Mechanisms of steroid impairment of growth

Area of Science:

• Pediatric Endocrinology
• Pharmacology
• Growth Biology

Background:

• Child growth is a complex process influenced by numerous factors.
• Glucocorticoids (GC) are potent medications with widespread physiological effects.
• GC exert significant anti-anabolic and catabolic influences on developing tissues.

Purpose of the Study:

• To elucidate the multifaceted mechanisms by which glucocorticoids impede child growth.
• To identify key molecular and physiological pathways affected by GC during development.
• To explore potential strategies for mitigating GC-induced growth retardation.

Main Methods:

• Review of existing literature on glucocorticoid effects on growth.
• Analysis of GC interactions with the growth hormone-insulin-like growth factor 1 (GH-IGF-1) axis.
• Examination of GC impact on bone, cartilage, muscle, and calcium homeostasis.

Main Results:

• GC interfere with the GH-IGF-1 axis at multiple levels, including hormone release and signaling.
• GC suppress chondrocyte proliferation, matrix synthesis, and mineralization in the growth plate.
• GC disrupt calcium balance and negatively affect osteoblast and osteoclast function, alongside muscle strength.

Conclusions:

• GC significantly impair child growth through direct and indirect mechanisms affecting hormonal axes and tissue development.
• Growth damage from GC is most pronounced early in treatment, emphasizing the importance of preventive strategies.
• Reducing GC dosage, utilizing alternative-day regimens, and considering specific analogs or growth factors may mitigate adverse effects.