2023
Genetic variants in the vitamin D pathway and their association with vitamin D metabolite levels: Detailed studies of an inner-city pediatric population suggest a modest but significant effect in early childhood
Fu L, Wong B, Li Z, Horst R, Williams R, Lee B, Miller J, Carpenter T, Cole D. Genetic variants in the vitamin D pathway and their association with vitamin D metabolite levels: Detailed studies of an inner-city pediatric population suggest a modest but significant effect in early childhood. The Journal Of Steroid Biochemistry And Molecular Biology 2023, 233: 106369. PMID: 37490983, DOI: 10.1016/j.jsbmb.2023.106369.Peer-Reviewed Original ResearchConceptsVitamin D pathwayD binding proteinPediatric populationInner-city pediatric populationVitamin D metabolite levelsVitamin D insufficiencyRisk pediatric populationsVitamin D metabolismVitamin D binding proteinVitamin D metabolitesD pathwayMonths of ageSanger sequencing confirmationD insufficiencyHealthy infantsD metabolismD levelsD metabolitesMultivariate regression modelLarge cohortMetabolite levelsRelevant associationsPotential roleEarly childhoodInter-individual differences
2022
The efficacy and safety of burosumab in two patients with cutaneous skeletal hypophosphatemia syndrome
Sugarman J, Maruri A, Hamilton D, Tabatabai L, Luca D, Cimms T, Krolczyk S, Roberts M, Carpenter T. The efficacy and safety of burosumab in two patients with cutaneous skeletal hypophosphatemia syndrome. Bone 2022, 166: 116598. PMID: 36341949, DOI: 10.1016/j.bone.2022.116598.Peer-Reviewed Original ResearchConceptsCutaneous skeletal hypophosphatemia syndromeTumor-induced osteomalaciaBurosumab therapyDaily dosesMild injection site reactionsActive vitamin D analoguesExtra-cutaneous manifestationsMore daily dosesMultiple daily dosesSafety of burosumabTreatment of XLHDihydroxyvitamin D levelsInjection site reactionsCurrent treatment optionsLow serum phosphorusPromising therapeutic optionVitamin D analogsHuman monoclonal antibodyOral phosphorusAdult patientsAdverse eventsBone healthSerum phosphorusTherapeutic optionsD levels
2021
Novel homozygous variant in BMP1 associated with a rare osteogenesis imperfecta phenotype
Choksi I, Cox A, Robinson C, Bale A, Carpenter T. Novel homozygous variant in BMP1 associated with a rare osteogenesis imperfecta phenotype. Osteoporosis International 2021, 32: 1239-1244. PMID: 33624138, DOI: 10.1007/s00198-021-05838-1.Peer-Reviewed Original ResearchConceptsVertebral compression fracturesNovel homozygous variantOsteogenesis imperfectaMultiple vertebral compression fracturesZ-scoreHomozygous variantBilateral tibial fracturesLumbar spine BMDTotal hip BMDEffectiveness of bisphosphonatesFemoral neck BMDHeight z-scoreHomozygous missense variantBroad phenotypic spectrumBisphosphonate therapyBP therapySpinal osteopeniaSymptomatic reliefClinical presentationRecurrent fracturesSpine BMDTibial fracturesCompression fracturesHip BMDNeck BMD
2019
Relationship of Total and Free 25-Hydroxyvitamin D to Biomarkers and Metabolic Indices in Healthy Children
Simpson CA, Zhang JH, Vanderschueren D, Fu L, Pennestri TC, Bouillon R, Cole DEC, Carpenter TO. Relationship of Total and Free 25-Hydroxyvitamin D to Biomarkers and Metabolic Indices in Healthy Children. The Journal Of Clinical Endocrinology & Metabolism 2019, 105: dgz230. PMID: 31774125, PMCID: PMC7174047, DOI: 10.1210/clinem/dgz230.Peer-Reviewed Original ResearchConceptsBody mass indexVitamin D statusParathyroid hormoneUrban-dwelling childrenD statusGC haplotypeHomeostatic model assessmentSystolic blood pressureAcademic medical centerHeathy childrenBlood pressureClinical outcomesMass indexInsulin resistanceHealthy childrenMedical CenterMetabolic indicesModel assessmentRegistration noOutcome variablesHispanic backgroundChildrenStrongest correlateInsulinAvailable assessmentsSeverity of reduced bone mineral density and risk of fractures in long‐term survivors of childhood leukemia and lymphoma undergoing guideline‐recommended surveillance for bone health
