Regulation Of Phosphate Metabolism Research Articles

Bone Sialoprotein Regulates Phosphate Metabolism and Reduces Hyperparathyroidism in Mice with CKD

Bone Sialoprotein Regulates Phosphate Metabolism and Reduces Hyperparathyroidism in Mice with CKD

Higher serum phosphate within the normal range is associated with the development of calcified aortic valve disease.

Despite the essential role of ectopic osteogenic calcium-phosphate metabolism in the development of calcific aortic valve disease (CAVD), the implications of high serum phosphate levels in CAVD development are not fully understood. Asymptomatic individuals who underwent health screening using serial cardiac computed tomography (CT) and echocardiography were selected from a multicenter registry. CAVD was identified and quantified on CT images using the aortic valve calcification (AVC) score. The associations between initial serum phosphate levels and the presence of baseline CAVD, development of new CAVD, and the AVC score progression rate were investigated using multivariable regression models. A total of 736 individuals were selected for analysis, and the median interscan duration was 36.4 months. On initial CT, 83 (13.7%) participants had baseline CAVD, while 52 (7.0%) individuals developed new CAVD during follow-up. Serum phosphate levels were not associated with a higher probability of baseline CAVD but were predictive of newly developed CAVD (odds ratio per 1 mg/dl, 1.05; 95% confidence interval, 1.01-1.10; p = 0.02). Higher phosphate levels were also associated with a faster AVC score progression in those with baseline CAVD (regression coefficient per 1 mg/dl, 15.55 Agatston units/year; 95% confidence interval, 6.02-25.07; p < 0.01), an association which remained significant when the analysis was extended to include newly developed CAVD. Even slight elevations in serum phosphate are associated with accelerated CAVD progression from an early stage. Further studies are needed to investigate whether the regulation of phosphate metabolism can slow the progression of CAVD to aortic stenosis.

Regulation of Phosphate Transporters and Novel Regulator of Phosphate Metabolism

Phosphorus is essential for all living organisms. It plays an important role in maintaining biological functions, such as energy metabolism, cell membrane formation, and bone mineralization. Various factors in the intestine, kidneys, and bones regulate the homeostasis of the inorganic phosphate (Pi) concentration in the body. X-linked hypophosphatemia (XLH), the most common form of hereditary hypophosphatemic rickets, is characterized by an impaired mineralization of the bone matrix, hypertrophic chondrocytes with hypophosphatemia, and active vitamin D resistance in childhood. Phosphate-regulating gene with homologies to endopeptidases on the X chromosome was recognized as the responsible gene for XLH. XLH is classified as fibroblast growth factor 23 (FGF23)-related hypophosphatemic rickets. The enhanced FGF23 stimulates renal phosphate wasting by downregulating sodium-dependent Pi cotransporters, NaPi2a and NaPi2c proteins, in the proximal tubules. Recently, transmembrane protein (Tmem) 174 has been identified as a novel regulator of phosphate transporters. This review introduces the role of Tmem174 in the Pi homeostasis in the body.

One half-century of advances in the evaluation and management of disorders of bone and mineral metabolism in children and adolescents.

The past 50years of research in pediatric bone and mineral metabolism have led to remarkable progress in the identification and characterization of disorders that affect the developing skeleton. Progress has been facilitated through advances in both technology and biology and this paper provides a brief description of some but not all of the key findings, including identification of the calcium sensing receptor and the polypeptides parathyroid hormone and parathyroid hormone-related protein as well as their shared receptor and signal generating pathways; the elucidation of vitamin D metabolism and actions; discovery of fibroblast growth factor 23 (FGF23), the sodium-phosphate co-transporters and the other components that regulate phosphate metabolism. Moreover, the past half-century of research has led to the delineation of the molecular bases for genetic forms ofhypoparathyroidism, pseudohypoparathyroidism, and primary hyperparathyroidism as well as the determination of the genetic causes of osteogenesis imperfecta, osteopetrosis, hypophosphatasia, and other disorders of mineral/bone homeostasis. During the next decade we expect that many of these fundamental discoveries will lead to the development of innovative treatments that will improve thelives of children with these disorders.

