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
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 subscale
2017
The Effect of Dietary Glycemic Properties on Markers of Inflammation, Insulin Resistance, and Body Composition in Postmenopausal American Women: An Ancillary Study from a Multicenter Protein Supplementation Trial
Stojkovic V, Simpson CA, Sullivan RR, Cusano AM, Kerstetter JE, Kenny AM, Insogna KL, Bihuniak JD. The Effect of Dietary Glycemic Properties on Markers of Inflammation, Insulin Resistance, and Body Composition in Postmenopausal American Women: An Ancillary Study from a Multicenter Protein Supplementation Trial. Nutrients 2017, 9: 484. PMID: 28492492, PMCID: PMC5452214, DOI: 10.3390/nu9050484.Peer-Reviewed Original ResearchConceptsMarkers of inflammationInsulin resistanceGI/GLBody compositionAncillary studiesLean massPRO groupSignificant associationGlycemic load dietDouble-blind trialFat mass ratioTotal lean massTotal fat massPostmenopausal American womenTrunk lean massAge-related alterationsWhey protein supplementLoad dietInflammatory markersSerum CRPChronic inflammationIL-6Fat massSupplementation trialBone density
2015
Pharmacokinetics and pharmacodynamics of a human monoclonal anti‐FGF23 antibody (KRN23) in the first multiple ascending‐dose trial treating adults with X‐linked hypophosphatemia
Zhang X, Imel EA, Ruppe MD, Weber TJ, Klausner MA, Ito T, Vergeire M, Humphrey J, Glorieux FH, Portale AA, Insogna K, Carpenter TO, Peacock M. Pharmacokinetics and pharmacodynamics of a human monoclonal anti‐FGF23 antibody (KRN23) in the first multiple ascending‐dose trial treating adults with X‐linked hypophosphatemia. The Journal Of Clinical Pharmacology 2015, 56: 176-185. PMID: 26073451, PMCID: PMC5042055, DOI: 10.1002/jcph.570.Peer-Reviewed Original ResearchConceptsConcentration-time curveSerum fibroblast growth factor 23Multiple ascending dose trialFibroblast growth factor 23Ascending dose trialHuman IgG1 monoclonal antibodyLow-normal serumRecombinant human IgG1 monoclonal antibodyDihydroxyvitamin D concentrationsGlomerular filtration rateGrowth factor 23Serum inorganic phosphorusSerum Pi concentrationIgG1 monoclonal antibodyFGF23 antibodyDose adjustmentFactor 23Serum PiFiltration ratePhosphate reabsorptionBone markersKRN23D concentrationsNormal serumMonoclonal antibodies
2014
Increased bone resorption during tenofovir plus lopinavir/ritonavir therapy in Chinese individuals with HIV
Hsieh E, Fraenkel L, Xia W, Hu YY, Han Y, Insogna K, Yin MT, Xie J, Zhu T, Li T. Increased bone resorption during tenofovir plus lopinavir/ritonavir therapy in Chinese individuals with HIV. Osteoporosis International 2014, 26: 1035-1044. PMID: 25224293, PMCID: PMC4334679, DOI: 10.1007/s00198-014-2874-3.Peer-Reviewed Original ResearchConceptsHuman immunodeficiency virusLopinavir/ritonavirBone turnover markersBone resorption marker levelsResorption marker levelsNon-Chinese populationsAntiretroviral therapyTreatment failureImmunodeficiency virusMarker levelsSkeletal metabolismC-terminal cross-linking telopeptideLopinavir/ritonavir therapyTreatment-naïve patientsFirst-line therapyBone resorption markersProcollagen type 1Multi-center trialPlasma samplesChinese individualsN-terminal propeptideType 1 collagenRitonavir therapyTurnover markersResorption markers
2013
Dietary Protein-Induced Increases in Urinary Calcium Are Accompanied by Similar Increases in Urinary Nitrogen and Urinary Urea: A Controlled Clinical Trial
