Altered Osteocyte-Specific Protein Expression in Bone after Childhood Solid Organ Transplantation.

Renata C Pereira,Katherine Wesseling Perry,Isidro B Salusky,Helena Valta,Hannu Jalanko,Navdeep Tumber,Outi Mäkitie,Niels Olsen Saraiva Câmara

doi:10.1371/journal.pone.0138156

Abstract

BackgroundBone 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.MethodsTransiliac 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.ResultsFGF23 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).ConclusionsSolid-organ transplantation is associated with increased FGF23 and sclerostin expression. The contribution of these findings to compromised bone health post transplantation warrants further evaluation.

Highlights

Skeletal problems are common in pediatric recipients of solid organ allografts, with fractures in general occurring 6 times as commonly as in the general population and vertebral fractures, occurring at even higher rates [1,2]
fibroblast growth factor 23 (FGF23) and sclerostin were increased in transplant recipients relative to non-transplant chronic kidney disease (CKD), regardless of the type of allograft received and despite, in the case of liver and heart recipients, a higher glomerular filtration rate (GFR)
In order to gain more knowledge on the pathological processes contributing to skeletal fragility after pediatric solid organ transplantation, in which the presence of CKD and the use of immunosuppressant agents may both contribute to skeletal pathology, we evaluated osteocytic protein expression and bone histology in a cohort of kidney, liver, and heart transplant recipients and in subjects with pre-dialysis CKD

Summary

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. Data Availability Statement: All relevant data are within the paper

Methods

Results

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Discussion