title: Thalidomide affects the skeletal system of young rats.
abstract: Thalidomide has indications for the treatment of several immune-related, neoplastic, and inflammatory diseases, in both adults and children. Despite numerous therapeutic indications for the application of thalidomide, the influence of that drug upon skeletal system has not been recognized. The aim of the present study was to investigate the effects of thalidomide on the osseous tissue in young rats. The experiments were carried out on 5-week-old male Wistar rats. The animals were administered thalidomide in the doses of 15, 30 or 60 mg/kg p.o. over the period of 1, 3 or 6 weeks. The body mass gain, bone mass in the tibia, femur and L-4 vertebra, histomorphometric parameters of the femur (width of trabeculae, width of epiphyseal cartilage, the transverse cross-sectional area of the bone marrow cavity and the cortical bone) and the tibia (width of osteoid, diaphysis transverse growth, the transverse cross-sectional area of the bone marrow cavity and the cortical bone) were studied. The investigations carried out provide, for the first time, information concerning the influence of thalidomide upon bone remodeling processes in young rats. The effects of thalidomide on the skeletal system of young rats depended on the dose and upon application time. After administration of doses 15, 30 and 60 mg/kg p.o. for 1 and 3 weeks, no influence of thalidomide was noted upon the examined macrometric parameters and histomorphometric parameters of femur, tibia and L-4 vertebra in young rats. Significant disturbances of bone remodeling in young rats have been observed after 6 weeks of thalidomide application, while the progression of those changes increased with the increase of the dose administered. After administering the dose of 15 mg/kg p.o. for the period of 6 weeks, no significant changes were found, as regards the macrometric and histomorphometric parameters of bones. Thalidomide, applied 6 weeks in the dose of 30 mg/kg p.o., and in particular in the dose of 60 mg/kg p.o., turned out to disturb bone remodeling processes. In animals administered thalidomide in the dose of 60 mg/kg p.o., reduction mass of tibia, femur, and L-4 vertebra has been observed. In compact bone, thalidomide reduced the diaphysis transverse growth of tibia, reduced the width of osteoid, as well as reduced the transverse cross-sectional area of cortical bone, increased the transverse cross-sectional area of marrow cavity, and increased the transverse cross-sectional area of the marrow cavity/transverse cross-sectional area of the diaphysis ratio of tibia and femur. In cancellous bone, thalidomide reduced the width of bone trabeculae, and increased the width of epiphyseal cartilage. On the basis of the results obtained, one can conclude that thalidomide applied for 6 weeks in the dose of 60 mg/kg p.o. inhibited the bone formation processes and increased the bone resorption in young rats.
authors.affiliation: Department of Pharmacognosy and Phytochemistry, Medical University of Silesia, Jagiellońska 4, 41-200 Sosnowiec, Poland. farmafit@sum.edu.pl
authors.forename: Ilona
authors.initials: I
authors.lastname: Kaczmarczyk-Sedlak
authors.forename: Lech
authors.initials: L
authors.lastname: Sedlak
authors.forename: Igor
authors.initials: I
authors.lastname: Rymkiewicz
mesh_terms: D000367:Age Factors; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D016723:Bone Remodeling / Q000187:drug effects*; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005269:Femur / Q000187:drug effects / Q000378:metabolism; D007155:Immunologic Factors / Q000633:toxicity*; D008159:Lumbar Vertebrae / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013792:Thalidomide / Q000633:toxicity*; D013977:Tibia / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents; D007155:Immunologic Factors; D013792:Thalidomide