2022
Long-term Burosumab Administration Is Safe and Effective in Adults With X-linked Hypophosphatemia
Weber TJ, Imel EA, Carpenter TO, Peacock M, Portale AA, Hetzer J, Merritt JL, Insogna K. Long-term Burosumab Administration Is Safe and Effective in Adults With X-linked Hypophosphatemia. The Journal Of Clinical Endocrinology & Metabolism 2022, 108: 155-165. PMID: 36072994, PMCID: PMC9759172, DOI: 10.1210/clinem/dgac518.Peer-Reviewed Original ResearchConceptsSerum phosphate levelsPatient-reported outcomesNormal rangeBurosumab therapyTreatment optionsEffective long-term treatment optionLong-term extension studyLong-term treatment optionNew safety findingsBone turnover markersLong-term administrationPhosphate levelsRespective normal rangesProportion of subjectsLong-term safetyLast doseAdult patientsClinical responseSafety findingsTurnover markersSerum phosphateBone biomarkersStudy endWeek 12Burosumab treatment
2020
New Therapies for Hypophosphatemia-Related to FGF23 Excess
Athonvarangkul D, Insogna KL. New Therapies for Hypophosphatemia-Related to FGF23 Excess. Calcified Tissue International 2020, 108: 143-157. PMID: 32504139, DOI: 10.1007/s00223-020-00705-3.BooksConceptsTumor-induced osteomalaciaCutaneous skeletal hypophosphatemia syndromeEpidermal nevus syndromeAutosomal dominant hypophosphatemic ricketsAutosomal recessive hypophosphatemic ricketsHypophosphatemic ricketsForms of FGF23Treatment of XLHActive comparator trialsMainstay of therapyMonoclonal blocking antibodyNew treatment modalitiesMcCune-Albright syndromeRenal phosphate wastingRecessive hypophosphatemic ricketsDominant hypophosphatemic ricketsFGF23 excessComparator trialsSkeletal complicationsChronic hypophosphatemiaMusculoskeletal syndromeOngoing trialsClinical presentationTreatment modalitiesClinical trials
2018
Three-Month Randomized Clinical Trial of Nasal Calcitonin in Adults with X-linked Hypophosphatemia
Sullivan R, Abraham A, Simpson C, Olear E, Carpenter T, Deng Y, Chen C, Insogna KL. Three-Month Randomized Clinical Trial of Nasal Calcitonin in Adults with X-linked Hypophosphatemia. Calcified Tissue International 2018, 102: 666-670. PMID: 29383408, PMCID: PMC5957766, DOI: 10.1007/s00223-017-0382-0.Peer-Reviewed Original ResearchConceptsLevels of FGF23Nasal salmon calcitoninSalmon calcitoninStudy drugVisit 2Day 2Levels of PTHPrincipal outcome variableTmP/GFRSingle subcutaneous dosePlacebo nasal sprayNasal calcitoninSerum calciumSubcutaneous doseVisit 4Dihydroxyvitamin DSerum phosphorusVisit 3Final doseVisit 1Nasal sprayClinical trialsSerial measurementsDrug doseFGF23 production
2016
Hypophosphatemia promotes lower rates of muscle ATP synthesis
Pesta DH, Tsirigotis DN, Befroy DE, Caballero D, Jurczak MJ, Rahimi Y, Cline GW, Dufour S, Birkenfeld AL, Rothman DL, Carpenter TO, Insogna K, Petersen KF, Bergwitz C, Shulman GI. Hypophosphatemia promotes lower rates of muscle ATP synthesis. The FASEB Journal 2016, 30: 3378-3387. PMID: 27338702, PMCID: PMC5024687, DOI: 10.1096/fj.201600473r.Peer-Reviewed Original ResearchConceptsMuscle ATP synthesisATP synthesisMuscle weaknessIsolated muscle mitochondriaSolute carrier familyWild-type littermate controlsSolute carrier family 34Carrier familyLower ratesInsulin-stimulated ratesMuscle mitochondriaChronic hypophosphatemiaHeart failureHypophosphatemic groupHypophosphatemic miceHypophosphatemiaLittermate controlsKnockout miceBlood PLow ratePlasma PPatientsSimilar findingsMember 1Plasma inorganic phosphate
2015
Conventional Therapy in Adults With X-Linked Hypophosphatemia: Effects on Enthesopathy and Dental Disease
