Glucagon-like peptide-1 (GLP-1) receptor agonists, including semaglutide (Ozempic, Wegovy) and liraglutide (Victoza, Saxenda), are increasingly prescribed for type 2 diabetes and weight management. As their use expands, questions have emerged about potential effects on bone health. Current evidence does not establish that GLP-1 medications directly cause bone loss, though the substantial weight reduction they produce may influence bone density through indirect mechanisms. Large clinical trials have not identified increased fracture risk with these treatments. Understanding the relationship between GLP-1 therapy and skeletal health helps patients and clinicians make informed decisions whilst implementing strategies to protect bone integrity during treatment.

What Are GLP-1 Medications and How Do They Work?

Glucagon-like peptide-1 (GLP-1) receptor agonists are a class of medications primarily prescribed for managing type 2 diabetes and, in specific formulations, for weight management in adults with obesity. These medicines include semaglutide (Ozempic for diabetes; Wegovy for weight management), dulaglutide (Trulicity), liraglutide (Victoza for diabetes; Saxenda for weight management), and exenatide (Byetta, Bydureon). They work by mimicking the action of a naturally occurring hormone called GLP-1, which is released from the intestine after eating.

The mechanism of action involves several complementary pathways. GLP-1 receptor agonists stimulate insulin secretion from the pancreas in a glucose-dependent manner, meaning they only promote insulin release when blood glucose levels are elevated. This reduces the risk of hypoglycaemia compared to some other diabetes medications, though this risk can increase when combined with insulin or sulfonylureas. Simultaneously, these drugs suppress glucagon secretion, a hormone that raises blood glucose levels. They also slow gastric emptying, which helps control post-meal glucose spikes and promotes satiety.

For weight management, GLP-1 agonists act on appetite centres in the brain, particularly the hypothalamus, reducing hunger and food intake. This leads to significant weight loss in many patients. The MHRA has approved specific GLP-1 receptor agonists for weight management (Wegovy and Saxenda) in individuals with a body mass index (BMI) of 30 kg/m² or above, or 27 kg/m² with weight-related comorbidities, while others are approved only for glycaemic control in type 2 diabetes.

Understanding how these medications work is essential context for evaluating their potential effects on bone health, as both their metabolic actions and the weight loss they induce may theoretically influence bone density and skeletal integrity.

Research Evidence on GLP-1 Agonists and Bone Health

The relationship between GLP-1 receptor agonists and bone health has been the subject of considerable research interest, though the evidence remains somewhat mixed and continues to evolve. Current data does not establish a definitive causal link between GLP-1 medications and bone loss, but several studies have examined potential associations.

Large-scale clinical trials, including cardiovascular outcome studies, have not identified increased fracture risk as a prominent adverse effect of GLP-1 therapy. The LEADER trial (liraglutide), SUSTAIN-6 (semaglutide), and EXSCEL (exenatide) studies, which collectively followed thousands of patients for several years, did not report significant increases in fracture rates compared to placebo groups. These findings have been reassuring from a safety perspective.

Some observational studies have noted changes in bone turnover markers with GLP-1 use, though these biochemical changes do not necessarily translate to clinically significant bone loss or increased fracture risk. Animal studies have shown that GLP-1 receptors are present on bone cells, including osteoblasts and osteoclasts, suggesting a potential direct effect on bone metabolism, though the clinical relevance in humans remains uncertain.

Recent systematic reviews and meta-analyses have generally concluded that there is no consistent evidence that GLP-1 receptor agonists directly cause bone loss or increase fracture risk in adults with type 2 diabetes. The European Medicines Agency (EMA) and MHRA have not issued specific warnings about bone health concerns with these medications. Nevertheless, the rapid weight loss associated with GLP-1 therapy, particularly at higher doses used for obesity management, has prompted ongoing investigation into potential indirect effects on skeletal health, particularly in populations already at risk for osteoporosis.

