Liraglutide exerts a bone-protective effect in ovariectomized rats with streptozotocin-induced diabetes by inhibiting...

Liraglutide, a glucagon-like peptide-1 receptor agonist, is an anti-diabetic medicine associated with a reduced risk of fracture in diabetic patients. In the present study, rats with streptozotocin (STZ)-induced diabetes and/or bilateral ovariectomy (OVX) were treated with liraglutide for eight weeks. Liraglutide treatment increased insulin secretion and managed blood glucose levels in the rats following STZ-induced diabetes. In addition, STZ- and OVX-induced reduction of femoral bone mineral density and destruction of bone microarchitecture were alleviated by liraglutide. STZ decreased, whereas OVX increased, serum osteocalcin (OC) level (a bone formation marker) and osteoblast counts in the trabecular bone. OVX, however not STZ, markedly increased the level of serum c-terminal telopeptide of type 1 collagen (CTX-1, a bone resorption marker) and osteoclast counts in the trabecular area. Liraglutide treatment significantly increased serum OC levels in all three osteoporotic models, however had minimal effects on osteoblast counts. Furthermore, liraglutide significantly decreased serum CTX-1 level and osteoclast numbers in OVX and STZ+OVX rats. Furthermore, the present study examined the mRNA expression and serum concentrations of osteoprotegerin (OPG) and receptor activator of nuclear factor-κB ligand (RANKL), and liraglutide significantly decreased the RANKL/OPG ratio compared with the untreated rats, indicating that osteoclastogenesis was inhibited by liraglutide. In summary, the results suggested that liraglutide ameliorates STZ+OVX-induced bone deterioration in the rat model, primarily through the inhibition of osteoclastogenesis. These preliminary findings propose a potentially beneficial effect of liraglutide on the bone health of postmenopausal diabetic patients.