GLP-1 and fracture risk in women: what the SELECT trial data actually shows

TL;DR

A comprehensive 2025 systematic review published in Osteoporosis International synthesised GLP-1 bone data from preclinical studies and human trials. The most alarming finding came from the SELECT trial: women on semaglutide had five times the hip and pelvic fracture rate of those on placebo (1.0% vs 0.2%). In women over 75, the gap widened to 2.4% vs 0.6%. The authors recommend resistance training as the best available protective intervention while the evidence base continues to develop.

The SELECT trial was celebrated for showing semaglutide reduces major cardiovascular events in people with obesity. But buried in that same dataset is a bone signal that the mainstream coverage barely touched. A systematic review published in Osteoporosis International in September 2025 has now put that data in context, comparing it across the full landscape of GLP-1 bone health research.

The SELECT trial fracture data: putting numbers in context

SELECT enrolled 17,604 participants with cardiovascular disease and obesity but without type 2 diabetes. The trial ran for over four years on semaglutide 2.4 mg weekly (the Wegovy dose). The pre-specified fracture analysis showed:

• Hip and pelvic fractures in females on semaglutide: 1.0% (24 out of 2,448 women)
• Hip and pelvic fractures in females on placebo: 0.2% (5 out of 2,424 women)
• Women aged 75 and over on semaglutide: 2.4% fracture rate
• Women aged 75 and over on placebo: 0.6% fracture rate

A five-fold elevation in hip fracture risk in women - and a four-fold elevation in the oldest subgroup - is a clinically significant finding. Hip fractures in women over 70 carry 20-30% one-year mortality rates. The absolute numbers are still relatively small (24 vs 5 fractures), but the relative risk in a large well-controlled trial demands attention.

The SELECT population is non-diabetic, which actually makes this data particularly useful - it isolates the GLP-1 and weight loss effect without the confounding of diabetic bone disease. The message for women using semaglutide or any GLP-1 medication for weight loss is clear: bone health monitoring is not optional.

What other human trials have found

The systematic review, authored by Léa Karam and colleagues from the University of Lille, covered studies from January 2013 to December 2024. Beyond SELECT, key human trial findings included:

Semaglutide 2024 study (64 participants)

Participants lost an average of 9.4% body weight over 52 weeks. The bone impact was measurable and significant:

• Bone resorption marker CTX increased 54.8% more in semaglutide than placebo
• Lumbar spine BMD decreased 2.1% (p=0.01)
• Total hip BMD decreased 2.6% (p=0.001)

CTX is a marker for bone breakdown. A 54.8% greater increase in CTX means the skeleton is resorbing - breaking down - at an accelerated rate relative to controls. This is how weight loss and GLP-1 therapy together create the conditions for net bone loss.

Liraglutide plus exercise study (195 participants)

This study tested a critical practical question: can exercise offset GLP-1 bone loss? The results were encouraging. Liraglutide alone reduced hip and lumbar spine BMD compared to placebo. But liraglutide combined with exercise mitigated BMD loss. Resistance training specifically, not aerobic exercise alone, was the most protective intervention.

This finding has direct practical implications. If you are on Ozempic, Wegovy, Mounjaro, or Zepbound and not doing resistance training, your bones are likely losing density without a counterbalancing stimulus. The drug is driving weight loss - removing mechanical load from the skeleton. Exercise puts that load back.

The calorie restriction parallel

The review draws a direct comparison to what researchers know about calorie restriction and weight loss surgery. The LOOK-AHEAD study, which followed 5,145 participants in an intensive lifestyle weight loss program, found a 39% increased risk of major osteoporotic fractures (HR 1.39, 95% CI 1.02-1.89) in the calorie restriction group compared to controls. Bariatric surgery produces more severe bone loss than diet alone.

GLP-1 medications sit between these two in terms of weight loss magnitude - typically above diet alone, but below bariatric surgery for most patients. The bone effect appears to follow the same gradient: significant but modifiable.

The role of vitamin D, calcium, and bone remodelling nutrients

Calorie restriction reduces intake of calcium, vitamin D, vitamin K2, magnesium, and protein - all nutrients essential for bone formation and mineralisation. GLP-1 users, eating significantly less than before treatment, face compounding deficiency risk in every one of these nutrients. This is not theoretical. Studies consistently find that GLP-1 users have lower vitamin D levels, lower calcium intake, and lower magnesium status than comparable non-users. Addressing these gaps through targeted supplementation is one of the most actionable steps a GLP-1 user can take for bone protection.

Standard calcium and vitamin D tablets may not be sufficient if absorption is compromised by altered gastric emptying. Fat-soluble vitamins like vitamin D and vitamin K2 require adequate dietary fat to be absorbed - and on a GLP-1 medication with very low fat intake, absorption can be suboptimal even when supplements are taken. GLP-1 Shield is formulated with this absorption challenge in mind, including nutrients at doses and forms suited to GLP-1 users' specific physiological context.

What the evidence gaps still are

The review is honest about what we do not yet know. There is limited data on:

• The bone effects of massive weight loss exceeding 15-20% on GLP-1 medications - the territory where tirzepatide and upcoming triple agonists like retatrutide regularly operate
• Bone microarchitecture changes - standard BMD scans do not capture bone quality, only density
• Long-term fracture outcomes beyond five years
• Whether newer agents (tirzepatide, retatrutide) produce different bone effects than semaglutide

Researchers are still investigating the precise mechanisms and are building the evidence base for clinical guidelines. But the weight of evidence now says: treat bone health as a priority on GLP-1 therapy, not an afterthought.

Frequently asked questions

Does semaglutide (Wegovy) cause hip fractures?

The SELECT trial found women on semaglutide had five times the hip and pelvic fracture rate of women on placebo (1.0% vs 0.2%). In women over 75, the rate was 2.4% vs 0.6%. The absolute numbers are small, but the relative risk in a well-controlled large trial is clinically significant. This risk appears to be driven by the combination of reduced mechanical bone loading from weight loss and GLP-1 effects on bone remodelling.

How does exercise protect bones during GLP-1 therapy?

Resistance training creates mechanical loading forces on the skeleton that stimulate osteoblasts (bone-building cells) to maintain and build bone density. A 2024 clinical study found that combining liraglutide with exercise prevented the BMD decline seen with liraglutide alone. Two to three resistance training sessions per week are recommended as a minimum. Weight-bearing aerobic exercise (walking, hiking) adds additional benefit but is less powerful than resistance training for bone specifically.

What nutrients protect bone on GLP-1 medications?

Vitamin D, calcium, vitamin K2, magnesium, and protein are the most important bone-protective nutrients. GLP-1 medications reduce appetite and food intake, making deficiency in all of these more likely. Vitamin D and calcium are often targeted with standard supplements, but vitamin K2 (which directs calcium into bone rather than arteries) and magnesium (essential for vitamin D metabolism) are frequently overlooked. A GLP-1-specific supplement like GLP-1 Shield covers these gaps more comprehensively.

Who is most at risk for bone loss on GLP-1 medications?

Women over 60, particularly post-menopausal women, are at highest risk. People with pre-existing osteopenia or osteoporosis, those with a prior fragility fracture, patients with type 2 diabetes (which independently impairs bone quality), and anyone losing more than 10% of body weight are all elevated-risk groups. These patients should discuss bone density monitoring and protective strategies with their prescriber.