Impact of treatment with active vitamin D calcitriol on bone turnover markers in people with type 2 diabetes and stage 3 chronic kidney disease

TY - JOUR

T1 - Impact of treatment with active vitamin D calcitriol on bone turnover markers in people with type 2 diabetes and stage 3 chronic kidney disease

AU - Stathi, Dimitra

AU - Fountoulakis, Nikos

AU - Panagiotou, Angeliki

AU - Maltese, Giuseppe

AU - Corcillo, Antonella

AU - Mangelis, Anastasios

AU - Ayis, Salma

AU - Gnudi, Luigi

AU - Karalliedde, Janaka

N1 - Funding Information: The study was funded by a research grant from Diabetes UK . We wish to thank the support and help of the trial data monitoring committee, which included Dr. Peter Watkins, Dr. Phil Chowienczyk and Dr. Richard Hooper. We also thank the research nurses and participants who assisted in this work. Publisher Copyright: © 2022

PY - 2023/1/1

Y1 - 2023/1/1

N2 - People with diabetes and chronic kidney disease (CKD) are predisposed to bone mineral disorders and increased fracture risk. There is limited data on the effect of calcitriol on bone turnover markers (BTMs) in people with type 2 diabetes (T2DM) and stage 3 CKD. In a pre-specified secondary endpoint analysis of a 48-week randomized placebo controlled double-blind trial, we studied the effects of oral calcitriol 0.25 μg once daily on circulating BTMs that included osteocalcin (OCN), C-terminal telopeptide of type I collagen (CTX[sbnd]I), procollagen type I N-propeptide (PINP) and fibroblast growth factor-23 (FGF-23). Inclusion criteria were people with T2DM with stable stage 3 CKD stage and intact parathyroid hormone (iPTH) >30 pg/ml. In total, 127 people [calcitriol (n = 64), placebo (n = 63)] were eligible for analyses. Baseline median (interquartile range) age of the cohort was 67 (60.5–70) years, iPTH (median range) 73.9 (55, 105) pg/ml and eGFR 40 (33, 48.5) ml/min. Calcitriol treatments resulted in a significant fall in iPTH, CTX, PINP and OCN levels and rise FGF-23, with mean (95 % confidence interval) between group differences in iPTH [−27.8 pg/ml; 95 % CI (−42.3 to −13.2); p < 0.001], FGF-23 [30.6 pg/ml; 95 % CI (14.8 to 46.3); p < 0.001], CTX [0.12 μg/l; 95 % CI (−0.19 to −0.06); (p < 0.001) and OCN [−4.03 ng/ml; 95 % CI (−7.8 to −0.27); p = 0.036]. Similarly we observed with calcitriol, as between treatment percentage change, a reduction of −38 % for iPTH, −34 % for CTX, and −28 % for OCN levels respectively (p < 0.05 for all). In people with T2DM and stage 3 CKD, calcitriol reduces the levels of CTX, OCN, PINP and iPTH. Further studies are needed to assess the clinical significance of our findings and the related long term impact on bone health.

AB - People with diabetes and chronic kidney disease (CKD) are predisposed to bone mineral disorders and increased fracture risk. There is limited data on the effect of calcitriol on bone turnover markers (BTMs) in people with type 2 diabetes (T2DM) and stage 3 CKD. In a pre-specified secondary endpoint analysis of a 48-week randomized placebo controlled double-blind trial, we studied the effects of oral calcitriol 0.25 μg once daily on circulating BTMs that included osteocalcin (OCN), C-terminal telopeptide of type I collagen (CTX[sbnd]I), procollagen type I N-propeptide (PINP) and fibroblast growth factor-23 (FGF-23). Inclusion criteria were people with T2DM with stable stage 3 CKD stage and intact parathyroid hormone (iPTH) >30 pg/ml. In total, 127 people [calcitriol (n = 64), placebo (n = 63)] were eligible for analyses. Baseline median (interquartile range) age of the cohort was 67 (60.5–70) years, iPTH (median range) 73.9 (55, 105) pg/ml and eGFR 40 (33, 48.5) ml/min. Calcitriol treatments resulted in a significant fall in iPTH, CTX, PINP and OCN levels and rise FGF-23, with mean (95 % confidence interval) between group differences in iPTH [−27.8 pg/ml; 95 % CI (−42.3 to −13.2); p < 0.001], FGF-23 [30.6 pg/ml; 95 % CI (14.8 to 46.3); p < 0.001], CTX [0.12 μg/l; 95 % CI (−0.19 to −0.06); (p < 0.001) and OCN [−4.03 ng/ml; 95 % CI (−7.8 to −0.27); p = 0.036]. Similarly we observed with calcitriol, as between treatment percentage change, a reduction of −38 % for iPTH, −34 % for CTX, and −28 % for OCN levels respectively (p < 0.05 for all). In people with T2DM and stage 3 CKD, calcitriol reduces the levels of CTX, OCN, PINP and iPTH. Further studies are needed to assess the clinical significance of our findings and the related long term impact on bone health.

UR - http://www.scopus.com/inward/record.url?scp=85140416000&partnerID=8YFLogxK

U2 - 10.1016/j.bone.2022.116581

DO - 10.1016/j.bone.2022.116581

M3 - Article

SN - 8756-3282

VL - 166

JO - Bone

JF - Bone

M1 - 116581

ER -