When do you start bisphosphonates (BPs) in a patient diagnosed with osteopenia?

When to Start Bisphosphonates in Osteopenia

Bisphosphonates should be initiated in patients with osteopenia when they have a high fracture risk, defined as a FRAX score of ≥20% for major osteoporotic fracture or ≥3% for hip fracture, rather than based on T-score alone. 1

Risk Assessment for Bisphosphonate Initiation

The decision to start bisphosphonates in patients with osteopenia should be based on comprehensive fracture risk assessment, not just bone mineral density (BMD) measurements:

• T-score alone is insufficient: Approximately 60% of osteoporotic fractures occur in patients with T-scores higher than -2.5 1
• FRAX calculation required: Calculate 10-year fracture probability using the FRAX tool to guide treatment decisions 1
• High-risk indicators:
  • FRAX score ≥20% for major osteoporotic fracture or ≥3% for hip fracture
  • Prior fragility fracture
  • Additional clinical risk factors (low body weight, smoking, alcohol excess, family history)

Treatment Algorithm for Osteopenia

1. Low fracture risk:

   • Lifestyle modifications only
   • Calcium 1,000-1,200 mg daily
   • Vitamin D 800-1,000 IU daily
   • Regular weight-bearing exercise
   • Reassess in 2-3 years

2. Moderate to high fracture risk (FRAX ≥20% for major osteoporotic fracture or ≥3% for hip fracture):

   • Initiate oral bisphosphonate therapy
   • First-line: Alendronate (preferred due to efficacy and cost-effectiveness) 1
   • Alternatives: Risedronate or IV zoledronic acid if oral therapy contraindicated

3. Very high fracture risk (FRAX ≥30% for major osteoporotic fracture or ≥4.5% for hip fracture, T-score ≤-3.5, or recent fracture):

   • Consider anabolic agents before bisphosphonates 1

Monitoring After Bisphosphonate Initiation

• BMD testing should be performed every 2-3 years for patients on bisphosphonate therapy 1
• Reassess fracture risk every 1-2 years 1
• Consider a drug holiday after 5 years of treatment for moderate-risk patients if BMD is stable and no fractures have occurred 2
• Higher-risk patients should continue treatment for up to 10 years 1

Special Considerations

• Renal impairment: Adjust dosing for patients with compromised renal function; consider denosumab as an alternative 3
• Cancer patients: For patients with cancer-related bone loss, bisphosphonates may be initiated when T-score is less than -2.0 or if they have major risk factors such as prior fracture 3
• Corticosteroid use: Patients on corticosteroids should receive bisphosphonates at the onset of steroid therapy if at high risk for osteoporosis 3

Practical Recommendations

• Ensure adequate calcium (1,000-1,200 mg/day) and vitamin D (800-1,000 IU/day) intake before and during bisphosphonate therapy 1
• Counsel patients on proper administration of oral bisphosphonates (taking with plain water, remaining upright for 30-60 minutes)
• Monitor for potential adverse effects including esophageal irritation with oral formulations and acute phase response with IV administration 1
• Consider the rare but serious risks of atypical femur fractures and osteonecrosis of the jaw with long-term use 1, 2

The key takeaway is that treatment decisions for osteopenia should be based on overall fracture risk assessment rather than BMD measurements alone, with bisphosphonates initiated when fracture risk is high despite T-scores in the osteopenic range.