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
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
Primary Hyperparathyroidism
Insogna KL. Primary Hyperparathyroidism. New England Journal Of Medicine 2018, 379: 1050-1059. PMID: 30207907, DOI: 10.1056/nejmcp1714213.BooksA Randomized, Double‐Blind, Placebo‐Controlled, Phase 3 Trial Evaluating the Efficacy of Burosumab, an Anti‐FGF23 Antibody, in Adults With X‐Linked Hypophosphatemia: Week 24 Primary Analysis
Insogna KL, Briot K, Imel EA, Kamenický P, Ruppe MD, Portale AA, Weber T, Pitukcheewanont P, Cheong HI, de Beur S, Imanishi Y, Ito N, Lachmann RH, Tanaka H, Perwad F, Zhang L, Chen C, Theodore‐Oklota C, Mealiffe M, San Martin J, Carpenter TO, Investigators O. A Randomized, Double‐Blind, Placebo‐Controlled, Phase 3 Trial Evaluating the Efficacy of Burosumab, an Anti‐FGF23 Antibody, in Adults With X‐Linked Hypophosphatemia: Week 24 Primary Analysis. Journal Of Bone And Mineral Research 2018, 33: 1383-1393. PMID: 29947083, DOI: 10.1002/jbmr.3475.Peer-Reviewed Original ResearchConceptsTreatment-related serious adverse eventsMean serum phosphate concentrationWOMAC physical function subscaleFibroblast growth factor 23Intact parathyroid hormoneSerious adverse eventsPhase 3 trialPhysical function subscaleChronic musculoskeletal painGrowth factor 23Serum phosphate concentrationRenal phosphate wastingHuman monoclonal antibodyLower limb deformitiesImportant medical needStiffness subscalePlacebo groupUrine calciumWorst painAdverse eventsWeek 24Dental abscessMusculoskeletal painFactor 23Function subscale
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
Phosphoenolpyruvate Is a Metabolic Checkpoint of Anti-tumor T Cell Responses
Ho PC, Bihuniak JD, Macintyre AN, Staron M, Liu X, Amezquita R, Tsui YC, Cui G, Micevic G, Perales JC, Kleinstein SH, Abel ED, Insogna KL, Feske S, Locasale JW, Bosenberg MW, Rathmell JC, Kaech SM. Phosphoenolpyruvate Is a Metabolic Checkpoint of Anti-tumor T Cell Responses. Cell 2015, 162: 1217-1228. PMID: 26321681, PMCID: PMC4567953, DOI: 10.1016/j.cell.2015.08.012.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCalciumCD4-Positive T-LymphocytesEndoplasmic ReticulumGlycolysisHexokinaseImmunotherapyLymphocytes, Tumor-InfiltratingMelanomaMiceMonitoring, ImmunologicNFATC Transcription FactorsPhosphoenolpyruvateReceptors, Antigen, T-CellSarcoplasmic Reticulum Calcium-Transporting ATPasesSignal TransductionTransforming Growth Factor betaTumor MicroenvironmentConceptsAnti-tumor T cell responsesT cell responsesT cellsEffector functionsCell responsesTumor-reactive T cellsTumor-infiltrating T cellsPhosphoenolpyruvate carboxykinase 1Tumoricidal effector functionsTumor-specific CD4CD8 T cellsT cell activityMelanoma-bearing miceAerobic glycolysisActivated T cellsMetabolic checkpointTumor growthCell activityTumor microenvironmentNFAT SignalingMetabolic reprogrammingCarboxykinase 1Anabolic metabolismCellsATPase activity
2014
Randomized 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
2013
Dietary 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 intakeDietary Protein-Induced Increases in Urinary Calcium Are Accompanied by Similar Increases in Urinary Nitrogen and Urinary Urea: A Controlled Clinical Trial
Bihuniak JD, Simpson CA, Sullivan RR, Caseria DM, Kerstetter JE, Insogna KL. Dietary Protein-Induced Increases in Urinary Calcium Are Accompanied by Similar Increases in Urinary Nitrogen and Urinary Urea: A Controlled Clinical Trial. Journal Of The Academy Of Nutrition And Dietetics 2013, 113: 447-451. PMID: 23438496, PMCID: PMC5868414, DOI: 10.1016/j.jand.2012.11.002.Peer-Reviewed Original ResearchConceptsBone turnover markersDietary protein intakeUrinary creatinineUrinary calciumProtein intakeUrinary ureaTurnover markersUrinary nitrogenNutrition intervention trialMaltodextrin controlPostmenopausal womenIntervention trialsClinical trialsUrinary metabolitesCreatinineDay 0Whey supplementationWhey supplementsIntakeSample t-testSimilar increaseTrialsT-testSupplementationMarkers
2011
Dietary 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
Inhibiting gastric acid production does not affect intestinal calcium absorption in young, healthy individuals: A randomized, crossover, controlled clinical trial