Paracrine and endocrine functions of osteocytes

Osteocytes are dendritic-shaped cells embedded in the bone matrix and are terminally differentiated from osteoblasts. Inaccessibility due to their location has hindered the understanding of the molecular functions of osteocytes. However, scientific advances in the past few decades have revealed that osteocytes play critical roles in bone and mineral metabolism through their paracrine and endocrine functions. Sclerostin produced by osteocytes regulates bone formation and resorption by inhibiting Wnt/β-catenin signaling in osteoblast-lineage cells. Receptor activator of nuclear factor κ B ligand (RANKL) derived from osteocytes is essential for osteoclastogenesis and osteoclast activation during postnatal life. Osteocytes also secrete fibroblast growth factor 23 (FGF23), an endocrine FGF that regulates phosphate metabolism mainly by increasing phosphate excretion and decreasing 1, 25-dihydroxyvitamin D production in the kidneys. The regulation of FGF23 production in osteocytes is complex and multifactorial, involving many local and systemic regulators. Antibodies against sclerostin, RANKL, and FGF23 have emerged as new strategies for the treatment of metabolic bone diseases. Improved undrstanding of the paracrine and endocrine functions of osteocytes will provide insight into future therapeutic options.

Cancer Cachexia and Dysregulated Phosphate Metabolism: Insights from Mutant p53 and Mutant Klotho Mouse Models.

The present perspective article proposes that cachexia, muscle wasting in cancer, is mediated by dysregulated phosphate metabolism and phosphate toxicity that can damage tissues in most major organ systems. A diet high in phosphorus fed to mice deficient in klotho, a cofactor that regulates phosphate metabolism, accelerates aging, sarcopenia, general organ atrophy, kyphosis, and osteoporosis. Similar effects are seen in phenotypes of mutant p53 mice that overexpress the p53 tumor suppressor gene. Although mutant p53 mice do not develop tumors compared to wild-type mice, mutant p53 mice have shorter mean lifespans. Furthermore, tumorigenesis is associated with the sequestration of excessive inorganic phosphate, and dangerous levels of phosphate are released into circulation during tumor lysis syndrome. In total, this evidence implies that tumorigenesis may be a compensatory mechanism that provides protective effects against systemic exposure to dysregulated phosphate metabolism and phosphate toxicity related to cachexia in cancer. Moreover, the hypothetical protection against phosphate toxicity afforded by tumorigenesis also provides an alternate explanation for putative tumor evasion of the immune system. Insights proposed in this perspective paper provide new directions for further research, with potential to develop novel interventions and clinical applications that modify dietary phosphate intake to reduce cachexia in cancer patients.

Disruption of phosphate metabolism and sterol transport-related genes conferring yeast resistance to vanillin and rapid ethanol production

Vanillin is a potent growth-inhibiting factor in Saccharomyces cerevisiae during lignocellulose biorefineries. Here, a haploid gene-deletion library was screened to search for vanillin-tolerant mutants and explain the possible tolerance mechanisms. Twenty-two deletion mutants were identified. The deleted genes in these mutants were involved in phosphate and inositol polyphosphate metabolism and intracellular sterol transport. Activation of the phosphate signaling pathway is not conducive to yeast against the pressure of vanillin. Furthermore, the findings indicate the role of inositol polyphosphates in altering vanillin tolerance by regulating phosphate metabolism. Meanwhile, reducing the transport of sterols from the plasma membrane enhanced tolerance to vanillin. In the presence of vanillin, the representative yeast deletions, pho84Δ and lam3Δ, showed good growth performance and promoted rapid ethanol production. Overall, this study identifies robust yeast strain alternatives for ethanol fermentation of cellulose and provides guidance for further genomic reconstruction of yeast strains.

Obesity and Cancer: Potential Mediation by Dysregulated Dietary Phosphate

Next to smoking, obesity is the second leading preventable risk factor for cancer, but increasing rates of obesity and overweight are estimated to overtake smoking as the leading preventable cancer risk factor. Few research studies have investigated the dysregulated endocrine metabolism of dietary phosphate as a potential mediating factor in the association of obesity with cancer. Phosphate toxicity, the accumulation of excess phosphate in the body from dysregulated phosphate metabolism, is associated with tumorigenesis. High levels of hormones that regulate phosphate metabolism, such as parathyroid hormone and fibroblast growth factor 23, are also associated with obesity, providing a potential link between obesity and phosphate toxicity. Increased dietary intake of inorganic phosphate is linked to excessive consumption of foods processed with phosphate additives, and consumption of ultra-processed foods is associated with an increase in the incidence of obesity. Sugar-sweetened beverages provide the single largest source of sugar and energy intake in the U.S. population, and colas containing phosphoric acid are associated with tumorigenesis, suggesting another potential connection between obesity and cancer. Furthermore, dietary phosphate is positively correlated with increases in obesity, central obesity, and metabolic syndrome. The present perspective article proposes that dysregulated dietary phosphate potentially mediates the association of obesity with cancer.

