Bone Abstracts

Type 2 diabetes and osteoporosis often occur together in postmenopausal women. Sitagliptin is a new drug used in the therapy of type 2 diabetes; it affects incretin system as a result of inhibition of dipeptidyl peptidase-4. So far, the impact of the drug on bone remodeling processes is unknown. The aim of this study was to investigate the effect of sitagliptin on bone growth and remodeling in non-ovariectomized and ovariectomized rats.

The experiments were carried out on 3-month-old female Wistar rats divided into 4 groups (n=9–10 per group): I – non-ovariectomized control rats, II – ovariectomized control rats, III – non-ovariectomized rats receiving sitagliptin (15 mg/kg p.o.), IV – ovariectomized rats receiving sitagliptin (15 mg/kg p.o.). Bilateral ovariectomy was performed 7 days before the start of the experiment, under ketamine–xylazine anesthesia. Sitagliptin was administered once daily for 28 days. Bone growth and remodeling after the use of sitagliptin was assessed based on macrometric parameters (the length and diameter in the mid-length of the tibia and femur), and histomorphometric parameters including measurements of the tibial and femoral diaphysis (endosteal and periosteal transverse growth, transverse cross-section area of the cortical bone and marrow cavity) and femoral epiphysis and metaphysis (width of trabeculae and epiphyseal cartilage). Bone mass, mineral mass, calcium and phosphorus content, as well as serum estradiol, osteocalcin and RatLaps levels were also studied.

In ovariectomized rats, estrogen deficiency caused increased bone remodeling with intensification of bone resorption and impairment of mineralization. Sitagliptin favorably affected the skeletal system of ovariectomized rats, inducing intensification of bone formation and mineralization, and inhibition of bone resorption. In non-ovariectomized rats, sitagliptin only slightly intensified bone formation.