Bloomhardt HM, Sint K, Ross WL, Rotatori J, Ness K, Robinson C, Carpenter TO, Chow EJ, Kadan‐Lottick N. Severity of reduced bone mineral density and risk of fractures in long‐term survivors of childhood leukemia and lymphoma undergoing guideline‐recommended surveillance for bone health. Cancer 2019, 126: 202-210. PMID: 31536650, DOI: 10.1002/cncr.32512.Peer-Reviewed Original ResearchConceptsLow bone mineral densityReduced bone mineral densityBone mineral densityLymphoma survivorsMineral densityLumbar spine BMD Z-scoreChildhood leukemia/lymphomaPatient/treatment factorsSpine BMD Z-scoreDual-energy X-ray absorptiometryGuideline-recommended surveillanceBMD Z-scoresLong-term survivorsRisk of fractureCross-sectional studyLeukemia/lymphomaLong bone fracturesX-ray absorptiometrySurvivorship clinicBone healthMultivariable analysisMean ageChronic conditionsMedical recordsWhite raceRickets severity predicts clinical outcomes in children with X-linked hypophosphatemia: Utility of the radiographic Rickets Severity Score
Thacher TD, Pettifor JM, Tebben PJ, Creo AL, Skrinar A, Mao M, Chen CY, Chang T, San Martin J, Carpenter TO. Rickets severity predicts clinical outcomes in children with X-linked hypophosphatemia: Utility of the radiographic Rickets Severity Score. Bone 2019, 122: 76-81. PMID: 30772600, DOI: 10.1016/j.bone.2019.02.010.Peer-Reviewed Original ResearchConceptsRickets Severity ScoreSerum alkaline phosphataseSeverity scoreSevere self-reported painPediatric Outcomes Data Collection InstrumentPhase 2 clinical trialAlkaline phosphataseLess physical functionSelf-reported painSevere clinical featuresHeight z-scoreRadiographic Global ImpressionPediatric Orthopaedic SocietyIntra-rater reliabilitySubstantial inter-rater reliabilityClinical featuresClinical outcomesBilateral kneesGlobal ImpressionPhysical functionSubstantial intra-rater reliabilityWeek 64Clinical trialsBurosumab treatmentFunctional impairment
2018
Burosumab Therapy in Children with X-Linked Hypophosphatemia
Carpenter TO, Whyte MP, Imel EA, Boot AM, Högler W, Linglart A, Padidela R, Van't Hoff W, Mao M, Chen CY, Skrinar A, Kakkis E, San Martin J, Portale AA. Burosumab Therapy in Children with X-Linked Hypophosphatemia. New England Journal Of Medicine 2018, 378: 1987-1998. PMID: 29791829, DOI: 10.1056/nejmoa1714641.Peer-Reviewed Original ResearchMeSH KeywordsAlkaline PhosphataseAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedChildChild, PreschoolFamilial Hypophosphatemic RicketsFemaleFibroblast Growth Factor-23Fibroblast Growth FactorsGenetic Diseases, X-LinkedGrowthHumansKidney TubulesKnee JointMalePain ManagementPhosphorusRadiographySeverity of Illness IndexConceptsSerum phosphorus levelsRenal tubular phosphate reabsorptionTubular phosphate reabsorptionWeek 40Week 64Adverse eventsPhosphate reabsorptionNormal rangeMean serum phosphorus levelFibroblast growth factor 23End pointMean serum alkaline phosphatase levelSerum alkaline phosphatase levelsTotal scorePrimary end pointPhase 2 trialGrowth factor 23Additional end pointsPatient-reported outcomesAlkaline phosphatase levelsRadiographic Global ImpressionPhosphorus levelsOverall mean increaseBurosumab therapySubcutaneous burosumab
