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Published on: September 17, 2019
Prednisolone Effects on Urine Cross-Linked N-Telopeptides of Type I Collagen (Ntx) Diurnal Rhythms in Children
Ole D Wolthers1, Carsten Heuck1
1Asthma and Allergy Clinic, Children`s Clinic Randers, Randers, Denmark.
Insights
Administering prednisolone in the evening significantly suppressed urine Ntx levels and disrupted diurnal rhythms. Morning administration also altered Ntx rhythms, indicating timing impacts corticosteroid effects on bone turnover.
Area of Science:
- Endocrinology
- Pediatric Endocrinology
- Pharmacology
Background:
- Exogenous corticosteroids can cause adverse effects, prompting research into mimicking cortisol rhythms.
- Urine cross-linked N-telopeptides of Type I collagen (Ntx) are sensitive markers of bone resorption with distinct diurnal variations.
- Patented methods exist for detecting corticosteroid-induced bone turnover changes and mimicking natural cortisol patterns.
Purpose of the Study:
- To investigate the impact of prednisolone administration timing on the diurnal rhythm of urinary Ntx levels.
- To determine if evening versus morning prednisolone affects bone resorption markers differently.
Main Methods:
- An open-label, randomized cross-over trial involving 8 pubertal children (4 girls, 4 boys).
- Participants received 5mg of prednisolone daily for 4 days, either in the morning or evening, with a 3-week washout period.
- Urine Ntx levels were measured at multiple intervals over 24 hours on the last day of each treatment period and during a run-in phase.
Main Results:
- Evening prednisolone significantly suppressed urine Ntx levels from 24:00 to 08:00 and abolished the typical diurnal rhythm.
- Morning prednisolone also reduced Ntx levels between 12:00 and 20:00 compared to baseline and evening administration.
- Morning administration resulted in Ntx troughs from 16:00-20:00 and peaks from 24:00-08:00.
Conclusions:
- The timing of prednisolone administration significantly influences diurnal rhythms of urinary Ntx.
- Evening administration appears to have a more pronounced effect on suppressing Ntx and disrupting circadian patterns.
- These findings highlight the importance of considering administration timing to mitigate corticosteroid-induced bone turnover effects.
Background:
Recently, methods for mimicking endogenous cortisol rhythms hereby potentially reducing the risk of systemic adverse effects of exogenous corticosteroids have been patented. Methods for sensitive detection of adverse effects on bone turnover of various doses, administration routes and regimens of exogenous corticosteroids have been patented. Urine cross-linked Ntelopeptides of Type I collagen (Ntx) have been established as a sensitive bone resorption marker and urine levels of Ntx have been found to exhibit a distinct diurnal rhythm.
Objective:
To assess whether the timing of administration of prednisolone affects the diurnal rhythm of Ntx in urine.
Methods:
Four girls and four boys aged 10.6 to 15.8 (mean 13.2) years with normal weight and height and pubertal stages I-IV were studied in an open randomized 2-periods cross-over trial, with a 1-day run in, and two 4-day periods of 5mg prednisolone in the morning and in the evening, respectively, separated by a 3-week washout period. At run in and on the last day of each treatment period, the first sample of urine was collected from 24.00 to 08.00h in the morning of the day of investigation. Thereafter, urine was collected in 4~hour intervals until 24.00 and in another 08.00h interval from 24.00 to 08.00h.
Results:
Compared to run in and morning prednisolone treatment urine Ntx levels were suppressed from 24.00 to 8.00h during treatment with prednisolone in the evening (P < 0.01 for both comparisons) and no statistically significant circadian rhythm was observed. During morning prednisolone treatment Ntx trough and peak levels occurred from 16.00 to 20.00 and 24.00 to 08.00h, respectively, and the Ntx levels were significantly reduced from 12.00 to 20.00h as compared to run in (P < 0.005) and prednisolone treatment in the evening (P < 0.01).
Conclusions:
Depending on the time of administration, prednisolone interferes with diurnal rhythms in urine Ntx.
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