New evidence is emerging on the relationship between widely used diabetes and weight‑loss medications known as glucagon‑like peptide‑1 receptor agonists (GLP‑1 RAs) and bone health outcomes, including fracture risk and musculoskeletal health , important considerations for patients and clinicians in orthopaedics across.
GLP‑1 RAs such as semaglutide (brand names Ozempic and Wegovy) and liraglutide were initially developed to improve blood glucose control in type 2 diabetes mellitus (T2DM), and have more recently been prescribed for obesity and cardiovascular risk reduction. Beyond their established metabolic benefits, researchers are now investigating whether these therapies also affect bone mineral density (BMD), skeletal fragility and fracture risk, which are key concerns in orthopaedic care and public health.
Several clinical analyses suggest that GLP‑1 RAs do not significantly increase fracture risk and may even be neutral or beneficial for bone structure in people with T2DM.
A 2024 systematic review and meta‑analysis found no significant increase in fracture risk in people taking GLP‑1 RAs, while noting improvements in bone density measures such as lumbar spine and hip BMD compared with controls.
Another Bayesian network meta‑analysis of randomised clinical trials involving nearly 50 000 patients found that certain GLP‑1 RAs, notably exenatide, were associated with a lower risk of fracture versus placebo or other diabetes drugs.
These findings hint that the class of drugs may not adversely affect skeletal health in a broad sense, and in some contexts could correlate with improved bone strength.
However, not all evidence is uniform: Some analyses note that bone outcomes can vary depending on the specific GLP‑1 RA or patient group, with longer durations of treatment needed to see meaningful differences in fracture incidence.
Emerging observational data from large real‑world cohorts suggest that certain drugs like tirzepatide (a dual GLP‑1/GIP receptor agonist) may be linked with a higher incidence of osteoporosis or fragility fractures compared with other GLP‑1 RAs, particularly among older adults.
Such mixed results indicate that skeletal effects may be drug‑specific and patient‑specific, and not a class‑wide assumption. Why might a glucose‑lowering drug affect bone health at all?
Experts highlight several possible mechanisms: Improved blood sugar regulation may reduce diabetes‑related bone fragility, which is an established risk factor for poor skeletal health.
Rapid weight reduction , often seen with GLP‑1 therapies , can reduce mechanical load on bones, which theoretically might lower BMD if not balanced with nutrition and exercise.
GLP‑1 receptors are present on bone‑forming cells (osteoblasts) and bone‑resorbing cells (osteoclasts), suggesting biochemical interactions that could influence bone turnover, although human studies have been inconsistent.
Importantly, weight loss itself , rather than the medications per se , may drive some negative bone outcomes, particularly when diets are overly restrictive or lack adequate nutrients such as calcium, protein and vitamin D.
For clinicians and patients, these findings raise several practical considerations:
Older adults and people with T2DM are already at higher risk of osteoporosis and fragility fractures. In patients starting or currently on GLP‑1 treatment, it may be prudent to:
Perform baseline and periodic bone density scans (DEXA), especially for those aged 65+, postmenopausal women, and individuals with other risk factors.
Monitor for early signs of bone frailty and advise on bone‑supportive nutrition and physical activity.
Given the overlap of endocrinology, diabetes care and musculoskeletal health, a multidisciplinary approach involving orthopaedic surgeons, endocrinologists, dietitians and physiotherapists can optimise overall patient outcomes.
Clinicians should counsel patients that: Maintaining weight‑bearing and resistance exercise helps support bone and muscle mass.
Adequate intake of protein, calcium and vitamin D is essential , particularly during rapid weight loss.Bone health should be part of routine monitoring when prescribing GLP‑1 RAs.
Dr Jane Smith, an orthopaedic consultant in London, notes: “While GLP‑1 therapies have transformed diabetes and obesity treatment, their broad systemic effects , including on bone biology , warrant careful clinical attention, especially in frail and elderly patients.”
Researchers agree that longer‑term, well‑controlled trials, including fracture outcomes and mechanistic studies, are needed to clarify the nature of GLP‑1 interactions with the skeleton.
Sources
- PubMed meta‑analyses on GLP‑1 RAs and fracture risk , evidence of neutral/beneficial bone effects PubMed
- Bayesian network meta‑analysis on GLP‑1 and fracture outcomes PubMed
- GLP‑1 RA duration and fracture risk variability PubMed
- Real‑world cohort on tirzepatide and osteoporosis risk Medical Dialogues
- Medical overview of GLP‑1 drug effects on bone metabolism Drugs.com
