title: Clinical Trial of the Protein Farnesylation Inhibitors Lonafarnib, Pravastatin, and Zoledronic Acid in Children With Hutchinson-Gilford Progeria Syndrome.
abstract: Hutchinson-Gilford progeria syndrome is an extremely rare, fatal, segmental premature aging syndrome caused by a mutation in LMNA yielding the farnesylated aberrant protein progerin. Without progerin-specific treatment, death occurs at an average age of 14.6 years from an accelerated atherosclerosis. A previous single-arm clinical trial demonstrated that the protein farnesyltransferase inhibitor lonafarnib ameliorates some aspects of cardiovascular and bone disease. This present trial sought to further improve disease by additionally inhibiting progerin prenylation.
  
  
  
  Thirty-seven participants with Hutchinson-Gilford progeria syndrome received pravastatin, zoledronic acid, and lonafarnib. This combination therapy was evaluated, in addition to descriptive comparisons with the prior lonafarnib monotherapy trial.
  
  
  
  No participants withdrew because of side effects. Primary outcome success was predefined by improved per-patient rate of weight gain or carotid artery echodensity; 71.0% of participants succeeded (P<0.0001). Key cardiovascular and skeletal secondary variables were predefined. Secondary improvements included increased areal (P=0.001) and volumetric (P<0.001-0.006) bone mineral density and 1.5- to 1.8-fold increases in radial bone structure (P<0.001). Median carotid artery wall echodensity and carotid-femoral pulse wave velocity demonstrated no significant changes. Percentages of participants with carotid (5% to 50%; P=0.001) and femoral (0% to 12%; P=0.13) artery plaques and extraskeletal calcifications (34.4% to 65.6%; P=0.006) increased. Other than increased bone mineral density, no improvement rates exceeded those of the prior lonafarnib monotherapy treatment trial.
  
  
  
  Comparisons with lonafarnib monotherapy treatment reveal additional bone mineral density benefit but likely no added cardiovascular benefit with the addition of pravastatin and zoledronic acid.
  
  
  
  URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00879034 and NCT00916747.
authors.affiliation: From Departments of Anesthesia (L.B.G., M.E.K., A.A.D., K.L., M.M.G.), Cardiology (L.B.S.), Radiology (R.H.C., V.M.S.), Orthopedics (B.D.S.), Neurology (N.J.U.), Dermatology (M.G.L.), Genetics and Genomics (D.T.M.), Gastroenterology and Nutrition (S.Y.H.), and Hematology Oncology (M.W.K.), and Clinical Translational Study Unit (N.Q.), Boston Children's Hospital and Harvard Medical School, MA; Department of Pediatrics, Hasbro Children's Hospital and Warren Alpert Medical School of Brown University, Providence, RI (L.B.G.); Department of Biostatistics, Boston University School of Public Health and Harvard Clinical Research Institute, MA (J.M., R.B.D., H.S.); Division of Cardiology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (M.G.-H.); Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati Children's Hospital Medical Center, OH (C.M.G.); Center for Advanced Orthopaedic Studies, Department of Orthopedic Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA (A.N.); and Division of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA (M.W.K.). Leslie_Gordon@brown.edu Mark_Kieran@dfci.harvard.edu.
authors.forename: Leslie B
authors.initials: LB
authors.lastname: Gordon
authors.affiliation: From Departments of Anesthesia (L.B.G., M.E.K., A.A.D., K.L., M.M.G.), Cardiology (L.B.S.), Radiology (R.H.C., V.M.S.), Orthopedics (B.D.S.), Neurology (N.J.U.), Dermatology (M.G.L.), Genetics and Genomics (D.T.M.), Gastroenterology and Nutrition (S.Y.H.), and Hematology Oncology (M.W.K.), and Clinical Translational Study Unit (N.Q.), Boston Children's Hospital and Harvard Medical School, MA; Department of Pediatrics, Hasbro Children's Hospital and Warren Alpert Medical School of Brown University, Providence, RI (L.B.G.); Department of Biostatistics, Boston University School of Public Health and Harvard Clinical Research Institute, MA (J.M., R.B.D., H.S.); Division of Cardiology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (M.G.-H.); Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati Children's Hospital Medical Center, OH (C.M.G.); Center for Advanced Orthopaedic Studies, Department of Orthopedic Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA (A.N.); and Division of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA (M.W.K.).
