ABSTRACT
The aim of this study was to assess the possible modulatory effects of rofecoxib [selective cyclooxygenase -2 inhibitor], and indomethacin [non-selective cyclooxygenase inhibitor], on the development of osteoporosis in experimentally induced postmenopausal osteoporosis in female rats. This study was carried out on sixty-four adult female albino rats weighing 180-190 grams of nine months of age. Under light ether anesthesia, the rats underwent ovariectomy [OVX] or Sham operation by the dorsal approach and assigned to eight groups of eight rats each. Group 1: Sham operated and treated with vehicle and served as a control for groups 2-4. Groups 2, 3 and 4: OVX treated with; vehicle, rofecoxib [3mg/kg BW/day] and indomethacin [1mg/kg BW/day] respectively. Groups 1-4 were given vehicle or respective drugs daily orally for six weeks through gavage starting immediately after OVX. Group 5: Sham operated and treated with vehicle and served as a control for groups 6-8. Groups 6, 7 and 8: OVX treated with; vehicle, rofecoxib [3mg/kg BW/day] and indomethacin [1mg/kg BW/day] respectively. Groups 5-8 were given vehicle or the respective drugs daily orally through gavage started at the sixth week after OVX and continued for consecutive six weeks. At the end of the experiment period, six weeks of groups 1-4 and twelve weeks for groups 5-8, 24 hours urine was collected after the last treatment for estimation of urinary hydroxyproline and calcium. Under light ether anesthesia blood samples were collected from the retro-orbital venous plexus. Sera were separated for estimation of osteocalcin, bone specific alkaline phosphatase and serum calcium. Then, the animals were sacrificed and the lumbar vertebrae and both femurs were excised for histological and immunohistochemical studies. The present study demonstrated that estrogen deficiency induced by OVX was clearly associated with increased bone turnover. The bone resorption was manifested by a significant increase in the mean value of urinary hydroxyproline, and urinary calcium excretion, thinning of bone trabeculae, widening of bone lamellae, anastmosis of bone marrow cavities and decreased expression of collagen type I staining. The trabecular bone was affected earlier and to a greater extent than long cortical bone. Bone formation was also evident by a significant increase in the mean value of serum osteocalcin, bone specific alkaline phosphatase and a significant decrease in mean value of serum calcium, presence of many osteogenic cells at the periosteal and endosteal surface, multiple cement lines and random orientation of less flattened osteocyte's lacunae. There was no significant difference between the mean values of the studied parameters in the vehicle treated ovariectomized groups at the 6[th] and 12[th] weeks after OVX. Immediate administration of rofecoxib [but not indomethacin] after OVX produced remarkable protective effect on the development of osteoporosis as manifested by decreased bone turnover markers and normal histological and immunohistochemical structure. On the other hand, administration of either rofecoxcib or indomethacin six weeks after OVX for another consecutive six weeks failed to produce significant protective effect but improve the quality of the newly formed bones. Selective cyclooxygenase -2 inhibitors are recommended early during development of osteoporosis as they have a protective effect on bone resorption. Nonsteroidal anti-inflammatory drugs [either selective or non-selective] would be beneficial when given after the development of osteoporosis as they improve the quality of the newly formed bones