2022
Long-term Burosumab Administration Is Safe and Effective in Adults With X-linked Hypophosphatemia
Weber TJ, Imel EA, Carpenter TO, Peacock M, Portale AA, Hetzer J, Merritt JL, Insogna K. Long-term Burosumab Administration Is Safe and Effective in Adults With X-linked Hypophosphatemia. The Journal Of Clinical Endocrinology & Metabolism 2022, 108: 155-165. PMID: 36072994, PMCID: PMC9759172, DOI: 10.1210/clinem/dgac518.Peer-Reviewed Original ResearchConceptsSerum phosphate levelsPatient-reported outcomesNormal rangeBurosumab therapyTreatment optionsEffective long-term treatment optionLong-term extension studyLong-term treatment optionNew safety findingsBone turnover markersLong-term administrationPhosphate levelsRespective normal rangesProportion of subjectsLong-term safetyLast doseAdult patientsClinical responseSafety findingsTurnover markersSerum phosphateBone biomarkersStudy endWeek 12Burosumab treatmentDiffering effects of oral conjugated equine estrogen and transdermal estradiol on vitamin D metabolism in postmenopausal women: a 4-year longitudinal study
Santoro AM, Simpson CA, Cong E, Haas A, Sullivan RR, Parziale S, Deng Y, Insogna KL. Differing effects of oral conjugated equine estrogen and transdermal estradiol on vitamin D metabolism in postmenopausal women: a 4-year longitudinal study. Menopause The Journal Of The North American Menopause Society 2022, 29: 1200-1203. PMID: 35969885, DOI: 10.1097/gme.0000000000002045.Peer-Reviewed Original ResearchConceptsTransdermal estradiol groupConjugated equine estrogensVitamin D metabolismTransdermal estradiolEquine estrogensPostmenopausal womenEstradiol groupTreatment armsD metabolismVitamin DD levelsKronos Early Estrogen Prevention StudyConjugated equine estrogen groupOral conjugated equine estrogenVitamin D insufficientLeast square mean valuesEstrogen groupMicronized progesteroneEstrogen replacementPrevention StudySignificant treatment effectStudy groupTreatment groupsShort-term benefitsTreatment assignmentEfficacy of Burosumab in Adults with X-linked Hypophosphatemia (XLH): A Post Hoc Subgroup Analysis of a Randomized Double-Blind Placebo-Controlled Phase 3 Study
Brandi ML, Jan de Beur S, Briot K, Carpenter T, Cheong HI, Cohen-Solal M, Crowley RK, Eastell R, Imanishi Y, Imel EA, Ing SW, Insogna K, Ito N, Javaid K, Kamenicky P, Keen R, Kubota T, Lachmann RH, Perwad F, Pitukcheewanont P, Portale A, Ralston SH, Tanaka H, Weber TJ, Yoo HW, Sun W, Williams A, Nixon A, Takeuchi Y. Efficacy of Burosumab in Adults with X-linked Hypophosphatemia (XLH): A Post Hoc Subgroup Analysis of a Randomized Double-Blind Placebo-Controlled Phase 3 Study. Calcified Tissue International 2022, 111: 409-418. PMID: 35927518, DOI: 10.1007/s00223-022-01006-7.Peer-Reviewed Original ResearchConceptsPhase 3 studySubgroup analysisPhysical functionMean serum phosphate concentrationPost-hoc subgroup analysesAdditional efficacy endpointsPlacebo-controlled periodDouble-blind placeboSerum phosphate concentrationEfficacy endpointPain domainPain medicationTreatment armsSymptomatic adultsOpioid/Western OntarioBurosumabPlaceboTest distanceHypophosphatemiaRelevant subgroupsTotal scoreEndpointConfidence intervalsSubgroup variablesThe 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 participantsBurosumab treatment in adults with X-linked hypophosphataemia: 96-week patient-reported outcomes and ambulatory function from a randomised phase 3 trial and open-label extension