Bihuniak JD, Simpson CA, Sullivan RR, Caseria DM, Kerstetter JE, Insogna KL. Dietary Protein-Induced Increases in Urinary Calcium Are Accompanied by Similar Increases in Urinary Nitrogen and Urinary Urea: A Controlled Clinical Trial. Journal Of The Academy Of Nutrition And Dietetics 2013, 113: 447-451. PMID: 23438496, PMCID: PMC5868414, DOI: 10.1016/j.jand.2012.11.002.Peer-Reviewed Original ResearchConceptsBone turnover markersDietary protein intakeUrinary creatinineUrinary calciumProtein intakeUrinary ureaTurnover markersUrinary nitrogenNutrition intervention trialMaltodextrin controlPostmenopausal womenIntervention trialsClinical trialsUrinary metabolitesCreatinineDay 0Whey supplementationWhey supplementsIntakeSample t-testSimilar increaseTrialsT-testSupplementationMarkers
2010
The Effect of Dietary Protein on Intestinal Calcium Absorption in Rats
Gaffney-Stomberg E, Sun BH, Cucchi CE, Simpson CA, Gundberg C, Kerstetter JE, Insogna KL. The Effect of Dietary Protein on Intestinal Calcium Absorption in Rats. Endocrinology 2010, 151: 1071-1078. PMID: 20147526, PMCID: PMC2840679, DOI: 10.1210/en.2009-0744.Peer-Reviewed Original ResearchConceptsIntestinal Ca absorptionCa absorptionHigh-protein dietUrinary calciumBrush border membrane vesiclesProtein intakeFemale Sprague-Dawley ratsProtein dietProtein intake resultsIntestinal calcium absorptionDietary protein intakeHigh protein intakeSprague-Dawley ratsLow-protein groupHigh protein groupDietary protein effectsCalcium absorptionAcute increaseDawley ratsDuodenal mucosaIntake resultsRatsCa balanceTranscellular CaDietary protein
2009
Survey of the Enthesopathy of X-Linked Hypophosphatemia and Its Characterization in Hyp Mice
Liang G, Katz LD, Insogna KL, Carpenter TO, Macica CM. Survey of the Enthesopathy of X-Linked Hypophosphatemia and Its Characterization in Hyp Mice. Calcified Tissue International 2009, 85: 235-246. PMID: 19609735, PMCID: PMC2988401, DOI: 10.1007/s00223-009-9270-6.Peer-Reviewed Original ResearchMeSH KeywordsAchilles TendonAdolescentAdultAgedAnimalsBiomarkersCalcinosisChildDisease Models, AnimalDisease ProgressionFamilial Hypophosphatemic RicketsFemaleFibroblast Growth Factor-23Fibroblast Growth FactorsGenetic Diseases, X-LinkedHumansMiceMice, Inbred C57BLMiddle AgedPatellar LigamentPhenotypeQuadriceps MuscleRadiographyRheumatic DiseasesTendinopathyTendonsYoung AdultConceptsFGF-23Fibroblast growth factor receptor 3Hyp miceMajority of patientsHigh circulating levelsPhosphate-regulating hormoneBone spur formationTendon insertion siteGrowth factor receptor 3Insertion siteLigament insertion sitesCirculating LevelsPhosphate excretionBone-forming osteoblastsHeterotopic calcificationOsteophyte formationHistological examinationMurine modelReceptor 3Spur formationHypophosphatemiaEnthesis fibrocartilageBone mineralizationBiochemical milieuMice
2005
Glucose-dependent insulinotropic polypeptide receptor knockout mice have altered bone turnover
Xie D, Cheng H, Hamrick M, Zhong Q, Ding KH, Correa D, Williams S, Mulloy A, Bollag W, Bollag RJ, Runner RR, McPherson JC, Insogna K, Isales CM. Glucose-dependent insulinotropic polypeptide receptor knockout mice have altered bone turnover. Bone 2005, 37: 759-769. PMID: 16219496, DOI: 10.1016/j.bone.2005.06.021.Peer-Reviewed Original ResearchConceptsGlucose-dependent insulinotropic polypeptideGipr-/- miceReceptor knockout miceBone turnoverBone massGlucose-dependent insulinotropic polypeptide receptor knockout miceKnockout miceRole of GIPGIP receptor knockout miceEffects of GIPLow bone massBiomechanical bone strengthWild-type miceLean body massEarly age-related changesAge-related changesIncretin hormonesSerum markersMeal ingestionInsulinotropic polypeptideAnabolic effectsBone densityBone microarchitectureNutrient ingestionVivo effects
