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Effects of methylphenidate on femoral bone growth in male rats
Gökçe Nur Say1, Mehmet Emin Önger2, Ferhat Say3
1Department of Child and Adolescent Psychiatry, Faculty of Medicine, Ondokuz Mayıs University, Samsun, Turkey.
Abstract:
The use of Methylphenidate (MP) can have adverse effects on bone growth and mineralization. This study aimed to investigate the underlying pathophysiology of MP-induced skeletal deficits in growing rats using stereological and immunohistochemical methods. Male rats, aged 4 weeks, were orally treated with MP through an 8-h/day water drinking protocol. The rats (n=30) were randomly divided into three groups: MP-High Dose (30/60 mg/kg/day MP), MP-Low Dose (4/10 mg/kg/day MP), and control (water only). After 13 weeks, the femoral bones were assessed using calliper measurements, dual-energy X-ray absorptiometry, and biomechanical evaluation. The total femur volume, cartilage volume, growth zone volume, and volume fractions were determined using the Cavalieri method. Immunohistochemical analyses were conducted using alkaline phosphatase and anti-calpain antibody staining. Rats exposed to MP exhibited significant reductions in weight gain, femoral growth, bone mineralization, and biomechanical integrity compared to the control group. The total femoral volume of MP-treated rats was significantly lower than that of the control group. The MP-High Dose group showed significantly higher ratios of total cartilage volume/total femoral volume and total growth zone volume/total femoral volume than the other groups. Immunohistochemical evaluation of the growth plate revealed reduced osteoblastic activity and decreased intracellular calcium deposition with chronic MP exposure. The possible mechanism of MP-induced skeletal growth retardation may involve the inhibition of intracellular calcium deposition in chondrocytes of the hypertrophic zone in the growth plate. In this way, MP may hinder the differentiation of cartilage tissue from bone tissue, resulting in reduced bone growth and mineralization.
Insights
Methylphenidate (MP) negatively impacts bone growth and mineralization in rats. This study suggests MP hinders cartilage-to-bone differentiation by inhibiting calcium deposition in growth plates, leading to skeletal deficits.
Area of Science:
- Pharmacology
- Skeletal Biology
- Developmental Toxicology
Background:
- Methylphenidate (MP) is a stimulant medication.
- Adverse effects of MP on bone growth and mineralization are a concern.
- Understanding the mechanisms of MP-induced skeletal deficits is crucial.
Purpose of the Study:
- To investigate the pathophysiology of Methylphenidate (MP)-induced skeletal deficits in growing rats.
- To evaluate the impact of MP on bone growth, mineralization, and biomechanical properties.
- To elucidate the cellular mechanisms underlying MP's effects on the growth plate.
Main Methods:
- Stereological analysis of femoral bone parameters (volume, cartilage, growth zone).
- Dual-energy X-ray absorptiometry and biomechanical testing of femurs.
- Immunohistochemical analysis of alkaline phosphatase and calpain in growth plates.
Main Results:
- MP treatment significantly reduced weight gain, femoral growth, bone mineralization, and biomechanical integrity.
- MP exposure led to decreased total femur volume and altered cartilage/growth zone volume ratios.
- Reduced osteoblastic activity and intracellular calcium deposition were observed in MP-treated rats' growth plates.
Conclusions:
- Methylphenidate (MP) exposure causes significant skeletal deficits in growing rats.
- MP-induced growth retardation may stem from inhibited intracellular calcium deposition in chondrocytes.
- This inhibition potentially impairs cartilage-to-bone differentiation, affecting bone growth and mineralization.
