We utilized the 4C cohort to characterize the patterns of these novel serum bone markers in pediatric CKD and to DIPSO describe their associations with endpoints of statural growth, i.e. height standard deviation score and its BMS 509744 change over time, in children with and without concomitant recombinant growth hormone treatment. In all multivariate analyses, variables with a p value <0.15 were kept in the model during the selection procedure. Variables were tested for normality and log-transformed in case of violation of normality assumption. To compare bone marker levels of patients with and without rhGH treatment with the best possible exclusion of confounding factors, the group of patients with rhGH treatment were compared to an untreated control group matched individually for age, sex, eGFR, CRP, and iPTH. Of the original cohort, the control group was selected out of 186 patients who were not treated with rhGH and were living in the same countries as children with rhGH treatment. Matching of rhGH treated and untreated patients was performed using SAS 9.2. Matches were available for 41 out of 42 rhGH treated patients. Post hoc testing for significant differences of matching variables and additional confounding factors between groups was performed. Paired t-tests were applied to test for differences of bone marker levels between the matched groups. Statistical analyses were performed using SAS 9.2 and R. A p-value _ 0.05 was considered statistically significant. This is the first comprehensive study of novel circulating markers of bone activity performed in a large, representative cohort of children with moderate to severe CKD. Within the pediatric age range, bone formation rate and bone turnover are essentially based on the developmental state of the skeleton. Relating our results to recently established age-specific reference values allowed us to account for the physiological variability of bone markers during childhood. We demonstrated abnormal distributions of the osteoblast marker BAP, the osteoclast marker TRAP5b and the osteocyte markers cFGF-23 and sclerostin, compatible with a major alteration of bone turnover in this population. Furthermore, we observed significant changes of the bone marker profile in children undergoing rhGH treatment. Normalizing BAP and TRAP5B plasma levels for age and sex in this large pediatric cohort with CKD stage 3 to 5, we observed a clear increase of BAP and a slight but significant increase of TRAP5B levels. This finding is compatible with a preferential high bone turnover in this patient group. A small association of BAP SDS with eGFR emerged in multivariate but not univariate analysis, indicating a higher bone turnover rate in earlier CKD stages.