2024
Mitofusin 2 plays a critical role in maintaining the functional integrity of the neuromuscular-skeletal axis
Zhu M, Zeiss C, Hamrick M, Weinstein R, Sun B, Brotto M, Liu X, Siu E, Huttner A, Tommasini S, Simpson C, Insogna K. Mitofusin 2 plays a critical role in maintaining the functional integrity of the neuromuscular-skeletal axis. Bone 2024, 184: 117086. PMID: 38552893, DOI: 10.1016/j.bone.2024.117086.Peer-Reviewed Original ResearchConceptsDeletion of Mfn2Bone mineral densityMitofusin 2Reduced expression of Mfn2Myofiber atrophySpinal cordTransgenic mice expressing CreMice expressing CreNon-redundant roleSkeletal muscle histologyLumbar spinal cordTrabecular bone massLean body massExpression of Mfn2Mitochondrial reticulumMFN2 geneDisruption of cellular architectureImpaired osteoblast differentiationOsteoblast lineage commitmentMfn2Mitochondrial sizeMitofusinMineral densityCo-expressionDisorganized sarcomeres
2022
The clinician’s guide to prevention and treatment of osteoporosis
LeBoff M, Greenspan S, Insogna K, Lewiecki E, Saag K, Singer A, Siris E. The clinician’s guide to prevention and treatment of osteoporosis. Osteoporosis International 2022, 33: 2049-2102. PMID: 35478046, PMCID: PMC9546973, DOI: 10.1007/s00198-021-05900-y.Peer-Reviewed Original ResearchConceptsTreatment of osteoporosisClinician's GuideVertebral fracturesFracture riskElevated riskCommon metabolic bone diseaseSubclinical vertebral fracturesAvoidance of smokingHigh-risk womenExpert clinical experiencePrimary care providersExcessive alcohol intakeFuture fracture riskNational Osteoporosis FoundationAdditional vertebral fracturesMetabolic bone diseaseDXA T-scoresAdult healthcare settingsDiagnosis of osteoporosisResistance training exercisesSignificant economic tollIncident fracturesNormal BMDUntreated osteoporosisPostmenopausal women
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
Primary Hyperparathyroidism
Insogna KL. Primary Hyperparathyroidism. New England Journal Of Medicine 2018, 379: 1050-1059. PMID: 30207907, DOI: 10.1056/nejmcp1714213.BooksAssociations 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 correlationVertebral fractures among breast cancer survivors in China: a cross-sectional study of prevalence and health services gaps
Hsieh E, Wang Q, Zhang R, Niu X, Xia W, Fraenkel L, Insogna KL, Li J, Smith JS, Zhou C, Qiao YL, Zhang P. Vertebral fractures among breast cancer survivors in China: a cross-sectional study of prevalence and health services gaps. BMC Cancer 2018, 18: 104. PMID: 29378534, PMCID: PMC5789645, DOI: 10.1186/s12885-018-4014-5.Peer-Reviewed Original ResearchConceptsBreast cancer survivorsVertebral fracturesCancer survivorsCross-sectional studyBreast cancerBone lossCancer treatment-induced bone lossHealthy community-dwelling postmenopausal womenProgesterone receptor-positive breast cancerHealth servicesBreast cancer survivor cohortCommunity-dwelling postmenopausal womenFracture-related risk factorsPeking Vertebral Fracture StudyTreatment-induced bone lossReceptor-positive breast cancerChinese breast cancer survivorsCancer survivor cohortLarge cancer hospitalThoracolumbar X-rayVitamin D supplementsPrevalent vertebral fracturesBone density scanInitiation of treatmentAdjusted odds ratio
2017
Dietary protein and bone health: a systematic review and meta-analysis from the National Osteoporosis Foundation 1 , 2
