2025
Advancing patient evidence in XLH (APEX): rationale and design of a real-world XLH global data unification program
Brandi M, Carpenter T, Fukumoto S, Haffner D, Imel E, Kanematsu M, McCullough K, Ozono K. Advancing patient evidence in XLH (APEX): rationale and design of a real-world XLH global data unification program. Frontiers In Endocrinology 2025, 16: 1471127. PMID: 40260280, PMCID: PMC12009718, DOI: 10.3389/fendo.2025.1471127.Peer-Reviewed Original ResearchConceptsX-linked hypophosphatemiaRandomized clinical trialsExcessive fibroblast growth factor 23Human anti-FGF23 antibodyObservational studyPhosphate-regulating endopeptidase homologAnti-FGF23 antibodyFibroblast growth factor 23Renal phosphate wastingLong-term outcomesStudy of patientsLong-term observational studiesPatient-reported outcomesPatients evidenceOral phosphateDosing regimensBone turnoverDental healthSerum phosphateChronic hypophosphatemiaClinical decision-makingPhosphate wastingPathogenic variantsClinical trialsGastrointestinal disturbances
2024
Both enantiomers of β-aminoisobutyric acid BAIBA regulate Fgf23 via MRGPRD receptor by activating distinct signaling pathways in osteocytes
Sakamoto E, Kitase Y, Fitt A, Zhu Z, Awad K, Brotto M, White K, Welc S, Bergwitz C, Bonewald L. Both enantiomers of β-aminoisobutyric acid BAIBA regulate Fgf23 via MRGPRD receptor by activating distinct signaling pathways in osteocytes. Cell Reports 2024, 43: 114397. PMID: 38935499, PMCID: PMC11350516, DOI: 10.1016/j.celrep.2024.114397.Peer-Reviewed Original ResearchActivate distinct signaling pathwaysSignaling pathwayFibroblast growth factor 23Urinary phosphate excretionReceptor type DInduce FGF23Urine phosphateElevated FGF23Phosphate excretionFGF23L-BAIBAExercise-induced increasePhosphate homeostasisSclerostinPhosphate metabolismReceptorsD-enantiomerBonePathwayHealthcare Resource Use Associated With Tumor-Induced Osteomalacia: A Literature Review
de Beur S, Dahir K, Imel E, Zanchetta M, Williams A, Li Z, Webb N, Crowe V, Johnson B, Carpenter T. Healthcare Resource Use Associated With Tumor-Induced Osteomalacia: A Literature Review. The Journal Of Clinical Endocrinology & Metabolism 2024, 110: 102-113. PMID: 38913723, PMCID: PMC11651676, DOI: 10.1210/clinem/dgae431.Peer-Reviewed Original ResearchTumor-induced osteomalaciaHealthcare resource useResection outcomesCase reportHigher probability of tumor recurrenceSecrete fibroblast growth factor 23Probability of tumor recurrenceAssociated with tumor-induced osteomalaciaFibroblast growth factor 23Symptoms to diagnosisHealthcare resource burdenTumor recurrenceParaneoplastic syndromeTumor resectionAssociated with greater usePharmacological treatmentDisease characteristicsImaging testsPatientsMusculoskeletal symptomsTargeted literature reviewResource useOrthopedic surgeryProgressive disabilityMean time
2023
Klotho Overexpression Is Frequently Associated With Upstream Rearrangements in Fusion-Negative Phosphaturic Mesenchymal Tumors of Bone and Sinonasal Tract
Lee J, Hsieh T, Kao Y, Tsai C, Huang H, Shih C, Song H, Oda Y, Chih-Hsueh Chen P, Pan C, Sittampalam K, Petersson F, Konishi E, Chiu W, Chen C, Carpenter T, Lu T, Chang C, Huang S, Folpe A. Klotho Overexpression Is Frequently Associated With Upstream Rearrangements in Fusion-Negative Phosphaturic Mesenchymal Tumors of Bone and Sinonasal Tract. Modern Pathology 2023, 36: 100336. PMID: 37742927, DOI: 10.1016/j.modpat.2023.100336.Peer-Reviewed Original ResearchConceptsPhosphaturic mesenchymal tumorMesenchymal tumorsSinonasal tractFibroblast growth factor 23Growth factor 23Fusion-positive casesBreak-apart fluorescenceSinonasal locationFISH-positive casesFinal cohortFactor 23Situ hybridizationUncommon neoplasmLarge cohortKlotho overexpressionFGFR1 inhibitionTumorsKL expressionCohortSoft tissueWhole genomic sequencingPromoter methylationConcordant resultsPatientsFurther investigationA De Novo Deleterious PHEX Variant Without Clinical Features of X-Linked Hypophosphatemia