2017
Rickets
Carpenter TO, Shaw NJ, Portale AA, Ward LM, Abrams SA, Pettifor JM. Rickets. Nature Reviews Disease Primers 2017, 3: 17101. PMID: 29265106, DOI: 10.1038/nrdp.2017.101.Peer-Reviewed Original ResearchConceptsVitamin D metabolismNutritional ricketsD metabolismVitamin DFibroblast growth factor 23 productionAbnormal serum calciumActivated vitamin DOral phosphate supplementationVitamin D supplementationRenal phosphate handlingVitamin D metabolitesAge of onsetDarker skin typesD supplementationFGF23 antibodyClinical presentationSerum calciumPhysical examinationD metabolitesMedical historyPhosphate handlingBone diseasePhosphopenic ricketsPhosphate supplementationConventional treatmentUnexpected widespread hypophosphatemia and bone disease associated with elemental formula use in infants and children
Ballesteros L, S. N, Gordon RJ, Ward L, Backeljauw P, Wasserman H, Weber DR, DiMeglio LA, Gagne J, Stein R, Cody D, Simmons K, Zimakas P, Topor LS, Agrawal S, Calabria A, Tebben P, Faircloth R, Imel EA, Casey L, Carpenter TO. Unexpected widespread hypophosphatemia and bone disease associated with elemental formula use in infants and children. Bone 2017, 97: 287-292. PMID: 28167344, PMCID: PMC5884631, DOI: 10.1016/j.bone.2017.02.003.Peer-Reviewed Original ResearchConceptsElemental formula useFormula useSkeletal diseaseRetrospective chart reviewInadequate dietary intakeCertain clinical settingsFormula productsEffect of treatmentSevere malabsorptionChart reviewSevere hypocalcemiaClinical featuresClinical profileRenal excretionDietary intakeCommon findingMineral metabolismBone diseaseHypophosphatemiaPhosphate supplementationSkeletal radiographsCareful monitoringComplex illnessRenal conservationClinical setting
2015
A Practical Clinical Approach to Paediatric Phosphate Disorders
Imel EA, Carpenter TO. A Practical Clinical Approach to Paediatric Phosphate Disorders. Endocrine Development 2015, 28: 134-161. PMID: 26138840, DOI: 10.1159/000381036.Peer-Reviewed Original ResearchConceptsPhosphate disordersPractical clinical approachChronic clinical conditionsPhosphate metabolismChronic hypophosphataemiaPhosphate abnormalitiesAppropriate therapyChronic disordersPathophysiologic assessmentClinical conditionsClinical approachPhosphate physiologyCareful evaluationHyperphosphataemiaHypophosphataemiaDisordersMetabolismPatientsTherapyEtiologyAbnormalitiesDiseaseContemporary Medical and Surgical Management of X-linked Hypophosphatemic Rickets
Sharkey MS, Grunseich K, Carpenter TO. Contemporary Medical and Surgical Management of X-linked Hypophosphatemic Rickets. Journal Of The American Academy Of Orthopaedic Surgeons 2015, 23: 433-442. PMID: 26040953, DOI: 10.5435/jaaos-d-14-00082.Peer-Reviewed Original ResearchConceptsBony deformityProgressive bony deformityCornerstone of treatmentCareful surgical planningOrthopedic surgical proceduresMedical therapyMedical managementSurgical managementGradual correctionSurgical techniqueDeformity correctionSurgical proceduresBone deformitiesHypophosphatemic ricketsMedical treatmentRenal phosphateHypophosphatemiaContemporary medicalBone pathologySuccessful correctionSurgical planningDeformityInheritable disorderTreatmentAdultsAssociation between serum 25‐hydroxyvitamin D level and pulmonary exacerbations in cystic fibrosis