authors.forename: Monica E
authors.initials: ME
authors.lastname: Kleinman
authors.affiliation: From Departments of Anesthesia (L.B.G., M.E.K., A.A.D., K.L., M.M.G.), Cardiology (L.B.S.), Radiology (R.H.C., V.M.S.), Orthopedics (B.D.S.), Neurology (N.J.U.), Dermatology (M.G.L.), Genetics and Genomics (D.T.M.), Gastroenterology and Nutrition (S.Y.H.), and Hematology Oncology (M.W.K.), and Clinical Translational Study Unit (N.Q.), Boston Children's Hospital and Harvard Medical School, MA; Department of Pediatrics, Hasbro Children's Hospital and Warren Alpert Medical School of Brown University, Providence, RI (L.B.G.); Department of Biostatistics, Boston University School of Public Health and Harvard Clinical Research Institute, MA (J.M., R.B.D., H.S.); Division of Cardiology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (M.G.-H.); Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati Children's Hospital Medical Center, OH (C.M.G.); Center for Advanced Orthopaedic Studies, Department of Orthopedic Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA (A.N.); and Division of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA (M.W.K.).
authors.forename: Joe
authors.initials: J
authors.lastname: Massaro
authors.affiliation: From Departments of Anesthesia (L.B.G., M.E.K., A.A.D., K.L., M.M.G.), Cardiology (L.B.S.), Radiology (R.H.C., V.M.S.), Orthopedics (B.D.S.), Neurology (N.J.U.), Dermatology (M.G.L.), Genetics and Genomics (D.T.M.), Gastroenterology and Nutrition (S.Y.H.), and Hematology Oncology (M.W.K.), and Clinical Translational Study Unit (N.Q.), Boston Children's Hospital and Harvard Medical School, MA; Department of Pediatrics, Hasbro Children's Hospital and Warren Alpert Medical School of Brown University, Providence, RI (L.B.G.); Department of Biostatistics, Boston University School of Public Health and Harvard Clinical Research Institute, MA (J.M., R.B.D., H.S.); Division of Cardiology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (M.G.-H.); Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati Children's Hospital Medical Center, OH (C.M.G.); Center for Advanced Orthopaedic Studies, Department of Orthopedic Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA (A.N.); and Division of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA (M.W.K.).
authors.forename: Ralph B
authors.initials: RB
authors.lastname: D'Agostino
authors.affiliation: From Departments of Anesthesia (L.B.G., M.E.K., A.A.D., K.L., M.M.G.), Cardiology (L.B.S.), Radiology (R.H.C., V.M.S.), Orthopedics (B.D.S.), Neurology (N.J.U.), Dermatology (M.G.L.), Genetics and Genomics (D.T.M.), Gastroenterology and Nutrition (S.Y.H.), and Hematology Oncology (M.W.K.), and Clinical Translational Study Unit (N.Q.), Boston Children's Hospital and Harvard Medical School, MA; Department of Pediatrics, Hasbro Children's Hospital and Warren Alpert Medical School of Brown University, Providence, RI (L.B.G.); Department of Biostatistics, Boston University School of Public Health and Harvard Clinical Research Institute, MA (J.M., R.B.D., H.S.); Division of Cardiology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (M.G.-H.); Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati Children's Hospital Medical Center, OH (C.M.G.); Center for Advanced Orthopaedic Studies, Department of Orthopedic Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA (A.N.); and Division of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA (M.W.K.).
authors.forename: Heather
authors.initials: H
authors.lastname: Shappell
authors.affiliation: From Departments of Anesthesia (L.B.G., M.E.K., A.A.D., K.L., M.M.G.), Cardiology (L.B.S.), Radiology (R.H.C., V.M.S.), Orthopedics (B.D.S.), Neurology (N.J.U.), Dermatology (M.G.L.), Genetics and Genomics (D.T.M.), Gastroenterology and Nutrition (S.Y.H.), and Hematology Oncology (M.W.K.), and Clinical Translational Study Unit (N.Q.), Boston Children's Hospital and Harvard Medical School, MA; Department of Pediatrics, Hasbro Children's Hospital and Warren Alpert Medical School of Brown University, Providence, RI (L.B.G.); Department of Biostatistics, Boston University School of Public Health and Harvard Clinical Research Institute, MA (J.M., R.B.D., H.S.); Division of Cardiology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (M.G.-H.); Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati Children's Hospital Medical Center, OH (C.M.G.); Center for Advanced Orthopaedic Studies, Department of Orthopedic Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA (A.N.); and Division of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA (M.W.K.).
