The evaluation of bone metabolism in children with renal transplantation B€ uy€ ukkarag€ oz B, Bakkaloglu SA, Kandur Y, Isiyel E, Akcaboy M, Buyan N, Hasanoglu E. (2015) The evaluation of bone metabolism in children with renal transplantation. Pediatr Transplant, 19: 351–357. DOI: 10.1111/petr.12469. Abstract: This study aims to evaluate BMD and bone biomarkers and to investigate the effects of immunosuppressives on bone disease after RTx. Thirty-three RTR aged 16.7  3.7 yr and healthy controls (n = 32) were enrolled. There was no difference between pre-RTx BMD and BMD at the time of study (45.9  30.9 months after RTx), while both values were lower than controls (p < 0.01 and p < 0.05, respectively). Worst BMD scores were obtained at sixth month after RTx (0.2  0.9) and best at fourth year (1.4  1.3). 25-hydroxy- (OH) vitamin D and OPG were higher in RTR (p < 0.001). BMD z scores negatively correlated with OPG and cumulative CS doses at the time of study (r = 0.344, p < 0.05 and r = 0.371, p < 0.05, respectively). Regression analysis revealed OPG as the only predictor of BMD (b 0.78, 95% CI 0.004 to 0.013, p < 0.001). The increase in OPG, a significant predictor of BMD, could either be secondary to graft dysfunction or for protection against bone loss. CS doses should be minimized to avoid their untoward effects on bone metabolism. Bahar B€ uy€ ukkarag€ oz, Sevcan A. Bakkaloglu, Yas ßar Kandur, Emel Isiyel, Meltem Akcaboy, Necla Buyan and Enver Hasanoglu Division of Pediatric Nephrology, Gazi University, Ankara, Turkey Key words: renal transplantation – children – bone mineral density – bone metabolism – corticosteroids Bahar B€ uy€ ukkarag€ oz, Division of Pediatric Nephrology, Gazi University, Gazi University Hospital Besevler, Ankara 06520, Turkey Tel.: +90 312 286 06 47 Fax: +90 312 356 90 02 E-mail: karamanbahar@yahoo.com Accepted for publication 11 March 2015 Although CKD-MBD improves after RTx, it remains one of the main causes of morbidity and mortality (1–3). Osteopenia and osteoporosis can develop or worsen, and ultimately, bone fractures can be detected in post-RTx period (4–6). Various risk factors including immunosuppressive medica- tions, predominantly CS, persistent hyperparathy- roidism, deficiency of vitamin D, and allograft dysfunction are considered to be responsible for the post-RTx bone disease (3, 7, 8). The preva- lence of post-RTx osteoporosis is 45–62% (9–12). Currently, BMD with DEXA method is the most commonly used diagnostic technique for evaluat- ing post-RTx osteoporosis (13). However, this technique has low reliability for the determination of BMD as it enables only two-dimensional evalu- ation instead of volumetric measurement and is insufficient for demonstrating underlying abnor- malities of bone histology (14, 15). In the last few decades, bone research focused on new potential biomarkers of bone turnover. Among these, RANK, RANK-L, and OPG have important effects on osteoclastic differentiation and proliferation (16). RANK-L binds to its receptor RANK in order to induce osteoclast dif- ferentiation, activation, and survival, whereas OPG acts as a decoy receptor to RANK-L and therefore inhibits osteoclast activation and bone resorption (17, 18). The fine balance of RANK- L/RANK/OPG is thus essential to regulate os- teoclastogenesis and bone remodeling (16). Various studies demonstrate that the high OPG levels in the CKD period diminish after RTx and this biomarker is considered as an independent predictor of bone loss (19–21). FGF-23, a phosphaturic hormone released from osteocytes, is suggested to be linked to post-RTx osteoporosis either by causing phos- phaturia or due to its direct effects on bone min- eralization (22, 23). Its circulatory levels begin to increase in the early stages of CKD and become Abbreviations: ALP, alkaline phosphatase; AR, acute rejection; BMD, bone mineral density; BUN, blood urea nitrogen; CKD-MBD, chronic kidney disease-mineral and bone disorder; CS, corticosteroids; DEXA, dual-energy X- ray adsorptiometry; FGF-23, fibroblast growth factor-23; HAZ, height for age z scores; HD, hemodialysis; OPG, os- teoprotegerin; PD, peritoneal dialysis; PTH, parathormone; RANK-L, receptor activator of nuclear factor kappa B- ligand; RANK, receptor activator of nuclear factor kappa B; RTR, renal transplant recipients; RTx, renal transplanta- tion. 351 Pediatr Transplantation 2015: 19: 351–357 © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd Pediatric Transplantation DOI: 10.1111/petr.12469