Impact ofMtrAon phosphate metabolism genes and the response to altered phosphate conditions inStreptomyces

Phosphate metabolism is known to be regulated by the PhoPR regulatory system in Streptomyces and some other bacteria. In this study, we report that MtrA also regulates phosphate metabolism in Streptomyces. Our data showed that, in Streptomyces coelicolor, MtrA regulates not only phosphate metabolism genes such as phoA but also phoP under different phosphate conditions, including growth on rich complex media without added inorganic phosphate and on defined media with low or high concentrations of inorganic phosphate. Cross-regulation was also observed among mtrA, phoP and glnR under these conditions. We demonstrated both in vitro and in vivo binding of MtrA to the promoter regions of genes associated with phosphate metabolism and to the intergenic region between phoR and phoU, indicating that these phosphate metabolism genes are targets of MtrA. We further showed that MtrA in S. lividans and S. venezuelae has detectable regulatory effects on expression of phosphate metabolism genes. Additionally, the MtrA homologue from Corynebacterium glutamicum bound predicted MtrA sites of multiple phosphate metabolism genes, implying its potential for regulating phosphate metabolism in this species. Overall, our findings support MtrA as a major regulator for phosphate metabolism in Streptomyces and also potentially in other actinobacteria.

Favorable Effects of Burosumab on Fibroblast Growth Factor 23-Related Osteomalacia: A Case Report

Background: Fibroblast growth factor 23 (FGF23) decreases serum phosphate levels by inhibiting proximal tubular phosphate reabsorption and intestinal phosphate absorption by decreasing serum 1,25-dihydroxyvitamin D level, thereby regulating phosphate metabolism. Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused by FGF23 overproduction by tumor tissue. Resecting the responsible tumor is a radical treatment for TIO. When the responsible tumor is undetectable, phosphate and active vitamin D administration is recommended. However, supplementation alone is frequently insufficient to maintain phosphate levels and it is difficult to prevent the complications associated with medical therapy, including hypercalciuria and nephrocalcinosis. Recently, burosumab, a human monoclonal anti-FGF23 antibody, has been approved in Japan as a therapeutic agent for FGF23-related hypophosphatemia. Here, we present a patient with TIO effectively treated with burosumab in the absence of identification of tumour location. Clinical case: A 47-year-old female developed pain and edema of the feet; however, the cause could not be determined at local hospitals. Afterwards, she developed marked bone atrophy in the feet and was referred to our hospital. Her age at symptom onset, hypophosphatemia (serum P, 1.9 mg/dl, 2.7 mg/dl < n < 4.6 mg/dl), high serum FGF23 level (630 pg/ml, 16 pg/ml < n < 69 pg/ml), and decreased 1,25-dihydroxyvitamin D level (12.9 pg/ml, 20 pg/ml < n < 60 pg/ml) indicated FGF23-related osteomalacia. She was not having any medication at the time of diagnosis, including saccharified iron oxide or iron polymaltose. Urinary phosphate excretion increased without renal tubular defect; therefore, hypophosphatemic osteomalacia was diagnosed. MRI showed high signal intensity in the talus, sacral, and L5 vertebral regions, indicating multiple pseudofractures. Comprehensive imaging studies, including systemic CT scan and 111In-pentetreotide scintigraphy, did not reveal any tumors despite the suspicion of TIO. Next, we performed systemic venous sampling, which revealed high FGF23 level in the left external iliac vein. Second venous sampling limited to the left lower limb exhibited high FGF23 level in the posterior tibial vein. However, an additional imaging study limited to the left foot could not identify any tumors. Genetic variation was negative for potentially responsible genes, including PHEX and FGF23. We decided to administer burosumab to normalize serum phosphate level without phosphate supplementation. Within 2 months, pain was relieved and the visual analog scale scores also improved from 10 to 6. Moreover, bone MRI showed improved pseudofractures. Conclusion: Burosumab administration was effective for TIO of unknown origin, and it improved not only laboratory findings but also clinical symptoms in this case.

FGF23 functions and disease.

The main function of fibroblast growth factor 23 (FGF23) is the regulation of phosphate metabolism through its action on the sodium-dependent phosphate cotransporters in the proximal renal tubules. Additionally, FGF23 interacts with vitamin D and parathyroid hormone in a complex metabolic pathway whose detailed mechanisms are still not clear in human physiology and disease. More recently, research has also focused on the understanding of mechanisms of FGF23 action on organs and system other than the kidneys and bone, as well as on its interaction with other metabolic pathways. Collectively, the new evidence are successfully used for the clinical evaluation and management of FGF23-related disorders, for which new therapies with many potential applications are now available.

