2021
An Unanticipated Role for Sphingosine Kinase-2 in Bone and in the Anabolic Effect of Parathyroid Hormone
Walker JM, Yao GQ, Siu E, Zhu M, Sun BH, Simpson C, Insogna KL. An Unanticipated Role for Sphingosine Kinase-2 in Bone and in the Anabolic Effect of Parathyroid Hormone. Endocrinology 2021, 162: bqab042. PMID: 33640975, PMCID: PMC8095390, DOI: 10.1210/endocr/bqab042.Peer-Reviewed Original ResearchConceptsSphk2-/- miceParathyroid hormoneAnabolic responseFemoral trabecular BV/TVLower spinal bone mineral densityTrabecular BV/TVSpinal bone mineral densityDaily parathyroid hormoneFemoral bone volumeSuppression of sclerostinEnd of treatmentNormal bone massBone mineral densityNormal bone remodelingRole of SphK1BV/TVFemale control animalsSphingosine kinase 2Sphingosine kinaseControl miceLow BMDAnabolic effectsBone massMineral densityControl animals
2020
Epidemiology, Pathophysiology, and Genetics of Primary Hyperparathyroidism
Minisola S, Arnold A, Belaya Z, Brandi ML, Clarke BL, Hannan FM, Hofbauer LC, Insogna KL, Lacroix A, Liberman U, Palermo A, Pepe J, Rizzoli R, Wermers R, Thakker RV. Epidemiology, Pathophysiology, and Genetics of Primary Hyperparathyroidism. Journal Of Bone And Mineral Research 2020, 37: 2315-2329. PMID: 36245271, PMCID: PMC10092691, DOI: 10.1002/jbmr.4665.Peer-Reviewed Original ResearchConceptsPrimary hyperparathyroidismFamilial hypocalciuric hypercalcemiaMultiple endocrine neoplasia syndromeCalcium-containing kidney stonesIntestinal calcium hyperabsorptionMore parathyroid glandsParathyroid hormone levelsAsymptomatic primary hyperparathyroidismCalcium-sensing receptorEndocrine neoplasia syndromeNeonatal severe hyperparathyroidismHyperparathyroidism-jaw tumor syndromeJaw tumor syndromeCalcium hyperabsorptionPostmenopausal womenSevere hyperparathyroidismParathyroid hormoneSerum calciumHypocalciuric hypercalcemiaPathophysiologic basisParathyroid cellsParathyroid glandsHormone levelsFiltered loadMetabolic factors
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 osteoblastsChapter 83 The Hypocalcemic Disorders
Gafni R, Insogna K, Carpenter T. Chapter 83 The Hypocalcemic Disorders. 2018, 527-547. DOI: 10.1016/b978-0-12-809963-6.00083-3.ChaptersHypocalcemic disordersParathyroid hormoneVitamin DHypocalcemic conditionsLong-term managementPTH secretionChronic hypocalcemiaNarrow normal rangeCalciotropic hormonesFunctional etiologyClinical manifestationsVitamin D.PTH actionHomeostatic disturbancesNormal rangePhysiologic consequencesClinical scenariosHypocalcemiaMetabolic activationDisordersMolecular actionsEtiologyHormoneFunctional mechanismsTherapy
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 resorptionAn Unusual Case of Rickets and How Whole Exome Sequencing Helped to Correct a Diagnosis
Peter P, Brownstein C, Yao G, Olear E, Simpson C, Agrawal P, Carpenter T, Insogna K. An Unusual Case of Rickets and How Whole Exome Sequencing Helped to Correct a Diagnosis. AACE Clinical Case Reports 2016, 2: ee278-ee283. DOI: 10.4158/ep15944.cr.Peer-Reviewed Original ResearchWhole-exome sequencingForms of ricketsExome sequencingGrowth factor 23Classic clinical featuresClinical suspicionClinical featuresClinical presentationFactor 23Parathyroid hormoneDihydroxyvitamin D3Correct diagnosisMistaken diagnosisUnusual caseNutritional deficienciesRicketsPatientsDiagnosisDiseaseHypophosphatemiaGenetic defectsCompound heterozygotesCYP27B1Gene sequencing technologyXLH
2015
Deletion of Rac in Mature Osteoclasts Causes Osteopetrosis, an Age‐Dependent Change in Osteoclast Number, and a Reduced Number of Osteoblasts In Vivo
