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
2020
Burosumab 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 healthOR29-01 Long-Term Safety in Adults with X-Linked Hypophosphatemia (XLH) Treated with Burosumab, a Fully Human Monoclonal Antibody Against FGF23: Final Results of a Phase 3 Trial
Perwad F, Portale A, Carpenter T, Briot K, Imel E, Kamenicky P, Weber T, Pitukcheewanont P, Cheong H, De Beur S, Imanishi Y, Ito N, Lachmann R, Tanaka H, Zhang L, Skrinar A, Rees L, Insogna K. OR29-01 Long-Term Safety in Adults with X-Linked Hypophosphatemia (XLH) Treated with Burosumab, a Fully Human Monoclonal Antibody Against FGF23: Final Results of a Phase 3 Trial. Journal Of The Endocrine Society 2020, 4: or29-01. PMCID: PMC7209551, DOI: 10.1210/jendso/bvaa046.147.Peer-Reviewed Original ResearchYears of ageSerum phosphorusWeek 96Dose reductionLong-term safety resultsTreatment-emergent adverse eventsMonoclonal antibodiesBaseline serum phosphorusHuman IgG1 monoclonal antibodyMean iPTH levelPhase 3 trialLong-term safetyHuman monoclonal antibodyConditional marketing authorizationMonths of ageIgG1 monoclonal antibodyIPTH levelsPlacebo groupAdverse eventsTreatment withdrawalWeek 24Radiographic evidenceMulticenter studyBurosumab treatmentMild hyperphosphatemiaOR29-06 Burosumab Improves Biochemical, Skeletal, and Clinical Features of Tumor-Induced Osteomalacia Syndrome
Carpenter T, Miller P, Weber T, Peacock M, Insogna K, Kumar R, Luca D, Cimms T, Roberts M, de Beur S. OR29-06 Burosumab Improves Biochemical, Skeletal, and Clinical Features of Tumor-Induced Osteomalacia Syndrome. Journal Of The Endocrine Society 2020, 4: or29-06. PMCID: PMC7208350, DOI: 10.1210/jendso/bvaa046.403.Peer-Reviewed Original ResearchTumor-induced osteomalaciaCutaneous skeletal hypophosphatemia syndromeSerious adverse eventsAdverse eventsSerum phosphorusBone biopsyPhysical functioningMean physical component summary scoreOpen-label phase 2 studyPhysical component summary scoreOsteoid volume/bone volumeSurface/bone surfaceProximal muscle functionBrief Pain InventoryOsteoid surface/bone surfacePhase 2 studyComponent summary scoresTmP/GFRCrest bone biopsiesRenal phosphate wastingHuman monoclonal antibodyMineralization lag timeQuality of lifeExcess FGF23Bone scan
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 biopsyOR13-1 Burosumab Improves the Biochemical, Skeletal, and Clinical Symptoms of Tumor-Induced Osteomalacia Syndrome
De Beur S, Miller P, Weber T, Peacock M, Insogna K, Kumar R, Luca D, Theodore-Oklota C, Lampl K, San Martin J, Carpenter T. OR13-1 Burosumab Improves the Biochemical, Skeletal, and Clinical Symptoms of Tumor-Induced Osteomalacia Syndrome. Journal Of The Endocrine Society 2019, 3: or13-1. PMCID: PMC6554835, DOI: 10.1210/js.2019-or13-1.Peer-Reviewed Original ResearchMineralization lag timeTumor-induced osteomalaciaSerum phosphorusAdverse eventsOsteoid thicknessTumor progressionBone biopsyDose intervalMean physical component summary scoreOpen-label phase 2 studyPP groupPhysical component summary scoreOsteoid volume/bone volumeSurface/bone surfaceMean serum phosphorusPhase 2 studySerious adverse eventsOsteoid surface/bone surfaceComponent summary scoresCrest bone biopsiesMean percentage changeEpidermal nevus syndromeRenal phosphate wastingHuman monoclonal antibodyOS/BS
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
Effect of Paricalcitol on Circulating Parathyroid Hormone in X-Linked Hypophosphatemia: A Randomized, Double-Blind, Placebo-Controlled Study
