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
Musculoskeletal Features in Adults With X-linked Hypophosphatemia: An Analysis of Clinical Trial and Survey Data
Javaid MK, Ward L, Pinedo-Villanueva R, Rylands AJ, Williams A, Insogna K, Imel EA. Musculoskeletal Features in Adults With X-linked Hypophosphatemia: An Analysis of Clinical Trial and Survey Data. The Journal Of Clinical Endocrinology & Metabolism 2021, 107: e1249-e1262. PMID: 34636401, PMCID: PMC8852215, DOI: 10.1210/clinem/dgab739.Peer-Reviewed Original ResearchConceptsMusculoskeletal featuresClinical trialsHistory of fractureClinical Trials GroupAge 20 yearsClinical trial subjectsProportion of adultsMusculoskeletal manifestationsPain subgroupsSpinal stenosisGroup of adultsOverall prevalenceTrial groupLow prevalenceAge bandsTrial subjectsOnline survey participantsAdultsAgeSurgeryHigh ratePrevalenceXLHTrialsSurvey participants
2019
Continued Beneficial Effects of Burosumab in Adults with X-Linked Hypophosphatemia: Results from a 24-Week Treatment Continuation Period After a 24-Week Double-Blind Placebo-Controlled Period
Portale AA, Carpenter TO, Brandi ML, Briot K, Cheong HI, Cohen-Solal M, Crowley R, Jan De Beur S, Eastell R, Imanishi Y, Imel EA, Ing S, Ito N, Javaid M, Kamenicky P, Keen R, Kubota T, Lachmann R, Perwad F, Pitukcheewanont P, Ralston SH, Takeuchi Y, Tanaka H, Weber TJ, Yoo HW, Zhang L, Theodore-Oklota C, Mealiffe M, San Martin J, Insogna K. Continued Beneficial Effects of Burosumab in Adults with X-Linked Hypophosphatemia: Results from a 24-Week Treatment Continuation Period After a 24-Week Double-Blind Placebo-Controlled Period. Calcified Tissue International 2019, 105: 271-284. PMID: 31165191, DOI: 10.1007/s00223-019-00568-3.Peer-Reviewed Original ResearchConceptsWeek 48Adverse eventsWeek 24Sustained improvementTreatment-related serious adverse eventsOpen-label treatment periodSafety of burosumabDouble-blind placeboFatal adverse eventsSerious adverse eventsSerum phosphorus levelsPatient-reported outcomesSerum phosphorus concentrationRenal phosphate wastingHuman monoclonal antibodyContinued beneficial effectsHealing of fracturesRare genetic disorderMusculoskeletal morbidityPhysical functionContinuation periodMusculoskeletal impairmentsPhosphate wastingTreatment periodBurosumab
2018
Vertebral 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
The Yale Fitness Intervention Trial in female cancer survivors: Cardiovascular and physiological outcomes
Knobf MT, Jeon S, Smith B, Harris L, Thompson S, Stacy MR, Insogna K, Sinusas AJ. The Yale Fitness Intervention Trial in female cancer survivors: Cardiovascular and physiological outcomes. Heart & Lung 2017, 46: 375-381. PMID: 28803675, PMCID: PMC6129386, DOI: 10.1016/j.hrtlng.2017.06.001.Peer-Reviewed Original ResearchConceptsFemale cancer survivorsCancer survivorsCenter interventionMET-minutes/weekStable insulin levelsMetabolic risk factorsResistance exercise programExercise stress testCardiovascular disease riskPhysical activity groupImproved insulin resistanceHeart rate recoveryMinutes/weekRisk reduction interventionsMajority of subjectsAdjuvant chemotherapyPremature menopauseExercise programInsulin levelsInsulin resistanceIntervention trialsRisk factorsCardiovascular functionBreast cancerRate recoveryThe Effect of Dietary Glycemic Properties on Markers of Inflammation, Insulin Resistance, and Body Composition in Postmenopausal American Women: An Ancillary Study from a Multicenter Protein Supplementation Trial
Stojkovic V, Simpson CA, Sullivan RR, Cusano AM, Kerstetter JE, Kenny AM, Insogna KL, Bihuniak JD. The Effect of Dietary Glycemic Properties on Markers of Inflammation, Insulin Resistance, and Body Composition in Postmenopausal American Women: An Ancillary Study from a Multicenter Protein Supplementation Trial. Nutrients 2017, 9: 484. PMID: 28492492, PMCID: PMC5452214, DOI: 10.3390/nu9050484.Peer-Reviewed Original ResearchConceptsMarkers of inflammationInsulin resistanceGI/GLBody compositionAncillary studiesLean massPRO groupSignificant associationGlycemic load dietDouble-blind trialFat mass ratioTotal lean massTotal fat massPostmenopausal American womenTrunk lean massAge-related alterationsWhey protein supplementLoad dietInflammatory markersSerum CRPChronic inflammationIL-6Fat massSupplementation trialBone densityImpact of gain-of-function mutations in the low-density lipoprotein receptor-related protein 5 (LRP5) on glucose and lipid homeostasis