authors.forename: Marie
authors.initials: M
authors.lastname: Gerhard-Herman
authors.affiliation: From Departments of Anesthesia (L.B.G., M.E.K., A.A.D., K.L., M.M.G.), Cardiology (L.B.S.), Radiology (R.H.C., V.M.S.), Orthopedics (B.D.S.), Neurology (N.J.U.), Dermatology (M.G.L.), Genetics and Genomics (D.T.M.), Gastroenterology and Nutrition (S.Y.H.), and Hematology Oncology (M.W.K.), and Clinical Translational Study Unit (N.Q.), Boston Children's Hospital and Harvard Medical School, MA; Department of Pediatrics, Hasbro Children's Hospital and Warren Alpert Medical School of Brown University, Providence, RI (L.B.G.); Department of Biostatistics, Boston University School of Public Health and Harvard Clinical Research Institute, MA (J.M., R.B.D., H.S.); Division of Cardiology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (M.G.-H.); Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati Children's Hospital Medical Center, OH (C.M.G.); Center for Advanced Orthopaedic Studies, Department of Orthopedic Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA (A.N.); and Division of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA (M.W.K.).
authors.forename: Leslie B
authors.initials: LB
authors.lastname: Smoot
authors.affiliation: From Departments of Anesthesia (L.B.G., M.E.K., A.A.D., K.L., M.M.G.), Cardiology (L.B.S.), Radiology (R.H.C., V.M.S.), Orthopedics (B.D.S.), Neurology (N.J.U.), Dermatology (M.G.L.), Genetics and Genomics (D.T.M.), Gastroenterology and Nutrition (S.Y.H.), and Hematology Oncology (M.W.K.), and Clinical Translational Study Unit (N.Q.), Boston Children's Hospital and Harvard Medical School, MA; Department of Pediatrics, Hasbro Children's Hospital and Warren Alpert Medical School of Brown University, Providence, RI (L.B.G.); Department of Biostatistics, Boston University School of Public Health and Harvard Clinical Research Institute, MA (J.M., R.B.D., H.S.); Division of Cardiology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (M.G.-H.); Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati Children's Hospital Medical Center, OH (C.M.G.); Center for Advanced Orthopaedic Studies, Department of Orthopedic Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA (A.N.); and Division of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA (M.W.K.).
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Gordon
authors.affiliation: From Departments of Anesthesia (L.B.G., M.E.K., A.A.D., K.L., M.M.G.), Cardiology (L.B.S.), Radiology (R.H.C., V.M.S.), Orthopedics (B.D.S.), Neurology (N.J.U.), Dermatology (M.G.L.), Genetics and Genomics (D.T.M.), Gastroenterology and Nutrition (S.Y.H.), and Hematology Oncology (M.W.K.), and Clinical Translational Study Unit (N.Q.), Boston Children's Hospital and Harvard Medical School, MA; Department of Pediatrics, Hasbro Children's Hospital and Warren Alpert Medical School of Brown University, Providence, RI (L.B.G.); Department of Biostatistics, Boston University School of Public Health and Harvard Clinical Research Institute, MA (J.M., R.B.D., H.S.); Division of Cardiology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (M.G.-H.); Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati Children's Hospital Medical Center, OH (C.M.G.); Center for Advanced Orthopaedic Studies, Department of Orthopedic Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA (A.N.); and Division of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA (M.W.K.).
authors.forename: Robert H
authors.initials: RH
authors.lastname: Cleveland
authors.affiliation: From Departments of Anesthesia (L.B.G., M.E.K., A.A.D., K.L., M.M.G.), Cardiology (L.B.S.), Radiology (R.H.C., V.M.S.), Orthopedics (B.D.S.), Neurology (N.J.U.), Dermatology (M.G.L.), Genetics and Genomics (D.T.M.), Gastroenterology and Nutrition (S.Y.H.), and Hematology Oncology (M.W.K.), and Clinical Translational Study Unit (N.Q.), Boston Children's Hospital and Harvard Medical School, MA; Department of Pediatrics, Hasbro Children's Hospital and Warren Alpert Medical School of Brown University, Providence, RI (L.B.G.); Department of Biostatistics, Boston University School of Public Health and Harvard Clinical Research Institute, MA (J.M., R.B.D., H.S.); Division of Cardiology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (M.G.-H.); Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati Children's Hospital Medical Center, OH (C.M.G.); Center for Advanced Orthopaedic Studies, Department of Orthopedic Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA (A.N.); and Division of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA (M.W.K.).
