When should bisphosphonates (Bisphosphonate) be started in patients with osteopenia?

When to Start Bisphosphonate Therapy for Osteopenia

Bisphosphonate therapy should be initiated in patients with osteopenia who have a FRAX 10-year risk of major osteoporotic fracture ≥10% or hip fracture >1%, or who have additional risk factors such as glucocorticoid therapy. 1

Risk Assessment for Treatment Decision

Treatment decisions for osteopenia should be based on fracture risk assessment rather than BMD values alone:

High-Risk Patients (Start Treatment)

• FRAX 10-year risk of major osteoporotic fracture ≥10% or hip fracture >1% 1
• History of fragility fracture 1
• Patients on glucocorticoid therapy ≥7.5 mg/day for ≥6 months 2
• Postmenopausal women receiving aromatase inhibitors 2
• Patients with rapid bone loss (≥10%/year at hip or spine) 2

Low-Risk Patients (No Treatment)

• FRAX 10-year risk of major osteoporotic fracture <10% and hip fracture ≤1% 1
• No additional risk factors
• Monitor with BMD testing every 2-3 years 2

Treatment Recommendations by Patient Population

Postmenopausal Women with Osteopenia

• Oral bisphosphonates are first-line therapy for those meeting treatment criteria 1
• Risedronate has shown 73% reduction in fragility fracture risk over 3 years in osteopenic women without prevalent vertebral fractures 3
• For women on aromatase inhibitors, bisphosphonates prevent bone loss; consider treatment if T-score is less than -2.0 or if major risk factors present 2

Men with Osteopenia

• Similar treatment thresholds apply as for women 1
• Consider treatment if FRAX scores meet treatment thresholds or if on long-term glucocorticoid therapy 2

Patients on Glucocorticoid Therapy

• For adults ≥40 years with moderate-to-high fracture risk on glucocorticoids, oral bisphosphonates are strongly recommended 2
• For adults <40 years on glucocorticoids (≥7.5 mg/day for ≥6 months) with Z-score <-2.3 or bone loss ≥10%/year, oral bisphosphonates are recommended 2
• For very high-dose glucocorticoid treatment (≥30 mg/day with cumulative annual dose >5g), start bisphosphonate therapy regardless of BMD 2

Choice of Bisphosphonate

Alendronate (70mg weekly) is recommended as first-line therapy due to:

• Strong evidence for fracture reduction
• Favorable safety profile
• Cost-effectiveness 1

Alternative options:

1. Risedronate (35mg weekly)
2. Zoledronic acid (IV) - if GI issues prevent oral administration
3. Ibandronate (monthly) 1

Duration of Therapy

• Initial treatment duration is typically 5 years 4
• After 5 years, reassess fracture risk:
  • If risk remains high, continue treatment or switch to another agent
  • If risk is low, consider a drug holiday 4

Monitoring Response

• BMD testing every 1-2 years to monitor treatment response 1
• Reassess FRAX score every 1-2 years 1

Adjunctive Measures

All patients should receive:

• Calcium supplementation (1,000-1,200 mg daily)
• Vitamin D supplementation (800-1,000 IU daily)
• Weight-bearing exercise program (30 minutes at least 3 days/week)
• Smoking cessation
• Alcohol limitation (1-2 drinks/day)
• Fall prevention strategies 1

Important Considerations

• Treatment adherence is critical for efficacy, with 30-50% of patients not taking medications correctly 1
• Bisphosphonates have demonstrated good safety and tolerability in long-term studies (8-10 years) 4
• Uncommon side effects include esophageal irritation, acute phase response, osteonecrosis of the jaw, and atypical fractures 4
• Bisphosphonates accumulate in bone, providing residual anti-fracture benefits after discontinuation 4

By following these guidelines, clinicians can appropriately identify osteopenic patients who would benefit from bisphosphonate therapy while avoiding unnecessary treatment in low-risk individuals.