Kayser M, Jain P, Bale A, Carpenter T. A De Novo Deleterious PHEX Variant Without Clinical Features of X-Linked Hypophosphatemia. JCEM Case Reports 2023, 1: luad082. PMID: 37908207, PMCID: PMC10586592, DOI: 10.1210/jcemcr/luad082.Peer-Reviewed Original ResearchSkewed X-inactivationFibroblast growth factor 23Growth factor 23Intrauterine growth restrictionSingle nucleotide polymorphismsDiagnosis of XLHClinical featuresFactor 23Duodenal atresiaRadiographic featuresGrowth restrictionPostnatal genetic testingAndrogen receptor locusPotential treatmentGenetic testingHypophosphatemiaXLHHereditary ricketsDominant disorderPrenatal identificationCommon formHemizygous malesHeterozygous disruptionRicketsHeterozygous femalesBone marrow sinusoidal endothelial cells are a site of Fgf23 upregulation in a mouse model of iron deficiency anemia
Li X, Lozovatsky L, Tommasini S, Fretz J, Finberg K. Bone marrow sinusoidal endothelial cells are a site of Fgf23 upregulation in a mouse model of iron deficiency anemia. Blood Advances 2023, 7: 5156-5171. PMID: 37417950, PMCID: PMC10480544, DOI: 10.1182/bloodadvances.2022009524.Peer-Reviewed Original ResearchConceptsSinusoidal endothelial cellsEndothelial cellsBone marrowBM sectionsFGF23 upregulationFibroblast growth factor 23Iron deficiencyElevated serum erythropoietinFGF23 promoter activityBM endothelial cellsGrowth factor 23Vitamin D metabolismIron deficiency anemiaSystemic iron deficiencyKnockout mice exhibitBone marrow sinusoidal endothelial cellsNormal iron balanceNonanemic controlsChronic anemiaFactor 23D metabolismEndothelial cell populationErythropoietin treatmentDeficiency anemiaMouse modelGenetics of Diffuse Idiopathic Skeletal Hyperostosis and Ossification of the Spinal Ligaments
Kato H, Braddock D, Ito N. Genetics of Diffuse Idiopathic Skeletal Hyperostosis and Ossification of the Spinal Ligaments. Current Osteoporosis Reports 2023, 21: 552-566. PMID: 37530996, PMCID: PMC10543536, DOI: 10.1007/s11914-023-00814-6.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsDiffuse idiopathic skeletal hyperostosisAutosomal recessive hypophosphatemic rickets type 2Idiopathic skeletal hyperostosisSkeletal hyperostosisOPLL patientsGenetic factorsPathogenic variantsFibroblast growth factor 23Growth factor 23Posterior longitudinal ligamentSpinal ligament ossificationRecent FindingsRecent studiesStrong genetic factorImportant new biomarkerDisease courseFactor 23Longitudinal ligamentClinical evaluationPlasma biomarkersClinical trialsLigament ossificationPlasma PPiCalcification disordersPatientsEctopic calcificationMineral bone disorder in children with chronic kidney disease: Data from the KNOW-Ped CKD (Korean cohort study for outcome in patients with pediatric chronic kidney disease) study