authors.forename: Ara
authors.initials: A
authors.lastname: Nazarian
authors.affiliation: From Departments of Anesthesia (L.B.G., M.E.K., A.A.D., K.L., M.M.G.), Cardiology (L.B.S.), Radiology (R.H.C., V.M.S.), Orthopedics (B.D.S.), Neurology (N.J.U.), Dermatology (M.G.L.), Genetics and Genomics (D.T.M.), Gastroenterology and Nutrition (S.Y.H.), and Hematology Oncology (M.W.K.), and Clinical Translational Study Unit (N.Q.), Boston Children's Hospital and Harvard Medical School, MA; Department of Pediatrics, Hasbro Children's Hospital and Warren Alpert Medical School of Brown University, Providence, RI (L.B.G.); Department of Biostatistics, Boston University School of Public Health and Harvard Clinical Research Institute, MA (J.M., R.B.D., H.S.); Division of Cardiology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (M.G.-H.); Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati Children's Hospital Medical Center, OH (C.M.G.); Center for Advanced Orthopaedic Studies, Department of Orthopedic Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA (A.N.); and Division of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA (M.W.K.).
authors.forename: Brian D
authors.initials: BD
authors.lastname: Snyder
authors.affiliation: From Departments of Anesthesia (L.B.G., M.E.K., A.A.D., K.L., M.M.G.), Cardiology (L.B.S.), Radiology (R.H.C., V.M.S.), Orthopedics (B.D.S.), Neurology (N.J.U.), Dermatology (M.G.L.), Genetics and Genomics (D.T.M.), Gastroenterology and Nutrition (S.Y.H.), and Hematology Oncology (M.W.K.), and Clinical Translational Study Unit (N.Q.), Boston Children's Hospital and Harvard Medical School, MA; Department of Pediatrics, Hasbro Children's Hospital and Warren Alpert Medical School of Brown University, Providence, RI (L.B.G.); Department of Biostatistics, Boston University School of Public Health and Harvard Clinical Research Institute, MA (J.M., R.B.D., H.S.); Division of Cardiology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (M.G.-H.); Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati Children's Hospital Medical Center, OH (C.M.G.); Center for Advanced Orthopaedic Studies, Department of Orthopedic Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA (A.N.); and Division of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA (M.W.K.).
authors.forename: Nicole J
authors.initials: NJ
authors.lastname: Ullrich
authors.affiliation: From Departments of Anesthesia (L.B.G., M.E.K., A.A.D., K.L., M.M.G.), Cardiology (L.B.S.), Radiology (R.H.C., V.M.S.), Orthopedics (B.D.S.), Neurology (N.J.U.), Dermatology (M.G.L.), Genetics and Genomics (D.T.M.), Gastroenterology and Nutrition (S.Y.H.), and Hematology Oncology (M.W.K.), and Clinical Translational Study Unit (N.Q.), Boston Children's Hospital and Harvard Medical School, MA; Department of Pediatrics, Hasbro Children's Hospital and Warren Alpert Medical School of Brown University, Providence, RI (L.B.G.); Department of Biostatistics, Boston University School of Public Health and Harvard Clinical Research Institute, MA (J.M., R.B.D., H.S.); Division of Cardiology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (M.G.-H.); Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati Children's Hospital Medical Center, OH (C.M.G.); Center for Advanced Orthopaedic Studies, Department of Orthopedic Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA (A.N.); and Division of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA (M.W.K.).
authors.forename: V Michelle
authors.initials: VM
authors.lastname: Silvera
authors.affiliation: From Departments of Anesthesia (L.B.G., M.E.K., A.A.D., K.L., M.M.G.), Cardiology (L.B.S.), Radiology (R.H.C., V.M.S.), Orthopedics (B.D.S.), Neurology (N.J.U.), Dermatology (M.G.L.), Genetics and Genomics (D.T.M.), Gastroenterology and Nutrition (S.Y.H.), and Hematology Oncology (M.W.K.), and Clinical Translational Study Unit (N.Q.), Boston Children's Hospital and Harvard Medical School, MA; Department of Pediatrics, Hasbro Children's Hospital and Warren Alpert Medical School of Brown University, Providence, RI (L.B.G.); Department of Biostatistics, Boston University School of Public Health and Harvard Clinical Research Institute, MA (J.M., R.B.D., H.S.); Division of Cardiology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (M.G.-H.); Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati Children's Hospital Medical Center, OH (C.M.G.); Center for Advanced Orthopaedic Studies, Department of Orthopedic Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA (A.N.); and Division of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA (M.W.K.).
