title: Altered Osteocyte-Specific Protein Expression in Bone after Childhood Solid Organ Transplantation.
abstract: BACKGROUND
  Bone fragility is common post solid organ transplantation but little is known about bone pathology on a tissue level. Abnormal osteocytic protein expression has been linked to compromised bone health in chronic kidney disease (CKD) and immunosuppressant medications may impact osteocyte function.
  
  
  METHODS
  Transiliac bone biopsies were obtained from 22 pediatric solid organ allograft recipients (average age 15.6 years) an average of 6.3 ± 1.2 years after transplantation and from 12 pediatric pre-dialysis CKD patients (average age 13.2 years). Histomorphometry and immunohistochemistry for FGF23, DMP1, sclerostin, and osteopontin were performed on all biopsies.
  
  
  RESULTS
  FGF23 and sclerostin were increased in transplant recipients relative to non-transplant CKD, regardless of the type of allograft received and despite, in the case of liver and heart recipients, a higher GFR. Bone DMP1 expression was higher in liver or heart than in kidney recipients, concomitant with higher serum phosphate values. Osteopontin expression was higher in CKD than in transplant recipients (p<0.01). Bone FGF23 and sclerostin correlated directly (r = 0.38, p<0.05); bone FGF23 expression and osteoid thickness correlated inversely (r = - 0.46, p<0.01).
  
  
  CONCLUSIONS
  Solid-organ transplantation is associated with increased FGF23 and sclerostin expression. The contribution of these findings to compromised bone health post transplantation warrants further evaluation.
authors.affiliation: Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, United States of America.
authors.forename: Renata C
authors.initials: RC
authors.lastname: Pereira
authors.affiliation: Children's Hospital, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland.
authors.forename: Helena
authors.initials: H
authors.lastname: Valta
authors.affiliation: Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, United States of America.
authors.forename: Navdeep
authors.initials: N
authors.lastname: Tumber
authors.affiliation: Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, United States of America.
authors.forename: Isidro B
authors.initials: IB
authors.lastname: Salusky
authors.affiliation: Children's Hospital, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland.
authors.forename: Hannu
authors.initials: H
authors.lastname: Jalanko
authors.affiliation: Children's Hospital, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland; Folkhälsan Research Center, Helsinki, Finland; Department of Molecular Medicine and Surgery and Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Outi
authors.initials: O
authors.lastname: Mäkitie
authors.affiliation: Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, United States of America.
authors.forename: Katherine
authors.initials: K
authors.lastname: Wesseling Perry
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000293:Adolescent; D019485:Bone Morphogenetic Proteins / Q000032:analysis*; D001842:Bone and Bones / Q000378:metabolism / Q000473:pathology*; D002648:Child; D003430:Cross-Sectional Studies; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000032:analysis*; D005819:Genetic Markers; D016027:Heart Transplantation / Q000009:adverse effects; D006801:Humans; D016030:Kidney Transplantation / Q000009:adverse effects; D016031:Liver Transplantation / Q000009:adverse effects; D008297:Male; D010011:Osteocytes / Q000378:metabolism / Q000473:pathology*; D051436:Renal Insufficiency, Chronic / Q000150:complications; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D019485:Bone Morphogenetic Proteins; C000717427:FGF23 protein, human; D005819:Genetic Markers; C422903:SOST protein, human; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23