Shams-White MM, Chung M, Du M, Fu Z, Insogna KL, Karlsen MC, LeBoff MS, Shapses SA, Sackey J, Wallace TC, Weaver CM. Dietary protein and bone health: a systematic review and meta-analysis from the National Osteoporosis Foundation 1 , 2. American Journal Of Clinical Nutrition 2017, 105: 1528-1543. PMID: 28404575, DOI: 10.3945/ajcn.116.145110.Peer-Reviewed Original ResearchConceptsBone mineral densityHigh protein intakeProspective cohort studyProtein intakeSystematic reviewCohort studyBone healthTotal hipFemoral neckModerate evidenceLumbar spine bone mineral densityTotal body bone mineral densityTH bone mineral densityLS bone mineral densityBody bone mineral densitySpine bone mineral densityFN bone mineral densityBone health measuresBone health outcomesDietary proteinLow protein intakeFull-text screeningStrength of evidenceOverall RoBNonpharmacologic approaches
2016
Effect of a randomized controlled exercise trial on bone outcomes: influence of adjuvant endocrine therapy
Knobf MT, Jeon S, Smith B, Harris L, Kerstetter J, Thompson AS, Insogna K. Effect of a randomized controlled exercise trial on bone outcomes: influence of adjuvant endocrine therapy. Breast Cancer Research And Treatment 2016, 155: 491-500. PMID: 26850265, DOI: 10.1007/s10549-016-3693-3.Peer-Reviewed Original ResearchConceptsFemale cancer survivorsPhysical activity groupEndocrine therapyBone outcomesExercise interventionBone lossFemoral neckAromatase inhibitorsActivity groupAdjuvant AI therapyChemotherapy-induced menopauseSufficient serum levelsAdjuvant endocrine therapyVitamin D supplementsHealthy postmenopausal womenLess bone lossHome-based groupSignificant BMD lossSignificant clinical problemMajority of subjectsAI therapyD supplementsPostmenopausal womenBMD lossBMD outcomes
2015
AgRP 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 StatementsMeSH KeywordsBone DensityExerciseFemaleHumansMenopauseOsteoporosis, PostmenopausalOsteoporotic FracturesRisk FactorsConceptsBone 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 massThe effects of dietary protein and amino acids on skeletal metabolism
Bihuniak JD, Insogna KL. The effects of dietary protein and amino acids on skeletal metabolism. Molecular And Cellular Endocrinology 2015, 410: 78-86. PMID: 25843057, PMCID: PMC5852680, DOI: 10.1016/j.mce.2015.03.024.BooksConceptsDietary proteinDietary protein intakeOptimal skeletal growthRecent data bearingSkeletal healthCalcium economyMineral metabolismSkeletal metabolismProtein intakeDietary allowanceSkeletal homeostasisNutrient intakeSkeletal massIntakeSkeletal growthSite-specific effectsMolecular mechanismsMetabolismVariable levelsLife continuumProtein
2014
Serum levels of sclerostin, Dickkopf-1, and secreted frizzled-related protein-4 are not changed in individuals with high bone mass causing mutations in LRP5
Simpson CA, Foer D, Lee GS, Bihuniak J, Sun B, Sullivan R, Belsky J, Insogna KL. Serum levels of sclerostin, Dickkopf-1, and secreted frizzled-related protein-4 are not changed in individuals with high bone mass causing mutations in LRP5. Osteoporosis International 2014, 25: 2383-2388. PMID: 24927689, PMCID: PMC4659359, DOI: 10.1007/s00198-014-2767-5.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAdultAgedBone DensityBone Morphogenetic ProteinsCase-Control StudiesFemaleGenetic MarkersGenotypeHumansIntercellular Signaling Peptides and ProteinsLow Density Lipoprotein Receptor-Related Protein-5MaleMiddle AgedMutationOsteoprotegerinProto-Oncogene ProteinsRANK LigandSex CharacteristicsWnt Signaling PathwayConceptsFrizzled-related protein 4Serum levelsWnt inhibitorsDickkopf-1Normal controlsUnrelated normal controlsHigh bone mass mutationsHigh bone mass syndromeFunction mutationsNormal age-matched controlsProtein 4Cross-sectional studyAge-matched controlsLRP5 resultSkeletal effectsEndogenous Wnt inhibitorsMass syndromeConsented volunteersUnrelated normal individualsDkk-1Different kindredsNormal individualsLRP5 signalingPatientsSclerostinThe Transcription Factor T-box 3 Regulates Colony-stimulating Factor 1-dependent Jun Dimerization Protein 2 Expression and Plays an Important Role in Osteoclastogenesis*