authors.forename: Marilyn G
authors.initials: MG
authors.lastname: Liang
authors.affiliation: From Departments of Anesthesia (L.B.G., M.E.K., A.A.D., K.L., M.M.G.), Cardiology (L.B.S.), Radiology (R.H.C., V.M.S.), Orthopedics (B.D.S.), Neurology (N.J.U.), Dermatology (M.G.L.), Genetics and Genomics (D.T.M.), Gastroenterology and Nutrition (S.Y.H.), and Hematology Oncology (M.W.K.), and Clinical Translational Study Unit (N.Q.), Boston Children's Hospital and Harvard Medical School, MA; Department of Pediatrics, Hasbro Children's Hospital and Warren Alpert Medical School of Brown University, Providence, RI (L.B.G.); Department of Biostatistics, Boston University School of Public Health and Harvard Clinical Research Institute, MA (J.M., R.B.D., H.S.); Division of Cardiology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (M.G.-H.); Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati Children's Hospital Medical Center, OH (C.M.G.); Center for Advanced Orthopaedic Studies, Department of Orthopedic Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA (A.N.); and Division of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA (M.W.K.).
authors.forename: Nicolle
authors.initials: N
authors.lastname: Quinn
authors.affiliation: From Departments of Anesthesia (L.B.G., M.E.K., A.A.D., K.L., M.M.G.), Cardiology (L.B.S.), Radiology (R.H.C., V.M.S.), Orthopedics (B.D.S.), Neurology (N.J.U.), Dermatology (M.G.L.), Genetics and Genomics (D.T.M.), Gastroenterology and Nutrition (S.Y.H.), and Hematology Oncology (M.W.K.), and Clinical Translational Study Unit (N.Q.), Boston Children's Hospital and Harvard Medical School, MA; Department of Pediatrics, Hasbro Children's Hospital and Warren Alpert Medical School of Brown University, Providence, RI (L.B.G.); Department of Biostatistics, Boston University School of Public Health and Harvard Clinical Research Institute, MA (J.M., R.B.D., H.S.); Division of Cardiology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (M.G.-H.); Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati Children's Hospital Medical Center, OH (C.M.G.); Center for Advanced Orthopaedic Studies, Department of Orthopedic Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA (A.N.); and Division of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA (M.W.K.).
authors.forename: David T
authors.initials: DT
authors.lastname: Miller
authors.affiliation: From Departments of Anesthesia (L.B.G., M.E.K., A.A.D., K.L., M.M.G.), Cardiology (L.B.S.), Radiology (R.H.C., V.M.S.), Orthopedics (B.D.S.), Neurology (N.J.U.), Dermatology (M.G.L.), Genetics and Genomics (D.T.M.), Gastroenterology and Nutrition (S.Y.H.), and Hematology Oncology (M.W.K.), and Clinical Translational Study Unit (N.Q.), Boston Children's Hospital and Harvard Medical School, MA; Department of Pediatrics, Hasbro Children's Hospital and Warren Alpert Medical School of Brown University, Providence, RI (L.B.G.); Department of Biostatistics, Boston University School of Public Health and Harvard Clinical Research Institute, MA (J.M., R.B.D., H.S.); Division of Cardiology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (M.G.-H.); Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati Children's Hospital Medical Center, OH (C.M.G.); Center for Advanced Orthopaedic Studies, Department of Orthopedic Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA (A.N.); and Division of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA (M.W.K.).
authors.forename: Susanna Y
authors.initials: SY
authors.lastname: Huh
authors.affiliation: From Departments of Anesthesia (L.B.G., M.E.K., A.A.D., K.L., M.M.G.), Cardiology (L.B.S.), Radiology (R.H.C., V.M.S.), Orthopedics (B.D.S.), Neurology (N.J.U.), Dermatology (M.G.L.), Genetics and Genomics (D.T.M.), Gastroenterology and Nutrition (S.Y.H.), and Hematology Oncology (M.W.K.), and Clinical Translational Study Unit (N.Q.), Boston Children's Hospital and Harvard Medical School, MA; Department of Pediatrics, Hasbro Children's Hospital and Warren Alpert Medical School of Brown University, Providence, RI (L.B.G.); Department of Biostatistics, Boston University School of Public Health and Harvard Clinical Research Institute, MA (J.M., R.B.D., H.S.); Division of Cardiology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (M.G.-H.); Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati Children's Hospital Medical Center, OH (C.M.G.); Center for Advanced Orthopaedic Studies, Department of Orthopedic Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA (A.N.); and Division of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA (M.W.K.).