Zhu M, Sun B, Saar K, Simpson C, Troiano N, Dallas SL, Tiede‐Lewis L, Nevius E, Pereira JP, Weinstein RS, Tommasini SM, Insogna KL. Deletion of Rac in Mature Osteoclasts Causes Osteopetrosis, an Age‐Dependent Change in Osteoclast Number, and a Reduced Number of Osteoblasts In Vivo. Journal Of Bone And Mineral Research 2015, 31: 864-873. PMID: 26496249, PMCID: PMC4826801, DOI: 10.1002/jbmr.2733.Peer-Reviewed Original ResearchConceptsDual-energy X-ray absorptiometryBone mineral densityDKO miceParathyroid hormoneOsteoclast numberDKO animalsSerum cross-linked C-telopeptideCross-linked C-telopeptideDaily parathyroid hormoneTrabecular bone massX-ray absorptiometryMetaphyseal trabecular boneNormal differentiation markersAge-dependent changesC-telopeptideMineral densityBone massBone densityActin ring formationSkeletal metabolismOsteoblast numberTooth eruptionResorptive activityNormal responseFocal disruption
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 improvementRandomized 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
Targeted overexpression of Dkk1 in osteoblasts reduces bone mass but does not impair the anabolic response to intermittent PTH treatment in mice
Yao GQ, Wu JJ, Troiano N, Insogna K. Targeted overexpression of Dkk1 in osteoblasts reduces bone mass but does not impair the anabolic response to intermittent PTH treatment in mice. Journal Of Bone And Mineral Metabolism 2010, 29: 141-148. PMID: 20602130, PMCID: PMC3457021, DOI: 10.1007/s00774-010-0202-3.Peer-Reviewed Original ResearchConceptsParathyroid hormonePTH treatmentBone massTg miceAnabolic responseDKK1 expressionSingle daily subcutaneous doseDaily subcutaneous doseBone formationIntermittent PTH treatmentPotent anabolic agentOverexpression of DKK1Number of osteoblastsSubcutaneous doseWT miceReal-time PCRSkeletal sitesDickkopf-1Anabolic agentsBody weightTransgenic miceHistomorphometric parametersHistomorphometric analysisTargeted overexpressionPrimary murine osteoblasts
2009
Dominant role of CD47–thrombospondin-1 interactions in myeloma-induced fusion of human dendritic cells: implications for bone disease
Kukreja A, Radfar S, Sun BH, Insogna K, Dhodapkar MV. Dominant role of CD47–thrombospondin-1 interactions in myeloma-induced fusion of human dendritic cells: implications for bone disease. Blood 2009, 114: 3413-3421. PMID: 19661269, PMCID: PMC2765677, DOI: 10.1182/blood-2009-03-211920.Peer-Reviewed Original ResearchConceptsHuman dendritic cellsDendritic cellsBone diseaseOsteoclast formationRecruitment of DCsTumor cellsThrombospondin-1Regulation of CD47Tumor-associated osteoclastsNuclear factor-kappaB ligandMyeloma bone diseaseLytic bone diseasePrimary myeloma cellsHuman osteoclast formationMyeloma cell linesParathyroid hormoneKappaB ligandReceptor activatorOsteoclast precursorsGiant cellsSpontaneous cell-cell fusionMyeloma cellsHuman monocytesMyeloma tumorsDisease
2008
The Anabolic Response to Parathyroid Hormone Is Augmented in Rac2 Knockout Mice
Kawano T, Troiano N, Adams DJ, Wu JJ, Sun BH, Insogna K. The Anabolic Response to Parathyroid Hormone Is Augmented in Rac2 Knockout Mice. Endocrinology 2008, 149: 4009-4015. PMID: 18467443, PMCID: PMC2488220, DOI: 10.1210/en.2008-0034.Peer-Reviewed Original ResearchConceptsAnabolic responseType 1 collagenWild-type animalsPTH treatmentKnockout miceResorptive activityAvailable anabolic therapyTotal bone densityAge-matched wild-type animalsSerum aminoterminal propeptideWild-type groupRac2 knockout miceGroups of animalsAnabolic therapyParathyroid hormoneResorptive responseSerum markersOsteoclast numberTherapeutic responseAminoterminal propeptideBone massBone densitySkeletal responseCortical thicknessGenetic absence
2006
Meat and Soy Protein Affect Calcium Homeostasis in Healthy Women 1 , 2