Значение фактора роста Фибробластов 23 (FGF-23) в организме человека

Nowadays chronic kidney disease (CKD) is one of the leading chronic non-communicable diseases in terms of morbidity and mortality. One of the most serious complications is mineral-bone disorder, which worsen the clinical course and prognosis of patients. Fibroblast growth factor 23 (FGF-23) is a new biomarker that regulates phosphate metabolism and plays an important role in the pathogenesis of many complications in CKD. Purpose. To study the physiological role of FGF-23, as well as its potential clinical significance in the progression of CKD and its complications. Material and methods. A 20-year-deep literature search was conducted in the international scientific databases PubMed / Medline, Web of Science and Google Scholar for the following keywords: "Fibroblast growth factor 23", "FGF-23", "phosphate homeostasis", "chronic kidney disease", "Mineral and bone disorders", "left ventricular hypertrophy". Results and discussion. FGF-23 is a protein secreted by bone cells and its primary physiological role is to regulate urinary excretion of phosphate to maintain a stable level in serum. Moreover, FGF-23 decreases calcitriol levels and inhibits parathyroid hormone secretion. In CKD, there is a gradual increase in FGF-23 levels as renal function declines, which can be regarded as physiological compensation to stabilize serum phosphate levels. According to the several studies, FGF-23 might be associated with cardiovascular complications, such as left ventricular hypertrophy and heart failure. Conclusion. Thus, FGF-23 is not only a marker of mineral-bone disorders in CKD, but also a key link in the pathogenesis of the development of secondary hyperparathyroidism and cardiovascular complications. With this in mind, FGF-23 may represent a multifunctional therapeutic target that may improve the prognosis of patients with CKD. Keywords: fibroblast growth factor-23, phosphate, parathyroid hormone, left ventricular hypertrophy, mineral-bone disorder.

Abstract 15859: Fibroblast Growth Factor 23 and Myocardial Infarction in the Boston Puerto Rican Health Study

Background: FGF-23 is an endocrine regulator of phosphate metabolism as well as also a potent biomarker that mediates cardiovascular remodeling, with markedly elevated plasma concentration associated with the occurrence of morbid cardiovascular events such as myocardial infarction. This association usually indicates risk of developing further adverse cardiovascular events in individuals that are already susceptible to repeat morbid cardiovascular outcomes. This cross-sectional epidemiological study aims at investigating the risk association between FGF-23 and individuals in the 8 th year cohort of the Boston Puerto Rican Health Study (BPRHS) that have self-reported clinical cardiovascular disease in the form of myocardial infarction. Methods: FGF-23 plasma concentration was measured by ELISA in 496 participants of the fourth wave of the Boston Puerto Rican Health Study (BPRHS). Multivariate logistic regressions were used to analyze the cross-sectional association of plasma FGF-23 quartile distribution with self-reported clinical diagnosis of myocardial infarction (MI). Results: The crude model for the association between FGF-23 and MI showed increased risk across the 2 nd , 3 rd and 4 th quartiles, OR (95% CI); 1.27 (0.48-3.34), 1.13 (0.42-3.04), and 3.13 (1.33-7.33), respectively. The relationship with the highest vs lowest quartile remained significant after adjusting for age, sex and BMI, OR (95% CI); 2.91 (1.15-7.36). With further adjustment for diabetes, smoking, plasma total cholesterol, HDL cholesterol and triglycerides, results were attenuated, and the latter comparison was no longer statistically significant, OR (95% CI); 2.15 (0.79-5.79). The test for trend across the quartiles yielded a p value of 0.03. Conclusion: Within this population of older Puerto Rican adults, FGF-23 was not significantly associated with increased likelihood of self-reported history of myocardial infarction. Longitudinal studies, using clinical parameters that objectively measure the progression of cardiovascular disease are needed to assess the prognostic value of FGF-23 for future cardiovascular outcomes.

Evaluation of Selected Parameters of Calcium and Phosphate Metabolism in Children with Adolescent Idiopathic Scoliosis.

