2018
The contribution of cross-talk between the cell-surface proteins CD36 and CD47–TSP-1 in osteoclast formation and function
Koduru SV, Sun BH, Walker JM, Zhu M, Simpson C, Dhodapkar M, Insogna KL. The contribution of cross-talk between the cell-surface proteins CD36 and CD47–TSP-1 in osteoclast formation and function. Journal Of Biological Chemistry 2018, 293: 15055-15069. PMID: 30082316, PMCID: PMC6166722, DOI: 10.1074/jbc.ra117.000633.Peer-Reviewed Original ResearchConceptsOsteoclast formationTSP-1Competitive NO synthase inhibitorPro-osteoclastogenic effectAntibody-mediated blockadeNitroarginine methyl esterNO synthase inhibitorNitric Oxide SignalingPTH infusionDifferentiation 47Parathyroid hormoneBone resorptionFemale miceHypercalcemic responseOsteoclast maturationSynthase inhibitorResorptive activitySynthetic agonistsCD36Osteoclast progenitorsMiceInhibitory effectCD47OsteoclastsWT osteoblastsAssociations among circulating colony-stimulating factor-1, estrogen, and bone mineral density in postmenopausal women
Haas AV, Cong E, Simpson CA, Sukumar N, Deng Y, Insogna KL. Associations among circulating colony-stimulating factor-1, estrogen, and bone mineral density in postmenopausal women. Menopause The Journal Of The North American Menopause Society 2018, 25: 197-201. PMID: 28816930, DOI: 10.1097/gme.0000000000000974.Peer-Reviewed Original ResearchConceptsBone mineral densityEstrogen-deficient womenMineral densityBone lossColony-stimulating factor-1Kronos Early Estrogen Prevention StudyPostmenopausal bone lossPlacebo-controlled studyOsteoclastic bone resorptionFactor 1CSF-1 levelsCSF-1Estrogen replacementEstrogen therapyPlacebo groupPostmenopausal womenCardiovascular endpointsSerum levelsFemoral neckBone resorptionPrevention StudyAncillary studiesTreatment groupsWomenSignificant correlation
2016
Longitudinal increase in vitamin D binding protein levels after initiation of tenofovir/lamivudine/efavirenz among individuals with HIV
Hsieh E, Fraenkel L, Han Y, Xia W, Insogna KL, Yin MT, Zhu T, Cheng X, Li T. Longitudinal increase in vitamin D binding protein levels after initiation of tenofovir/lamivudine/efavirenz among individuals with HIV. AIDS 2016, 30: 1935-1942. PMID: 27124896, PMCID: PMC4949136, DOI: 10.1097/qad.0000000000001131.Peer-Reviewed Original ResearchConceptsTenofovir disoproxil fumarateVitamin DProcollagen type 1 N-terminal propeptideInitiation of TDFTenofovir/lamivudine/efavirenzVitamin D binding protein (VDBP) levelsCollagen type 1 cross-linked C-telopeptideIntact parathyroid hormone levelsCross-linked C-telopeptideIntact parathyroid hormoneParathyroid hormone levelsTotal procollagen type 1 N-terminal propeptideBinding protein levelsProtein levelsMulticenter clinical trialPlasma samplesOngoing multicenter clinical trialsN-terminal propeptideClinical characteristicsParathyroid hormoneBone lossFormation markersDisoproxil fumarateC-telopeptideBone resorption
2015
The Effect of a Whey Protein Supplement on Bone Mass in Older Caucasian Adults
Kerstetter JE, Bihuniak JD, Brindisi J, Sullivan RR, Mangano KM, Larocque S, Kotler BM, Simpson CA, Cusano A, Gaffney-Stomberg E, Kleppinger A, Reynolds J, Dziura J, Kenny AM, Insogna KL. The Effect of a Whey Protein Supplement on Bone Mass in Older Caucasian Adults. The Journal Of Clinical Endocrinology & Metabolism 2015, 100: 2214-2222. PMID: 25844619, PMCID: PMC4454800, DOI: 10.1210/jc.2014-3792.Peer-Reviewed Original ResearchConceptsBone mineral densityBone resorptionL-spine bone mineral densitySelf-reported protein intakeDual-energy X-ray absorptiometryTruncal lean massPlacebo-controlled trialGlomerular filtration rateBody mass indexProtein supplementationC-terminal telopeptideX-ray absorptiometryFat-free massWhey protein supplementHigh-protein dietHealthy older adultsOlder Caucasian adultsUrine calciumRenal functionMass indexSkeletal healthUsual dietFiltration rateMineral densityBone mass
2014
Denosumab for Treatment of Hypercalcemia of Malignancy
Hu MI, Glezerman IG, Leboulleux S, Insogna K, Gucalp R, Misiorowski W, Yu B, Zorsky P, Tosi D, Bessudo A, Jaccard A, Tonini G, Ying W, Braun A, Jain RK. Denosumab for Treatment of Hypercalcemia of Malignancy. The Journal Of Clinical Endocrinology & Metabolism 2014, 99: 3144-3152. PMID: 24915117, PMCID: PMC4154084, DOI: 10.1210/jc.2014-1001.Peer-Reviewed Original ResearchConceptsHypercalcemia of malignancyProportion of patientsDay 10Serum calciumBone resorptionCommon serious adverse eventsMedian response durationSerious adverse eventsSerum calcium levelsTreatment of hypercalcemiaDuration of responseNew treatment optionsBisphosphonate therapyPrimary endpointSecondary endpointsAdverse eventsBisphosphonate treatmentDurable responsesComplete responseAdvanced cancerTreatment optionsHematologic malignanciesResponse durationDenosumabCalcium levels
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 analysisPatientsDenosumab for the treatment of bisphosphonate-refractory hypercalcemia of malignancy (HCM).