Foer D, Zhu M, Cardone RL, Simpson C, Sullivan R, Nemiroff S, Lee G, Kibbey RG, Petersen KF, Insogna KL. Impact of gain-of-function mutations in the low-density lipoprotein receptor-related protein 5 (LRP5) on glucose and lipid homeostasis. Osteoporosis International 2017, 28: 2011-2017. PMID: 28283687, PMCID: PMC6693506, DOI: 10.1007/s00198-017-3977-4.Peer-Reviewed Original ResearchMeSH KeywordsAgedBlood GlucoseCase-Control StudiesCholesterol, LDLFemaleGain of Function MutationGlucose Tolerance TestGlycated HemoglobinHomeostasisHumansIslets of LangerhansLipid MetabolismLow Density Lipoprotein Receptor-Related Protein-5MaleMiddle AgedTissue Culture TechniquesWnt Signaling PathwayConceptsLow-density lipoprotein receptor-related protein 5Insulin sensitivity indexType 2 diabetesInsulin secretionLRP5 mutationsLipid metabolismSerum LDLInsulin sensitivityLipid homeostasisGlucose metabolismAnimal modelsMean insulin sensitivity indexFunction mutationsHigh bone mass phenotypeLipoprotein receptor-related protein 5Augment insulin secretionGlucose-stimulated insulin secretionCoronary artery diseaseMajor risk factorCase-control studyImpaired insulin sensitivityHepatic lipid contentBone mass phenotypeProton magnetic resonance spectroscopyAcademic medical center
2016
Pioglitazone and Risk for Bone Fracture: Safety Data From a Randomized Clinical Trial
Viscoli CM, Inzucchi SE, Young LH, Insogna KL, Conwit R, Furie KL, Gorman M, Kelly MA, Lovejoy AM, Kernan WN, Investigators F. Pioglitazone and Risk for Bone Fracture: Safety Data From a Randomized Clinical Trial. The Journal Of Clinical Endocrinology & Metabolism 2016, 102: 914-922. PMID: 27935736, PMCID: PMC5460686, DOI: 10.1210/jc.2016-3237.Peer-Reviewed Original ResearchConceptsTransient ischemic attackIschemic strokeFracture riskBone fracturesRisk/benefit ratioAbsolute fracture riskInsulin Resistance InterventionPlacebo-treated patientsIschemic attackNondiabetic patientsPlacebo groupCardiovascular riskBone healthStroke trialsNondiabetic participantsPrevent fallsClinical trialsRelative riskSafety dataFracture classificationQuarterly interviewsPioglitazonePatientsResistance InterventionRisk incrementLongitudinal 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 resorptionEffect 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
Pharmacokinetics and pharmacodynamics of a human monoclonal anti‐FGF23 antibody (KRN23) in the first multiple ascending‐dose trial treating adults with X‐linked hypophosphatemia
Zhang X, Imel EA, Ruppe MD, Weber TJ, Klausner MA, Ito T, Vergeire M, Humphrey J, Glorieux FH, Portale AA, Insogna K, Carpenter TO, Peacock M. Pharmacokinetics and pharmacodynamics of a human monoclonal anti‐FGF23 antibody (KRN23) in the first multiple ascending‐dose trial treating adults with X‐linked hypophosphatemia. The Journal Of Clinical Pharmacology 2015, 56: 176-185. PMID: 26073451, PMCID: PMC5042055, DOI: 10.1002/jcph.570.Peer-Reviewed Original ResearchConceptsConcentration-time curveSerum fibroblast growth factor 23Multiple ascending dose trialFibroblast growth factor 23Ascending dose trialHuman IgG1 monoclonal antibodyLow-normal serumRecombinant human IgG1 monoclonal antibodyDihydroxyvitamin D concentrationsGlomerular filtration rateGrowth factor 23Serum inorganic phosphorusSerum Pi concentrationIgG1 monoclonal antibodyFGF23 antibodyDose adjustmentFactor 23Serum PiFiltration ratePhosphate reabsorptionBone markersKRN23D concentrationsNormal serumMonoclonal antibodiesDietary Protein and Vitamin D Intake and Risk of Falls: A Secondary Analysis of Postmenopausal Women from the Study of Osteoporotic Fractures