Jung J, Lee K, Park E, Park Y, Kang H, Ahn Y, Ha I, Kim S, Cho H, Han K, Cho M, Choi H, Lee J, Shin J. Mineral bone disorder in children with chronic kidney disease: Data from the KNOW-Ped CKD (Korean cohort study for outcome in patients with pediatric chronic kidney disease) study. Frontiers In Pediatrics 2023, 11: 994979. PMID: 36873652, PMCID: PMC9982157, DOI: 10.3389/fped.2023.994979.Peer-Reviewed Original ResearchChronic kidney disease stageFractional excretion of phosphateMineral bone disorderChronic kidney diseasePediatric CKD patientsIntact parathyroid hormoneVitamin DSerum phosphateCKD patientsFGF-23Levels of 1,25-dihydroxy vitamin DUrine calcium-to-creatinine ratioMedian serum calcium levelBone disordersKidney diseaseSerum intact parathyroid hormoneCalcium to creatinine ratioChronic kidney disease stage 3bZ-scorePrevalence of hyperphosphatemiaSerum calcium levelsSerum vitamin DActive vitamin DFibroblast growth factor 23Abnormal mineral metabolism
2022
OR13-1 Long-Term Burosumab Therapy Provides Sustained Benefit in Patients with Tumor-Induced Osteomalacia: End of Study Findings From the Pivotal Phase 2 Study
Carpenter T, Cimms T, Hetzer J, Insogna K, Kumar R, Merritt J, Miller P, Peacock M, Rauch F, Stanciu I, Weber T, De Beur S. OR13-1 Long-Term Burosumab Therapy Provides Sustained Benefit in Patients with Tumor-Induced Osteomalacia: End of Study Findings From the Pivotal Phase 2 Study. Journal Of The Endocrine Society 2022, 6: a191-a191. PMCID: PMC9624705, DOI: 10.1210/jendso/bvac150.394.Peer-Reviewed Original ResearchTumor-induced osteomalaciaWeek 240Week 144Week 24Serum phosphorusBurosumab therapyWeek 48Bone biomarkersSafety profileNormal rangeExcess fibroblast growth factor 23SF-36 bodily pain scoresTreatment of TIOPivotal phase 2 studySF-36 physical healthSF-36 vitality scoreFibroblast growth factor 23Surface/bone surfaceBodily pain scoresMean serum phosphorusObserved safety profileRadionucleotide bone scansRare paraneoplastic syndromeBrief Pain InventoryOsteoid surface/bone surface
2021
Serum Levels of Lipocalin Are Lower in Adolescents With X-Linked Hypophosphatemia
Simpson C, Santoro A, Carpenter T, Insogna K. Serum Levels of Lipocalin Are Lower in Adolescents With X-Linked Hypophosphatemia. Journal Of The Endocrine Society 2021, 5: a27-a27. PMCID: PMC8089365, DOI: 10.1210/jendso/bvab048.052.Peer-Reviewed Original ResearchWeight/height z-scoreHeight z-scoreExcessive weight gainZ-scoreFibroblast growth factor 23Greater riskWeight gainRegular aerobic exerciseDirect pathogenic roleGrowth factor 23Impaired glucose metabolismVitamin D testingElderly normal individualsAbility of patientsAccelerated osteoarthritisAdult patientsPediatric patientsSerum levelsFactor 23Metabolic abnormalitiesAbnormal biomechanicsInsulin levelsAerobic exerciseInsulin sensitivityPathogenic rolePhosphorus bioaccessibility measured in four amino acid–based formulas using in-vitro batch digestion translates well into phosphorus bioavailability in mice
Chande S, Dijk F, Fetene J, Yannicelli S, Carpenter TO, van Helvoort A, Bergwitz C. Phosphorus bioaccessibility measured in four amino acid–based formulas using in-vitro batch digestion translates well into phosphorus bioavailability in mice. Nutrition 2021, 89: 111291. PMID: 34111672, PMCID: PMC8588148, DOI: 10.1016/j.nut.2021.111291.Peer-Reviewed Original ResearchConceptsPhosphorus bioavailabilityAmino acid-based formulaProton pump inhibitorsDigestion modelBioavailability analysisPlasma phosphorus levelsLow phosphorus dietDigestion conditionsBioaccessibilityBioavailabilityStomach acidificationDigestive conditionsIntact fibroblast growth factor 23Phosphorus dietFibroblast growth factor 23Stomach pH.Intact parathyroid hormoneAcid-suppressive medicationsDihydroxy vitamin DGrowth factor 23Phosphorus levelsPhosphorus bioaccessibilityAcidificationPhosphorusIntact fibroblast growth factorFGF23 signalling and physiology.
