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Effects of growth hormone therapy on circadian osteocalcin rhythms in idiopathic short stature
M E Markowitz1, J DiMartino-Nardi, F Gasparini
1Division of Pediatric Endocrinology, Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, New York 10467.
Insights
Growth hormone (GH) treatment in children with idiopathic short stature significantly increases osteocalcin (Oc) levels and synchronizes its circadian rhythm. This suggests GH impacts bone metabolism regulation beyond just growth velocity.
Area of Science:
- Pediatric Endocrinology
- Bone Metabolism
- Circadian Rhythms
Background:
- Idiopathic short stature (ISS) affects children's growth, with growth hormone (GH) therapy being a common treatment.
- Osteocalcin (Oc) is a bone-specific protein reflecting bone turnover, and its rhythmicity may be influenced by GH.
Purpose of the Study:
- To investigate the effects of GH administration on the 24-hour circadian rhythm of osteocalcin in prepubertal children with ISS.
- To assess changes in osteocalcin levels and pattern synchronization during GH treatment.
Main Methods:
- Four prepubertal children with ISS received GH treatment for 12 months.
- Sequential 24-hour blood sampling was performed before treatment, at 6 months, and at 12 months.
- Osteocalcin levels and circadian patterns were analyzed and compared to a normative model.
Main Results:
- GH treatment led to a significant upward shift in mean 24-hour osteocalcin levels.
- The circadian pattern of osteocalcin showed progressive improvement and synchronization with a normative model during treatment.
- Insulin-like growth factor-I levels increased, and growth rate improved in most children.
Conclusions:
- GH administration increases osteocalcin concentrations in children with ISS by modulating its circadian rhythm.
- The synchronization of the osteocalcin rhythm suggests a broader impact of GH on bone metabolism regulation.
- The rise in osteocalcin may not directly correlate with increased growth velocity.
Abstract:
The effects of GH administration on the circadian osteocalcin (Oc) rhythm were determined in four prepubertal children with idiopathic short stature (height, less than 5th percentile; growth velocity, less than 50th percentile for age). Each child underwent 24-h sequential blood sampling on three occasions: immediately before the initiation of GH treatment, 6 months later, and at the end of 12 months of treatment. The growth rate increased more than 50% over baseline in three of the four children during at least one of the 6-month periods. Insulin-like growth factor-I levels increased during treatment in all of the children. Twenty-four-hour Oc levels increased on 7 of the 8 treatment days evaluated. When mean 24-h Oc patterns for each of the 3 study days were derived by averaging across individual subjects at each time point and then compared, we noted an upward shift in the entire pattern during treatment (t = 13.2 at P less than 0.001 and t = 5.9 at P less than 0.001 for 6 and 12 month comparisons vs. the pretreatment day, respectively). This was more easily appreciated after the data were smoothed using the method of running means. There was, in addition, a progressive improvement in the shape of the Oc pattern compared to a normative model derived from a study of healthy adult men. The correlation between the model and the pre-GH day was 0.46, that between the model and the 6 months of GH day was 0.77, and that between the model and the 12 months of GH day was 0.96. Cross-correlation analyses showed that the peak correlation between the 2 treatment days and the model occurred at zero lag. In contrast, the peak correlation between the pre-GH day and the model or the pre-GH day and either of the 2 treatment days occurred when the pre-GH series was lagged by 2-3 h. Thus, an additional finding is the synchronization of the Oc series that occurred during treatment. We conclude that GH treatment increases Oc concentrations in children with idiopathic short stature by affecting its circadian rhythm. This rise in Oc values may not necessarily reflect an increase in growth velocity.