الفهرس 
IntroductionOnly 14 pages are availabe for public view
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Abstract
One of the major health threats associated effective chemotherapy regimens is the detrimental side effects on bone. Methotrexate (MTX) is a folic acid antagonist and chemotherapeutic agent widely used in cancer treatment. MTX was known to cause bone defects in the form of fractures and bone in growth defects especially in pediatric patient. So the present work was carried out to show the effects of methotrexate on bone and possible protective role of folic acid supplementation. This study was conducted on adult 30 male albino rats. They were divided into 3 groups: Control group (10): rats in this group were given distilled water, experimental group (A) (10): rats in this group were given MTX in a dose of once daily at 0.75 mg/kg for two separate 5-day courses (5 days on/9 days off/5 days on) . Experimental group (B)(10): rats in this group were given methotrexate at the same regimen as experimental group(A) plus folic acid injection 6 hours after MTX at dose of 1mg/kg. For each group, the rats were sacrificed and tibia and lumbar vertebrae disarticulated, extracted, fixed in 10% Formaldehyde solution for 24 h – 72 h, decalcified, dehydrated, embedded in paraffin blocks, cut at 5micrometer, stained by Haematoxylin and eosin staining and examined by light microscopy. The tibia and lumbar vertebrae were taken and prepared for examination by electron microscope. Weight and crown rump length were measured. In addition, the thickness of epiphyseal cartilage plate of tibia , thickness of epiphyses of lumbar vertebrae, number of chondrocytes in the proliferative layer of growth plate of the tibia and lumbar vertebrae, the thickness of articular cartilage and number of chondrocytes in the articular cartilage were measured at magnification (100 for thickness and 400 for number of cells) using OLYMPUS DP27 digital camera attached to an OLYMPUS CX41 light microscope and PC running cellSens Standard software (version 1.7) . Statistical analysis of the morphometric measurements was carried out using the SPSS software, version 13 program (USA). Comparison of the significance between the control and treated groups was carried out using ANOVA test. Histological examination of the proximal end of the tibia and epiphyses of the lumbar vertebrae of MTX treated group revealed disorganization of cells in the arrangement of growing chondrocytes especially in the proliferative zone. Some cells exhibits degeneration. The proliferative zone showed decrease in chondrocyte number in comparison to control group. With failure of the secondary ossification center to appear as compared to control and folic acid treated group. Histological examination of the diaphysis of the tibia and centrum of the lumbar vertebra showed destruction of most bone marrow cells and overexpression of fat cell. Also examination of the articular cartilage of the proximal end of tibia showed apparent decrease in thickness and crowding of cells. The cells of the intermediate zone showed hypertrophy .The cells of the radial zone showed hypertrophied lacunae and vacuolization as compared to control and folic acid treated group. The matrix of the epiphyseal growth plate of tibia and epiphysis of lumbar vertebrae showed less staining with toluidine blue stain. Electron microscopic results in reserve cell zone revealed dilated cells with excessive vacuolization of the cytoplasm. Abnormal shape of the nuclei was observed with the outline of nuclear membrane not well demarcated. The rough endoplasmic reticulum wa less numerous or absent and the collagen fibers in the extracellular matrix were less apparent. In proliferating cell zone the nuclei had abnormal shape and position with excessive vacuolization of the cytoplasm. Folic acid treatment revert most of these changes when given with MTX therapy, so it has a protective role against most of the MTX side effects. Conclusion: from the present study it was observed that MTX therapy has marked harmful effects on bone growth and structure. So folic acid treatment should be started with methotrexate therapy to protect against these effects.