2021
Update on Osteoporosis Screening and Management
Anam AK, Insogna K. Update on Osteoporosis Screening and Management. Medical Clinics Of North America 2021, 105: 1117-1134. PMID: 34688418, DOI: 10.1016/j.mcna.2021.05.016.ChaptersConceptsLimited alcohol intakeNew anabolic therapiesLow bone massDual-energy X-ray absorptiometry measurementsBone mineral densityMetabolic bone diseasePostmenopausal womenAnabolic therapyFragility fracturesMicroarchitectural deteriorationSevere osteoporosisBone healthAlcohol intakeOsteoporosis screeningSmoking cessationVitamin DMineral densityPharmacologic agentsBone massBone diseaseHigh riskAbsorptiometry measurementsGold standardOsteoporosisBone tissueAn 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 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
2018
Skeletal disease in a father and daughter with a novel monoallelic WNT1 mutation
Ang K, Rangel E, Yuan Q, Wu D, Carpenter TO, Insogna K. Skeletal disease in a father and daughter with a novel monoallelic WNT1 mutation. Bone Reports 2018, 9: 154-158. PMID: 30364642, PMCID: PMC6197702, DOI: 10.1016/j.bonr.2018.09.001.Peer-Reviewed Original ResearchLow bone mineral densityLow bone massBone mineral densityWNT1 mutationsMineral densityMonoallelic mutationsBone massSame heterozygous missense mutationLow-impact fracturesExtra-skeletal manifestationsSevere osteogenesis imperfectaCanonical Wnt-β-catenin pathwayWnt-β-catenin pathwayType 1 collagen genesType 1 collagenHeterozygous missense mutationAdult skeletal homeostasisTraumatic fracturesSevere diseaseBiallelic diseaseIndex caseTherapeutic benefitRelated patientsSkeletal homeostasisSkeletal disease
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 disruptionAgRP Neurons Regulate Bone Mass
Kim JG, Sun BH, Dietrich MO, Koch M, Yao GQ, Diano S, Insogna K, Horvath TL. AgRP Neurons Regulate Bone Mass. Cell Reports 2015, 13: 8-14. PMID: 26411686, PMCID: PMC5868421, DOI: 10.1016/j.celrep.2015.08.070.Peer-Reviewed Original ResearchMeSH KeywordsAgouti-Related ProteinAnimalsArcuate Nucleus of HypothalamusBone DensityBone Diseases, MetabolicFemurGene Expression RegulationHomeostasisHypothalamusIon ChannelsLeptinMaleMiceMice, KnockoutMitochondrial ProteinsNeuronsNorepinephrinePhenotypePropranololReceptors, Adrenergic, betaReceptors, LeptinSignal TransductionSirtuin 1TibiaUncoupling Protein 2ConceptsAgRP neuronsCell-autonomous deletionSignificant regulatory roleAgRP neuronal functionBone massLeptin receptor deletionSkeletal bone metabolismTransgenic animalsRegulatory roleGene deletionBone homeostasisDeletionNeuronal functionPostnatal deletionSympathetic toneReceptor deletionArcuate nucleusLeptin actionBone metabolismSkeletal metabolismMultiple linesNeuronsMiceMetabolismCircuit integrityBone Health and Osteoporosis
Lupsa BC, Insogna K. Bone Health and Osteoporosis. Endocrinology And Metabolism Clinics Of North America 2015, 44: 517-530. PMID: 26316240, DOI: 10.1016/j.ecl.2015.05.002.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsBone healthBone lossLow bone massAdditional risk factorsDual-energy X-ray absorptiometry measurementsLow-energy fracturesBone mineral densityMicroarchitectural deteriorationEstrogen levelsSmoking cessationRisk factorsMineral densityPharmacologic agentsBone massHigh riskOlder womenWomen's ageBone strengthAbsorptiometry measurementsOsteoporosisGold standardBone tissueRiskHealthFracturesThe 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
2013
Measurement of Plasma, Serum, and Platelet Serotonin in Individuals With High Bone Mass and Mutations in LRP5
Lee GS, Simpson C, Sun B, Yao C, Foer D, Sullivan B, Matthes S, Alenina N, Belsky J, Bader M, Insogna KL. Measurement of Plasma, Serum, and Platelet Serotonin in Individuals With High Bone Mass and Mutations in LRP5. Journal Of Bone And Mineral Research 2013, 29: 976-981. PMID: 24038240, PMCID: PMC3935983, DOI: 10.1002/jbmr.2086.Peer-Reviewed Original ResearchConceptsLow-density lipoprotein receptor-related protein 5Age-matched controlsPlatelet-poor plasmaSerum serotonin levelsLRP5 mutationsSerotonin levelsBone massAffected individualsPlatelet pelletLipoprotein receptor-related protein 5Duodenal enterochromaffin cellsLevels of serotoninHigh bone massSecretion of serotoninMeasurement of plasmaSerum levelsEnterochromaffin cellsSubgroup analysisBlood serotoninPlatelet serotoninPossible associationSerotoninPoor plasmaGenetic deletionELISA
