2022
Efficacy of Burosumab in Adults with X-linked Hypophosphatemia (XLH): A Post Hoc Subgroup Analysis of a Randomized Double-Blind Placebo-Controlled Phase 3 Study
Brandi ML, Jan de Beur S, Briot K, Carpenter T, Cheong HI, Cohen-Solal M, Crowley RK, Eastell R, Imanishi Y, Imel EA, Ing SW, Insogna K, Ito N, Javaid K, Kamenicky P, Keen R, Kubota T, Lachmann RH, Perwad F, Pitukcheewanont P, Portale A, Ralston SH, Tanaka H, Weber TJ, Yoo HW, Sun W, Williams A, Nixon A, Takeuchi Y. Efficacy of Burosumab in Adults with X-linked Hypophosphatemia (XLH): A Post Hoc Subgroup Analysis of a Randomized Double-Blind Placebo-Controlled Phase 3 Study. Calcified Tissue International 2022, 111: 409-418. PMID: 35927518, DOI: 10.1007/s00223-022-01006-7.Peer-Reviewed Original ResearchMeSH KeywordsAdultAntibodies, Monoclonal, HumanizedDouble-Blind MethodFamilial Hypophosphatemic RicketsHumansPainTreatment OutcomeConceptsPhase 3 studySubgroup analysisPhysical functionMean serum phosphate concentrationPost-hoc subgroup analysesAdditional efficacy endpointsPlacebo-controlled periodDouble-blind placeboSerum phosphate concentrationEfficacy endpointPain domainPain medicationTreatment armsSymptomatic adultsOpioid/Western OntarioBurosumabPlaceboTest distanceHypophosphatemiaRelevant subgroupsTotal scoreEndpointConfidence intervalsSubgroup variables
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 biopsyContinued Beneficial Effects of Burosumab in Adults with X-Linked Hypophosphatemia: Results from a 24-Week Treatment Continuation Period After a 24-Week Double-Blind Placebo-Controlled Period
Portale AA, Carpenter TO, Brandi ML, Briot K, Cheong HI, Cohen-Solal M, Crowley R, Jan De Beur S, Eastell R, Imanishi Y, Imel EA, Ing S, Ito N, Javaid M, Kamenicky P, Keen R, Kubota T, Lachmann R, Perwad F, Pitukcheewanont P, Ralston SH, Takeuchi Y, Tanaka H, Weber TJ, Yoo HW, Zhang L, Theodore-Oklota C, Mealiffe M, San Martin J, Insogna K. Continued Beneficial Effects of Burosumab in Adults with X-Linked Hypophosphatemia: Results from a 24-Week Treatment Continuation Period After a 24-Week Double-Blind Placebo-Controlled Period. Calcified Tissue International 2019, 105: 271-284. PMID: 31165191, DOI: 10.1007/s00223-019-00568-3.Peer-Reviewed Original ResearchConceptsWeek 48Adverse eventsWeek 24Sustained improvementTreatment-related serious adverse eventsOpen-label treatment periodSafety of burosumabDouble-blind placeboFatal adverse eventsSerious adverse eventsSerum phosphorus levelsPatient-reported outcomesSerum phosphorus concentrationRenal phosphate wastingHuman monoclonal antibodyContinued beneficial effectsHealing of fracturesRare genetic disorderMusculoskeletal morbidityPhysical functionContinuation periodMusculoskeletal impairmentsPhosphate wastingTreatment periodBurosumab
2018
A Randomized, Double‐Blind, Placebo‐Controlled, Phase 3 Trial Evaluating the Efficacy of Burosumab, an Anti‐FGF23 Antibody, in Adults With X‐Linked Hypophosphatemia: Week 24 Primary Analysis
Insogna KL, Briot K, Imel EA, Kamenický P, Ruppe MD, Portale AA, Weber T, Pitukcheewanont P, Cheong HI, de Beur S, Imanishi Y, Ito N, Lachmann RH, Tanaka H, Perwad F, Zhang L, Chen C, Theodore‐Oklota C, Mealiffe M, San Martin J, Carpenter TO, Investigators O. A Randomized, Double‐Blind, Placebo‐Controlled, Phase 3 Trial Evaluating the Efficacy of Burosumab, an Anti‐FGF23 Antibody, in Adults With X‐Linked Hypophosphatemia: Week 24 Primary Analysis. Journal Of Bone And Mineral Research 2018, 33: 1383-1393. PMID: 29947083, DOI: 10.1002/jbmr.3475.Peer-Reviewed Original ResearchConceptsTreatment-related serious adverse eventsMean serum phosphate concentrationWOMAC physical function subscaleFibroblast growth factor 23Intact parathyroid hormoneSerious adverse eventsPhase 3 trialPhysical function subscaleChronic musculoskeletal painGrowth factor 23Serum phosphate concentrationRenal phosphate wastingHuman monoclonal antibodyLower limb deformitiesImportant medical needStiffness subscalePlacebo groupUrine calciumWorst painAdverse eventsWeek 24Dental abscessMusculoskeletal painFactor 23Function subscaleThree-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
2017