Factors That May Affect Bone Density During GLP-1 Treatment

While GLP-1 medications themselves may not directly cause bone loss, several factors associated with their use warrant consideration, particularly the significant weight loss many patients experience. Rapid or substantial weight reduction can affect bone density through multiple mechanisms, as bone tissue responds to mechanical loading and metabolic changes.

Key factors that may influence bone health during GLP-1 treatment include:

• Rate and magnitude of weight loss: Losing weight rapidly or losing a substantial percentage of body weight may reduce mechanical stress on bones, potentially leading to decreased bone mineral density. This effect is not unique to GLP-1 medications but applies to any significant weight loss intervention.

• Nutritional adequacy: Reduced caloric intake and appetite suppression may lead to inadequate consumption of calcium, vitamin D, and protein—all essential nutrients for maintaining bone health. Patients experiencing nausea or gastrointestinal side effects may be particularly vulnerable to nutritional deficiencies.

• Pre-existing risk factors: Individuals with established osteoporosis, previous fragility fractures, advanced age (particularly postmenopausal women), low baseline BMI, or those taking medications that affect bone metabolism (such as corticosteroids) may be more susceptible to bone density changes during weight loss.

• Reduced physical activity: Some patients may experience temporary reductions in physical activity due to gastrointestinal side effects, potentially decreasing weight-bearing activity that helps maintain bone strength.

• Hormonal changes: Weight loss can affect sex hormone levels, which play important roles in bone metabolism. In women, significant weight loss may impact oestrogen levels, whilst in men, testosterone levels may be affected.

The NICE guidelines for obesity management emphasise the importance of comprehensive lifestyle interventions alongside pharmacological treatment, including adequate nutrition and physical activity, which indirectly support bone health. Patients with multiple risk factors for osteoporosis should be identified early in treatment for appropriate monitoring and preventive strategies.

Protecting Your Bone Health While Taking GLP-1 Medications

If you are taking or considering GLP-1 receptor agonist therapy, several practical strategies can help protect your bone health throughout treatment. These recommendations are particularly important for individuals with pre-existing risk factors for osteoporosis or those experiencing substantial weight loss.

Nutritional optimisation is fundamental. Ensure adequate daily intake of:

• Calcium: Adults typically require 700mg daily (NHS recommendation), obtainable through dairy products, fortified plant-based alternatives, leafy green vegetables, and tinned fish with bones. Supplements may be necessary if dietary intake is insufficient.

• Vitamin D: UK guidelines recommend 10 micrograms (400 IU) daily, particularly during autumn and winter months. Many people in the UK have suboptimal vitamin D levels, and supplementation is often advisable, especially for those with limited sun exposure.

• Protein: Adequate protein intake supports both muscle and bone health during weight loss. Distribute protein intake across meals to optimise utilisation.

Weight-bearing and resistance exercise should be incorporated into your routine. Activities such as walking, jogging, dancing, and strength training provide mechanical stimulus to bones, promoting bone formation and reducing resorption. Aim for at least 150 minutes of moderate-intensity activity weekly, as recommended by NHS guidelines.

Medical monitoring may be appropriate for higher-risk individuals. Discuss with your GP whether you should have:

• Fracture risk assessment using tools such as FRAX or QFracture

• DXA scan if indicated by risk assessment results

• Monitoring of calcium and vitamin D levels if you have risk factors for deficiency

• Review of other medications that may affect bone health

When to contact your GP:

• If you experience unexplained bone pain or suspect a fracture

• If you have concerns about rapid weight loss (>1-2kg per week sustained)

• If you develop persistent nausea or vomiting affecting nutritional intake

• If you have a history of osteoporosis or fragility fractures

Your healthcare team can provide personalised advice based on your individual risk profile. For most patients taking GLP-1 medications, maintaining a balanced diet, staying physically active, and ensuring adequate calcium and vitamin D intake will support bone health throughout treatment. The benefits of improved glycaemic control and weight management typically outweigh theoretical bone-related concerns for appropriately selected patients, but individualised assessment and monitoring remain important components of comprehensive care.

If you experience any suspected side effects from your medication, report them to the MHRA Yellow Card Scheme.

Frequently Asked Questions