Connor J, Olear EA, Insogna KL, Katz L, Baker S, Kaur R, Simpson CA, Sterpka J, Dubrow R, Zhang JH, Carpenter TO. Conventional Therapy in Adults With X-Linked Hypophosphatemia: Effects on Enthesopathy and Dental Disease. The Journal Of Clinical Endocrinology & Metabolism 2015, 100: 3625-3632. PMID: 26176801, PMCID: PMC4596038, DOI: 10.1210/jc.2015-2199.Peer-Reviewed Original ResearchConceptsSevere dental diseaseHospital research unitDental diseaseDisease severityXLH patientsMajor long-term morbidityActive vitamin D metaboliteAdult XLH patientsLong-term morbidityVitamin D metabolitesAdult lifeMultiple logistic regressionRadiographic skeletal surveySignificant predictorsProportion of adultsConventional therapyD metabolitesSkeletal surveyLower riskExposure variablesLogistic regressionDiseaseEnthesopathySkeletal deformitiesTreatment variables
2014
Randomized trial of the anti-FGF23 antibody KRN23 in X-linked hypophosphatemia
Carpenter TO, Imel EA, Ruppe MD, Weber TJ, Klausner MA, Wooddell MM, Kawakami T, Ito T, Zhang X, Humphrey J, Insogna KL, Peacock M. Randomized trial of the anti-FGF23 antibody KRN23 in X-linked hypophosphatemia. Journal Of Clinical Investigation 2014, 124: 1587-1597. PMID: 24569459, PMCID: PMC3973088, DOI: 10.1172/jci72829.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedCalciumFamilial Hypophosphatemic RicketsFemaleFibroblast Growth Factor-23Fibroblast Growth FactorsGlomerular Filtration RateHalf-LifeHumansInjections, IntravenousInjections, SubcutaneousKidney TubulesMaleMiddle AgedPhosphatesVitamin DYoung AdultConceptsTmP/GFRSerum PiParathyroid hormonePhosphate reabsorptionXLH patientsRenal tubular thresholdSerum parathyroid hormoneFavorable safety profileElevated serum FGF23Renal phosphate reabsorptionLow serum concentrationsPhosphate-regulating endopeptidaseSerum Pi concentrationFGF23 antibodySerum FGF23Dihydroxyvitamin DSafety profileTubular thresholdSingle doseSerum concentrationsKRN23Mean t1/2Potential treatmentPatientsEffect duration
2010
Circulating Levels of Soluble Klotho and FGF23 in X-Linked Hypophosphatemia: Circadian Variance, Effects of Treatment, and Relationship to Parathyroid Status
Carpenter TO, Insogna KL, Zhang JH, Ellis B, Nieman S, Simpson C, Olear E, Gundberg CM. Circulating Levels of Soluble Klotho and FGF23 in X-Linked Hypophosphatemia: Circadian Variance, Effects of Treatment, and Relationship to Parathyroid Status. The Journal Of Clinical Endocrinology & Metabolism 2010, 95: e352-e357. PMID: 20685863, PMCID: PMC2968736, DOI: 10.1210/jc.2010-0589.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAge FactorsAgedBone Density Conservation AgentsCalcitriolChildCircadian RhythmEnzyme-Linked Immunosorbent AssayFamilial Hypophosphatemic RicketsFemaleFibroblast Growth Factor-23Fibroblast Growth FactorsGenetic Diseases, X-LinkedGlucuronidaseHumansKlotho ProteinsMaleMiddle AgedParathyroid HormonePhosphatesVitamin DConceptsSerum KlothoSerum FGF23Higher klotho levelsHospital research unitRenal phosphate handlingAcademic medical centerEffect of treatmentFibroblast growth factorKlotho levelsPTH secretionMedical therapySoluble KlothoDihydroxyvitamin DFGF23 regulationPhosphate handlingMedical CenterFGF23KlothoXLHCircadian variationGrowth factorPTHAdultsHypophosphatemiaTherapy
1994
Nocturnal hyperparathyroidism: a frequent feature of X-linked hypophosphatemia
Carpenter TO, Mitnick MA, Ellison A, Smith C, Insogna KL. Nocturnal hyperparathyroidism: a frequent feature of X-linked hypophosphatemia. The Journal Of Clinical Endocrinology & Metabolism 1994, 78: 1378-1383. PMID: 8200940, DOI: 10.1210/jcem.78.6.8200940.Peer-Reviewed Original ResearchConceptsHypophosphatemic ricketsFrequency of hyperparathyroidismMean iPTH valueNephrogenous cAMP excretionPathogenesis of nephrocalcinosisInitiation of therapyVitamin D preparationsGroup of patientsOnset of treatmentExaggerated secretionParathyroid statusIPTH valuesTertiary hyperparathyroidismParathyroid functionUntreated patientsOccasional complicationCAMP excretionHyperparathyroidismPhosphopenic ricketsD preparationsPatientsControl individualsRicketsIntact hormoneNocturnal rise