Wright MJ, Sullivan RR, Gaffney‐Stomberg E, Caseria DM, O'Brien KO, Proctor DD, Simpson CA, Kerstetter JE, Insogna KL. Inhibiting gastric acid production does not affect intestinal calcium absorption in young, healthy individuals: A randomized, crossover, controlled clinical trial. Journal Of Bone And Mineral Research 2010, 25: 2205-2211. PMID: 20499372, PMCID: PMC3312746, DOI: 10.1002/jbmr.108.Peer-Reviewed Original ResearchConceptsIntestinal calcium absorptionProton pump inhibitorsCalcium absorptionGastric acidDual-stable calcium isotopesYoung adultsChronic PPI therapyPotent gastric acidGastric acid suppressionNegative calcium balanceGastric acid productionHealthy young adultsPPI esomeprazolePPI therapyPlacebo groupUrinary calciumAcid suppressionCrossover studyBone lossPump inhibitorsClinical trialsIntervention periodAcute effectsCalcium balanceHealthy individualsThe Effect of Dietary Protein on Intestinal Calcium Absorption in Rats
Gaffney-Stomberg E, Sun BH, Cucchi CE, Simpson CA, Gundberg C, Kerstetter JE, Insogna KL. The Effect of Dietary Protein on Intestinal Calcium Absorption in Rats. Endocrinology 2010, 151: 1071-1078. PMID: 20147526, PMCID: PMC2840679, DOI: 10.1210/en.2009-0744.Peer-Reviewed Original ResearchConceptsIntestinal Ca absorptionCa absorptionHigh-protein dietUrinary calciumBrush border membrane vesiclesProtein intakeFemale Sprague-Dawley ratsProtein dietProtein intake resultsIntestinal calcium absorptionDietary protein intakeHigh protein intakeSprague-Dawley ratsLow-protein groupHigh protein groupDietary protein effectsCalcium absorptionAcute increaseDawley ratsDuodenal mucosaIntake resultsRatsCa balanceTranscellular CaDietary protein
2009
Increasing Dietary Protein Requirements in Elderly People for Optimal Muscle and Bone Health
Gaffney‐Stomberg E, Insogna KL, Rodriguez NR, Kerstetter JE. Increasing Dietary Protein Requirements in Elderly People for Optimal Muscle and Bone Health. Journal Of The American Geriatrics Society 2009, 57: 1073-1079. PMID: 19460090, DOI: 10.1111/j.1532-5415.2009.02285.x.BooksConceptsRecommended Dietary AllowanceCurrent Recommended Dietary AllowanceDietary proteinImportant public health goalOlder individualsInsulin-like growth factorElderly peopleNormal calcium metabolismLoss of boneMuscle protein synthesisShort-term proteinMaintenance of musclePublic health goalsRenal functionBone healthSignificant morbidityCalcium absorptionCalcium metabolismSupplement trialAnabolic effectsClinical studiesProtein adequacyAnabolic responseProtein intakeMuscle massThe Effect of Proton Pump-Inhibiting Drugs on Mineral Metabolism
Insogna KL. The Effect of Proton Pump-Inhibiting Drugs on Mineral Metabolism. The American Journal Of Gastroenterology 2009, 104: ajg200944. PMID: 19262542, DOI: 10.1038/ajg.2009.44.BooksConceptsProton pump inhibitorsMineral metabolismLong-term proton pump inhibitorsIntestinal calcium absorptionHip fracture ratesClass of drugsFragility fracturesBone lossCalcium economyPump inhibitorsCalcium absorptionFracture ratesCalcium balanceSkeletal homeostasisGreater riskAdverse effectsHigh rateDrugsRecent studiesMetabolismLong term
2008
Proton pump-inhibiting drugs, calcium homeostasis, and bone health
Wright MJ, Proctor DD, Insogna KL, Kerstetter JE. Proton pump-inhibiting drugs, calcium homeostasis, and bone health. Nutrition Reviews 2008, 66: 103-108. PMID: 18254877, DOI: 10.1111/j.1753-4887.2008.00015.x.Books
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 Impact of Dietary Protein on Calcium Absorption and Kinetic Measures of Bone Turnover in Women
Kerstetter JE, O’Brien K, Caseria DM, Wall DE, Insogna KL. The Impact of Dietary Protein on Calcium Absorption and Kinetic Measures of Bone Turnover in Women. The Journal Of Clinical Endocrinology & Metabolism 2004, 90: 26-31. PMID: 15546911, DOI: 10.1210/jc.2004-0179.Peer-Reviewed Original ResearchConceptsHigh-protein dietUrinary calciumBone turnoverCalcium absorptionDual-stable calcium isotopesAdditional urinary calciumIntestinal calcium absorptionHealthy womenStable calcium isotopesBone balanceNonsignificant trendSkeletal resorptionCalcium kineticsAcid loadBone originProtein-induced effectsLevels of proteinRandom orderDietary proteinDietHypercalciuriaWomenExperimental dietsSignificant reductionCalcium
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