| Summary: | Aim of the work: To study the possible protective and therapeutic effects of exenatide on experimentally-induced osteoporosis in adult ovariectomized female albino rats. Materials and methods: The study included 40 mature female albino rats, matched for age and weight (150–250 gm). Osteoporosis was experimentally-induced by bilateral ovariectomy (OVX) and the animals were left untreated for 6 weeks. Rats were divided into 4 groups: Sham group (group-I), ovariectomized (OVX) non-treated (group-II), prophylactic exenatide (group-III: received 1 μg/kg/d SC for 6 weeks immediately after ovariectomy) and treated group-IV (Left untreated for 6 weeks after ovariectomy then received treatment for 8 weeks) was subdivided into subgroup-IVa: treated with exenatide in a dose of 1 μg/kg/d SC and subgroup IVb: treated with vitamin Din a dose 0.25 µg/day orally for 5 days/week. Serum bone-specific alkaline phosphatase (BsALP) level was measured and bone histomorphometry assessed. Results: Non-treated rats showed a significant elevation of BsALP level by 182%, reduction of cortical thickness by 36% and osteocyte number by 29% compared to Sham group-I. Rats of prophylactic exenatide, therapeutic exenatide and therapeutic vitamin D showed a significant reduction of BsALP level by 62.4%,62.5% and 62.2%, respectively, increase of the cortical thickness by 38.7%, 29.4% and40.9% respectively and osteocyte number by 29%,26% and 42%, respectively compared to OVX non-treated group-II. The mean BsALP in group IV improved to levels comparable to Sham group-I. There was no significant difference in all previous results between groups-III and IVa or IVb. Conclusion: Exenatide has a potential prophylactic and therapeutic role in the management postmenopausal osteoporosis. The non-inferiority of exenatide to vitamin D in treatment of osteoporosis is deduced. Keywords: Osteoporosis, Vitamin D, Exenatide, Ovariectomy, Experimentally-induced
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