Can bisphosphonates (BPs) reduce the risk of cancer?

Bisphosphonates and Cancer Risk Reduction

Bisphosphonates have shown potential to reduce the risk of bone metastases in certain cancer patients, but there is insufficient evidence to recommend them for primary cancer prevention in the general population. 1

Primary Role of Bisphosphonates in Cancer

Bisphosphonates are primarily indicated for:

• Treatment of bone metastases in patients with established cancer
• Prevention of skeletal-related events (SREs) in patients with bone metastases
• Management of cancer treatment-induced bone loss

Established Benefits in Cancer Patients

• Reduce frequency of skeletal-related events by approximately 30% 1
• Delay onset of skeletal complications 1
• Improve pain control and quality of life in patients with bone metastases 1
• Reduce risk of hypercalcemia of malignancy 1

Evidence for Cancer Prevention

The evidence regarding bisphosphonates for primary cancer prevention or reduction of metastatic risk is limited and inconsistent:

Potential for Preventing Bone Metastases

• Some preclinical studies suggest bisphosphonates may have direct anti-tumor effects by:

  • Preventing tumor cell homing to bone 1
  • Inducing tumor cell apoptosis 2
  • Maintaining dormancy of tumor cells in bone 1
  • Inhibiting release of growth factors from bone 1

• Clinical evidence is mixed:

  • Two small trials with oral clodronate showed reduction in skeletal metastases in high-risk breast cancer patients 1
  • Other trials showed inconsistent results, with some showing benefit and others showing no effect 1

Limitations of Current Evidence

• Most positive studies were small or had methodological limitations
• Larger trials have shown conflicting results 1
• No consistent evidence for reduction of primary cancer risk
• Benefits appear limited to specific patient populations (e.g., postmenopausal women with breast cancer) 1

Clinical Recommendations

1. For patients with established bone metastases:

   • Bisphosphonates should be added to standard treatment to prevent skeletal-related events 1
   • Continue treatment as long as practically feasible in the absence of adverse effects 1

2. For patients without bone metastases:

   • Routine use of bisphosphonates solely for cancer prevention is not recommended 1
   • Consider bisphosphonates in clinical trials for high-risk patients 1

3. For postmenopausal women with breast cancer:

   • Some evidence suggests potential benefit in reducing bone metastases 1
   • Discuss potential benefits and risks on an individual basis

Important Considerations and Caveats

• Adverse effects include osteonecrosis of the jaw, renal toxicity, and atypical fractures
• Cost-benefit ratio does not support widespread use for cancer prevention
• Different bisphosphonates have varying potencies and potentially different anti-tumor effects
• Zoledronic acid appears to have the strongest evidence for anti-tumor activity 2, 3
• Optimal dosing and duration for potential cancer prevention remains unknown

The field continues to evolve, with ongoing clinical trials investigating the potential preventive effects of bisphosphonates against cancer, particularly in high-risk populations.