What is the recommended duration of bisphosphonate therapy for postmenopausal women and older adults with osteoporosis?

Duration of Bisphosphonate Therapy

Patients should be treated with bisphosphonates for 5 years as the standard duration, after which treatment should be stopped unless they remain at very high fracture risk. 1

Standard Treatment Duration

• The American College of Physicians strongly recommends 5 years as the standard treatment duration for bisphosphonate therapy in postmenopausal women and older adults with osteoporosis. 1, 2
• The FDA label for risedronate explicitly states that "for patients at low-risk for fracture, consider drug discontinuation after 3 to 5 years of use." 3
• Evidence shows that extending treatment beyond 5 years probably reduces vertebral fractures but does NOT reduce hip or other non-vertebral fractures, while increasing the risk of long-term harms. 1, 2

Risk Stratification After 5 Years: Who Should Continue vs. Stop

High-Risk Patients Who Should Continue Beyond 5 Years:

• Previous hip or vertebral fractures during treatment 2, 4
• Multiple non-spine fractures 2
• Hip BMD T-score ≤ -2.5 despite treatment 2, 4
• Age >80 years 2
• Ongoing glucocorticoid use (≥7.5 mg prednisone daily) 2
• Fracture occurring after ≥18 months of bisphosphonate treatment 2

These high-risk patients can be treated for up to 10 years with oral bisphosphonates or 6 years with intravenous bisphosphonates, with periodic reevaluation. 4

Low-Risk Patients Who Should Stop After 5 Years:

• No previous hip or vertebral fractures during treatment 2
• Hip BMD T-score > -2.5 after treatment 2
• No multiple risk factors for fracture 2

These patients should be considered for a drug holiday of 2-5 years with continued monitoring. 2, 4, 5

Evidence Supporting the 5-Year Duration

• The FLEX trial demonstrated that women who discontinued alendronate after 5 years had only a modest increase in clinical vertebral fractures (5.3% vs 2.4%) but no difference in non-vertebral or hip fractures over the subsequent 5 years. 2, 6
• The HORIZON extension showed that women receiving 6 annual infusions of zoledronic acid had fewer morphometric vertebral fractures compared with those switched to placebo after 3 years, but benefits were limited to those with hip T-score below -2.5. 4

Long-Term Risks That Increase After 5 Years

• Atypical femoral fractures: Risk increases from 1.78 per 100,000 person-years to 113 per 100,000 person-years with exposure greater than 8 years. 2
• Osteonecrosis of the jaw: Incidence is <1 case per 100,000 person-years with standard dosing but increases significantly with longer duration. 2, 4
• Asian patients face up to 8 times higher risk for atypical femoral fractures compared to White patients. 2

Monitoring During Drug Holiday

• Do NOT perform routine BMD monitoring during the initial 5-year treatment period, as fracture reduction occurs even without BMD increases. 1, 2
• During the drug holiday, reassess patients regularly for: 2
  • New fractures (clinical assessment)
  • Changes in fracture risk profile
  • BMD changes, particularly femoral neck T-score
• Resume bisphosphonate therapy if: 2
  • A new fracture occurs during the holiday
  • Fracture risk increases significantly
  • BMD remains low (femoral neck T-score ≤ -2.5)

Critical Pitfalls to Avoid

• Never discontinue denosumab without immediately starting bisphosphonate therapy within 6 months, as rebound vertebral fractures can occur. 2
• Ensure dental work is completed before initiating or continuing bisphosphonate therapy beyond 5 years to reduce osteonecrosis of the jaw risk. 2
• Do not automatically continue bisphosphonates beyond 5 years without reassessing fracture risk, as this exposes patients to unnecessary rare adverse events without proven additional benefit in low-risk individuals. 2

Special Considerations

• Patients initially treated with anabolic agents (teriparatide, romosozumab) must be offered an antiresorptive agent after discontinuation to preserve gains and prevent serious rebound vertebral fractures. 2
• Adequate calcium (1000-1200 mg/day) and vitamin D (800 IU/day) intake should continue throughout treatment and during drug holidays. 2
• For patients with renal impairment (creatinine clearance <60 ml/min), consider switching to denosumab rather than continuing bisphosphonates. 2