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Dexamethasone acts locally to inhibit longitudinal bone growth in rabbits
1Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892.
Abstract:
Excess glucocorticoid is a potent inhibitor of epiphysial growth. Several mechanisms have been suggested to explain this growth inhibition, including both direct local effects of glucocorticoid on the epiphysial growth plate and indirect systemic effects. Previous studies do not distinguish which of these proposed mechanisms is actually responsible for the growth suppression in vivo. To resolve this controversy, we developed a method for delivering glucocorticoid directly into the rabbit epiphysial growth plate and for accurately measuring the resulting epiphysial growth rate. Five-week-old male rabbits received a local infusion of dexamethasone phosphate (80 ng/microliters, 1 microliters/h) into one proximal tibial growth plate and an infusion of vehicle into the contralateral growth plate. Growth rate was determined by inserting metal pins into the bone immediately adjacent to the growth plate and measuring the change in distance between pins on serial radiographs. This method permitted growth rates to be measured over intervals as short as 3 days, with an error of approximately 5%. Local dexamethasone administration decreased proximal tibial growth rate by 77% compared with the contralateral vehicle-treated tibia (P less than 0.0001). We conclude that excess glucocorticoid causes a rapid potent inhibition of growth by a direct local action on the growth plate.
Insights
Excess glucocorticoid rapidly inhibits bone growth. This study demonstrates that glucocorticoids directly impact the growth plate, causing significant growth suppression in rabbits.
Area of Science:
- Endocrinology
- Orthopedics
- Developmental Biology
Background:
- Glucocorticoids are known to inhibit epiphysial growth.
- The precise mechanism, whether local or systemic, remains unclear.
Purpose of the Study:
- To investigate the direct local effect of glucocorticoids on epiphysial growth plate function.
- To differentiate between local and systemic mechanisms of glucocorticoid-induced growth inhibition.
Main Methods:
- Developed a novel method for direct glucocorticoid (dexamethasone phosphate) infusion into the rabbit proximal tibial growth plate.
- Utilized serial radiography with implanted metal pins to accurately measure epiphysial growth rates over short intervals (as little as 3 days).
Main Results:
- Local administration of dexamethasone phosphate resulted in a significant 77% reduction in proximal tibial growth rate compared to vehicle-treated controls.
- The observed growth inhibition was rapid and potent, demonstrating a direct local action.
Conclusions:
- Excess glucocorticoid exerts a potent and rapid inhibitory effect on epiphysial growth.
- This inhibition occurs primarily through a direct local action on the growth plate, not indirect systemic effects.