2011
Control of bone formation by the serpentine receptor Frizzled-9
Albers J, Schulze J, Beil FT, Gebauer M, Baranowsky A, Keller J, Marshall RP, Wintges K, Friedrich FW, Priemel M, Schilling AF, Rueger JM, Cornils K, Fehse B, Streichert T, Sauter G, Jakob F, Insogna KL, Pober B, Knobeloch KP, Francke U, Amling M, Schinke T. Control of bone formation by the serpentine receptor Frizzled-9. Journal Of Cell Biology 2011, 192: 1057-1072. PMID: 21402791, PMCID: PMC3063134, DOI: 10.1083/jcb.201008012.Peer-Reviewed Original ResearchConceptsBone formationLow bone massBone loss disordersPotential downstream mediatorsBone massUbiquitin-like modifier ISG15Interferon-regulated genesTherapeutic implicationsLoss disordersCanonical Wnt signalingBone remodelingFrizzled 9Reduced expressionDownstream mediatorDifferentiation markersWnt signalingWnt receptorsNormal expressionPrimary osteoblastsFZD9OsteoblastsOsteoblast differentiationMatrix mineralizationMolecular analysisChemokinesDietary 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 differencesTargeted 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
LDL-Receptor Related Protein Five Controls Bone Formation by Inhibiting Serotonin Synthesis in the Duodenum
Yadav V, Ryu J, Suda N, Tanaka K, Gingrich J, Schütz G, Glorieux F, Chiang C, Zajac J, Insogna K, Mann J, Hen R, Ducy P, Karsenty G. LDL-Receptor Related Protein Five Controls Bone Formation by Inhibiting Serotonin Synthesis in the Duodenum. Obstetrical & Gynecological Survey 2009, 64: 240-242. DOI: 10.1097/01.ogx.0000345723.85624.24.Peer-Reviewed Original ResearchLDL receptor-related protein 5Function mutationsHigh bone mass syndromeTryptophan hydroxylase 1Bone massSerotonin synthesisGene deletion experimentsBone formationLrp5 lossEnterochromaffin cellsMajor regulatory roleMass syndromeBone diseaseVertebrate homologsOsteoporosis pseudogliomaTranscriptional effectorsWnt proteinsBiosynthetic enzymesDeletion experimentsRegulatory roleRare bone diseasesProtein 5Rate-limiting biosynthetic enzymeMutationsLRP5 gain
2008
Lrp5 Controls Bone Formation by Inhibiting Serotonin Synthesis in the Duodenum
Yadav VK, Ryu JH, Suda N, Tanaka KF, Gingrich JA, Schütz G, Glorieux FH, Chiang CY, Zajac JD, Insogna KL, Mann JJ, Hen R, Ducy P, Karsenty G. Lrp5 Controls Bone Formation by Inhibiting Serotonin Synthesis in the Duodenum. Cell 2008, 135: 825-837. PMID: 19041748, PMCID: PMC2614332, DOI: 10.1016/j.cell.2008.09.059.Peer-Reviewed Original ResearchConceptsBone massBone formationLrp5-deficient miceSerotonin blood levelsExpression of TPH1High bone massOsteoblast-specific disruptionRate-limiting biosynthetic enzymeBone lossEnterochromaffin cellsBlood levelsSerotonin synthesisPotential therapyBone remodelingWnt coreceptorSerotoninLRP5Function mutationsDuodenumTPH1Independent mannerOsteoporosisTherapyBiosynthetic enzymesMiceAn 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 riskThe 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 absenceImpact of Glucose‐Dependent Insulinotropic Peptide on Age‐Induced Bone Loss*
Ding K, Shi X, Zhong Q, Kang B, Xie D, Bollag WB, Bollag RJ, Hill W, Washington W, Mi Q, Insogna K, Chutkan N, Hamrick M, Isales CM. Impact of Glucose‐Dependent Insulinotropic Peptide on Age‐Induced Bone Loss*. Journal Of Bone And Mineral Research 2008, 23: 536-543. PMID: 18072880, PMCID: PMC2669161, DOI: 10.1359/jbmr.071202.Peer-Reviewed Original ResearchConceptsGlucose-dependent insulinotropic peptideAge-induced bone lossBone marrow stromal cellsGIP receptor expressionBone lossBone massMo of ageGIP effectsInsulinotropic peptideReceptor expressionEffects of GIPBone strengthOsteoblastic activityAge-associated bone lossElevated GIP levelsFunctional GIP receptorsWildtype control miceBone histomorphometric dataC57BL/6 transgenic miceAge-dependent fashionAge-related decreaseAge-related lossDifferentiation of BMSCsAge-dependent mannerAge-related changes
2007
Glucose-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
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