Improvements in Bone Density and Structure during Anti-TNF-α Therapy in Pediatric Crohn's Disease.
BACKGROUND
Pediatric Crohn's Disease (CD) is associated with deficits in trabecular bone mineral density (BMD) and cortical structure, potentially related to TNF-α effects to decrease bone formation and promote bone resorption.


OBJECTIVE
This study aimed to examine changes in bone density and structure in children and adolescents with CD following initiation of anti-TNF-α therapy.


METHODS
Participants (n = 74; age 5-21 years) with CD completed a 12-month prospective cohort study.


METHODS
Tibia peripheral quantitative computed tomography scans were obtained at initiation of anti-TNF-α therapy and 12 months later. Musculoskeletal outcomes were expressed as sex-and race-specific z scores relative to age, based on >650 reference participants.


RESULTS
At baseline, CD participants had lower height, trabecular BMD, cortical area (due to smaller periosteal and larger endocortical circumferences), and muscle area z scores, compared with reference participants (all P < .01). Pediatric CD activity index decreased during the 10-week induction (P < .001), in association with subsequent gains in height, trabecular BMD, cortical area (due to recovery of endocortical bone), and muscle area z scores over 12 months (height P < .05; others P < .001). Bone-specific alkaline phosphatase levels, a biomarker of bone formation, increased a median of 75% (P < .001) during induction with associated 12-month improvements in trabecular BMD and cortical area z scores (both P < .001). Younger age was associated with greater increases in trabecular BMD z scores (P < .001) and greater linear growth with greater recovery of cortical area (P < .001).


