Effect of GLP-1 receptor agonists on bone mineral density, bone metabolism markers, and fracture risk in type 2 diabetes: a systematic review and meta-analysis

Feb 22, 2025Acta diabetologica

GLP-1 drugs and their links to bone strength, bone health markers, and fracture risk in type 2 diabetes

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Abstract

The meta-analysis of 25 studies indicated that GLP-1 receptor agonists are not significantly associated with an increased risk of fracture (RR = 0.80; 95% CI 0.47 to 1.36; P = 0.41).

Treatment with GLP-1 receptor agonists showed a significant improvement in lumbar spine bone mineral density (BMD) with an increase of 0.07 g/cm.
Hip neck BMD improved by 0.05 g/cm and total hip BMD by 0.06 g/cm compared to the control group.
GLP-1 receptor agonists significantly improved several bone metabolism markers, including P1NP, osteocalcin (OC), 25-hydroxyvitamin D, and bone-specific alkaline phosphatase (b-ALP).
A reduction in β-CTX was observed, suggesting a potential decrease in bone resorption.
No significant effects were found on other bone metabolism markers such as N-MID-OT, alkaline phosphatase (ALP), calcium, and phosphate.

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AIM: To systematically assess randomized controlled trials that evaluated the effect of glucagon-like peptide-1 (GLP-1) receptor agonists on fracture incidence, bone mineral density, and bone metabolism markers in individuals with type 2 diabetes.

METHODS: From database setup to March 21, 2024, a search was conducted across nine Chinese and English databases. The Cochrane Risk of Bias Tool was applied to assess potential bias. Data analysis was performed using RevMan 5.3 and Stata 14.0. Subgroup analysis and meta regression were employed to explore sources of heterogeneity, and publication bias was evaluated using funnel plots and Egger's test.

RESULTS: Twenty-five studies were included. The results of the meta-analysis indicated that GLP-1 receptor agonist was not significantly associated with an increased risk of fracture (RR = 0.80; 95% CI 0.47 to 1.36; P = 0.41). Additionally, improvement in lumbar spine BMD (MD = 0.07 g/cm, 95% CI 0.06 to 0.09, P < 0.00001), hip neck BMD (MD = 0.05 g/cm, 95% CI 0.03 to 0.08, P = 0.0001) and total hip BMD (MD = 0.06 g/cm, 95% CI 0.04 to 0.07, P < 0.00001) was superior to the control group. Similarly, GLP-1 receptor agonists significantly improved P1NP (SMD = 0.33, 95% CI 0.07 to 0.59, P = 0.01), OC (MD = 1.46 ug/L, 95% CI 1.10 to 1.83, P < 0.00001), 25-OH-D (SMD = 0.45, 95% CI 0.06 to 0.83, P = 0.02), and b-ALP (MD = 0.91ug/L, 95% CI 0.19 to 1.63, P = 0.01) while reducing β-CTX (SMD = - 0.34, 95% CI - 0.54 to - 0.14, P = 0.001). There was no significant impact on other bone metabolism markers, including N-MID-OT (SMD = 0.43, 95% CI 0.01 to 0.86, P = 0.05), ALP (SMD = - 0.00, 95% CI: - 0.25 to 0.25, P = 0.98), Calcium (MD = 0.00 mmol/L, 95% CI - 0.04 to 0.04, P = 0.94) and Phosphate (MD = 0.02 mmol/L, 95% CI - 0.04 to 0.07, P = 0.57). 2 2 2

CONCLUSION: This meta-analysis demonstrated no significant effect of GLP-1 receptor agonists on elevated fracture risk. There was a statistically significant improvement in BMD and certain bone turnover markers (β-CTX, P1NP, OC, b-ALP, and 25-OH-D). However, due to some limitations, further high-quality clinical studies with sufficient follow-up time are needed to draw more definitive conclusions.

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Effect of GLP-1 receptor agonists on bone mineral density, bone metabolism markers, and fracture risk in type 2 diabetes: a systematic review and meta-analysis

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