Kerstetter JE, Wall DE, O’Brien K, Caseria DM, Insogna KL. Meat and Soy Protein Affect Calcium Homeostasis in Healthy Women 1 , 2. Journal Of Nutrition 2006, 136: 1890-1895. PMID: 16772455, DOI: 10.1093/jn/136.7.1890.Peer-Reviewed Original ResearchConceptsIntestinal calcium absorptionUrinary calciumCalcium absorptionLow-protein dietHealthy womenCalcium homeostasisHigher protein interventionNet acid excretionSubset of subjectsHigh-protein dietSoy interventionParathyroid hormoneExperimental periodSerum concentrationsAcid excretionSoy dietAcute declineWomen 1Calcium bioavailabilityRandom orderDietary proteinMeat dietDietSoy proteinIntervention
2004
The Effect of Aging on the Skeletal Response to Intermittent Treatment with Parathyroid Hormone
Knopp E, Troiano N, Bouxsein M, Sun BH, Lostritto K, Gundberg C, Dziura J, Insogna K. The Effect of Aging on the Skeletal Response to Intermittent Treatment with Parathyroid Hormone. Endocrinology 2004, 146: 1983-1990. PMID: 15618351, DOI: 10.1210/en.2004-0770.Peer-Reviewed Original ResearchConceptsBody bone mineral densitySkeletal responseAged animalsIntermittent treatmentTotal body bone mineral densityYoung adult C57BL/6 miceDaily sc injectionsVehicle-treated animalsTrabecular bone volume fractionYoung adult miceBone mineral densityYoung adult animalsVertebral histomorphometryEffect of ageBone volume fractionParathyroid hormoneC57BL/6 miceSC injectionPTH treatmentMineral densityBody weightOsteoblast numberPTHCultured marrowYounger counterparts
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
Parathyroid hormone induces hepatic production of bioactive interleukin-6 and its soluble receptor
Mitnick M, Grey A, Masiukiewicz U, Bartkiewicz M, Rios-Velez L, Friedman S, Xu L, Horowitz M, Insogna K. Parathyroid hormone induces hepatic production of bioactive interleukin-6 and its soluble receptor. AJP Endocrinology And Metabolism 2001, 280: e405-e412. PMID: 11171594, DOI: 10.1152/ajpendo.2001.280.3.e405.Peer-Reviewed Original ResearchConceptsInterleukin-6IL-6sRParathyroid hormoneSoluble receptorBioactive interleukin-6Hepatic IL-6 productionBioactive IL-6IL-6 productionType 1 receptorHepatic stellate cellsDose-dependent productionIsolated rat liverHepatic endothelial cellsIL-6sR.Serum levelsBone resorptionHepatic productionEndocrine effectsKupffer cellsStellate cellsPTHImportant mediatorEndothelial cellsLiverHormoneChapter 25 Cytokines in Primary Hyperparathyroidism
Nakchbandi I, Grey A, Masiukiewicz U, Mitnick M, Insogna K. Chapter 25 Cytokines in Primary Hyperparathyroidism. 2001, 411-421. DOI: 10.1016/b978-012098651-4/50027-4.ChaptersOsteoclast differentiation factorParathyroid hormonePrimary hyperparathyroidismImmune cell functionColony-stimulating factorResorptive actionSevere inflammationBone resorptionInterleukin-6Resorptive effectsCatabolic cytokinesCytokinesMature osteoclastsPleiotropic actionsImportant mediatorKey mediatorCell functionDifferentiation factorHyperparathyroidismOsteoclastogenesisMediatorsHematopoietic microenvironmentInflammationInfectionCell communication
2000
A threshold for low-protein-diet–induced elevations in parathyroid hormone 1 , 2 , 3
Kerstetter J, Svastisalee C, Caseria D, Mitnick M, Insogna K. A threshold for low-protein-diet–induced elevations in parathyroid hormone 1 , 2 , 3. American Journal Of Clinical Nutrition 2000, 72: 168-173. PMID: 10871576, DOI: 10.1093/ajcn/72.1.168.Peer-Reviewed Original ResearchConceptsYoung healthy womenParathyroid hormoneHealthy womenCalcium homeostasisDay 4Nephrogenous cyclic adenosine monophosphateDiet-induced elevationIntestinal calcium absorptionBody mass indexDietary proteinDietary protein intakeParathyroid hormone 1Protein/Urinary calciumCalcitropic hormonesMass indexCalcium absorptionPerturb calcium homeostasisMean 24Normal rangeAverage ageProtein intakeDietary allowanceCyclic adenosine monophosphateHormone 1