1992
A prospective trial of phosphate and 1,25-dihydroxyvitamin D3 therapy in symptomatic adults with X-linked hypophosphatemic rickets
Sullivan W, Carpenter T, Glorieux F, Travers R, Insogna K. A prospective trial of phosphate and 1,25-dihydroxyvitamin D3 therapy in symptomatic adults with X-linked hypophosphatemic rickets. The Journal Of Clinical Endocrinology & Metabolism 1992, 75: 879-885. PMID: 1517380, DOI: 10.1210/jcem.75.3.1517380.Peer-Reviewed Original ResearchConceptsSymptomatic adultsOral phosphateOsteoid volumeCessation of therapyUrinary calcium excretionSymptomatic adult patientsMean serum phosphateDihydroxyvitamin D3 therapyMineral apposition rateCalcium excretionD3 therapyRenal insufficiencyTertiary hyperparathyroidismAdult patientsDrug regimenJoint painMost patientsPretreatment serumProspective trialClinical courseSerum phosphateSymptom scoresBone biopsyCombined administrationCurrent treatmentSynthetic parathyroid hormone-like protein (1–74) is anabolic for bone in vivo
Weir E, Terwilliger G, Sartori L, Insogna K. Synthetic parathyroid hormone-like protein (1–74) is anabolic for bone in vivo. Calcified Tissue International 1992, 51: 30-34. PMID: 1393774, DOI: 10.1007/bf00296214.Peer-Reviewed Original ResearchConceptsBovine parathyroid hormoneSerum calciumParathyroid hormone-like proteinDaily subcutaneous injectionsPotent bone-resorbing agentHormone-related proteinDose-dependent increaseDry bone weightHighest dose levelHormone-like proteinBone-resorbing agentsBone dry weightLow dosage levelsHumoral hypercalcemiaParathyroid hormoneDihydroxyvitamin DMale SpragueDawley ratsSubcutaneous injectionHuman PTHrPBone calciumAnabolic agentsPTHrP actionDose levelsHigh doses
1989
Trichlormethiazide and Oral Phosphate Therapy in Patients with Absorptive Hypercalciuria
Insogna K, Ellison A, Burtis W, Sartori L, Lang R, Broadus A. Trichlormethiazide and Oral Phosphate Therapy in Patients with Absorptive Hypercalciuria. Journal Of Urology 1989, 141: 269-273. PMID: 2913343, DOI: 10.1016/s0022-5347(17)40737-3.Peer-Reviewed Original ResearchConceptsOral phosphate therapyDihydroxyvitamin D levelsAbsorptive hypercalciuriaUrinary calciumParathyroid functionPhosphate therapyPhosphate administrationD levelsOral phosphate administrationRenal phosphate thresholdTreatment urinary calciumStudy 36 patientsPre-treatment valuesTrichlormethiazide treatmentCalcium excretionDihydroxyvitamin DBiochemical abnormalitiesSecond drugPharmacological meansStudy subjectsHypercalciuriaPatientsTherapyPer cent decreaseTreatment
1988
Renal phosphate transport in humoral hypercalcemia of malignancy
Sartori L, Insogna KL, Barrett PQ. Renal phosphate transport in humoral hypercalcemia of malignancy. American Journal Of Physiology 1988, 255: f1078-f1084. PMID: 2974244, DOI: 10.1152/ajprenal.1988.255.6.f1078.Peer-Reviewed Original ResearchConceptsLeydig cell tumorHumoral hypercalcemiaOnset of hypercalcemiaTumor-bearing animalsPhosphate metabolismRenal phosphate transportCortical brush border membraneParathyroid hormoneDaily injectionsTumor transplantationCell tumorsDichloromethylene diphosphonateMicrovillus membrane vesiclesRenal cortexRenal cortical brush border membraneSodium-dependent phosphate uptakeFisher ratsAnimal modelsPersistent impairmentHypercalcemiaLow-affinity systemBrush border membraneSpecific decreaseMalignancyRatsSYNTHETIC AND PARTIALLY-PURIFIED ADENYLATE CYCLASE-STIMULATING PROTEINS FROM TUMORS ASSOCIATED WITH HUMORAL HYPERCALCEMIA OF MALIGNANCY INHIBIT PHOSPHATE TRANSPORT IN A PTH-RESPONSIVE RENAL CELL LINE