Briot K, Portale AA, Brandi ML, Carpenter TO, Cheong HI, Cohen-Solal M, Crowley RK, Eastell R, Imanishi Y, Ing S, Insogna K, Ito N, de Beur S, Javaid MK, Kamenicky P, Keen R, Kubota T, Lachmann RH, Perwad F, Pitukcheewanont P, Ralston SH, Takeuchi Y, Tanaka H, Weber TJ, Yoo HW, Nixon A, Nixon M, Sun W, Williams A, Imel EA. Burosumab treatment in adults with X-linked hypophosphataemia: 96-week patient-reported outcomes and ambulatory function from a randomised phase 3 trial and open-label extension. RMD Open 2021, 7: e001714. PMID: 34548383, PMCID: PMC8458321, DOI: 10.1136/rmdopen-2021-001714.Peer-Reviewed Original ResearchConceptsBrief Pain Inventory-Short FormPatient-reported outcomesBrief Fatigue InventoryBPI-SF scoresAmbulatory functionWeek 96Burosumab treatmentMcMaster Universities Osteoarthritis IndexOpen-label extensionDouble-blinded trialPhase 3 trialMin walk testSignificant improvementWOMAC stiffnessOsteoarthritis IndexWeek 48Worse fatigueWeek 24Walk testFatigue InventoryWestern OntarioBFI scoresSubstantial burdenWOMACBurosumabUpdate 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 tissueSelective 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
Burosumab for the Treatment of Tumor‐Induced Osteomalacia
de Beur S, Miller PD, Weber TJ, Peacock M, Insogna K, Kumar R, Rauch F, Luca D, Cimms T, Roberts MS, San Martin J, Carpenter TO. Burosumab for the Treatment of Tumor‐Induced Osteomalacia. Journal Of Bone And Mineral Research 2020, 36: 627-635. PMID: 33338281, PMCID: PMC8247961, DOI: 10.1002/jbmr.4233.Peer-Reviewed Original ResearchConceptsTumor-induced osteomalaciaCutaneous skeletal hypophosphatemia syndromeSerious adverse eventsAdverse eventsWeek 144Week 48Serum phosphorusTreatment-related adverse eventsFibroblast growth factor 23Surface/bone surfaceAcceptable safety profileOsteoid surface/bone surfacePhase 2 studyGrowth factor 23Phosphaturic mesenchymal tumorTransiliac bone biopsiesHuman monoclonal antibodyMineralization lag timePhosphate metabolismQuality of lifeDose titrationFactor 23Safety profileMesenchymal tumorsSkeletal healthReply to: Burosumab for Tumor‐Induced Osteomalacia: not Enough of a Good Thing
de Beur S, Miller PD, Weber TJ, Peacock M, Insogna K, Kumar R, Rauch F, Luca D, Cimms T, Roberts MS, San Martin J, Carpenter TO. Reply to: Burosumab for Tumor‐Induced Osteomalacia: not Enough of a Good Thing. Journal Of Bone And Mineral Research 2020, 36: 2455-2456. PMID: 34030212, PMCID: PMC9290665, DOI: 10.1002/jbmr.4317.Peer-Reviewed Original ResearchEpidemiology, 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 factorsNew Therapies for Hypophosphatemia-Related to FGF23 Excess
Athonvarangkul D, Insogna KL. New Therapies for Hypophosphatemia-Related to FGF23 Excess. Calcified Tissue International 2020, 108: 143-157. PMID: 32504139, DOI: 10.1007/s00223-020-00705-3.BooksConceptsTumor-induced osteomalaciaCutaneous skeletal hypophosphatemia syndromeEpidermal nevus syndromeAutosomal dominant hypophosphatemic ricketsAutosomal recessive hypophosphatemic ricketsHypophosphatemic ricketsForms of FGF23Treatment of XLHActive comparator trialsMainstay of therapyMonoclonal blocking antibodyNew treatment modalitiesMcCune-Albright syndromeRenal phosphate wastingRecessive hypophosphatemic ricketsDominant hypophosphatemic ricketsFGF23 excessComparator trialsSkeletal complicationsChronic hypophosphatemiaMusculoskeletal syndromeOngoing trialsClinical presentationTreatment modalitiesClinical trials