The multifactor aetiology of adolescent idiopathic scoliosis is commonly acknowledged. Both multivariate analyses of large study groups and the search for causes of adolescent idiopathic scoliosis and its progression in individual patients indicate that the aetiopathogenesis of this disorder is remarkably complex. The discovery of novel bone turnover markers, such as Klotho protein and FGF-23, means that their role in this condition also has to be considered. The aim of this paper is to evaluate the FGF-23 and Klotho protein concentration profiles as new contributors to the regulation of calcium and phosphate metabolism in children with adolescent idiopathic scoliosis and compare them with the values seen in healthy children. The study assessed a total of 70 children, including 35 children treated at the postural defects clinic of the Health Care Facility in Oleśno following a diagnosis of adolescent idiopathic scoliosis and 35 healthy children who constituted a control group. The levels of classic bone turnover markers, such as calcium and phosphorus concentration, alkaline phosphatase, 25-OH-D, and parathyroid hormone (PTH) activity, and of newly discovered contributors to calcium and phosphate metabolism regulation, namely Klotho protein and FGF-23, were determined in both groups. There were statistically significant differences in the levels of basic parameters of calcium and phosphate metabolism between children with scoliosis and the control group, with scoliotic patients showing elevated calcium and 25-OH-D levels and reduced parathyroid hormone levels. Klotho protein levels in children with scoliosis were significantly lower than in the control group. Moreover, the scoliotic patients showed a marked trend towards higher FGF-23 levels as compared to the control group. 1. Adolescent idiopathic scoliosis is characterised by multi-level abnormalities of calcium and phosphate metabolism. 2. The increased FGF-23 levels and reduced Klotho protein concentrations found in serum samples collected from children with ado-lescent idiopathic scoliosis may suggest that these hormones play a role in the aetiopathogenesis of the disorder.

Osteocytes and Wnt signaling.

Osteocytes has many functions such as sensing mechanical stress to bone, regulating formation and activity of osteoclasts as well as modulation of bone metabolism and function of other organs through production of humoral factors such as sclerostin and FGF23. Sclerostin suppresses bone formation and stimulate bone resorption by inhibiting Wnt activity. FGF23 regulates phosphate metabolism mainly acting on kidney. In contrast, it is also reported that sclerostin works in kidney and FGF23 inhibits Wnt activity in osteoblasts. However, the physiological significance of these actions of sclerostin and FGF23 needs to be established by future investigations.

Serum phosphate and phosphate-regulatory hormones in COPD patients

BackgroundFibroblast growth factor 23 (FGF23) regulates phosphate metabolism by increasing renal phosphate excretion and decreasing 1.25-dihydroxyvitamin D synthesis. Reports about hypophosphatemia in patients with chronic obstructive pulmonary disease (COPD) suggest altered phosphate metabolism. Therefore, we hypothesized that disturbances in phosphate-regulatory hormones such as FGF23 and parathyroid hormone (PTH) are present in COPD patients.MethodsWe investigated 40 COPD patients (63.5 ± 9.9 years, 27 male), each matched with two age- and sex-matched controls without any primary lung disease. COPD patients underwent lung function testing in advance. All patients had a glomerular filtration rate (GFR) > 60 mL/min/1.73m2. We measured concentrations of intact FGF23 (iFGF23) and c-terminal FGF23 (c-term FGF23), phosphate, parathyroid hormone (PTH) and C-reactive protein (CRP) levels in COPD patients and controls.ResultsPhosphate (1.0 ± 02 vs. 1.1 ± 0.2 mmol/L; p = 0.027), PTH (54.2 ± 29.4 vs. 68.7 ± 31.8 pg/mL; p = 0.002) and iFGF23 (46.3 ± 29.0 vs. 57.5 ± 33.5 pg/mL; p = 0.026 ) levels were significantly lower in COPD patients compared with controls. There was a significant negative correlation between c-term FGF23 and total lung capacity (r = − 0.4; p = 0.01), and between c-term FGF23 and CRP in COPD patients (r = 0.48; p = 0.002). iFGF23 and c-term FGF23 were positively correlated with phosphate and PTH in the control group.ConclusionWe confirmed lower average serum phosphate levels in COPD patients compared with controls. However, our data do not suggest a causative role for FGF23 or PTH in COPD because levels of both phosphate-lowering hormones appear to be adaptively decreased as well. Therefore, further investigations are needed to identify the pathogenesis of low phosphate levels in patients with COPD and the relationship between phosphate-regulatory hormones and disease progression.

