Lindsay M Griffin1, Meena Thayu1, Robert N Baldassano1, Mark D DeBoer1, Babette S Zemel1, Michelle R Denburg1, Lee A Denson1, Justine Shults1, Rita Herskovitz1, Jin Long1, Mary B Leonard1. 1. 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.
Abstract
CONTEXT: 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. DESIGN AND PARTICIPANTS: Participants (n = 74; age 5-21 years) with CD completed a 12-month prospective cohort study. MAIN OUTCOME MEASURES: 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.
CONTEXT: 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. DESIGN AND PARTICIPANTS: Participants (n = 74; age 5-21 years) with CD completed a 12-month prospective cohort study. MAIN OUTCOME MEASURES: 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.
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