The Impact of Glucagon-Like Peptide 1 Receptor Agonists on Bone Metabolism and Its Possible Mechanisms in Osteoporosis Treatment

Abstract

Diabetes mellitus and osteoporosis are closely related and have complex influencing factors. The impact of anti-diabetic drugs on bone metabolism has received more and more attention. Type 2 diabetes mellitus (T2DM) would lead to bone fragility, high risk of fracture, poor bone repair and other bone-related diseases. Furthermore, hypoglycemic drugs used to treat T2DM may have notable detrimental effects on bones. Thus, the clinically therapeutic strategy for T2DM should not only effectively control the patient’s glucose levels, but also minimize the complications of bone metabolism diseases. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are novel and promising drug for the treatment of T2DM. Some studies have found that GLP-1RAs may play an anti-osteoporotic effect by controlling blood sugar levels, promoting bone formation and inhibiting bone resorption. However, in clinical practice, the specific effects of GLP-1RA on fracture risk and osteoporosis have not been clearly defined and evidenced. This review summarizes the current research findings by which GLP-1RAs treatment of diabetic osteoporosis, postmenopausal osteoporosis and glucocorticoid-induced osteoporosis and describes possible mechanisms, such as GLP-1R/MAPK signaling pathway, GLP-1R/PI3K/AKT signaling pathway and Wnt/β-catenin pathway, that are associated with GLP-1RAs and osteoporosis. The specific role and related mechanisms of GLP-1RAs in the bone metabolism of patients with different types of osteoporosis need to be further explored and clarified.

The Impact of GLP1 Agonists on Bone Metabolism: A Systematic Review

“…This has been shown in a previous study on ovariectomized rats, where GLP1 agonist administration led to the upregulation of the aforementioned factors [7,8]. All previous studies agree on the fact that GLP1 can upregulate RUNX2, ALP, COL1 and OC as well as N-terminal propeptide of type I procollagen (P1NP) [9]. An additional mechanism through which GLP1 promotes bone formation is by regulating glucose metabolism.…”

“…cAMP: cyclic AMP, PI3K: Phosphoinositide 3-kinases, PKA: Protein kinase A, P38: p38 mitogenactivated protein kinase, ERK1/2: extracellular signal-regulated kinases, JNK: c-Jun N-terminal kinase, RUNX2: Runt-related transcription factor 2, SP7: Transcription factor Sp7, OPN: Osteopontin, ALP: Alkaline phosphatase, OPG: Osteoprotegerin, BGLAP: Osteocalcin gene, COL1: Type-1 collagen. Reproduced from Xie et al (2021) [9] under the Creative Common License CC BY 3.0 link: https://www.frontiersin.org/articles/10.3389/fphar.2021.697442/full, accessed on 28 January 2022).…”

Higher Dietary Se Intake Is Associated With the Risk of New-Onset Fracture: A National Longitudinal Study for 20 Years

“…First, long-term high Se intake is associated with an increased prevalence of diabetes (26, 28). It has been shown that the use of hypoglycemic drug is associated with a fracture in patients with type 2 diabetes (40), and that among medications, the use of thiazolidinediones and insulin has a greater impact (41). Besides, hyperglycemia may also result in the decline of osteogenic differentiation and bone turnover, reducing the bone quality and muscle mass of patients (42).…”

LncRNAs and Rheumatoid Arthritis: From Identifying Mechanisms to Clinical Investigation

“…For example, CRNDE is a newly discovered LncRNA with critical role in osteoclastogenesis and bone resorption. Studies have shown that the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway plays a significant role in the regulation of osteoclast proliferation, differentiation and apoptosis (75). Li et al found that CRNDE inhibits the expression of GSK-3b by promoting the phosphorylation of AKT (76).…”