2024
Item Response Theory Quantifies the Relationship Between Improvements in Serum Phosphate and Patient‐Reported Outcomes in Adults With X‐Linked Hypophosphatemia
Mehta K, Gosselin N, Insogna K, Barriere O, Quattrocchi E, Hruska M, Marsteller D. Item Response Theory Quantifies the Relationship Between Improvements in Serum Phosphate and Patient‐Reported Outcomes in Adults With X‐Linked Hypophosphatemia. Clinical Pharmacology & Therapeutics 2024, 116: 1343-1351. PMID: 39129452, DOI: 10.1002/cpt.3406.Peer-Reviewed Original ResearchPatient-reported outcomesPatient-reported outcome dataX-linked hypophosphatemiaItem response theory parametersBrief Fatigue Inventory scoreSerum phosphateWestern Ontario and McMaster Universities Osteoarthritis IndexTreatment-induced improvementMcMaster Universities Osteoarthritis IndexTreatment response biomarkersBrief Pain InventoryInventory scoresAssociated with improvementsPain InventoryOsteoarthritis IndexTreatment optimization strategiesDisability scoresPopulation pharmacokinetic-pharmacodynamic modelPhase III studySerum phosphate levelsRare bone diseasesExposure metricsPharmacokinetic-pharmacodynamic modelLongitudinal dataIII studiesMitofusin 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
2023
Effect of Burosumab on Muscle Function and Strength, and Rates of ATP Synthesis in Skeletal Muscle in Adults With XLH
Insogna K, Sullivan R, Parziale S, Deng Y, Carrano D, Simpson C, Dufour S, Carpenter T, Petersen K. Effect of Burosumab on Muscle Function and Strength, and Rates of ATP Synthesis in Skeletal Muscle in Adults With XLH. The Journal Of Clinical Endocrinology & Metabolism 2023, 109: e1061-e1071. PMID: 37930769, DOI: 10.1210/clinem/dgad642.Peer-Reviewed Original ResearchSymptoms of painMuscle function testsFunction testsMuscle strengthMuscle functionSkeletal muscleLower extremity joint painSTS testMuscle function studiesImproved muscle functionTreatment-naïve adultsSynthesis rateMonths of studyJoint painThird doseSymptomatic adultsClinical trialsRight calfATP synthesis rateBurosumabPainMuscle concentrationsXLHSymptomsMuscleCirculating Levels of Leptin and Lipocalin-2 in Patients With X-Linked Hypophosphatemia
Simpson C, Santoro A, Carpenter T, Deng Y, Parziale S, Insogna K. Circulating Levels of Leptin and Lipocalin-2 in Patients With X-Linked Hypophosphatemia. Journal Of The Endocrine Society 2023, 7: bvad116. PMID: 37860221, PMCID: PMC10583534, DOI: 10.1210/jendso/bvad116.Peer-Reviewed Original ResearchLipocalin-2Control subjectsGreater riskLevels of LCN2Excessive weight gainLevels of leptinSerum leptin levelsCirculating LevelsLCN2 levelsSerum levelsYear age cohortLeptin levelsMetabolic abnormalitiesRetrospective studyAge cohortsInsulin sensitivityHigh prevalencePatientsWeight gainXLHLeptinAge 2HypophosphatemiaObesityChildrenAltered Expression of Several Molecular Mediators of Cerebrospinal Fluid Production in Hyp Mice
Kaplan J, Tommasini S, Yao G, Zhu M, Nishimura S, Ghazarian S, Louvi A, Insogna K. Altered Expression of Several Molecular Mediators of Cerebrospinal Fluid Production in Hyp Mice. Journal Of The Endocrine Society 2023, 7: bvad022. PMID: 36819458, PMCID: PMC9936957, DOI: 10.1210/jendso/bvad022.Peer-Reviewed Original Research
2022
OR13-1 Long-Term Burosumab Therapy Provides Sustained Benefit in Patients with Tumor-Induced Osteomalacia: End of Study Findings From the Pivotal Phase 2 Study