CONCLUSIONS
Anti-TNF-α therapy was associated with improvements in trabecular BMD and cortical structure. Improvements were greater in younger and growing participants, suggesting a window of opportunity for treatment of bone deficits.
Department of Radiology (L.M.G.), New York University School of Medicine, New York, New York 10016; Janssen Pharmaceuticals (M.T.), Titusville, New Jersey 08560; Department of Pediatrics (R.N.B., B.S.Z., M.R.D., J.S., R.H., J.L., M.B.L.), The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104; Department of Pediatrics (M.D.D.), University of Virginia Health System, Charlottesville, Virginia 22908; Department of Pediatrics (L.A.D.), Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229; Department of Biostatistics and Epidemiology (J.S., M.B.L.), Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104; and Department of Pediatrics (M.B.L.), Stanford University Medical Center, Stanford, California 94025.
Lindsay M
LM
Griffin
Department of Radiology (L.M.G.), New York University School of Medicine, New York, New York 10016; Janssen Pharmaceuticals (M.T.), Titusville, New Jersey 08560; Department of Pediatrics (R.N.B., B.S.Z., M.R.D., J.S., R.H., J.L., M.B.L.), The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104; Department of Pediatrics (M.D.D.), University of Virginia Health System, Charlottesville, Virginia 22908; Department of Pediatrics (L.A.D.), Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229; Department of Biostatistics and Epidemiology (J.S., M.B.L.), Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104; and Department of Pediatrics (M.B.L.), Stanford University Medical Center, Stanford, California 94025.
Meena
M
Thayu
Department of Radiology (L.M.G.), New York University School of Medicine, New York, New York 10016; Janssen Pharmaceuticals (M.T.), Titusville, New Jersey 08560; Department of Pediatrics (R.N.B., B.S.Z., M.R.D., J.S., R.H., J.L., M.B.L.), The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104; Department of Pediatrics (M.D.D.), University of Virginia Health System, Charlottesville, Virginia 22908; Department of Pediatrics (L.A.D.), Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229; Department of Biostatistics and Epidemiology (J.S., M.B.L.), Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104; and Department of Pediatrics (M.B.L.), Stanford University Medical Center, Stanford, California 94025.
Robert N
RN
Baldassano
Department of Radiology (L.M.G.), New York University School of Medicine, New York, New York 10016; Janssen Pharmaceuticals (M.T.), Titusville, New Jersey 08560; Department of Pediatrics (R.N.B., B.S.Z., M.R.D., J.S., R.H., J.L., M.B.L.), The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104; Department of Pediatrics (M.D.D.), University of Virginia Health System, Charlottesville, Virginia 22908; Department of Pediatrics (L.A.D.), Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229; Department of Biostatistics and Epidemiology (J.S., M.B.L.), Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104; and Department of Pediatrics (M.B.L.), Stanford University Medical Center, Stanford, California 94025.
Mark D
MD
DeBoer
Department of Radiology (L.M.G.), New York University School of Medicine, New York, New York 10016; Janssen Pharmaceuticals (M.T.), Titusville, New Jersey 08560; Department of Pediatrics (R.N.B., B.S.Z., M.R.D., J.S., R.H., J.L., M.B.L.), The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104; Department of Pediatrics (M.D.D.), University of Virginia Health System, Charlottesville, Virginia 22908; Department of Pediatrics (L.A.D.), Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229; Department of Biostatistics and Epidemiology (J.S., M.B.L.), Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104; and Department of Pediatrics (M.B.L.), Stanford University Medical Center, Stanford, California 94025.
Babette S
BS
Zemel
Department of Radiology (L.M.G.), New York University School of Medicine, New York, New York 10016; Janssen Pharmaceuticals (M.T.), Titusville, New Jersey 08560; Department of Pediatrics (R.N.B., B.S.Z., M.R.D., J.S., R.H., J.L., M.B.L.), The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104; Department of Pediatrics (M.D.D.), University of Virginia Health System, Charlottesville, Virginia 22908; Department of Pediatrics (L.A.D.), Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229; Department of Biostatistics and Epidemiology (J.S., M.B.L.), Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104; and Department of Pediatrics (M.B.L.), Stanford University Medical Center, Stanford, California 94025.
Michelle R
MR
Denburg
Department of Radiology (L.M.G.), New York University School of Medicine, New York, New York 10016; Janssen Pharmaceuticals (M.T.), Titusville, New Jersey 08560; Department of Pediatrics (R.N.B., B.S.Z., M.R.D., J.S., R.H., J.L., M.B.L.), The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104; Department of Pediatrics (M.D.D.), University of Virginia Health System, Charlottesville, Virginia 22908; Department of Pediatrics (L.A.D.), Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229; Department of Biostatistics and Epidemiology (J.S., M.B.L.), Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104; and Department of Pediatrics (M.B.L.), Stanford University Medical Center, Stanford, California 94025.
Lee A
LA
Denson
Department of Radiology (L.M.G.), New York University School of Medicine, New York, New York 10016; Janssen Pharmaceuticals (M.T.), Titusville, New Jersey 08560; Department of Pediatrics (R.N.B., B.S.Z., M.R.D., J.S., R.H., J.L., M.B.L.), The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104; Department of Pediatrics (M.D.D.), University of Virginia Health System, Charlottesville, Virginia 22908; Department of Pediatrics (L.A.D.), Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229; Department of Biostatistics and Epidemiology (J.S., M.B.L.), Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104; and Department of Pediatrics (M.B.L.), Stanford University Medical Center, Stanford, California 94025.
Justine
J
Shults
Department of Radiology (L.M.G.), New York University School of Medicine, New York, New York 10016; Janssen Pharmaceuticals (M.T.), Titusville, New Jersey 08560; Department of Pediatrics (R.N.B., B.S.Z., M.R.D., J.S., R.H., J.L., M.B.L.), The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104; Department of Pediatrics (M.D.D.), University of Virginia Health System, Charlottesville, Virginia 22908; Department of Pediatrics (L.A.D.), Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229; Department of Biostatistics and Epidemiology (J.S., M.B.L.), Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104; and Department of Pediatrics (M.B.L.), Stanford University Medical Center, Stanford, California 94025.
Rita
R
Herskovitz
Department of Radiology (L.M.G.), New York University School of Medicine, New York, New York 10016; Janssen Pharmaceuticals (M.T.), Titusville, New Jersey 08560; Department of Pediatrics (R.N.B., B.S.Z., M.R.D., J.S., R.H., J.L., M.B.L.), The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104; Department of Pediatrics (M.D.D.), University of Virginia Health System, Charlottesville, Virginia 22908; Department of Pediatrics (L.A.D.), Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229; Department of Biostatistics and Epidemiology (J.S., M.B.L.), Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104; and Department of Pediatrics (M.B.L.), Stanford University Medical Center, Stanford, California 94025.
Jin
J
Long
Department of Radiology (L.M.G.), New York University School of Medicine, New York, New York 10016; Janssen Pharmaceuticals (M.T.), Titusville, New Jersey 08560; Department of Pediatrics (R.N.B., B.S.Z., M.R.D., J.S., R.H., J.L., M.B.L.), The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104; Department of Pediatrics (M.D.D.), University of Virginia Health System, Charlottesville, Virginia 22908; Department of Pediatrics (L.A.D.), Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229; Department of Biostatistics and Epidemiology (J.S., M.B.L.), Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104; and Department of Pediatrics (M.B.L.), Stanford University Medical Center, Stanford, California 94025.
Mary B
MB
Leonard
D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use*; D015519:Bone Density / Q000187:drug effects* / Q000502:physiology; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000648:ultrastructure; D002648:Child; D002675:Child, Preschool; D003424:Crohn Disease / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D000069285:Infliximab; D008137:Longitudinal Studies; D008297:Male; D011859:Radiography; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000276:immunology; D055815:Young Adult
D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab