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Rapamycin retards growth and causes marked alterations in the growth plate of young rats

Oscar Alvarez-Garcia1, Eduardo Carbajo-Pérez, Enrique Garcia

  • 1Universidad de Oviedo, Oviedo, Spain.

Pediatric Nephrology (Berlin, Germany)
|March 21, 2007
PubMed

Insights

Rapamycin significantly hinders bone growth and alters growth plate structure in young rats. These findings highlight potential risks for children receiving this immunosuppressant medication.

Area of Science:

  • Pharmacology
  • Pediatric Endocrinology
  • Orthopedics

Background:

  • Rapamycin is an immunosuppressant used in renal transplantation with known antitumoral effects.
  • Its antiproliferative and antiangiogenic properties raise concerns about potential impacts on growth.
  • The effect of rapamycin on the pediatric growth plate is not well understood.

Purpose of the Study:

  • To investigate the effects of rapamycin on longitudinal bone growth and growth plate dynamics.
  • To test the hypothesis that rapamycin interferes with normal growth plate structure and function.
  • To evaluate rapamycin's impact on body weight gain, food intake, and food efficiency.

Main Methods:

  • 4-week-old male rats received daily intraperitoneal injections of rapamycin (2 mg/kg) or vehicle for 14 days.
  • Longitudinal bone growth rate, body weight gain, food intake, and food efficiency were measured.
  • Growth plate structure was assessed by examining chondrocyte proliferation, maturation, hypertrophy, cartilage resorption, and vascular invasion.

Main Results:

  • Rapamycin significantly reduced bone longitudinal growth rate by approximately 50%.
  • Body weight gain, food intake, and food efficiency were markedly decreased in rapamycin-treated rats.
  • Histological analysis revealed reduced chondrocyte proliferation, disturbed chondrocyte maturation and hypertrophy, decreased cartilage resorption, and altered vascular invasion in the growth plates of rapamycin-treated animals.

Conclusions:

  • Rapamycin severely impairs body growth and distorts growth plate structure and dynamics in young, fast-growing rats.
  • The observed effects on growth plate cartilage formation and vascularization are significant.
  • Caution is advised regarding the administration of rapamycin to children due to potential adverse effects on growth.

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