- Design
- Systematic review and meta-analysis (46 randomised trials, 13 real-world studies, 1 pharmacovigilance study)
- Population
- 60 articles, 1,250,717 individuals on GLP-1 receptor agonists
- Primary outcome
- Bone mineral density, fractures, lean body mass and WOMAC scores
- Effect
- No effect on bone or joint outcomes; lean mass lower in 28 analyses, I² 88%
A systematic review and meta-analysis pooled 60 articles, 46 randomised trials, 13 real-world studies and one pharmacovigilance study, covering 1,250,717 people given GLP-1 receptor agonists such as semaglutide, liraglutide, dulaglutide and tirzepatide.
Using the most adjusted estimates, there was no effect on bone mineral density or fractures at any site, and no change in WOMAC pain, function or stiffness. Lean body mass or fat-free mass fell with GLP-1 agonists across 28 analyses, with high heterogeneity (I² 88%), driven mainly by liraglutide and semaglutide against placebo.
Certainty was low, and the lean mass change appeared largely related to weight loss. Whether it means weaker muscle or poorer function is not established. For orthopaedic patients on these drugs, the relevant question is recovery and rehabilitation, not a reason to stop treatment.
- No effect on bone density, fractures or osteoarthritis scores was found in the pooled estimates.
- Lean mass fell with these drugs, mostly in step with weight loss.
- Encourage protein intake and resistance exercise in perioperative patients on GLP-1 therapy.
- Muscle function was not measured, so avoid assuming weakness.
Why it matters
It moves the musculoskeletal question for these drugs from bone to muscle quality.
Don't overread it
Certainty was low and the lean mass change tracked weight loss; function was not shown to worsen.
The statistics, in plain English
An I² of 88% means the results varied widely between studies, so the pooled lean mass figure is an average across very different settings. A fall in lean mass is not the same as a fall in strength.
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