2019
Burosumab Improved Histomorphometric Measures of Osteomalacia in Adults with X‐Linked Hypophosphatemia: A Phase 3, Single‐Arm, International Trial
Insogna KL, Rauch F, Kamenický P, Ito N, Kubota T, Nakamura A, Zhang L, Mealiffe M, San Martin J, Portale AA. Burosumab Improved Histomorphometric Measures of Osteomalacia in Adults with X‐Linked Hypophosphatemia: A Phase 3, Single‐Arm, International Trial. Journal Of Bone And Mineral Research 2019, 34: 2183-2191. PMID: 31369697, PMCID: PMC6916280, DOI: 10.1002/jbmr.3843.Peer-Reviewed Original ResearchConceptsAdverse eventsWeek 48Fracture healingMore treatment-emergent adverse eventsTreatment-emergent adverse eventsProcedure-related adverse eventsOsteoid volume/bone volumeMost adverse eventsSerious adverse eventsTransiliac bone biopsiesSerum phosphorus concentrationPoor bone qualityRenal phosphate reabsorptionHuman monoclonal antibodyBone painPersistent osteomalaciaSubcutaneous burosumabPrimary endpointSkeletal complicationsAtraumatic fracturesChronic hypophosphatemiaSerum phosphorusDihydroxyvitamin DBone turnoverBone biopsy
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
2015
Prolonged Correction of Serum Phosphorus in Adults With X-Linked Hypophosphatemia Using Monthly Doses of KRN23
Imel EA, Zhang X, Ruppe MD, Weber TJ, Klausner MA, Ito T, Vergeire M, Humphrey JS, Glorieux FH, Portale AA, Insogna K, Peacock M, Carpenter TO. Prolonged Correction of Serum Phosphorus in Adults With X-Linked Hypophosphatemia Using Monthly Doses of KRN23. The Journal Of Clinical Endocrinology & Metabolism 2015, 100: 2565-2573. PMID: 25919461, PMCID: PMC4495171, DOI: 10.1210/jc.2015-1551.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedDose-Response Relationship, DrugDrug Administration ScheduleFamilial Hypophosphatemic RicketsFemaleFibroblast Growth Factor-23Fibroblast Growth FactorsGlomerular Filtration RateHumansImmunoglobulin GMaleMiddle AgedPhosphorusRecombinant ProteinsTreatment OutcomeYoung AdultConceptsTmP/GFRSerum PiNormal rangeOpen-label phase 1/2 studyElevated fibroblast growth factor 23Fibroblast growth factor 23Phase 1/2 studyDose-escalation studyGlomerular filtration ratePre-dose levelsGrowth factor 23Favorable safety profileMain outcome measuresProportion of subjectsAcademic medical centerPeak PiSerum inorganic phosphorusPg/mLUrinary calciumDose escalationFactor 23Monthly dosesSerum phosphorusDihydroxyvitamin DSafety profile
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
1999
Changes in Bone Turnover in Young Women Consuming Different Levels of Dietary Protein1
Kerstetter J, Mitnick M, Gundberg C, Caseria D, Ellison A, Carpenter T, Insogna K. Changes in Bone Turnover in Young Women Consuming Different Levels of Dietary Protein1. The Journal Of Clinical Endocrinology & Metabolism 1999, 84: 1052-1055. PMID: 10084594, DOI: 10.1210/jcem.84.3.5552.Peer-Reviewed Original ResearchUrinary N-telopeptide excretionBone-specific alkaline phosphataseN-telopeptide excretionUrinary calcium excretionBone turnoverLow-protein dietCalcium excretionUrinary calciumProtein dietBone resorptionDietary proteinYoung womenHealthy young womenNegative calcium balanceLow protein intakeHigh-protein dietAlkaline phosphataseSecondary hyperparathyroidismSerum PTHSerum osteocalcinDihydroxyvitamin DCalcium balanceProtein intakeCompensatory increaseDay 4
1992
Synthetic 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
1990
Vitamin D metabolism in chronic childhood hypoparathyroidism: Evidence for a direct regulatory effect of calcium
Carpenter T, Insogna K, Boulware S, Mitnick M. Vitamin D metabolism in chronic childhood hypoparathyroidism: Evidence for a direct regulatory effect of calcium. The Journal Of Pediatrics 1990, 116: 252-257. PMID: 2299496, DOI: 10.1016/s0022-3476(05)82883-5.Peer-Reviewed Original Research
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
Humoral Hypercalcemia of Malignancy in Canine Lymphosarcoma*