Vanstone MB, Egan ME, Zhang JH, Carpenter TO. Association between serum 25‐hydroxyvitamin D level and pulmonary exacerbations in cystic fibrosis. Pediatric Pulmonology 2015, 50: 441-446. PMID: 25657016, DOI: 10.1002/ppul.23161.Peer-Reviewed Original ResearchConceptsPulmonary function testsCystic fibrosisPulmonary exacerbationsPediatric patientsD levelsYale-New Haven HospitalPediatric CF patientsVitamin D sufficiencyRetrospective chart reviewVitamin D statusStrongest independent determinantCF care centersPatients ages 5Logistic regression analysisAnnual numberD sufficiencyD statusChart reviewClinic visitsLung functionPulmonary functionAntibiotic therapyFunction testsHospitalization ratesIndependent determinants
2014
Effect 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 improvementMutations in SLC34A3/NPT2c Are Associated with Kidney Stones and Nephrocalcinosis
Dasgupta D, Wee MJ, Reyes M, Li Y, Simm PJ, Sharma A, Schlingmann KP, Janner M, Biggin A, Lazier J, Gessner M, Chrysis D, Tuchman S, Baluarte HJ, Levine MA, Tiosano D, Insogna K, Hanley DA, Carpenter TO, Ichikawa S, Hoppe B, Konrad M, Sävendahl L, Munns CF, Lee H, Jüppner H, Bergwitz C. Mutations in SLC34A3/NPT2c Are Associated with Kidney Stones and Nephrocalcinosis. Journal Of The American Society Of Nephrology 2014, 25: 2366-2375. PMID: 24700880, PMCID: PMC4178443, DOI: 10.1681/asn.2013101085.Peer-Reviewed Original ResearchConceptsIdiopathic hypercalciuriaDecreased tubular reabsorption of phosphateIncreased risk of kidney stone formationSerum 1,25(OH)2 vitamin DTubular reabsorption of phosphateAssociated with kidney stonesVitamin D levelsSolute carrier family 34Renal phosphate wastingDecreased serum phosphateHereditary hypophosphatemic ricketsHealthy family membersReabsorption of phosphateRisk of kidney stone formationRickets/osteomalaciaDecreased tubular reabsorptionKidney stone formationSLC34A3 mutationsIndependent of genotypeMedullary nephrocalcinosisSerum phosphateVitamin DDependent phosphate cotransporterTubular reabsorptionD levels
2012
Hypercalcemia in Children Receiving Pharmacologic Doses of Vitamin D
Vanstone MB, Oberfield SE, Shader L, Ardeshirpour L, Carpenter TO. Hypercalcemia in Children Receiving Pharmacologic Doses of Vitamin D. Pediatrics 2012, 129: e1060-e1063. PMID: 22412034, PMCID: PMC8194455, DOI: 10.1542/peds.2011-1663.Peer-Reviewed Original ResearchConceptsVitamin DSerum calciumPeak serum calciumResolution of hypercalcemiaWide dosing rangeElevated serum calciumVitamin D deficiencyAge-specific guidelinesAge 2 weeksAdministration of dosagesDaily dietary intakeD deficiencyDeficient ricketsPharmacologic dosesTreatment regimensD levelsHypervitaminosis DDietary intakeDosage recommendationsDose selectionDosing rangeGeneral populationPharmacologic dosingHypercalcemiaSmall children
2010
Circulating Levels of Soluble Klotho and FGF23 in X-Linked Hypophosphatemia: Circadian Variance, Effects of Treatment, and Relationship to Parathyroid Status
Carpenter TO, Insogna KL, Zhang JH, Ellis B, Nieman S, Simpson C, Olear E, Gundberg CM. Circulating Levels of Soluble Klotho and FGF23 in X-Linked Hypophosphatemia: Circadian Variance, Effects of Treatment, and Relationship to Parathyroid Status. The Journal Of Clinical Endocrinology & Metabolism 2010, 95: e352-e357. PMID: 20685863, PMCID: PMC2968736, DOI: 10.1210/jc.2010-0589.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAge FactorsAgedBone Density Conservation AgentsCalcitriolChildCircadian RhythmEnzyme-Linked Immunosorbent AssayFamilial Hypophosphatemic RicketsFemaleFibroblast Growth Factor-23Fibroblast Growth FactorsGenetic Diseases, X-LinkedGlucuronidaseHumansKlotho ProteinsMaleMiddle AgedParathyroid HormonePhosphatesVitamin DConceptsSerum KlothoSerum FGF23Higher klotho levelsHospital research unitRenal phosphate handlingAcademic medical centerEffect of treatmentFibroblast growth factorKlotho levelsPTH secretionMedical therapySoluble KlothoDihydroxyvitamin DFGF23 regulationPhosphate handlingMedical CenterFGF23KlothoXLHCircadian variationGrowth factorPTHAdultsHypophosphatemiaTherapyTreatment of X-Linked Hypophosphatemia with Calcitriol and Phosphate Increases Circulating Fibroblast Growth Factor 23 Concentrations
