RESUMEN
Alendronate sodium [fosamax] is a potent inhibitor of osteoclast-mediated bone resorption and is used for treatment of osteoporosis and Paget's disease of bone. The aim of this work was to study the ultrastructural and immunohistochemical changes of liver of adult male albino rats after alendronate sodium [fosamax] administration. Thirty six adult male rats were used in this study and randomly divided into three groups; control, fosamax treated for short period and fosamax treated for long period. At sacrifice, blood samples were drawn for biochemical study and liver sections were prepared for histological, ultrastructural, histochemical and immunohistochemical study. Fosamax treated rats showed a time dependent highly significant increase in liver function tests. Liver sections of treated rats showed dilated congested central veins and blood sinusoids with interstitial hemorrhage, perivascular cellular infiltration and many necrotic cavities. Some nuclei were shrunken and others were fading out. Ultrastructurally, there was marked mitochondrial alterations, loss of studded ribosomes from RER and increased amount of dilated smooth endoplasmic reticulum, secondary lysosomes, lipid droplets and glycogen granules. Fosamax treated rats showed a decrease in succinic dehydrogenase enzyme activity with increase in acid phosphatase enzyme activity and a strong positive immunoreactivity for bcl-2 and galectin-3. These changes were time dependent and appeared more obviouse in fosamax treated rats for long period. In Conclusion, it has became clear that prolonged use of fosamax leads to subtle hepatic damage so it is recommended from physicians treating patients with alendronate or related drugs to be alert for the possibility of liver dysfunction by monitoring properly such effects by routine measurement of liver enzymes and to stop this medication on occurrence of liver dysfunction