Carpenter TO, Olear EA, Zhang JH, Ellis BK, Simpson CA, Cheng D, Gundberg CM, Insogna KL. Effect of Paricalcitol on Circulating Parathyroid Hormone in X-Linked Hypophosphatemia: A Randomized, Double-Blind, Placebo-Controlled Study. The Journal Of Clinical Endocrinology & Metabolism 2014, 99: 3103-3111. PMID: 25029424, PMCID: PMC4154090, DOI: 10.1210/jc.2014-2017.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAlkaline PhosphataseBone Density Conservation AgentsChildDouble-Blind MethodErgocalciferolsFamilial Hypophosphatemic RicketsFemaleFibroblast Growth Factor-23Fibroblast Growth FactorsHumansHyperparathyroidismMaleMiddle AgedParathyroid HormonePhosphorusPlacebosProspective StudiesTreatment OutcomeVitamin DYoung AdultConceptsRenal phosphate thresholdGlomerular filtration rateBone scanSerum phosphorusFiltration rateXLH patientsEffect of paricalcitolUse of paricalcitolPlacebo-treated subjectsElevated PTH levelsSerum calcium levelsSuppression of PTHHospital research unitSerum alkaline phosphatase activityPTH levelsCreatinine levelsSecondary outcomesStandard therapyUrinary calciumPlacebo subjectsParathyroid hormoneSerum calciumAlkaline phosphatase activityD levelsSkeletal improvement
1996
24,25 Dihydroxyvitamin D supplementation corrects hyperparathyroidism and improves skeletal abnormalities in X-linked hypophosphatemic rickets--a clinical research center study
Carpenter TO, Keller M, Schwartz D, Mitnick M, Smith C, Ellison A, Carey D, Comite F, Horst R, Travers R, Glorieux FH, Gundberg CM, Poole AR, Insogna KL. 24,25 Dihydroxyvitamin D supplementation corrects hyperparathyroidism and improves skeletal abnormalities in X-linked hypophosphatemic rickets--a clinical research center study. The Journal Of Clinical Endocrinology & Metabolism 1996, 81: 2381-2388. PMID: 8964881, DOI: 10.1210/jcem.81.6.8964881.Peer-Reviewed Original ResearchConceptsD3 supplementationStandard treatmentSkeletal lesionsClinical research center studyCorrection of hyperparathyroidismImprovement of ricketsPlacebo-controlled trialD supplementationRachitic abnormalitiesNephrogenous cAMPPTH secretionStandard therapyPTH valuesSerum phosphorusCenter studyRadiographic featuresBone biopsyOsteoid surfaceBone diseaseMurine modelHypophosphatemic ricketsUseful adjunctCalcium homeostasisHyperparathyroidismXLH
1990
Treatment of humoral hypercalcemia of malignancy in rats with inhibitors of carbonic anhydrase
Brown G, Morris C, Mitnick M, Insogna K. Treatment of humoral hypercalcemia of malignancy in rats with inhibitors of carbonic anhydrase. Journal Of Bone And Mineral Research 1990, 5: 1037-1041. PMID: 1964358, DOI: 10.1002/jbmr.5650051007.Peer-Reviewed Original ResearchConceptsSerum calciumBone resorptionHumoral hypercalcemiaCarbonic anhydrase inhibitorsNephrogenous cyclic AMP excretionCyclic AMP excretionMean serum calciumOsteoclastic bone resorptionDrug-treated animalsLeydig cell tumorMechanism of actionUrine phosphorusUrine calciumSerum phosphorusCell tumorsAcetazolamide treatmentHypercalcemiaSignificant fallFisher ratsObserved hypercalcemiaResorptionDirect inhibitionSignificant riseMalignancyRats
1982
Influence of pregnancy on immunoreactive parathyroid hormone levels
Gillette M, Insogna K, Lewis A, Baran D. Influence of pregnancy on immunoreactive parathyroid hormone levels. Calcified Tissue International 1982, 34: 9-12. PMID: 6279256, DOI: 10.1007/bf02411200.Peer-Reviewed Original ResearchConceptsImmunoreactive PTHTubular maximum phosphate reabsorptionImmunoreactive parathyroid hormone levelsAge-matched female controlsHealthy pregnant patientsNephrogenous cAMP excretionParathyroid hormone metabolismHealthy age-matched female controlsParathyroid hormone levelsInfluence of pregnancySignificant increaseBiological effectsIPTH levelsPregnant patientsCreatinine clearanceUrinary calciumCreatinine ratioPTH metabolismSerum calciumSerum phosphorusThird trimesterVitamin DBlood levelsBone resorptionPhosphate reabsorption