Hu M, Glezerman I, Leboulleux S, Insogna K, Gucalp R, Misiorowski W, Yu B, Zorsky P, Tosi D, Bessudo A, Jaccard A, Tonini G, Wang H, Braun A, Jain R. Denosumab for the treatment of bisphosphonate-refractory hypercalcemia of malignancy (HCM). Journal Of Clinical Oncology 2013, 31: e20512-e20512. DOI: 10.1200/jco.2013.31.15_suppl.e20512.Peer-Reviewed Original ResearchBone resorptionDay 10RANK ligandTumor-induced bone resorptionUnexpected safety findingsSerious adverse eventsNew treatment optionsDenosumab initiationSubcutaneous denosumabPrimary endpointDurable responsesFirst doseMedian durationSafety findingsAdverse eventsComplete responseMedian timeSerum calciumTreatment optionsDenosumabDay 1CSC levelsDlMedianTreatment
2011
Denosumab for Treatment of Hypercalcemia of Malignancy in Patients with Solid Tumors or Hematological Malignancies Refractory to IV Bisphosphonates: A Single-Arm Multicenter Study
Hu M, Gucalp R, Insogna K, Glezerman I, Leboulleux S, Misiorowski W, Yu B, Ying W, Yeh H. Denosumab for Treatment of Hypercalcemia of Malignancy in Patients with Solid Tumors or Hematological Malignancies Refractory to IV Bisphosphonates: A Single-Arm Multicenter Study. Blood 2011, 118: 2483. DOI: 10.1182/blood.v118.21.2483.2483.Peer-Reviewed Original ResearchHypercalcemia of malignancyDose of denosumabTreatment of hypercalcemiaAdverse eventsBP treatmentInterim analysisDay 10RANK ligandComplete responseAdvanced cancerCSC levelsBone resorptionHematological malignanciesTreatment of HCMSolid tumorsSingle-arm multicenter studyAmgen Inc.Denosumab-treated patientsDoses of denosumabStudy day 10Serious adverse eventsSerum calcium levelsSingle-arm studyStudy days 1Population of patientsDietary protein and skeletal health: a review of recent human research
Kerstetter JE, Kenny AM, Insogna KL. Dietary protein and skeletal health: a review of recent human research. Current Opinion In Lipidology 2011, 22: 16-20. PMID: 21102327, PMCID: PMC4659357, DOI: 10.1097/mol.0b013e3283419441.BooksConceptsSkeletal healthBone healthDietary proteinBone resorptionCalcium retentionInsulin-like growth factor-1Recent human researchOsteoclastic bone resorptionBone mineral densityHigh protein intakeLean body massGrowth factor-1High-protein dietMeta-analysis studyVitamin DDietary calciumCalcium absorptionCalcium metabolismBone metabolismClinical trialsMineral densityBone balanceBone massMetabolic acid loadSystemic pH
2010
Osteoclasts Lacking Rac2 Have Defective Chemotaxis and Resorptive Activity
Itokowa T, Zhu ML, Troiano N, Bian J, Kawano T, Insogna K. Osteoclasts Lacking Rac2 Have Defective Chemotaxis and Resorptive Activity. Calcified Tissue International 2010, 88: 75-86. PMID: 21110188, PMCID: PMC3155765, DOI: 10.1007/s00223-010-9435-3.Peer-Reviewed Original ResearchConceptsTrabecular bone massBone massMature osteoclastsFemoral cortical thicknessTotal bone areaNumber of osteoclastsWild-type miceNormal tooth eruptionNumber of osteoblastsWild-type animalsBone resorptionCortical porosityActin ring formationCortical thicknessTooth eruptionOsteoclast functionResorptive activityDefective chemotaxisBone areaFemale animalsMiceOsteoclastsMigratory rateNormal sizeSignificant differencesSix Weeks of a Low Protein Diet Impairs Calcium Homeostasis
Sullivan R, Rosewater I, Caseria D, O'Brien K, Kerstetter J, Insogna K. Six Weeks of a Low Protein Diet Impairs Calcium Homeostasis. The FASEB Journal 2010, 24: lb356-lb356. DOI: 10.1096/fasebj.24.1_supplement.lb356.Peer-Reviewed Original ResearchLow-protein dietProtein dietCalcium absorptionDual-stable calcium isotopesImpairs calcium homeostasisIntestinal calcium absorptionNegative bone balanceWeek 6.5Diet intervention trialLong-term ingestionUrinary calciumMetabolic kitchenBone lossVitamin DIntervention trialsStable calcium isotopesCalcium metabolismBone resorptionBone balanceIntestinal absorptionWeek 1Skeletal turnoverCalcium homeostasisMineral homeostasisYoung women
