ABSTRACT
Gastric ulceration associated with the use of nonsteroidal anti-inflammatory drugs [NSAIDs] is mostly observed in elderly women, the same sector of society most likely to be receiving therapy for osteoporosis. Alendronate sodium, an aminobisphosphonate, is a selective inhibitor of osteoclast-mediated bone resorption. It is used for treatment and prevention of postmenopausal osteoporosis. It can cause irritation and inflammation of the upper gastrointestinal mucosa. This study was designed to delineate the effects of combined alendronate-indomethacin therapy on gastric mucosa of rats and the possible modulatory effects of montelukast or rosiglitazone. Fifty six adult male albino rats weighing 200-250g were used in this study and divided into seven groups, each of eight animals as follows: group I used as control untreated animals and received 1 ml of 0.9% saline, the vehicle, orally daily for six days, group II used as control treated animals and received alendronate only, group III used as control treated animals and received alendronate combined with indomethacin, group IV received montelukast before alendronate administration, group V received montelukast before combined administration of alendronate-indomethacin, group VI received rosiglitazone before alendronate administration, and group VII received rosiglitazone before combined administration of alendronate and indomethacin. Alendronate treatment produced a significant increase in gastric acidity, ulcer index, gastric myeloperoxidase [MPO] activity and malondialdehyde [MDA] levels in the stomach accompanied by a significant reduction in glutathione levels. The combined alendronate-indomethacin administration produced further significant deleterious changes on the previous studied parameters when compared with the alendronate-treated group. The previous changes in biochemical parameters were accompanied by histopathological changes evidenced by epithelial ulceration, dilatation of gastric glands, and infiltration by inflammatory cells. The gastric mucosal damage was more pronounced by the combined use of alendronate with indomethacin. Montelukast or rosiglitazone therapy produced a significant reduction in gastric acidity, ulcer index, gastric MPO activity, and MDA levels in the stomach accompanied by a significant increase in glutathione levels, both in alendronate-treated group and in alendronate-indomethacin combined group. Moreover, both drugs reduced the histopathological changes. The results of the present study demonstrated that alendronate-indomethacin combined therapy induced gastric damage more significant than alendronate alone and that the use of either montelukast or rosiglitazone can reduce these hazardous effects in rat gastric mucosa. Further studies on humans are needed to evaluate the clinical use of the studied drugs in patients using alendronate alone or in combination with NSAIDs