Is the use of Pre-Exposure Prophylaxis (PrEP) a risk factor for osteoporosis?

PrEP Use and Risk of Osteoporosis

Tenofovir disoproxil fumarate (TDF)-based PrEP is associated with a small but significant risk of bone mineral density loss and should be considered a risk factor for osteoporosis, particularly in individuals with high adherence to the medication. 1

Bone Effects of TDF-Based PrEP

• TDF-based PrEP has been associated with a 1% to 1.5% loss of bone mineral density at 48 weeks at the hip and spine, with return to baseline upon discontinuation of PrEP 2
• A retrospective analysis of over 7,600 patients on TDF-FTC for PrEP found that approximately 3% developed osteopenia or osteoporosis, with higher risk in those with adherence rates ≥90% 1
• The magnitude of bone mineral density (BMD) decline appears to be dose-dependent, with greater decreases observed in individuals with higher adherence to PrEP 3

Risk Assessment and Recommendations

• Due to the TDF component, TDF-based PrEP is not recommended for those with pre-existing osteopenia or osteoporosis (evidence rating AIII) 2
• Individuals at high risk of osteopenia or osteoporosis should carefully weigh the risks and benefits of TDF-based PrEP 2
• For men who have sex with men (MSM) with or at risk for kidney dysfunction, osteopenia, or osteoporosis, daily tenofovir alafenamide/emtricitabine (TAF/FTC) is recommended instead of TDF/FTC (evidence rating: BIa) 2

Monitoring and Management

• BMD changes from TDF-based PrEP appear to be reversible upon discontinuation of the medication 2, 4
• Studies show that after discontinuation of TDF-based PrEP, there is a significant recovery in BMD with net increases of approximately +0.9% at the lumbar spine and +0.7% at the total hip compared to placebo 4
• While specific bone density monitoring guidelines for PrEP users are not established in current guidelines, clinicians should consider baseline and follow-up bone health assessments for individuals with risk factors for osteoporosis 2

Special Populations and Considerations

• A systematic review and meta-analysis found that TDF caused greater decreases in BMD than comparators when used for PrEP, HIV treatment, and HBV treatment, with larger decreases observed in HIV treatment compared to PrEP 5
• Despite BMD decreases, studies have not shown a significant increase in fracture risk among PrEP users compared to non-users 5
• In young, healthy African women, TDF-containing oral PrEP resulted in small but significant reversible decreases in hip and spine BMD 4

Clinical Decision Making

• For patients with pre-existing bone disease who require PrEP, consider:
  • Using TAF/FTC instead of TDF/FTC for MSM at risk for osteoporosis 2
  • More frequent monitoring of bone health in high-risk individuals 1
  • Implementing bone health optimization strategies (calcium/vitamin D supplementation, weight-bearing exercise) 6
• The clinical significance of the observed BMD decreases is likely minimal for most PrEP users without pre-existing bone disease, but may be more concerning for those planning prolonged PrEP use or with other risk factors for fracture 3

In summary, while TDF-based PrEP is highly effective for HIV prevention, it does pose a small but measurable risk to bone health that should be considered in clinical decision-making, particularly for individuals with pre-existing bone disease or other risk factors for osteoporosis.