2007
The Role of the Receptor Activator of Nuclear Factor-κB Ligand/Osteoprotegerin Cytokine System in Primary Hyperparathyroidism
Nakchbandi IA, Lang R, Kinder B, Insogna KL. The Role of the Receptor Activator of Nuclear Factor-κB Ligand/Osteoprotegerin Cytokine System in Primary Hyperparathyroidism. The Journal Of Clinical Endocrinology & Metabolism 2007, 93: 967-973. PMID: 18073309, PMCID: PMC2266956, DOI: 10.1210/jc.2007-1645.Peer-Reviewed Original ResearchConceptsNuclear factor-kappaB ligandPrimary hyperparathyroidismBone lossReceptor activatorTotal femurIL-6Bone resorptionIL-6 soluble receptorMild primary hyperparathyroidismBone mineral densitySoluble receptor activatorMechanism of actionIL-6sRSRANKL levelsSerum levelsBone turnoverMineral densityCytokine systemSoluble receptorHyperparathyroidismNormal rangeSkeletal responsivenessBiochemical markersPatientsGreater riskDietary protein increases intestinal calcium absorption and improves bone balance: An hypothesis
Kerstetter J, Gaffney E, O'Brien K, Caseria D, Insogna K. Dietary protein increases intestinal calcium absorption and improves bone balance: An hypothesis. International Congress Series 2007, 1297: 204-216. DOI: 10.1016/j.ics.2006.08.027.Peer-Reviewed Original ResearchBone mineral densityIntestinal calcium absorptionHigh-protein dietUrinary calciumBone lossCalcium absorptionProtein dietAccelerated bone lossMost cross-sectional studiesDietary proteinCross-sectional studyLow-protein dietBone turnoverBone resorptionMineral densityBone balanceCalcium studiesCalcium retentionSalutary effectsBone originPrincipal outcomeDietSignificant reductionCalciumResorptionGlucose-dependent insulinotropic peptide-overexpressing transgenic mice have increased bone mass
Xie D, Zhong Q, Ding KH, Cheng H, Williams S, Correa D, Bollag WB, Bollag RJ, Insogna K, Troiano N, Coady C, Hamrick M, Isales CM. Glucose-dependent insulinotropic peptide-overexpressing transgenic mice have increased bone mass. Bone 2007, 40: 1352-1360. PMID: 17321229, DOI: 10.1016/j.bone.2007.01.007.Peer-Reviewed Original ResearchConceptsGlucose-dependent insulinotropic peptideBone massGIP receptorBone resorptionBone formationNutrient ingestionTransgenic miceGIP receptor knockout miceLow bone mass phenotypeReceptor knockout miceBone mass phenotypeSignificant increaseCollagen type I synthesisGIP levelsInsulinotropic peptideAnabolic hormonesOsteoclastic activityMouse modelDietary zincMass phenotypeKnockout miceReceptor signalingReceptors resultsMiceHormone
2006
Effects of glucose-dependent insulinotropic peptide on osteoclast function
Zhong Q, Itokawa T, Sridhar S, Ding KH, Xie D, Kang B, Bollag WB, Bollag RJ, Hamrick M, Insogna K, Isales CM. Effects of glucose-dependent insulinotropic peptide on osteoclast function. AJP Endocrinology And Metabolism 2006, 292: e543-e548. PMID: 17003233, DOI: 10.1152/ajpendo.00364.2006.Peer-Reviewed Original ResearchConceptsGlucose-dependent insulinotropic peptideBone resorptionNutrient ingestionGIP receptorOrgan culture systemBone breakdownEffects of GIPOsteoclast functionMature osteoclastsGlucose-induced insulin secretionGIP receptor transcriptsImmediate postprandial periodBone formationAnti-resorptive effectsGlucose-dependent insulinotropicIntestinal endocrine cellsOsteoclast resorptive activityPostprandial reductionIncretin hormonesInsulinotropic peptidePostprandial periodInsulin secretionResorptive activityOsteoclastic cellsReceptor transcripts
2004
High Protein Diets, Calcium Economy, and Bone Health
