Changes in bone turnover markers after discontinuing long-term glucocorticoid administration in children with idiopathic nephrotic syndrome: a multicenter retrospective observational study.

BACKGROUND: Glucocorticoids affect bone turnover. Little is known about how bone turnover changes when glucocorticoids are discontinued following long-term administration. METHODS: This retrospective observational study was conducted on the relationship between discontinuation of long-term administration of glucocorticoid and bone turnover markers (BTMs) in patients with childhood-onset idiopathic nephrotic syndrome. Serum bone alkaline phosphatase (BAP), intact procollagen type 1 N-terminal propeptide (P1NP), and tartrate-resistant acid phosphatase-5b (TRACP-5b) were evaluated as BTMs. RESULTS: Thirty-eight pairs of BTMs at glucocorticoid administration and after discontinuation were analyzed in 29 patients. The median age at baseline was 12.4 (interquartile range, 9.0-14.5) years, and the median time from the onset of nephrotic syndrome was 5.9 (3.3-9.7) years. The mean period from prednisolone discontinuation to the measurement of BTMs after glucocorticoid discontinuation was 3.5 ± 1.0 months. Changes in BTMs after glucocorticoid discontinuation were modest when the daily prednisolone dose was < 0.25 mg/kg/day (ln BAP standard deviation [SD] score, p = 0.19; log intact P1NP SD score, p = 0.70; TRACP-5b, p = 0.95). When the daily prednisolone dose was ≥ 0.25 mg/kg/day, all BTMs increased significantly after glucocorticoid discontinuation (ln BAP SD score, p < 0.01; log intact P1NP SD score, p < 0.01; TRACP-5b, p < 0.01). CONCLUSIONS: Decreased BTMs can rise within a few months of discontinuing long-term glucocorticoid administration. When the administered glucocorticoid dose is low, changes in BTMs may be small. A higher resolution version of the Graphical abstract is available as Supplementary information.

Kinetic aspects of iron(III)-chelation therapy with deferasirox (DFX) revealed by the solvolytic dissociation rate of the Fe(III)-DFX complex estimated with capillary electrophoretic reactor.

Capillary electrophoresis was used to estimate the solvolytic dissociation rate (kd) of metal complexes of deferasirox (DFX, H3L), a drug used to treat iron overload. Inert CoIIIL23- did not dissociate. The estimated kd value for FeIIIL23- was (2.7 ± 0.3) × 10-4 s-1 (298 K, pH 7.4). The kd values of other complexes (AlIIIL23-, NiIIL24-, and MnIIL-) were in the range 10-3-10-4 s-1. In contrast, ZnIIL- and CuIIL- were too labile to allow kd estimation. The fact that the half-life of FeIIIL23- (43.3 min) is shorter than the blood half-life of DFX (8-16 h) implies that the blood concentration of DFX should be high enough to prevent dissociation of FeIIIL23-. The possibility of a safer iron-chelation therapy that avoids excretion of other essential metal ions such as ZnII is discussed, highlighting the importance of selectivity in terms of kinetic stability.