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 ResearchMeSH KeywordsAnabolic AgentsAnimalsBone DensityFemaleFemurMaleMiceMice, KnockoutOsteoclastsParathyroid HormonePhosphotransferases (Alcohol Group Acceptor)SpineConceptsSphk2-/- 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 animalsSelective deletion of the receptor for CSF1, c-fms, in osteoclasts results in a high bone mass phenotype, smaller osteoclasts in vivo and an impaired response to an anabolic PTH regimen
Zhu M, Sun BH, Nevius E, Kaplan J, Pereira J, Insogna K. Selective deletion of the receptor for CSF1, c-fms, in osteoclasts results in a high bone mass phenotype, smaller osteoclasts in vivo and an impaired response to an anabolic PTH regimen. PLOS ONE 2021, 16: e0247199. PMID: 33607650, PMCID: PMC7895546, DOI: 10.1371/journal.pone.0247199.Peer-Reviewed Original ResearchConceptsColony stimulating factor 1Mature osteoclastsBone massHigh bone mass phenotypeAttenuated anabolic responseDaily subcutaneous dosesTrabecular bone massBone mass phenotypeC-fmsNormal tooth eruptionTrabecular bone compartmentsMature osteoclast functionCathepsin K promoterFemurs of maleWild-type animalsOcS/BSFemale knockSubcutaneous dosesNormal weightSmall osteoclastsImpaired responseTrabecular numberAnabolic responseFlox miceMass phenotype
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 ResearchMeSH KeywordsCalciumFemaleHumansHypercalcemiaHyperparathyroidism, PrimaryInfant, NewbornParathyroid HormoneReceptors, Calcium-SensingConceptsPrimary 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
Primary Hyperparathyroidism
Insogna KL. Primary Hyperparathyroidism. New England Journal Of Medicine 2018, 379: 1050-1059. PMID: 30207907, DOI: 10.1056/nejmcp1714213.BooksThe 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 osteoblasts
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
2010
Circulating Levels of Soluble Klotho and FGF23 in X-Linked Hypophosphatemia: Circadian Variance, Effects of Treatment, and Relationship to Parathyroid Status
Carpenter TO, Insogna KL, Zhang JH, Ellis B, Nieman S, Simpson C, Olear E, Gundberg CM. Circulating Levels of Soluble Klotho and FGF23 in X-Linked Hypophosphatemia: Circadian Variance, Effects of Treatment, and Relationship to Parathyroid Status. The Journal Of Clinical Endocrinology & Metabolism 2010, 95: e352-e357. PMID: 20685863, PMCID: PMC2968736, DOI: 10.1210/jc.2010-0589.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAge FactorsAgedBone Density Conservation AgentsCalcitriolChildCircadian RhythmEnzyme-Linked Immunosorbent AssayFamilial Hypophosphatemic RicketsFemaleFibroblast Growth Factor-23Fibroblast Growth FactorsGenetic Diseases, X-LinkedGlucuronidaseHumansKlotho ProteinsMaleMiddle AgedParathyroid HormonePhosphatesVitamin DConceptsSerum KlothoSerum FGF23Higher klotho levelsHospital research unitRenal phosphate handlingAcademic medical centerEffect of treatmentFibroblast growth factorKlotho levelsPTH secretionMedical therapySoluble KlothoDihydroxyvitamin DFGF23 regulationPhosphate handlingMedical CenterFGF23KlothoXLHCircadian variationGrowth factorPTHAdultsHypophosphatemiaTherapyTargeted 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
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
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 risk
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
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 ResearchMeSH KeywordsAgingAnimalsBone and BonesBone DensityBone RemodelingMaleMiceMice, Inbred C57BLOsteoblastsParathyroid HormoneStem CellsConceptsBody 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
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 studiesTertileGroupRole of the interleukin-6/interleukin-6 soluble receptor cytokine system in mediating increased skeletal sensitivity to parathyroid hormone in perimenopausal women.
Insogna K, Mitnick M, Pascarella J, Nakchbandi I, Grey A, Masiukiewicz U. Role of the interleukin-6/interleukin-6 soluble receptor cytokine system in mediating increased skeletal sensitivity to parathyroid hormone in perimenopausal women. Journal Of Bone And Mineral Research 2002, 17 Suppl 2: n108-16. PMID: 12412787.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnimalsBone and BonesBone ResorptionCollagenCollagen Type ICytokinesDisease Models, AnimalEstrogensFemaleFollow-Up StudiesHumansHyperparathyroidismInterleukin-6MenopauseMiceMiddle AgedOsteoporosis, PostmenopausalParathyroid HormonePeptidesPostmenopausePredictive Value of TestsPremenopauseReceptors, Interleukin-6Reference ValuesRetrospective StudiesConceptsIL-6/ILInterleukin-6Skeletal sensitivityPerimenopausal periodPrimary hyperparathyroidismPerimenopausal womenCytokine systemInterleukin-6 soluble receptorSerum IL-6 valuesEstrogen-deficient stateUrine N-telopeptideInterleukin-6/interleukinAction of PTHGroup of patientsIL-6 valuesSerum IL-6/ILEstrogen modulatesIL-6sRIL-6sR.Perimenopausal groupUrine NTXPremenopausal womenSkeletal complicationsCytokine profileExaggerated releaseEvidence 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-1
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: 3850-6. PMID: 11517162, DOI: 10.1210/endo.142.9.8368.Peer-Reviewed Original ResearchConceptsIL-11 productionIL-6IL-11Bone resorptionOsteoclast formationIL-6 levelsIL-11 levelsFive-day infusionPTH excessPrimary hyperparathyroidismSerum levelsResorptive responseParathyroid adenomectomyPretreatment of cellsHuman PTHNonimmune serumPTHEffect of pretreatmentMRNA levelsSteady-state mRNA levelsPatientsCytokinesHuman osteoblast-like cellsResorptionSaos-2 cellsPARAMETERS 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 transplantationParathyroid 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 cellsLiverHormone
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 ResearchMeSH KeywordsAdultCalciumDiet, Protein-RestrictedDietary ProteinsFemaleHomeostasisHumansIntestinal AbsorptionNutritional RequirementsParathyroid HormoneConceptsYoung 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 1Estrogen 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