Does Ozempic (semaglutide) increase the risk of osteoporosis?

Does Ozempic Promote Osteoporosis?

Emerging evidence suggests that SGLT2 inhibitors (not GLP-1 receptor agonists like Ozempic/semaglutide) may increase osteoporotic fracture risk in older adults at high fracture risk, while data on semaglutide specifically shows mixed effects on bone health that appear related to weight loss rather than direct bone toxicity. 1

Key Distinction: SGLT2 Inhibitors vs GLP-1 Receptor Agonists

The 2025 American Diabetes Association guidelines specifically warn about SGLT2 inhibitors (empagliflozin, dapagliflozin, canagliflozin) causing increased osteoporotic bone fractures, particularly recommending clinicians minimize their use in older adults at high fracture risk. 1 Ozempic (semaglutide) is a GLP-1 receptor agonist, not an SGLT2 inhibitor—these are entirely different drug classes with different mechanisms and bone effects.

Evidence on Semaglutide and Bone Health

Clinical Trial Data in High-Risk Populations

A 2024 randomized controlled trial in adults with increased fracture risk (T-score < -1.0 or recent low-energy fracture) found that semaglutide 1.0 mg weekly for 52 weeks:

• Did not increase bone formation marker P-PINP (primary outcome showed no difference vs placebo, p=0.418) 2
• Increased bone resorption marker CTX (estimated treatment difference 166.4 ng/L, p=0.021) 2
• Decreased lumbar spine BMD by -0.018 g/cm³ (p=0.007) and total hip BMD by -0.020 g/cm² (p=0.001) compared to placebo 2
• Caused 6.8 kg weight loss (p<0.001), and the bone changes appeared attributable to weight loss rather than direct drug toxicity 2

Positive Findings in Type 2 Diabetes Patients

Conversely, a 2025 study of oral semaglutide in overweight/obese type 2 diabetes patients showed:

• Increased tibial total vBMD (317.4 vs 331.6 mg HA/cm³, p=0.06) 3
• Increased cortical vBMD at both radius and tibia (trend toward significance) 3
• Males showed significantly increased tibial total and cortical vBMD, while females showed no significant change 3
• These improvements occurred despite significant weight reduction 3

Preclinical Evidence

Animal studies demonstrate that semaglutide may have osteoprotective effects through activation of Wnt/β-catenin signaling, leading to increased bone formation and decreased RANKL activation. 4 However, most positive bone effects in rodent models occurred at concentrations much higher than approved for human obesity care. 5, 6

Clinical Interpretation and Mechanism

The bone effects of semaglutide appear primarily mediated by weight loss rather than direct skeletal toxicity. 5, 2 Significant weight loss from any intervention (caloric restriction, bariatric surgery, or GLP-1 receptor agonists) results in accelerated bone turnover and bone loss due to:

• Mechanical unloading from reduced body weight 5
• Nutritional factors and hormonal changes 5
• Alterations in adipokines 5

The 2025 review emphasizes that current evidence on GLP-1 receptor agonists and bone health is limited because most studies included diabetic patients at doses for diabetes (not obesity), lacked adequate bone parameters as primary endpoints, and had short follow-up periods. 6

Practical Recommendations

Risk Stratification

• Low fracture risk patients: Semaglutide can be used without specific bone-related concerns beyond standard osteoporosis screening 2
• High fracture risk patients (T-score ≤ -2.5, prior fragility fracture, age >65 with multiple risk factors): Consider baseline BMD assessment and closer monitoring 7, 2

Monitoring During Treatment

• Obtain baseline BMD (DXA scan) in patients with pre-existing osteoporosis or high fracture risk before initiating semaglutide 7
• Repeat BMD every 2 years in high-risk patients on semaglutide 7
• Monitor for clinical fractures, particularly vertebral compression fractures 2

Mitigation Strategies

• Ensure adequate calcium (1,000-1,200 mg daily) and vitamin D (800-1,000 IU daily) supplementation 7
• Implement weight-bearing exercise programs at least 3 days per week for 30 minutes, including resistance training 7
• Consider bisphosphonate therapy in patients with established osteoporosis (T-score ≤ -2.5) who require semaglutide for diabetes or obesity management 7

Common Pitfalls to Avoid

• Do not confuse SGLT2 inhibitors with GLP-1 receptor agonists—only SGLT2 inhibitors have clear guideline warnings about fracture risk 1
• Do not withhold semaglutide solely due to osteoporosis concerns in patients who would benefit from glycemic control or weight loss, as the bone effects appear manageable with appropriate monitoring and supplementation 2, 3
• Do not neglect calcium and vitamin D supplementation during weight loss with semaglutide, as nutritional deficiencies compound bone loss 7, 5