Effect of glimepiride on the skeletal system of ovariectomized and non-ovariectomized rats

Abstract

Background: Diabetes mellitus type 2 and osteoporosis are major health problem, especially in postmenopausal women. Glimepiride is a third-generation sulfonylurea derivative and is used as a first-line drug in the treatment of type 2 diabetes mellitus. The effect of this drug on bone tissue is unknown. The aim of the present study was to investigate the influence of glimepiride on the skeletal system in ovariectomized and non-ovariectomized rats.

Methods: The experiment was conducted on 3-month-old female Wistar rats, divided into 4 groups (n=10 per group): I (NOVX)-non-ovariectomized control rats, II (NOVX+G)-non-ovariectomized rats receiving glimepiride (0.8 mg/kg po), III (OVX)-ovariectomized control rats, IV (OVX+G)-ovariectomized rats receiving glimepiride (0.8 mg/kg po). Bilateral ovariectomy was performed 7 days before the start of the experiment, under ketamine-xylazine anesthesia. Glimepiride was administered once daily for 28 days. The effect of glimepiride on the skeletal system was assessed based on macrometric parameters, histomorphometric parameters and mechanical properties of the tibial metaphysis, femoral diaphysis and femoral neck. Bone mass, mineral mass, calcium and phosphorus content, as well as serum estrogen, osteocalcin and RatLaps levels were also studied.

Results: Estrogen deficiency in ovariectomized rats caused increased bone remodeling, with an intensification of bone resorption and formation, and mineralization impairment. Glimepiride in ovariectomized rats inhibited the development of changes in the skeletal system caused by estrogen deficiency, intensifying bone formation. In the presence of estrogens (in non-ovariectomized rats), glimepiride also intensified bone formation, but to a lesser extent.

Conclusions: Glimepiride, in the therapy of type 2 diabetes mellitus in postmenopausal women, may have a beneficial effect on bone remodeling and may reduce the risk of development of osteoporosis.

Keywords: Bone mechanical properties; Bone remodeling; Glimepiride; Osteopenia; Rats.