2020
Musculoskeletal Comorbidities and Quality of Life in ENPP1‐Deficient Adults and the Response of Enthesopathy to Enzyme Replacement Therapy in Murine Models
Ferreira CR, Ansh AJ, Nester C, O'Brien C, Stabach PR, Murtada S, Lester ER, Khursigara G, Molloy L, Carpenter TO, Braddock DT. Musculoskeletal Comorbidities and Quality of Life in ENPP1‐Deficient Adults and the Response of Enthesopathy to Enzyme Replacement Therapy in Murine Models. Journal Of Bone And Mineral Research 2020, 37: 494-504. PMID: 34882836, PMCID: PMC9667476, DOI: 10.1002/jbmr.4487.Peer-Reviewed Original ResearchConceptsENPP1 deficiencyAsj/Musculoskeletal complicationsBrief Pain Inventory-Short FormPhysical Function Short FormFibroblast growth factor 23Achilles tendon calcificationHealth-related qualityMajority of patientsGrowth factor 23Cervical spine fusionPresence of enthesopathyQuality of lifeAnalgesic medicationRegular chowResidual painAdult patientsDose escalationFactor 23Replacement therapyPhysical functionCardiovascular calcificationTendon calcificationAchilles tendonSpine fusionResponse of the ENPP1‐Deficient Skeletal Phenotype to Oral Phosphate Supplementation and/or Enzyme Replacement Therapy: Comparative Studies in Humans and Mice
Ferreira CR, Kavanagh D, Oheim R, Zimmerman K, Stürznickel J, Li X, Stabach P, Rettig RL, Calderone L, MacKichan C, Wang A, Hutchinson HA, Nelson T, Tommasini SM, von Kroge S, Fiedler IA, Lester ER, Moeckel GW, Busse B, Schinke T, Carpenter TO, Levine MA, Horowitz MC, Braddock DT. Response of the ENPP1‐Deficient Skeletal Phenotype to Oral Phosphate Supplementation and/or Enzyme Replacement Therapy: Comparative Studies in Humans and Mice. Journal Of Bone And Mineral Research 2020, 36: 942-955. PMID: 33465815, PMCID: PMC8739051, DOI: 10.1002/jbmr.4254.Peer-Reviewed Original ResearchConceptsBone mineral densityLow bone mineral densityTrabecular bone massBone massEarly-onset osteoporosisAsj/Conventional therapyLower trabecular bone massGreater bone fragilityRisk of nephrocalcinosisHigh-phosphate dietLow bone massCortical bone massDevelopment of nephrocalcinosisBone biomechanical propertiesAcademic medical centerPlasma phosphorus concentrationsAutosomal recessive hypophosphatemic ricketsRecessive hypophosphatemic ricketsENPP1 deficiencyRachitic phenotypeMedullary nephrocalcinosisRenal failureNormal chowMineral densityGenetic pathways disrupted by ENPP1 deficiency provide insight into mechanisms of osteoporosis, osteomalacia, and paradoxical mineralization
Maulding ND, Kavanagh D, Zimmerman K, Coppola G, Carpenter TO, Jue NK, Braddock DT. Genetic pathways disrupted by ENPP1 deficiency provide insight into mechanisms of osteoporosis, osteomalacia, and paradoxical mineralization. Bone 2020, 142: 115656. PMID: 32980560, PMCID: PMC7744330, DOI: 10.1016/j.bone.2020.115656.Peer-Reviewed Original ResearchConceptsGenetic pathwaysSkeletal phenotypeGene expressionHuman disease phenotypesAsj/Suppression of WntTranscript countsGene transcriptionENPP1-deficient miceGene pathwaysEnzyme functionENPP1 deficiencyWnt ligandsSoluble Wnt inhibitorsWnt activityReduced gene transcriptionBiomechanical phenotypeTranscriptionWnt inhibitorsBone findingsUnbiased analysisDisease phenotypePhenotypeOld miceStrong signature
2019
Human Heterozygous ENPP1 Deficiency Is Associated With Early Onset Osteoporosis, a Phenotype Recapitulated in a Mouse Model of Enpp1 Deficiency
Oheim R, Zimmerman K, Maulding ND, Stürznickel J, von Kroge S, Kavanagh D, Stabach PR, Kornak U, Tommasini SM, Horowitz MC, Amling M, Thompson D, Schinke T, Busse B, Carpenter TO, Braddock DT. Human Heterozygous ENPP1 Deficiency Is Associated With Early Onset Osteoporosis, a Phenotype Recapitulated in a Mouse Model of Enpp1 Deficiency. Journal Of Bone And Mineral Research 2019, 35: 528-539. PMID: 31805212, PMCID: PMC7184798, DOI: 10.1002/jbmr.3911.Peer-Reviewed Original ResearchConceptsAutosomal recessive hypophosphatemic rickets type 2ENPP1 deficiencyEarly-onset osteoporosisGene-dose effectOnset osteoporosisAsj/Bone mineral density scansBone mineralization disturbancesRenal phosphate wastingCortical boneDose effectMild osteomalaciaMineralization disturbancesFGF23 levelsMild elevationPlasma FGF23Arterial calcificationBone massPhosphate wastingSkeletal manifestationsBone fragilityThoracic spineWild-type family membersType 2Adult men