Yao C, Yao GQ, Sun BH, Zhang C, Tommasini SM, Insogna K. The Transcription Factor T-box 3 Regulates Colony-stimulating Factor 1-dependent Jun Dimerization Protein 2 Expression and Plays an Important Role in Osteoclastogenesis*. Journal Of Biological Chemistry 2014, 289: 6775-6790. PMID: 24394418, PMCID: PMC3945339, DOI: 10.1074/jbc.m113.499210.Peer-Reviewed Original Research
2013
An investigation of the association between omega 3 FA and bone mineral density among older adults: results from the National Health and Nutrition Examination Survey years 2005–2008
Mangano KM, Kerstetter JE, Kenny AM, Insogna KL, Walsh SJ. An investigation of the association between omega 3 FA and bone mineral density among older adults: results from the National Health and Nutrition Examination Survey years 2005–2008. Osteoporosis International 2013, 25: 1033-1041. PMID: 24121998, PMCID: PMC3969769, DOI: 10.1007/s00198-013-2501-8.Peer-Reviewed Original ResearchConceptsSpine bone mineral densityLumbar spine bone mineral densityBone mineral densityTotal femur bone mineral densityFemoral neck bone mineral densityFemur bone mineral densityNeck bone mineral densityFA supplement useSupplement useMineral densityFemoral neckNational HealthOlder adultsDietary omega-3 fatty acid intakeGreater femoral neck BMDHigher spine bone mineral densityHigher lumbar spine bone mineral densityOmega-3 fatty acid intakeDietary omega 3 FAHip bone mineral densityOmega-3 intakeFatty acid intakeNutrition Examination SurveyOmega-3 FAMultivariable regression modelsMeasurement 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 deletionELISADietary Acid Load Is Associated With Lower Bone Mineral Density in Men With Low Intake of Dietary Calcium
Mangano KM, Walsh SJ, Kenny AM, Insogna KL, Kerstetter JE. Dietary Acid Load Is Associated With Lower Bone Mineral Density in Men With Low Intake of Dietary Calcium. Journal Of Bone And Mineral Research 2013, 29: 500-506. PMID: 23873776, PMCID: PMC3946957, DOI: 10.1002/jbmr.2053.Peer-Reviewed Original ResearchConceptsPotential renal acid loadNet endogenous acid productionProximal femur bone mineral densityDietary acid loadFemur bone mineral densityBone mineral densityCalcium intakeDietary calciumAcid loadMineral densitySupplemental calciumHigh dietary acid loadNutrition Examination Survey 2005Low bone mineral densityMean bone mineral densityLow calcium intakeRenal acid loadLow dietary calciumEndogenous acid productionBone healthBMD sitesMean ageInverse associationNational HealthLow intake
2012
LIM kinase 1 deficient mice have reduced bone mass
Kawano T, Zhu M, Troiano N, Horowitz M, Bian J, Gundberg C, Kolodziejczak K, Insogna K. LIM kinase 1 deficient mice have reduced bone mass. Bone 2012, 52: 70-82. PMID: 23017662, PMCID: PMC3688839, DOI: 10.1016/j.bone.2012.09.024.Peer-Reviewed Original ResearchConceptsLIM kinase 1Cytoskeletal remodelingRole of LIMK1Specialized cellular functionsActin cytoskeletal remodelingActin-severing proteinBone cell biologyNormal osteoblast differentiationCellular functionsCell biologyCell motilityCell shapeKinase 1Cell cycleF-actinOsteoblast differentiationPhospho-cofilinActin monomersSkeletal phenotypeOsteoblast coloniesOsteoblastsMetalloproteinase activityDifferentiationRemodelingRate of mineralization