SARTORI L, WEIR EC, STEWART AF, BROADUS AE, MANGIN M, BARRETT PQ, INSOGNA KL. SYNTHETIC AND PARTIALLY-PURIFIED ADENYLATE CYCLASE-STIMULATING PROTEINS FROM TUMORS ASSOCIATED WITH HUMORAL HYPERCALCEMIA OF MALIGNANCY INHIBIT PHOSPHATE TRANSPORT IN A PTH-RESPONSIVE RENAL CELL LINE. The Journal Of Clinical Endocrinology & Metabolism 1988, 66: 459-461. PMID: 3339117, DOI: 10.1210/jcem-66-2-459.Peer-Reviewed Original ResearchConceptsAdenylate cyclase-stimulating activityHumoral hypercalcemiaPhosphate metabolismCyclase-stimulating activityCell linesSodium-dependent phosphate transportRenal cell linesEpithelial cell lineTumor productsTumor decreaseRenal epithelial cellsRenal epithelial cell lineAmino acid peptidePhosphate transportHypercalcemiaAnimal tumorsTumorsHuman tumorsEpithelial cellsHHMMalignancyNaPiTInhibitory activityMinutes exposureEpithelial monolayers
1984
Vitamin D metabolism and bone histomorphometry in a patient with antacid-induced osteomalacia
Godsall J, Baron R, Insogna K. Vitamin D metabolism and bone histomorphometry in a patient with antacid-induced osteomalacia. The American Journal Of Medicine 1984, 77: 747-750. PMID: 6486152, DOI: 10.1016/0002-9343(84)90378-4.Peer-Reviewed Original ResearchConceptsVitamin D metabolismD metabolismDihydroxyvitamin DBone histomorphometryNormal levelsAltered vitamin D metabolismPhosphate-binding antacidsVitamin D metabolitesHypophosphatemic osteomalaciaD metabolitesOsteomalaciaUndetectable levelsPatientsPossible roleHistomorphometryMetabolismMetabolitesHypophosphatemiaAntacidsPathogenesisIllnessResorptionElevated concentrationsLevelsIngestionEvidence for Disordered Control of 1,25-Dihydroxyvitamin D Production in Absorptive Hypercalciuria
Broadus A, Insogna K, Lang R, Ellison A, Dreyer B. Evidence for Disordered Control of 1,25-Dihydroxyvitamin D Production in Absorptive Hypercalciuria. New England Journal Of Medicine 1984, 311: 73-80. PMID: 6330548, DOI: 10.1056/nejm198407123110201.Peer-Reviewed Original ResearchConceptsAbsorptive hypercalciuriaCalcium intakeDietary calcium intakeDihydroxyvitamin D productionRenal phosphate handlingDihydroxyvitamin DPhosphate handlingSuppression testHypercalciuriaPatientsD productionShort-term increaseSyndromeIntakePresent studyInitial levelLarge majorityPrevious studiesEvidenceAbnormalitiesWeeksA Consideration of the Hormonal Basis and Phosphate Leak Hypothesis of Absorptive Hypercalciuria*
BROADUS A, INSOGNA K, LANG R, MALLETTE L, ORENLANG D, GERTNER J, KLIGER A, ELLISON A. A Consideration of the Hormonal Basis and Phosphate Leak Hypothesis of Absorptive Hypercalciuria*. The Journal Of Clinical Endocrinology & Metabolism 1984, 58: 161-169. PMID: 6546292, DOI: 10.1210/jcem-58-1-161.Peer-Reviewed Original ResearchConceptsAbsorptive hypercalciuriaNormal subjectsCalcium excretionOral calcium tolerance testCalcium tolerance testFractional calcium excretionRenal calcium leakRenal phosphate thresholdHypercalciuric patientsMild hypercalcemiaNephrogenous cAMPCalcium intakeDihydroxyvitamin DPathophysiological basisTolerance testPlasma concentrationsUrine collectionStone diseaseCalcium leakPatientsControl groupSevere patternSignificant negative correlationHormonal basisFindings 1
1980
Osteomalacia and Weakness From Excessive Antacid Ingestion
Insogna K, Bordley D, Caro J, Lockwood D. Osteomalacia and Weakness From Excessive Antacid Ingestion. JAMA 1980, 244: 2544-2546. PMID: 7431592, DOI: 10.1001/jama.1980.03310220042025.Peer-Reviewed Original ResearchConceptsAluminum hydroxide-containing antacidElevated alkaline phosphatase levelsSerum calcium levelsAlkaline phosphatase levelsAntacid ingestionBone painPhosphate malabsorptionSevere hypophosphatemiaX-ray filmsInitial laboratory studiesPhysician awarenessUrinary phosphorusPatient's failureDietary phosphateCalcium levelsPhosphatase levelsOsteomalaciaFurther studiesHypercalciuriaHypophosphatemiaMalabsorptionPainAntacidsFailureSyndrome