2019
Burosumab Improved Histomorphometric Measures of Osteomalacia in Adults with X‐Linked Hypophosphatemia: A Phase 3, Single‐Arm, International Trial
Insogna KL, Rauch F, Kamenický P, Ito N, Kubota T, Nakamura A, Zhang L, Mealiffe M, San Martin J, Portale AA. Burosumab Improved Histomorphometric Measures of Osteomalacia in Adults with X‐Linked Hypophosphatemia: A Phase 3, Single‐Arm, International Trial. Journal Of Bone And Mineral Research 2019, 34: 2183-2191. PMID: 31369697, PMCID: PMC6916280, DOI: 10.1002/jbmr.3843.Peer-Reviewed Original ResearchConceptsAdverse eventsWeek 48Fracture healingMore treatment-emergent adverse eventsTreatment-emergent adverse eventsProcedure-related adverse eventsOsteoid volume/bone volumeMost adverse eventsSerious adverse eventsTransiliac bone biopsiesSerum phosphorus concentrationPoor bone qualityRenal phosphate reabsorptionHuman monoclonal antibodyBone painPersistent osteomalaciaSubcutaneous burosumabPrimary endpointSkeletal complicationsAtraumatic fracturesChronic hypophosphatemiaSerum phosphorusDihydroxyvitamin DBone turnoverBone biopsyContinued 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 periodBurosumabClinical and genetic analysis in a large Chinese cohort of patients with X-linked hypophosphatemia
Zhang C, Zhao Z, Sun Y, Xu L, JiaJue R, Cui L, Pang Q, Jiang Y, Li M, Wang O, He X, He S, Nie M, Xing X, Meng X, Zhou X, Yan L, Kaplan JM, Insogna KL, Xia W. Clinical and genetic analysis in a large Chinese cohort of patients with X-linked hypophosphatemia. Bone 2019, 121: 212-220. PMID: 30682568, DOI: 10.1016/j.bone.2019.01.021.Peer-Reviewed Original ResearchAdolescentAdultChildChild, PreschoolChinaFamilial Hypophosphatemic RicketsFemaleFibroblast Growth Factor-23Fibroblast Growth FactorsGenetic Association StudiesHumansInfantMaleMiddle AgedMutationPHEX Phosphate Regulating Neutral EndopeptidasePoint MutationRetrospective StudiesSex CharacteristicsYoung Adult
2018
Primary Hyperparathyroidism
Insogna KL. Primary Hyperparathyroidism. New England Journal Of Medicine 2018, 379: e43. PMID: 30575486, DOI: 10.1056/nejmc1813648.BooksPrimary 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 subscaleAnimal versus plant protein and adult bone health: A systematic review and meta-analysis from the National Osteoporosis Foundation
Shams-White MM, Chung M, Fu Z, Insogna KL, Karlsen MC, LeBoff MS, Shapses SA, Sackey J, Shi J, Wallace TC, Weaver CM. Animal versus plant protein and adult bone health: A systematic review and meta-analysis from the National Osteoporosis Foundation. PLOS ONE 2018, 13: e0192459. PMID: 29474360, PMCID: PMC5825010, DOI: 10.1371/journal.pone.0192459.Peer-Reviewed Original ResearchConceptsBone mineral densityBone mineral contentTB bone mineral contentStrength of evidenceTotal hipLumbar spineBone healthTotal bodyFemoral neck (FN) BMDHealthy adultsSystematic reviewTB bone mineral densityIsoflavone-rich soy proteinProspective cohort studyAdult bone healthPost-menopausal womenSoy protein consumptionNational Osteoporosis FoundationMeta-analysis resultsCohort studyBMD outcomesBone biomarkersMineral densityStatistical heterogeneityResorption biomarkersAssociations 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 correlation