Imel EA, DiMeglio LA, Hui SL, Carpenter TO, Econs MJ. Treatment of X-Linked Hypophosphatemia with Calcitriol and Phosphate Increases Circulating Fibroblast Growth Factor 23 Concentrations. The Journal Of Clinical Endocrinology & Metabolism 2010, 95: 1846-1850. PMID: 20157195, PMCID: PMC2853995, DOI: 10.1210/jc.2009-1671.Peer-Reviewed Original ResearchConceptsFGF23 concentrationsXLH patientsFibroblast growth factor 23 concentrationsGrowth factor 23 concentrationsFibroblast Growth Factor 23 ExpressionComplications of therapyDihydroxyvitamin D concentrationsProspective observational studyTertiary referral centerIntact FGF23 concentrationsRoutine clinical managementOral calcitriolReferral centerClinical managementFGF23 elevationObservational studyTherapeutic effectRenal phosphateCalcitriolD concentrationsDisease severityNormal serumVivo modelTherapyMost subjects
2009
Survey of the Enthesopathy of X-Linked Hypophosphatemia and Its Characterization in Hyp Mice
Liang G, Katz LD, Insogna KL, Carpenter TO, Macica CM. Survey of the Enthesopathy of X-Linked Hypophosphatemia and Its Characterization in Hyp Mice. Calcified Tissue International 2009, 85: 235-246. PMID: 19609735, PMCID: PMC2988401, DOI: 10.1007/s00223-009-9270-6.Peer-Reviewed Original ResearchMeSH KeywordsAchilles TendonAdolescentAdultAgedAnimalsBiomarkersCalcinosisChildDisease Models, AnimalDisease ProgressionFamilial Hypophosphatemic RicketsFemaleFibroblast Growth Factor-23Fibroblast Growth FactorsGenetic Diseases, X-LinkedHumansMiceMice, Inbred C57BLMiddle AgedPatellar LigamentPhenotypeQuadriceps MuscleRadiographyRheumatic DiseasesTendinopathyTendonsYoung AdultConceptsFGF-23Fibroblast growth factor receptor 3Hyp miceMajority of patientsHigh circulating levelsPhosphate-regulating hormoneBone spur formationTendon insertion siteGrowth factor receptor 3Insertion siteLigament insertion sitesCirculating LevelsPhosphate excretionBone-forming osteoblastsHeterotopic calcificationOsteophyte formationHistological examinationMurine modelReceptor 3Spur formationHypophosphatemiaEnthesis fibrocartilageBone mineralizationBiochemical milieuMice
2008
Dual Energy X-ray Absorptiometry Interpretation and Reporting in Children and Adolescents: The 2007 ISCD Pediatric Official Positions
Gordon CM, Bachrach LK, Carpenter TO, Crabtree N, Fuleihan G, Kutilek S, Lorenc RS, Tosi LL, Ward KA, Ward LM, Kalkwarf HJ. Dual Energy X-ray Absorptiometry Interpretation and Reporting in Children and Adolescents: The 2007 ISCD Pediatric Official Positions. Journal Of Clinical Densitometry 2008, 11: 43-58. PMID: 18442752, DOI: 10.1016/j.jocd.2007.12.005.Peer-Reviewed Original Research
2007
Evaluation of bone and mineral disorders.
Ardeshirpour L, Cole DE, Carpenter TO. Evaluation of bone and mineral disorders. Pediatric Endocrinology Reviews : PER 2007, 5 Suppl 1: 584-98. PMID: 18167468.Peer-Reviewed Original ResearchConceptsParathyroid hormoneVitamin D homeostasisVitamin D metabolitesEvaluation of boneD homeostasisD metabolitesMineral disordersDiagnostic modalitiesHormonal imbalanceMetabolic diseasesDiagnostic acumenGenetic testingHereditary disorderSkeletal systemHormoneDisordersDiagnostic capabilitiesBoneConcise reviewCalciumWidespread useDiseaseImpairment