Liraglutide, a glucagon-like peptide-1 receptor agonist, inhibits bone loss in an animal model of osteoporosis with or without diabetes

Abstract

Introduction: Liraglutide (Lrg), a novel anti-diabetic drug that mimics the endogenous glucagon-like peptide-1 to potentiate insulin secretion, is observed to be capable of partially reversing osteopenia. The aim of the present study is to further investigate the efficacy and potential anti-osteoporosis mechanisms of Lrg for improving bone pathology, bone- related parameters under imageology, and serum bone metabolism indexes in an animal model of osteoporosis with or without diabetes.

Methods: Eight databases were searched from their inception dates to April 27, 2024. The risk of bias and data on outcome measures were analyzed by the CAMARADES 10-item checklist and Rev-Man 5.3 software separately.

Results: Seventeen eligible studies were ultimately included in this review. The number of criteria met in each study varied from 4/10 to 8/10 with an average of 5.47. The aspects of blinded induction of the model, blinding assessment of outcome and sample size calculation need to be strengthened with emphasis. The pre-clinical evidence reveals that Lrg is capable of partially improving bone related parameters under imageology, bone pathology, and bone maximum load, increasing serum osteocalcin, N-terminal propeptide of type I procollagen, and reducing serum c-terminal cross-linked telopeptide of type I collagen (P<0.05). Lrg reverses osteopenia likely by activating osteoblast proliferation through promoting the Wnt signal pathway, p-AMPK/PGC1α signal pathway, and inhibiting the activation of osteoclasts by inhibiting the OPG/RANKL/RANK signal pathway through anti-inflammatory, antioxidant and anti-autophagic pathways. Furthermore, the present study recommends that more reasonable usage methods of streptozotocin, including dosage and injection methods, as well as other types of osteoporosis models, be attempted in future studies.

Discussion: Based on the results, this finding may help to improve the priority of Lrg in the treatment of diabetes patients with osteoporosis.

Keywords: diabetes; efficacy; liraglutide; osteoporosis; possible mechanisms.

Figure 1

Summary of the process for identifying candidate studies.

Figure 2

Forest plot: effects of liraglutide for increasing femur bone mineral density (F-BMD) compared with the control group.

Figure 3

Forest plot: effects of liraglutide for increasing lumbar spine bone mineral density (L-BMD) compared with the control group.

Figure 4

(A) Forest plot: effects of liraglutide for increasing trabeculae linear density (Tb.N) compared with the control group. (B) Forest plot: effects of liraglutide for increasing trabeculae thickness (Tb.Th) compared with the control group. (C) Forest plot: effects of liraglutide for increasing object surface/volume ratio (BV/TV) compared with the control group.

Figure 5

Forest plot: effects of liraglutide for increasing the level of osteocalcin (OC) compared with the control group.

Figure 6

Forest plot: effects of liraglutide on femur bone mineral density in the subgroup of whether diabetes is combined.

Figure 7

Forest plot: effects of liraglutide for increasing the level of osteoprotegerin (OPG) both in serum and bone compared with the control group.

Figure 8

Forest plot: effects of liraglutide for reducing the level of receptor activator of nuclear factor-κ B ligand (RANKL) both in serum and bone compared with the control group.

Figure 9

Schematic representation of osteoprotective mechanisms of liraglutide for osteoporosis.