Weir EC, Norrdin RW, Matus RE, Brooks MB, Broadus AE, Mitnick M, Johnston SD, Insogna KL. Humoral Hypercalcemia of Malignancy in Canine Lymphosarcoma*. Endocrinology 1988, 122: 602-608. PMID: 2828006, DOI: 10.1210/endo-122-2-602.Peer-Reviewed Original ResearchConceptsAdenylate cyclase-stimulating activityHypercalcemic dogsCanine lymphosarcomaFractional phosphorus excretionEvidence of tumorQuantitative bone histomorphometryBone-resorbing factorsImmunoreactive PTH levelsPathogenesis of hypercalcemiaIliac crest biopsiesTumor tissue extractsCyclase-stimulating activityBone histomorphometric findingsCalcium excretionPTH levelsHumoral hypercalcemiaDihydroxyvitamin DBone resorptionHistomorphometric findingsBone histomorphometryPTH receptorBiopsy siteCrest biopsiesTumor extractsCompensatory increaseEnhanced Production Rate of 1,25-Dihydroxyvitamin D in Sarcoidosis*
INSOGNA K, DREYER B, MITNICK M, ELLISON A, BROADUS A. Enhanced Production Rate of 1,25-Dihydroxyvitamin D in Sarcoidosis*. The Journal Of Clinical Endocrinology & Metabolism 1988, 66: 72-75. PMID: 3335611, DOI: 10.1210/jcem-66-1-72.Peer-Reviewed Original Research
1985
Sensitivity of the Parathyroid Hormone–1, 25-Dihydroxyvitamin D Axis to Variations in Calcium Intake in Patients with Primary Hyperparathyroidism
Insogna K, Mitnick M, Stewart A, Burtis W, Mallette L, Broadus A. Sensitivity of the Parathyroid Hormone–1, 25-Dihydroxyvitamin D Axis to Variations in Calcium Intake in Patients with Primary Hyperparathyroidism. New England Journal Of Medicine 1985, 313: 1126-1130. PMID: 2995810, DOI: 10.1056/nejm198510313131805.Peer-Reviewed Original ResearchConceptsPrimary hyperparathyroidismParathyroid functionParathyroid hormone-vitamin D axisAutonomous parathyroid functionNephrogenous cyclic AMPImmunoreactive parathyroid hormoneNormal dietary intakeExtracellular calcium concentrationParathyroid hormone 1Calcium excretionCalcium intakeUnselected patientsSerum levelsParathyroid hormoneDihydroxyvitamin DDietary calciumPlasma levelsDietary intakePhysiologic amountsHyperparathyroidismPatientsHormone 1Calcium concentrationCyclic AMPSignificant reductionElevated Production Rate of 1,25-Dihydroxyvitamin D in Patients with Absorptive Hypercalciuria*
INSOGNA K, BROADUS A, DREYER B, ELLISON A, GERTNER J. Elevated Production Rate of 1,25-Dihydroxyvitamin D in Patients with Absorptive Hypercalciuria*. The Journal Of Clinical Endocrinology & Metabolism 1985, 61: 490-495. PMID: 2991323, DOI: 10.1210/jcem-61-3-490.Peer-Reviewed Original ResearchConceptsAbsorptive hypercalciuriaMicrograms/dayNormal subjectsMetabolic clearancePlasma radioactivityMean steady-state concentrationMCR valuesHypercalciuric patientsCalcium intakeDihydroxyvitamin DSerial measurementsHypercalciuriaPatientsConstant infusionConflicting resultsClearanceSteady-state concentrationsElevations in Circulating 1,25-Dihydroxyvitamin D in Three Patients with Lymphoma-Associated Hypercalcemia*
ROSENTHAL N, INSOGNA K, GODSALL J, GAC A, SMALDONE L, WALDRON J, STEWART A. Elevations in Circulating 1,25-Dihydroxyvitamin D in Three Patients with Lymphoma-Associated Hypercalcemia*. The Journal Of Clinical Endocrinology & Metabolism 1985, 60: 29-33. PMID: 3871092, DOI: 10.1210/jcem-60-1-29.Peer-Reviewed Original ResearchConceptsDihydroxyvitamin DBone marrow biopsyElevated plasma levelsImmunoreactive PTH levelsUrinary cAMP excretionVitamin D metabolitesAdenylate cyclase-stimulating activityCyclase-stimulating activityPTH levelsRadionuclide scansMedical therapyMalignant lymphomaSerum calciumSurgical excisionMarrow biopsyCertain patientsRapid normalizationSplenic lymphomaSystemic mediatorsUrinary excretionD metabolitesPlasma levelsCAMP excretionTumor extractsPatients
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 studiesEvidenceAbnormalitiesWeeksBiochemical and Histomorphometric Characterization of a Rat Model for Humoral Hypercalcemia of Malignancy*
INSOGNA K, STEWART A, VIGNERY A, WEIR E, NAMNUM P, BARON R, KIRKWOOD J, DEFTOS L, BROADUS A. Biochemical and Histomorphometric Characterization of a Rat Model for Humoral Hypercalcemia of Malignancy*. Endocrinology 1984, 114: 888-896. PMID: 6546543, DOI: 10.1210/endo-114-3-888.Peer-Reviewed Original ResearchConceptsTumor-bearing animalsBone-resorbing activityHumoral hypercalcemiaDay 13Dihydroxyvitamin D valuesFractional phosphorus excretionQuantitative bone histomorphometryAction of PTHImmunoreactive PTH levelsTumor-bearing groupLeydig cell tumorMale Fisher ratsBone cell functionPTH levelsNephrogenous cAMPDihydroxyvitamin DTumor transplantationCell tumorsBone resorptionBone histomorphometryRat modelTumor groupControl animalsFisher ratsMarked suppressionA 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