Diagnosis and Management of Osteopetrosis: Consensus Guidelines From the Osteopetrosis Working Group
Wu CC, Econs MJ, DiMeglio LA, Insogna KL, Levine MA, Orchard PJ, Miller WP, Petryk A, Rush ET, Shoback DM, Ward LM, Polgreen LE. Diagnosis and Management of Osteopetrosis: Consensus Guidelines From the Osteopetrosis Working Group. The Journal Of Clinical Endocrinology & Metabolism 2017, 102: 3111-3123. PMID: 28655174, DOI: 10.1210/jc.2017-01127.Peer-Reviewed Original ResearchConceptsHematopoietic cell transplantationDisease complicationsConsensus guidelinesHigher bone mineral densityRare metabolic bone diseaseCranial nerve impingementManagement of patientsEvidence-based guidelinesStrength of recommendationsCharacteristic radiographic findingsExpert opinion-based guidelinesQuality of evidenceStandard of careExpert consensus guidelinesBone mineral densityMetabolic bone diseaseOpinion-based guidelinesSevere infantile formNerve impingementRecommendations AssessmentSupportive therapyRadiographic findingsAreas of diagnosisCell transplantationDental disease
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 variablesProlonged 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
2013
Denosumab for Patients With Persistent or Relapsed Hypercalcemia of Malignancy Despite Recent Bisphosphonate Treatment
Hu MI, Glezerman I, Leboulleux S, Insogna K, Gucalp R, Misiorowski W, Yu B, Ying W, Jain RK. Denosumab for Patients With Persistent or Relapsed Hypercalcemia of Malignancy Despite Recent Bisphosphonate Treatment. Journal Of The National Cancer Institute 2013, 105: 1417-1420. PMID: 23990665, PMCID: PMC3776443, DOI: 10.1093/jnci/djt225.Peer-Reviewed Original ResearchConceptsHypercalcemia of malignancyBisphosphonate treatmentResponse durationDay 10Albumin-corrected serum calciumTumor-induced bone resorptionIntravenous bisphosphonate treatmentPrespecified interim analysisMedian response durationProportion of patientsKaplan-Meier methodNew treatment optionsDenosumab initiationIntravenous bisphosphonatesSubcutaneous denosumabPrimary endpointRenal failureComplete responseSerum calciumTreatment optionsHCM patientsBone resorptionDenosumabInterim analysisPatients
2008
Orthopaedic Management Improves the Rate of Early Osteoporosis Treatment After Hip Fracture
Miki RA, Oetgen ME, Kirk J, Insogna KL, Lindskog DM. Orthopaedic Management Improves the Rate of Early Osteoporosis Treatment After Hip Fracture. Journal Of Bone And Joint Surgery 2008, 90: 2346-2353. PMID: 18978403, DOI: 10.2106/jbjs.g.01246.Peer-Reviewed Original ResearchConceptsPrimary care physiciansHip fractureRate of treatmentCare physiciansOsteoporosis managementOsteoporosis treatmentOrthopaedic surgeonsOsteoporosis clinicPercentage of patientsManagement of osteoporosisMost patientsPharmacologic treatmentOsteoporosis educationOrthopaedic managementOrthopaedic teamIntervention groupPatientsOsteoporosisPhysiciansSurgeonsMonthsTreatmentClinicLower ratesFracturesAn Aerobic Weight-Loaded Pilot Exercise Intervention for Breast Cancer Survivors: Bone Remodeling and Body Composition Outcomes
Knobf MT, Insogna K, DiPietro L, Fennie K, Thompson AS. An Aerobic Weight-Loaded Pilot Exercise Intervention for Breast Cancer Survivors: Bone Remodeling and Body Composition Outcomes. Biological Research For Nursing 2008, 10: 34-43. PMID: 18705153, PMCID: PMC3540790, DOI: 10.1177/1099800408320579.Peer-Reviewed Original ResearchMeSH KeywordsAbsorptiometry, PhotonAnalysis of VarianceBody CompositionBody WeightBone ResorptionBreast NeoplasmsClinical Nursing ResearchCollagen Type IExerciseExercise TherapyFeasibility StudiesFemaleHumansMiddle AgedObesityOsteocalcinPerimenopausePilot ProjectsSurvivorsTime FactorsTreatment OutcomeWeight LiftingConceptsBreast cancer survivorsExercise interventionCancer survivorsBone remodelingBone lossFat massBody compositionTreadmill 3 times/weekDual-energy absorptiometry scansWeight gainNovel exercise interventionPilot exercise interventionYears of menopauseAdjuvant endocrine therapyBody composition outcomesOne-group pre-posttest designTimes/weekSerum NTxEndocrine therapySerum osteocalcinMean ageSerum biomarkersBone massHigh adherenceHigh risk