Effects of cyclophosphamide on the femoral epiphyseal growth plate in young Sprague-Dawley rats.
The purpose of this study was to assess the effects of cyclophosphamide on cartilaginous growth and differentiation. Cyclophosphamide is a drug commonly used in the treatment of neoplastic diseases and in preparation for bone marrow transplantation. Eighteen Sprague-Dawley rats divided into control and experimental groups received 2 i.p. injections of either saline or cyclophosphamide (30 mg/kg) with a 3-day interval starting from day 10 after birth. Effects on the proximal femoral epiphyses were evaluated histomorphometrically as well as semi-quantitatively at day 31 after birth. Results showed a significant reduction in length of the cyclophosphamide-treated femora compared to the controls. This could be attributed to a significant reduction in the thickness of the growth zone. Cell differentiation throughout the growth plates was clearly disturbed, involving nesting of cells, loss of polarity, and impaired maturation as seen by areas of excessive hyalinization. Although the effects of cyclophosphamide on the growth plates were significant compared to controls, the changes were not as extensive as previous reports have indicated. This could be attributed primarily to the fact that a comparatively low dose of the drug was used in the present study. Also, a period of recovery was allowed prior to evaluation. Nevertheless, significant effects remained which should be considered when treating young children with cyclophosphamide.
Zilberman
Oded
O
Department of Orthodontics, School of Dentristry, Karolinska Institutet, Huddinge, Sweden.
Närsman
Margareta
M
Forsberg
Carl-Magnus
CM
Sven
Lindskog
L
D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000633:toxicity*; D001846:Bone Development / Q000187:drug effects*; D003520:Cyclophosphamide / Q000633:toxicity*; D005260:Female; D005269:Femur / Q000187:drug effects; D006132:Growth Plate / Q000187:drug effects*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D018709:Statistics, Nonparametric
D018906:Antineoplastic Agents, Alkylating; D003520:Cyclophosphamide