2002
Circulating Levels of Interleukin-6 Soluble Receptor Predict Rates of Bone Loss in Patients with Primary Hyperparathyroidism
Nakchbandi IA, Mitnick MA, Lang R, Gundberg C, Kinder B, Insogna K. Circulating Levels of Interleukin-6 Soluble Receptor Predict Rates of Bone Loss in Patients with Primary Hyperparathyroidism. The Journal Of Clinical Endocrinology & Metabolism 2002, 87: 4946-4951. PMID: 12414855, DOI: 10.1210/jc.2001-011814.Peer-Reviewed Original ResearchConceptsBone lossIL-6sRTotal femurIL-6IL-6 soluble receptorPrimary hyperparathyroidism resultsYearly bone lossSubset of patientsUntreated hyperparathyroidismDisease activityPrimary hyperparathyroidismUpper tertileCytokine axisHyperparathyroidismSoluble receptorPatientsBiochemical markersClassical biochemical markersWhole groupFemurPredict rateGreater rateRecent studiesTertileGroupEvidence that the IL-6/IL-6 Soluble Receptor Cytokine System Plays a Role in the Increased Skeletal Sensitivity to PTH in Estrogen-Deficient Women
Masiukiewicz US, Mitnick M, Gulanski BI, Insogna KL. Evidence that the IL-6/IL-6 Soluble Receptor Cytokine System Plays a Role in the Increased Skeletal Sensitivity to PTH in Estrogen-Deficient Women. The Journal Of Clinical Endocrinology & Metabolism 2002, 87: 2892-2898. PMID: 12050269, DOI: 10.1210/jcem.87.6.8577.Peer-Reviewed Original ResearchConceptsEstrogen-deficient womenIL-6/ILSkeletal sensitivityIL-6IL-6sREstrogen deficiencyCytokine systemIL-6 soluble receptorUrine N-telopeptideAction of PTHPrevious animal studiesNTx excretionPTH infusionPostmenopausal womenSerum calciumN-telopeptideCytokine productionTNF-alphaExaggerated increaseIL-1betaHormonal statusBaseline valuesSoluble receptorAnimal studiesColony-stimulating factor-1High Bone Density Due to a Mutation in LDL-Receptor–Related Protein 5
Boyden LM, Mao J, Belsky J, Mitzner L, Farhi A, Mitnick MA, Wu D, Insogna K, Lifton RP. High Bone Density Due to a Mutation in LDL-Receptor–Related Protein 5. New England Journal Of Medicine 2002, 346: 1513-1521. PMID: 12015390, DOI: 10.1056/nejmoa013444.Peer-Reviewed Original ResearchMeSH KeywordsBiomarkersBone DensityCase-Control StudiesChromosomes, Human, Pair 11FemaleGenes, DominantGenotypeHumansIntercellular Signaling Peptides and ProteinsLDL-Receptor Related ProteinsLow Density Lipoprotein Receptor-Related Protein-5MaleMandibleMutation, MissenseOsteogenesisPalatePedigreePoint MutationProteinsProto-Oncogene ProteinsRadiographyReceptors, LDLSignal TransductionSyndromeWnt ProteinsZebrafish ProteinsConceptsLow-density lipoprotein receptor-related protein 5Higher bone densityProtein 5Bone densityDevelopmental proteinsLipoprotein receptor-related protein 5Fruit flyGenetic analysisDeep mandibleWnt activityTorus palatinusWnt pathwayFunction mutationsWntMajor public health problemNormal glycineBiochemical analysisMutationsTreatment of osteoporosisHigh bone massPublic health problemCodon 171Potential targetAutosomal dominant syndromeGenesTreatment of Osteoporosis and Osteopenia in Long‐term Renal Transplant Patients with Alendronate
Cruz DN, Brickel HM, Wysolmerski JJ, Gundberg CG, Simpson CA, Kliger AS, Lorber MI, Basadonna GP, Friedman AL, Insogna KL, Bia MJ. Treatment of Osteoporosis and Osteopenia in Long‐term Renal Transplant Patients with Alendronate. American Journal Of Transplantation 2002, 2: 62-67. PMID: 12095058, DOI: 10.1034/j.1600-6143.2002.020111.x.Peer-Reviewed Original ResearchConceptsBone mineral densityHigh bone turnoverRenal transplant patientsBone lossBone turnoverTransplant patientsTotal femurLumbar spineLong-term renal transplant patientsLong-term renal transplant recipientsBiochemical markersBiochemical parametersGood renal functionGroup A patientsRenal transplant recipientsBone turnover markersRegional bone mineral densityTreatment of osteoporosisSerum alkaline phosphataseFirst yearBisphosphonate therapyTransplant recipientsAlendronate therapyRenal functionA patients