authors.forename: Anne A
authors.initials: AA
authors.lastname: Dowton
authors.affiliation: From Departments of Anesthesia (L.B.G., M.E.K., A.A.D., K.L., M.M.G.), Cardiology (L.B.S.), Radiology (R.H.C., V.M.S.), Orthopedics (B.D.S.), Neurology (N.J.U.), Dermatology (M.G.L.), Genetics and Genomics (D.T.M.), Gastroenterology and Nutrition (S.Y.H.), and Hematology Oncology (M.W.K.), and Clinical Translational Study Unit (N.Q.), Boston Children's Hospital and Harvard Medical School, MA; Department of Pediatrics, Hasbro Children's Hospital and Warren Alpert Medical School of Brown University, Providence, RI (L.B.G.); Department of Biostatistics, Boston University School of Public Health and Harvard Clinical Research Institute, MA (J.M., R.B.D., H.S.); Division of Cardiology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (M.G.-H.); Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati Children's Hospital Medical Center, OH (C.M.G.); Center for Advanced Orthopaedic Studies, Department of Orthopedic Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA (A.N.); and Division of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA (M.W.K.).
authors.forename: Kelly
authors.initials: K
authors.lastname: Littlefield
authors.affiliation: From Departments of Anesthesia (L.B.G., M.E.K., A.A.D., K.L., M.M.G.), Cardiology (L.B.S.), Radiology (R.H.C., V.M.S.), Orthopedics (B.D.S.), Neurology (N.J.U.), Dermatology (M.G.L.), Genetics and Genomics (D.T.M.), Gastroenterology and Nutrition (S.Y.H.), and Hematology Oncology (M.W.K.), and Clinical Translational Study Unit (N.Q.), Boston Children's Hospital and Harvard Medical School, MA; Department of Pediatrics, Hasbro Children's Hospital and Warren Alpert Medical School of Brown University, Providence, RI (L.B.G.); Department of Biostatistics, Boston University School of Public Health and Harvard Clinical Research Institute, MA (J.M., R.B.D., H.S.); Division of Cardiology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (M.G.-H.); Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati Children's Hospital Medical Center, OH (C.M.G.); Center for Advanced Orthopaedic Studies, Department of Orthopedic Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA (A.N.); and Division of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA (M.W.K.).
authors.forename: Maya M
authors.initials: MM
authors.lastname: Greer
authors.affiliation: From Departments of Anesthesia (L.B.G., M.E.K., A.A.D., K.L., M.M.G.), Cardiology (L.B.S.), Radiology (R.H.C., V.M.S.), Orthopedics (B.D.S.), Neurology (N.J.U.), Dermatology (M.G.L.), Genetics and Genomics (D.T.M.), Gastroenterology and Nutrition (S.Y.H.), and Hematology Oncology (M.W.K.), and Clinical Translational Study Unit (N.Q.), Boston Children's Hospital and Harvard Medical School, MA; Department of Pediatrics, Hasbro Children's Hospital and Warren Alpert Medical School of Brown University, Providence, RI (L.B.G.); Department of Biostatistics, Boston University School of Public Health and Harvard Clinical Research Institute, MA (J.M., R.B.D., H.S.); Division of Cardiology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (M.G.-H.); Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati Children's Hospital Medical Center, OH (C.M.G.); Center for Advanced Orthopaedic Studies, Department of Orthopedic Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA (A.N.); and Division of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA (M.W.K.). Leslie_Gordon@brown.edu Mark_Kieran@dfci.harvard.edu.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Kieran
mesh_terms: D001842:Bone and Bones / Q000000981:diagnostic imaging; D002339:Carotid Arteries / Q000000981:diagnostic imaging; D002675:Child, Preschool; D004164:Diphosphonates / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects / Q000627:therapeutic use*; D007223:Infant; D008297:Male; D010880:Piperidines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D017035:Pravastatin / Q000009:adverse effects / Q000627:therapeutic use*; D011371:Progeria / Q000188:drug therapy*; D011446:Prospective Studies; D017368:Protein Prenylation / Q000187:drug effects; D011725:Pyridines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000077211:Zoledronic Acid; D003986:Dibenzocycloheptenes
chemical_list: D004164:Diphosphonates; D007093:Imidazoles; D010880:Piperidines; D017035:Pravastatin; D011725:Pyridines; D000077211:Zoledronic Acid; C115354:lonafarnib; D003986:Dibenzocycloheptenes
keywords: aging; atherosclerosis; progeria