Ho BB, Bergwitz C. FGF23 signalling and physiology. Journal Of Molecular Endocrinology 2021, 66: r23-r32. PMID: 33338030, PMCID: PMC8782161, DOI: 10.1530/jme-20-0178.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsO-glycosylation of FGF23FGF23 signalingSubtilisin-like proprotein convertase furinSuppressing phosphate reabsorptionProprotein convertase furinPost-translationallyO-glycosylationIntact FGF23C-terminusGenetic activityPrevent proteolysisParacrine FGFsHigh-affinity binding sitesFibroblast growth factor 23Fruit flyActive intact FGF23Convertase furinChronic kidney diseaseFGF23 fragmentsGrowth factor 23Physiological roleEndocrine FGFsDihydroxyvitamin D synthesisHyperphosphatemic disordersIntestinal phosphate absorptionChapter 10 Phosphatonins
Tebben P, Kumar R. Chapter 10 Phosphatonins. 2021, 215-233. DOI: 10.1016/b978-0-12-813073-5.00010-1.ChaptersSecreted frizzled-related protein 4X-linked hypophosphatemic ricketsPhosphorus balanceCell membrane integrityTumor-induced osteomalaciaFrizzled-related protein 4Fibroblast growth factor 23Matrix extracellular phosphoglycoproteinPhosphate homeostasisRenal phosphate reabsorptionPhosphate absorptionAbnormal phosphate homeostasisIntestinal phosphate absorptionMembrane integrityPhosphorusFibroblast growth factor 7Parathyroid hormonePhosphaturic peptidesHypophosphatemic ricketsPhosphate reabsorptionVitamin DRenal reabsorptionHypophosphatemic disordersNovel treatmentTumoral calcinosis
2020
Catalysis‐Independent ENPP1 Protein Signaling Regulates Mammalian Bone Mass
Zimmerman K, Liu X, von Kroge S, Stabach P, Lester ER, Chu EY, Srivastava S, Somerman MJ, Tommasini SM, Busse B, Schinke T, Carpenter TO, Oheim R, Braddock DT. Catalysis‐Independent ENPP1 Protein Signaling Regulates Mammalian Bone Mass. Journal Of Bone And Mineral Research 2020, 37: 1733-1749. PMID: 35773783, PMCID: PMC9709593, DOI: 10.1002/jbmr.4640.Peer-Reviewed Original ResearchConceptsHeterotopic mineralizationBone massFibroblast growth factor 23Growth factor 23Low bone massSoft tissue calcificationEarly-onset osteoporosisFrizzled-related protein 1Soluble Wnt inhibitorsTrabecular bone microarchitectureENPP1 deficiencyΒ-catenin signalingFactor 23Plasma FGF23Vascular calcificationArterial calcificationNuclear β-cateninPlasma PPiBone microarchitectureMurine modelTissue calcificationPlasma PiWnt inhibitorsCalcificationMiceBurosumab for the Treatment of Tumor‐Induced Osteomalacia
de Beur S, Miller PD, Weber TJ, Peacock M, Insogna K, Kumar R, Rauch F, Luca D, Cimms T, Roberts MS, San Martin J, Carpenter TO. Burosumab for the Treatment of Tumor‐Induced Osteomalacia. Journal Of Bone And Mineral Research 2020, 36: 627-635. PMID: 33338281, PMCID: PMC8247961, DOI: 10.1002/jbmr.4233.Peer-Reviewed Original ResearchConceptsTumor-induced osteomalaciaCutaneous skeletal hypophosphatemia syndromeSerious adverse eventsAdverse eventsWeek 144Week 48Serum phosphorusTreatment-related adverse eventsFibroblast growth factor 23Surface/bone surfaceAcceptable safety profileOsteoid surface/bone surfacePhase 2 studyGrowth factor 23Phosphaturic mesenchymal tumorTransiliac bone biopsiesHuman monoclonal antibodyMineralization lag timePhosphate metabolismQuality of lifeDose titrationFactor 23Safety profileMesenchymal tumorsSkeletal healthMusculoskeletal Comorbidities and Quality of Life in ENPP1‐Deficient Adults and the Response of Enthesopathy to Enzyme Replacement Therapy in Murine Models
Ferreira CR, Ansh AJ, Nester C, O'Brien C, Stabach PR, Murtada S, Lester ER, Khursigara G, Molloy L, Carpenter TO, Braddock DT. Musculoskeletal Comorbidities and Quality of Life in ENPP1‐Deficient Adults and the Response of Enthesopathy to Enzyme Replacement Therapy in Murine Models. Journal Of Bone And Mineral Research 2020, 37: 494-504. PMID: 34882836, PMCID: PMC9667476, DOI: 10.1002/jbmr.4487.Peer-Reviewed Original ResearchConceptsENPP1 deficiencyAsj/Musculoskeletal complicationsBrief Pain Inventory-Short FormPhysical Function Short FormFibroblast growth factor 23Achilles tendon calcificationHealth-related qualityMajority of patientsGrowth factor 23Cervical spine fusionPresence of enthesopathyQuality of lifeAnalgesic medicationRegular chowResidual painAdult patientsDose escalationFactor 23Replacement therapyPhysical functionCardiovascular calcificationTendon calcificationAchilles tendonSpine fusionIdentification of ENPP1 Haploinsufficiency in Patients With Diffuse Idiopathic Skeletal Hyperostosis and Early‐Onset Osteoporosis