2001
PARAMETERS OF HIGH BONE-TURNOVER PREDICT BONE LOSS IN RENAL TRANSPLANT PATIENTS: A LONGITUDINAL STUDY1,2
Cruz D, Wysolmerski J, Brickel H, Gundberg C, Simpson C, Mitnick M, Kliger A, Lorber M, Basadonna G, Friedman A, Insogna K, Bia M. PARAMETERS OF HIGH BONE-TURNOVER PREDICT BONE LOSS IN RENAL TRANSPLANT PATIENTS: A LONGITUDINAL STUDY1,2. Transplantation 2001, 72: 83-88. PMID: 11468539, DOI: 10.1097/00007890-200107150-00017.Peer-Reviewed Original ResearchConceptsBone mineral densityPosttransplant bone lossRenal transplant recipientsLong-term renal transplant recipientsDual-energy X-ray absorptiometryRenal transplant patientsBone lossTransplant recipientsBone resorptionBiochemical markersTransplant patientsLumbar spineLong-term renal transplant patientsEnergy X-ray absorptiometryAccelerated bone resorptionElevated urinary levelsUse of cyclosporineElevated biochemical markersPrevious cross-sectional studiesCross-sectional studyX-ray absorptiometryStable bone massPostrenal transplantationAntiresorptive therapyKidney transplantation
2000
Estrogen Modulates Parathyroid Hormone-Induced Interleukin-6 Production in Vivo and in Vitro*
Masiukiewicz U, Mitnick M, Grey A, Insogna K. Estrogen Modulates Parathyroid Hormone-Induced Interleukin-6 Production in Vivo and in Vitro*. Endocrinology 2000, 141: 2526-2531. PMID: 10875254, DOI: 10.1210/endo.141.7.7537.Peer-Reviewed Original Research
1996
Circulating levels of interleukin-6 and tumor necrosis factor-alpha are elevated in primary hyperparathyroidism and correlate with markers of bone resorption--a clinical research center study
Grey A, Mitnick MA, Shapses S, Ellison A, Gundberg C, Insogna K. Circulating levels of interleukin-6 and tumor necrosis factor-alpha are elevated in primary hyperparathyroidism and correlate with markers of bone resorption--a clinical research center study. The Journal Of Clinical Endocrinology & Metabolism 1996, 81: 3450-3454. PMID: 8855783, DOI: 10.1210/jcem.81.10.8855783.Peer-Reviewed Original ResearchConceptsPrimary hyperparathyroidismUntreated primary hyperparathyroidismSerum type ITumor necrosisInterleukin-6Bone resorptionSerum levelsBiochemical markersSerum deoxypyridinolineUrinary deoxypyridinolineUrinary pyridinolineBone lossCarboxyterminal telopeptideSoluble receptorClinical research center studyControl valuesNormal parathyroid functionSuccessful surgical treatmentBone-resorbing cytokinesInterleukin-1 betaType IIntact PTHParathyroid functionSurgical treatmentCenter studyEffects of continuous glucocorticoid infusion on bone metabolism in the rat
King CS, Weir EC, Gundberg CW, Fox J, Insogna KL. Effects of continuous glucocorticoid infusion on bone metabolism in the rat. Calcified Tissue International 1996, 59: 184-191. PMID: 8694896, DOI: 10.1007/s002239900107.Peer-Reviewed Original ResearchConceptsDEX treatmentBone metabolismUrinary calcium/creatinine ratioCalcium/creatinine ratioIntact parathyroid functionLevels of PTHSprague-Dawley ratsTartrate-resistant acid phosphataseParathyroid functionTime-dependent mannerCreatinine ratioSerum calciumBone turnoverContinuous administrationParathyroidectomized animalsSerum concentrationsSupraphysiologic dosesGlucocorticoid infusionDawley ratsFemoral weightHistomorphometric findingsBone massPTX animalsBone volumeDexamethasone