Exendin-4, a Glucagon-Like Peptide-1 Receptor Agonist, Prevents Osteopenia by Promoting Bone Formation and Suppressing Bone Resorption in Aged Ovariectomized Rats
Open accessAbstract
Osteoporosis mainly affects postmenopausal women and older men. Gastrointestinal hormones released after meal ingestion, such as glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide (GLP)-2, have been shown to regulate bone turnover. However, whether GLP-1, another important gastrointestinal hormone, and its analogues also have antiosteoporotic effects, especially in aged postmenopausal situation, has not been confirmed. In the present study, we evaluated the effects of the GLP-1 receptor agonist exendin-4 on ovariectomy (OVX)-induced osteoporosis in old rats. Twelve-month-old female Sprague-Dawley rats were subjected to OVX, and exendin-4 was administrated 4 weeks after the surgery and lasted for 16 weeks. Bone characters and related serum and gene biomarkers were analyzed. Sixteen weeks of treatment with exendin-4 slowed down body weight gain by decreasing fat mass and prevented the loss of bone mass in old OVX rats. Exendin-4 also enhanced bone strength and prevented the deterioration of trabecular microarchitecture. Moreover, exendin-4 decreased the urinary deoxypyridinoline (DPD)/creatinine ratio and serum C-terminal cross-linked telopeptides of type I collagen (CTX-I) and increased serum alkaline phosphatase (ALP), osteocalcin (OC), and N-terminal propeptide of type 1 procollagen (P1NP) levels, key biochemical markers of bone turnover. Interestingly, gene expression results further showed that exendin-4 not only inhibited bone resorption by increasing the osteoprotegerin (OPG)/receptor activator of NF-κB ligand (RANKL) ratio, but also promoted bone formation by increasing the expression of OC, Col1, Runx2, and ALP, which exhibited dual regulatory effects on bone turnover as compared with previous antiosteoporotic agents. In conclusion, these findings demonstrated for the first time the antiosteoporotic effects of exendin-4 in old OVX rats and that it might be a potential candidate for treatment of aged postmenopausal osteoporosis.
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Exendin-4 prevented deterioration of trabecular microarchitecture and increased bone strength by inhibiting bone resorption through increase in OPG/RANKL ratio and promoting bone formation by enhancing expression of osteoblast-specific transcription factors.
“This was achieved by inhibiting bone resorption through an increase in the OPG/RANKL ratio and promoting bone formation by enhancing the expression of osteoblast-specific transcription factors.374”
From Glucagon-like peptide-1 receptor: mechanisms and advances in therapy (2024) · cites this paper as [374]
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredExendin-4 stimulates osteoblast activity and mitigates bone loss in ovariectomized mouse model.
“Exendin-4 has also been shown to stimulate osteoblast activity and mitigate bone loss in an ovariectomized mouse model.374”
From Glucagon-like peptide-1 receptor: mechanisms and advances in therapy (2024) · cites this paper as [374]
The results (p. 7) report increased bone formation rates and osteoblast numbers, alongside prevention of bone loss, after exendin-4 treatment. But the study used ovariectomized rats, not mice, as stated in the Introduction (p. 2). (LLM, conf=0.91)
Experimental — accuracy not yet measuredAnimal models have indicated positive effects of the GLP-1 receptor agonists exendin-4 and liraglutide on bone metabolism.
“Animal models have indicated positive effects of the GLP-1 receptor agonists exendin-4 and liraglutide on bone metabolism (11–13).”
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- Authors
- Ma, X., Meng, J., Jia, M., Bi, L., Zhou, Y., Wang, Y., Hu, J., He, G., & Luo, X.
- Affiliations
- Air Force Medical University (CN)
- Xijing Hospital (CN)
- Department of PharmacyKunming General Hospital of Chengdu Military RegionKunmingChina
- Corresponding author
- Luo, Xiaoxing
- Venue
- Journal of Bone and Mineral Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2013-02-20
- Volume
- 28
- Issue
- 7
- Pages
- 1641-1652
- ISSN
- 0884-0431 (ISSN-L)
- 1523-4681
- OpenAlex
- W1579903446
- Cited by
- 200
- References
- 53
- Citations by year
- 2026: 14 · 2025: 26 · 2024: 22 · 2023: 11 · 2022: 12 · 2021: 11 · 2020: 11 · 2019: 25 · 2018: 17 · 2017: 14 · 2016: 12 · 2015: 16 · 2014: 8
- FWCI
- 12.27
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Journal of Bone and Mineral Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81100626)
- Topics
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Medicinal Plant Pharmacodynamics Research
- Keywords
- exendin-4, GLP-1 receptor agonists, postmenopausal osteoporosis, ovariectomy, bone turnover, bone formation, bone resorption, osteopenia, aged rats, bone turnover markers, Runx2, trabecular bone microarchitecture, anti-osteoporotic therapy
- MeSH terms
- Glucagon-Like Peptide-1 Receptor, Exenatide, Alkaline Phosphatase, Amino Acids, Animals, Creatinine, Female, Humans, Hypoglycemic Agents, Male, Osteoporosis, Ovariectomy, Peptides, Time Factors, Venoms, Osteocalcin, Rats, Sprague-Dawley, Receptors, Glucagon, Collagen Type I, Core Binding Factor Alpha 1 Subunit, Rats
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