stepwise, systematic approach is required. It starts with thorough medical history and physical examination, followed by functional imaging, and confirmation of identified lesions by anatomical imaging. If the tumor resection is not possible, medical therapy with phosphate and active vitamin D is indicated. Novel therapeutic approaches include image-guided tumor ablation and medical treatment with the anti-FGF23 antibody burosumab or the pan-FGFR tyrosine kinase inhibitor, BGJ398/infigratinib. Great progress has been made in the diagnosis and treatment of TIO, and more is likely to come, turning this challenging, debilitating disease into a gratifying cure for patients and their providers.
Topics: Antibodies, Monoclonal, Humanized; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Humans; Hypophosphatemia; Neoplasms, Connective Tissue; Osteomalacia; Paraneoplastic Syndromes; Phenylurea Compounds; Phosphates; Pyrimidines
PubMed: 32504138
DOI: 10.1007/s00223-020-00691-6 -
Best Practice & Research. Clinical... Mar 2024
Topics: Humans; Osteomalacia; Familial Hypophosphatemic Rickets; Rickets, Hypophosphatemic; Phosphates
PubMed: 38238129
DOI: 10.1016/j.beem.2024.101859 -
Best Practice & Research. Clinical... Mar 2024Hypophosphatemic rickets/osteomalacia caused by FGF23 excess is conventionally treated with multiple doses of inorganic phosphate salts and active vitamin D analogs.... (Review)
Review
Hypophosphatemic rickets/osteomalacia caused by FGF23 excess is conventionally treated with multiple doses of inorganic phosphate salts and active vitamin D analogs. However, conventional therapy targets the consequences of elevated FGF23 and not the elevated FGF23 itself and is associated with poor adherence and long-term complications such as nephrocalcinosis and secondary/tertiary hyperparathyroidism. Burosumab is a fully human IgG1 monoclonal antibody that binds to and neutralises FGF-23, thereby leading to improvement in phosphate homeostasis and healing of rickets and osteomalacia. Data from phase 2 and 3 trials report overall safety and efficacy and Burosumab is now FDA approved for treatment of XLH and TIO in children and adults. Cost and absence of long-term data are major issues with Burosumab which should be addressed in near future. At present, experts recommend Burosumab use in patients with severe disease or those with mild-moderate disease and a failed response to a trial of conventional therapy.
Topics: Adult; Child; Humans; Osteomalacia; Fibroblast Growth Factors; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Familial Hypophosphatemic Rickets
PubMed: 37858479
DOI: 10.1016/j.beem.2023.101826 -
Pediatric Nephrology (Berlin, Germany) Oct 2020Hypophosphatemic rickets is caused by renal phosphate wasting that is most commonly due to X-linked dominant mutations in PHEX. PHEX mutations cause hypophosphatemia... (Review)
Review
Hypophosphatemic rickets is caused by renal phosphate wasting that is most commonly due to X-linked dominant mutations in PHEX. PHEX mutations cause hypophosphatemia indirectly, through the increased expression of fibroblast growth factor 23 (FGF23) by osteocytes. FGF23 decreases renal phosphate reabsorption and thereby increases phosphate excretion. The lack of phosphate leads to a mineralization defect at the level of growth plates (rickets), bone tissue (osteomalacia), and teeth, where the defect facilitates the formation of abscesses. The bone tissue immediately adjacent to osteocytes often remains unmineralized ("periosteocytic lesions"), highlighting the osteocyte defect in this disorder. Common clinical features of XLH include deformities of the lower extremities, short stature, enthesopathies, dental abscesses, as well as skull abnormalities such as craniosynostosis and Chiari I malformation. For the past four decades, XLH has been treated by oral phosphate supplementation and calcitriol, which improves rickets and osteomalacia and the dental manifestations, but often does not resolve all aspects of the mineralization defects. A newer treatment approach using inactivating FGF23 antibodies leads to more stable control of serum inorganic phosphorus levels and seems to heal rickets more reliably. However, the long-term benefits of FGF23 antibody treatment remain to be elucidated.
Topics: Absorptiometry, Photon; Bone Development; Bone and Bones; Calcification, Physiologic; Calcitriol; Familial Hypophosphatemic Rickets; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Humans; Osteocytes; Osteomalacia; PHEX Phosphate Regulating Neutral Endopeptidase; Paracrine Communication; Phosphates; Renal Reabsorption; Tooth; Treatment Outcome
PubMed: 31392510
DOI: 10.1007/s00467-019-04290-y -
QJM : Monthly Journal of the... Feb 2023
Topics: Humans; Paraneoplastic Syndromes; Osteomalacia; Fibroblast Growth Factors
PubMed: 36066446
DOI: 10.1093/qjmed/hcac219 -
Calcified Tissue International Jan 2021Great strides over the past few decades have increased our understanding of the pathophysiology of hypophosphatemic disorders. Phosphate is critically important to a... (Review)
Review
Great strides over the past few decades have increased our understanding of the pathophysiology of hypophosphatemic disorders. Phosphate is critically important to a variety of physiologic processes, including skeletal growth, development and mineralization, as well as DNA, RNA, phospholipids, and signaling pathways. Consequently, hypophosphatemic disorders have effects on multiple systems, and may cause a variety of nonspecific signs and symptoms. The acute effects of hypophosphatemia include neuromuscular symptoms and compromise. However, the dominant effects of chronic hypophosphatemia are the effects on musculoskeletal function including rickets, osteomalacia and impaired growth during childhood. While the most common causes of chronic hypophosphatemia in children are congenital, some acquired conditions also result in hypophosphatemia during childhood through a variety of mechanisms. Improved understanding of the pathophysiology of these congenital conditions has led to novel therapeutic approaches. This article will review the pathophysiologic causes of congenital hypophosphatemia, their clinical consequences and medical therapy.
Topics: Child; Familial Hypophosphatemic Rickets; Fibroblast Growth Factor-23; Humans; Hypophosphatemia; Osteomalacia; Phosphates
PubMed: 32328695
DOI: 10.1007/s00223-020-00692-5 -
Kidney International Nov 2022
Topics: Humans; Osteomalacia; Paraneoplastic Syndromes
PubMed: 36272746
DOI: 10.1016/j.kint.2022.04.042