Os et métabolisme

Bone is now considered as a particular endocrine organ. Its endocrine function is not yet fully understood and has been the subject of several conferences at the European Society of Endocrinology Congress 2018. Bone regulates phosphate metabolism by secreting fibroblast growth factor 23; it also regulates glucose metabolism via osteocalcin and energy metabolism, thanks to lipocalin 2, a new hormone acting on the brain.In addition, the incidence of diabetes continues to grow, and its impact on bone has been demonstrated, with an increased risk of fractures regardless the type of diabetes. The mechanism of bone fragility in this disease is not fully known but it involves a decrease in bone turnover and bone demineralization.Recent findings on the role of bone on glucose and mineral metabolism could open therapeutic perspectives, especially for the treatment of diabetes or obesity.

Fibroblast growth factor 23 and renal function among young and healthy individuals.

Fibroblast growth factor 23 (FGF-23), an osteocyte hormone involved in the regulation of phosphate metabolism, is associated with incident and progressive chronic kidney disease. We aimed to assess the association of FGF-23 with renal parameters, vascular function and phosphate metabolism in a large cohort of young and healthy individuals. Healthy individuals aged 25-41 years were included in a prospective population-based study. Fasting venous blood and morning urinary samples were used to measure plasma creatinine, cystatin C, endothelin-1, phosphate and plasma FGF-23 as well as urinary creatinine and phosphate. Multivariable regression models were constructed to assess the relationship of FGF-23 with parameters of renal function, endothelin-1 and fractional phosphate excretion. The median age of 2077 participants was 37 years, 46% were males. The mean estimated glomerular filtration rate (eGFR - CKD-EPI creatinine-cystatin C equation) and fractional phosphate excretion were 110 mL/min/1.73 m2 and 8.7%, respectively. After multivariable adjustment, there was a significant inverse relationship of FGF-23 with eGFR (β per 1 log-unit increase -3.81; 95% CI [-5.42; -2.20]; p<0.0001). Furthermore, we found a linear association between FGF-23 and endothelin-1 (β per 1 log-unit increase 0.06; [0.01, 0.11]; p=0.01). In addition, we established a significant relationship of FGF-23 with fractional phosphate excretion (β per 1 log-unit increase 0.62; [0.08, 1.16]; p=0.03). Increasing plasma FGF-23 levels are strongly associated with decreasing eGFR and increasing urinary phosphate excretion, suggesting an important role of FGF-23 in the regulation of kidney function in young and healthy adults.

Bone-derived hormones and their systemic regulation.

Bone has several functions such as supporting our body, protecting internal organs and contributing to hematopoiesis. Recently, it has been revealed that bone also works as an endocrine tissue and systemically regulates functions of other organs. It has been reported that fibroblast growth factor 23(FGF23)regulates phosphate metabolism and osteocalcin affect glucose/energy metabolism. In addition, sclerostin, interleukin-11(IL-11)and lipocalin 2 have been also found to be bone-derived humoral factors. Further investigation concerning the network systems among multiple organs via bone-derived hormones may lead to the development of new drugs.

X-Linked Hypophosphatemia and FGF23-Related Hypophosphatemic Diseases: Prospect for New Treatment.

Phosphate plays essential roles in many biological processes, and the serum phosphate level is tightly controlled. Chronic hypophosphatemia causes impaired mineralization of the bone matrix and results in rickets and osteomalacia. Fibroblast growth factor 23 (FGF23) is a bone-derived hormone that regulates phosphate metabolism. FGF23 excess induces hypophosphatemia via impaired phosphate reabsorption in the renal proximal tubules and decreased phosphate absorption in the intestines. There are several types of genetic and acquired FGF23-related hypophosphatemic diseases. Among these diseases, X-linked hypophosphatemia (XLH), which is caused by inactivating mutations in the phosphate-regulating endopeptidase homolog, X-linked (PHEX) gene, is the most prevalent form of genetic FGF23-related hypophosphatemic rickets. Another clinically relevant form of FGF23-related hypophosphatemic disease is tumor-induced osteomalacia (TIO), a paraneoplastic syndrome associated with FGF23-producing tumors. A combination of active vitamin D and phosphate salts is the current medical therapy used to treat patients with XLH and inoperative TIO. However, this therapy has certain efficacy- and safety-associated limitations. Several measures to inhibit FGF23 activity have been considered as possible new treatments for FGF23-related hypophosphatemic diseases. In particular, a humanized monoclonal antibody for FGF23 (burosumab) is a promising treatment in patients with XLH and TIO. This review will focus on the phosphate metabolism and the pathogenesis and treatment of FGF23-related hypophosphatemic diseases.