Larocque SC, Kerstetter JE, Cauley JA, Insogna KL, Ensrud K, Lui LY, Allore HG. Dietary Protein and Vitamin D Intake and Risk of Falls: A Secondary Analysis of Postmenopausal Women from the Study of Osteoporotic Fractures. Journal Of Nutrition In Gerontology And Geriatrics 2015, 34: 305-318. PMID: 26267443, PMCID: PMC4547350, DOI: 10.1080/21551197.2015.1054574.Peer-Reviewed Original ResearchConceptsVitamin D intakeVitamin DD intakePostmenopausal womenOsteoporotic fracturesDietary proteinOdds ratioOlder adultsFood frequency questionnaireRisk of fallsOccurrence of fallsIncident fallsFrequency questionnaireProspective cohortHip fractureMusculoskeletal healthInadequate intakeAdequate intakeOlder womenProtein intakeMuscle massSecondary analysisLogistic regressionIntakeWomenProlonged Correction of Serum Phosphorus in Adults With X-Linked Hypophosphatemia Using Monthly Doses of KRN23
Imel EA, Zhang X, Ruppe MD, Weber TJ, Klausner MA, Ito T, Vergeire M, Humphrey JS, Glorieux FH, Portale AA, Insogna K, Peacock M, Carpenter TO. Prolonged Correction of Serum Phosphorus in Adults With X-Linked Hypophosphatemia Using Monthly Doses of KRN23. The Journal Of Clinical Endocrinology & Metabolism 2015, 100: 2565-2573. PMID: 25919461, PMCID: PMC4495171, DOI: 10.1210/jc.2015-1551.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedDose-Response Relationship, DrugDrug Administration ScheduleFamilial Hypophosphatemic RicketsFemaleFibroblast Growth Factor-23Fibroblast Growth FactorsGlomerular Filtration RateHumansImmunoglobulin GMaleMiddle AgedPhosphorusRecombinant ProteinsTreatment OutcomeYoung AdultConceptsTmP/GFRSerum PiNormal rangeOpen-label phase 1/2 studyElevated fibroblast growth factor 23Fibroblast growth factor 23Phase 1/2 studyDose-escalation studyGlomerular filtration ratePre-dose levelsGrowth factor 23Favorable safety profileMain outcome measuresProportion of subjectsAcademic medical centerPeak PiSerum inorganic phosphorusPg/mLUrinary calciumDose escalationFactor 23Monthly dosesSerum phosphorusDihydroxyvitamin DSafety profileThe 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
2014
Increased bone resorption during tenofovir plus lopinavir/ritonavir therapy in Chinese individuals with HIV
Hsieh E, Fraenkel L, Xia W, Hu YY, Han Y, Insogna K, Yin MT, Xie J, Zhu T, Li T. Increased bone resorption during tenofovir plus lopinavir/ritonavir therapy in Chinese individuals with HIV. Osteoporosis International 2014, 26: 1035-1044. PMID: 25224293, PMCID: PMC4334679, DOI: 10.1007/s00198-014-2874-3.Peer-Reviewed Original ResearchConceptsHuman immunodeficiency virusLopinavir/ritonavirBone turnover markersBone resorption marker levelsResorption marker levelsNon-Chinese populationsAntiretroviral therapyTreatment failureImmunodeficiency virusMarker levelsSkeletal metabolismC-terminal cross-linking telopeptideLopinavir/ritonavir therapyTreatment-naïve patientsFirst-line therapyBone resorption markersProcollagen type 1Multi-center trialPlasma samplesChinese individualsN-terminal propeptideType 1 collagenRitonavir therapyTurnover markersResorption markersEffect 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 improvementSerum 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 signalingPatientsSclerostinDenosumab for Treatment of Hypercalcemia of Malignancy
Hu MI, Glezerman IG, Leboulleux S, Insogna K, Gucalp R, Misiorowski W, Yu B, Zorsky P, Tosi D, Bessudo A, Jaccard A, Tonini G, Ying W, Braun A, Jain RK. Denosumab for Treatment of Hypercalcemia of Malignancy. The Journal Of Clinical Endocrinology & Metabolism 2014, 99: 3144-3152. PMID: 24915117, PMCID: PMC4154084, DOI: 10.1210/jc.2014-1001.Peer-Reviewed Original ResearchConceptsHypercalcemia of malignancyProportion of patientsDay 10Serum calciumBone resorptionCommon serious adverse eventsMedian response durationSerious adverse eventsSerum calcium levelsTreatment of hypercalcemiaDuration of responseNew treatment optionsBisphosphonate therapyPrimary endpointSecondary endpointsAdverse eventsBisphosphonate treatmentDurable responsesComplete responseAdvanced cancerTreatment optionsHematologic malignanciesResponse durationDenosumabCalcium levelsRandomized 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
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 models