Carpenter T, Cimms T, Hetzer J, Insogna K, Kumar R, Merritt J, Miller P, Peacock M, Rauch F, Stanciu I, Weber T, De Beur S. OR13-1 Long-Term Burosumab Therapy Provides Sustained Benefit in Patients with Tumor-Induced Osteomalacia: End of Study Findings From the Pivotal Phase 2 Study. Journal Of The Endocrine Society 2022, 6: a191-a191. PMCID: PMC9624705, DOI: 10.1210/jendso/bvac150.394.Peer-Reviewed Original ResearchTumor-induced osteomalaciaWeek 240Week 144Week 24Serum phosphorusBurosumab therapyWeek 48Bone biomarkersSafety profileNormal rangeExcess fibroblast growth factor 23SF-36 bodily pain scoresTreatment of TIOPivotal phase 2 studySF-36 physical healthSF-36 vitality scoreFibroblast growth factor 23Surface/bone surfaceBodily pain scoresMean serum phosphorusObserved safety profileRadionucleotide bone scansRare paraneoplastic syndromeBrief Pain InventoryOsteoid surface/bone surfaceLong-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 variablesCorrection to: The clinician’s guide to prevention and treatment of osteoporosis
LeBoff M, Greenspan S, Insogna K, Lewiecki E, Saag K, Singer A, Siris E. Correction to: The clinician’s guide to prevention and treatment of osteoporosis. Osteoporosis International 2022, 33: 2243-2243. PMID: 35900384, PMCID: PMC9546943, DOI: 10.1007/s00198-022-06479-8.Peer-Reviewed Original ResearchThe 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
Use of Denosumab after Zoledronic Acid in Patients with Multiple Myeloma: Real-World Experience from 2015 to 2019 at Yale Cancer Center
Dosani T, Poteraj A, Parker T, Bar N, Browning S, Gorshein E, Anderson T, Insogna K, Neparidze N. Use of Denosumab after Zoledronic Acid in Patients with Multiple Myeloma: Real-World Experience from 2015 to 2019 at Yale Cancer Center. Blood 2021, 138: 4756. DOI: 10.1182/blood-2021-147466.Peer-Reviewed Original ResearchBone-modifying agentsUse of denosumabYale Cancer CenterZoledronic acidMultiple myelomaMM patientsCancer CenterMedian numberPhysician preferenceCommon reasonClinical practiceNew fracturesNuclear factor kappa-B ligandStudy periodApproval of denosumabEfficacy of denosumabIncidence of SREsMain treatment centreSmilow Cancer HospitalSuppress bone turnoverPatient's renal functionBone resorption markersCohort of patientsGlomerular filtration rateDate of diagnosisMusculoskeletal 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 tissueCorticosteroid use in chronic dermatologic disorders and osteoporosis
Lupsa BC, Insogna KL, Micheletti RG, Caplan A. Corticosteroid use in chronic dermatologic disorders and osteoporosis. International Journal Of Women's Dermatology 2021, 7: 545-551. PMID: 35024411, PMCID: PMC8721058, DOI: 10.1016/j.ijwd.2021.07.014.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsGlucocorticoid-induced osteoporosisGlucocorticoid therapyChronic dermatologic disordersUse of glucocorticoidsSerious side effectsGlucocorticoid useCorticosteroid useBone healthBone lossDermatologic disordersSide effectsPatientsOsteoporosisGlucocorticoidsTherapyCase vignettesRiskComplicationsDermatologistsSerum Levels of Lipocalin Are Lower in Adolescents With X-Linked Hypophosphatemia
Simpson C, Santoro A, Carpenter T, Insogna K. Serum Levels of Lipocalin Are Lower in Adolescents With X-Linked Hypophosphatemia. Journal Of The Endocrine Society 2021, 5: a27-a27. PMCID: PMC8089365, DOI: 10.1210/jendso/bvab048.052.Peer-Reviewed Original ResearchWeight/height z-scoreHeight z-scoreExcessive weight gainZ-scoreFibroblast growth factor 23Greater riskWeight gainRegular aerobic exerciseDirect pathogenic roleGrowth factor 23Impaired glucose metabolismVitamin D testingElderly normal individualsAbility of patientsAccelerated osteoarthritisAdult patientsPediatric patientsSerum levelsFactor 23Metabolic abnormalitiesAbnormal biomechanicsInsulin levelsAerobic exerciseInsulin sensitivityPathogenic roleAn 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
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 health