Kerstetter J, O'Brien K, Insogna K. High Protein Diets, Calcium Economy, and Bone Health. Topics In Clinical Nutrition 2004, 19: 57-70. DOI: 10.1097/00008486-200401000-00010.Peer-Reviewed Original ResearchHigh-protein dietProtein dietDecrease bone densityUrinary calcium excretionDietary proteinHigh dietary proteinCalcium excretionUrinary calciumBone healthSkeletal healthCalcium economyBone resorptionBone densityLong-term consequencesDietBoneSignificant scientific dataPhysiological mechanismsHealthHumansExcretionResorptionProtein
2003
Dietary protein, calcium metabolism, and skeletal homeostasis revisited
Kerstetter JE, O'Brien KO, Insogna KL. Dietary protein, calcium metabolism, and skeletal homeostasis revisited. American Journal Of Clinical Nutrition 2003, 78: s584-s592. PMID: 12936953, DOI: 10.1093/ajcn/78.3.584s.BooksConceptsIntestinal calcium absorptionDietary protein intakeCalcium absorptionProtein intakeDietary proteinBone resorptionHigher dietary protein intakeSerum parathyroid hormoneUrinary calcium excretionCalcium balance studiesReduced bone densityRecent epidemiologic studiesLow protein intakeDiet-induced changesLow-protein dietCalcium excretionSecondary hyperparathyroidismCalcium intakeUrinary calciumParathyroid hormoneBone lossSkeletal healthCalcium metabolismDietary trialMineral metabolismLow Protein Intake: The Impact on Calcium and Bone Homeostasis in Humans
Kerstetter JE, O'Brien KO, Insogna KL. Low Protein Intake: The Impact on Calcium and Bone Homeostasis in Humans. Journal Of Nutrition 2003, 133: 855s-861s. PMID: 12612169, DOI: 10.1093/jn/133.3.855s.BooksConceptsIntestinal calcium absorptionLow-protein dietCalcium absorptionHigh-protein dietProtein dietSecondary hyperparathyroidismUrinary calciumBone resorptionDietary proteinAdditional urinary calciumDietary protein resultsSerum parathyroid hormoneNutrition intervention trialCalcium balance studiesRecent epidemiological studiesLow protein intakeNutrition intervention studiesParathyroid hormoneBone lossSkeletal healthIntervention trialsCalcium metabolismSkeletal fracturesBone densityLong-term consequences
2002
Overexpression of Parathyroid Hormone‐Related Protein Causes Hypercalcemia but Not Bone Metastases in a Murine Model of Mammary Tumorigenesis*
Wysolmerski JJ, Dann PR, Zelazny E, Dunbar ME, Insogna KL, Guise TA, Perkins AS. Overexpression of Parathyroid Hormone‐Related Protein Causes Hypercalcemia but Not Bone Metastases in a Murine Model of Mammary Tumorigenesis*. Journal Of Bone And Mineral Research 2002, 17: 1164-1170. PMID: 12096830, DOI: 10.1359/jbmr.2002.17.7.1164.Peer-Reviewed Original ResearchConceptsBone metastasesBreast cancer cellsCancer cellsTransgenic miceTumor-bearing transgenic miceParathyroid hormone-related proteinPrimary breast cancerProduction of PTHrPHormone-related proteinWild-type littermatesEffects of PTHrPCause hypercalcemiaWild-type controlsVisceral metastasesSkeletal metastasesParathyroid hormoneBone resorptionArterial circulationBreast cancerDMBA treatmentMammary carcinogenImmunodeficient miceMammary tumorigenesisMurine modelHigh incidence
2001
IL-6 Negatively Regulates IL-11 Production in Vitro and in Vivo
Nakchbandi I, Mitnick M, Masiukiewicz U, Sun B, Insogna K. IL-6 Negatively Regulates IL-11 Production in Vitro and in Vivo. Endocrinology 2001, 142: 3850-3856. DOI: 10.1210/en.142.9.3850.Peer-Reviewed Original ResearchCirculating levels of IL-6Levels of IL-6IL-11IL-6Circulating levelsBone resorptionSteady state mRNA levelsOsteoclast formationFive-day infusionHuman PTH-(1-84Pretreatment of cellsIL-11 levelsResponse to PTHIL-11 productionIncreased osteoclast formationIL-6 levelsPTH-(1-84Saos-2 cellsParathyroid adenomectomyDown-regulationProduction in vitroPrimary hyperparathyroidismPTH excessProduction in vivoSerum levels