Kato H, Ansh AJ, Lester ER, Kinoshita Y, Hidaka N, Hoshino Y, Koga M, Taniguchi Y, Uchida T, Yamaguchi H, Niida Y, Nakazato M, Nangaku M, Makita N, Takamura T, Saito T, Braddock DT, Ito N. Identification of ENPP1 Haploinsufficiency in Patients With Diffuse Idiopathic Skeletal Hyperostosis and Early‐Onset Osteoporosis. Journal Of Bone And Mineral Research 2020, 37: 1125-1135. PMID: 35340077, PMCID: PMC9177665, DOI: 10.1002/jbmr.4550.Peer-Reviewed Original ResearchConceptsAutosomal recessive hypophosphatemic rickets type 2Diffuse idiopathic skeletal hyperostosisEarly-onset osteoporosisENPP1 variantsHypophosphatemic ricketsENPP1 mutationsFibroblast growth factor 23Case 1Growth factor 23Serum phosphate levelsIdiopathic skeletal hyperostosisPosterior longitudinal ligamentCase 3Spinal ligament ossificationFactor 23Skeletal hyperostosisArterial calcificationLongitudinal ligamentPresumptive diagnosisLigament ossificationSevere ossificationMutational statusType 2Pathogenic lossGenetic testingEffects of Iron Isomaltoside vs Ferric Carboxymaltose on Hypophosphatemia in Iron-Deficiency Anemia
Wolf M, Rubin J, Achebe M, Econs MJ, Peacock M, Imel EA, Thomsen LL, Carpenter TO, Weber T, Brandenburg V, Zoller H. Effects of Iron Isomaltoside vs Ferric Carboxymaltose on Hypophosphatemia in Iron-Deficiency Anemia. JAMA 2020, 323: 432-443. PMID: 32016310, PMCID: PMC7042864, DOI: 10.1001/jama.2019.22450.Peer-Reviewed Original ResearchConceptsIron deficiency anemiaFerric carboxymaltoseIncidence of hypophosphatemiaIron isomaltosideDay 0Oral ironBone homeostasisCommon adverse drug reactionsFibroblast growth factor 23Trial ABiomarkers of mineralIntravenous iron isomaltosideRisk of hypophosphatemiaPrimary end pointReduced kidney functionGrowth factor 23Adverse drug reactionsIntravenous ironSerum phosphateFactor 23Kidney functionParathyroid hormoneRandomized trialsClinic sitesDrug reactions
2019
Earlier Onset in Autosomal Dominant Hypophosphatemic Rickets of R179 than R176 Mutations in Fibroblast Growth Factor 23: Report of 20 Chinese Cases and Review of the Literature
Liu C, Zhao Z, Wang O, Li M, Xing X, Hsieh E, Fukumoto S, Jiang Y, Xia W. Earlier Onset in Autosomal Dominant Hypophosphatemic Rickets of R179 than R176 Mutations in Fibroblast Growth Factor 23: Report of 20 Chinese Cases and Review of the Literature. Calcified Tissue International 2019, 105: 476-486. PMID: 31486862, DOI: 10.1007/s00223-019-00597-y.Peer-Reviewed Original ResearchConceptsAutosomal dominant hypophosphatemic ricketsLower extremity deformitiesDominant hypophosphatemic ricketsExtremity deformitiesOnset ageHypophosphatemic ricketsFibroblast growth factor 23Growth factor 23Onset of diseaseRU/mLHistory of ricketsEarlier onset ageAge of onsetRare hereditary disorderPg/mLGenotype-phenotype correlationI-FGF23Symptomatic patientsFactor 23More patientsSerum phosphateClinical manifestationsLaboratory examinationsOvert symptomsMutation carriersFGF-23 and Cardio-Renal Interactions in Heart Failure
Stewart B, Gomez N, Barnett J, Thomas A, Wycallis E, Pattoli M, Struyk G, Fleming J, Shamlian P, Raghavendra P, Mahoney D, Ivey-Miranda J, Griffin M, Rao V, Testani J. FGF-23 and Cardio-Renal Interactions in Heart Failure. Journal Of Cardiac Failure 2019, 25: s23-s24. DOI: 10.1016/j.cardfail.2019.07.545.Peer-Reviewed Original ResearchCardio-renal dysfunctionFGF-23 levelsFGF-23NT-proBNPDiuretic responsivenessIL-6Outpatient heart failure (HF) patientsPlasma FGF-23 levelsFibroblast growth factor 23Adverse left ventricular remodelingCardio-renal interactionsHigher NT-proBNPTotal renin levelsPlasma IL-6Heart failure patientsRenal sodium retentionGrowth factor 23High plasma reninLeft ventricular remodelingInduction of inflammationStrong independent associationResults Higher levelsDiuretic doseNeurohormonal activationPhosphaturic hormone
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