One year of GLP-1 receptor agonist therapy (dulaglutide or semaglutide) preserved bone quality and reactivated bone turnover in type 2 diabetes patients, despite causing weight loss and modest reductions in bone density.
Bone quality preserved at 12 monthsDespite weight loss and modest BMD reductions, trabecular bone score marginally improved and bone turnover markers significantly increased in T2DM patients on GLP-1RAs
What the researchers found
After 12 months of GLP-1RA therapy in 54 T2DM patients (30 on dulaglutide, 24 on semaglutide), bone turnover markers and adiponectin significantly increased while myostatin showed a modest but significant reduction. Lumbar spine BMD by DXA decreased significantly, though the decrease by REMS was not significant. Trabecular bone score showed marginal improvement. Femoral BMD showed modest but significant reduction by both DXA and REMS. The authors interpret the combined findings as preservation of bone quality with reactivation of bone turnover.
Why it matters
Type 2 diabetes already increases fracture risk, and weight loss — a primary benefit of GLP-1 drugs — can further reduce bone density. With millions of people now taking semaglutide and dulaglutide, understanding their bone effects is critical. This study provides reassurance that bone quality is preserved even as weight drops, though the density reductions warrant attention in patients already at risk for osteoporosis.
How the study worked
This was a 12-month prospective longitudinal study of 65 patients with type 2 diabetes starting GLP-1RA therapy (54 completed the study). Bone mineral density was measured by both DXA and REMS techniques at the lumbar spine and femoral neck. Trabecular bone score, bone turnover markers, adiponectin, and myostatin were assessed at baseline and 12 months.
What this study cannot tell us
The study had a relatively small sample size (54 completers) with no control group, making it impossible to separate GLP-1RA effects from weight loss effects. The 12-month follow-up may be too short to detect fracture outcomes. The two drugs (dulaglutide and semaglutide) were not directly compared. There was no randomization, and the single-center design limits generalizability.
How to read the evidence
This is a single-center prospective longitudinal study without a control group. While it provides useful real-world data on bone outcomes during GLP-1RA therapy, the lack of randomization and control limits causal conclusions.
When this study was published
Published in 2024, this study addresses a timely question as GLP-1RA prescriptions have surged globally. The findings are directly relevant to current clinical practice.
The bigger picture
As GLP-1 receptor agonists become among the most prescribed drugs globally for diabetes and obesity, their effects on bone health are a growing concern. Weight loss medications have historically been associated with bone loss, and diabetes itself compromises bone quality. This study suggests GLP-1RAs may have a more favorable bone profile than simple weight loss alone, possibly due to direct peptide effects on bone cells — consistent with preclinical evidence. However, the modest density reductions highlight the need for bone monitoring in at-risk patients.
Questions still open
- Do the modest BMD reductions stabilize or continue with longer GLP-1RA use beyond 12 months?
- Is the bone turnover reactivation truly protective, or could it lead to net bone loss over time?
- Do dulaglutide and semaglutide differ in their bone effects when directly compared?
Common questions
Can GLP-1 drugs like Ozempic cause bone loss?
Why are diabetic patients at higher risk for fractures?
Read the original research
Glucagon-like Peptide-1 Receptor Agonists and Diabetic Osteopathy: Another Positive Effect of Incretines? A 12 Months Longitudinal Study.
Calcified tissue international, 115(2), 160-168
Citation
Al Refaie, Antonella; Baldassini, Leonardo; Mondillo, Caterina; Ceccarelli, Elena; Tarquini, Roberto; Gennari, Luigi; Gonnelli, Stefano; Caffarelli, Carla. (2024). Glucagon-like Peptide-1 Receptor Agonists and Diabetic Osteopathy: Another Positive Effect of Incretines? A 12 Months Longitudinal Study.. Calcified tissue international, 115(2), 160-168. https://doi.org/10.1007/s00223-024-01240-1