What is the recommended duration of bisphosphonate therapy and frequency of Dual-Energy X-ray Absorptiometry (DEXA) scans for patients with osteoporosis or osteopenia?

Duration of Bisphosphonate Therapy and DEXA Monitoring Frequency

Treat with bisphosphonates for 5 years as the standard duration, then reassess fracture risk to determine whether to continue therapy or initiate a drug holiday; do NOT perform routine DEXA monitoring during the initial 5-year treatment period. 1, 2

Standard Treatment Duration

• The FDA label and American College of Physicians establish 5 years as the standard treatment duration for oral bisphosphonates (alendronate, risedronate) and 3 years for intravenous zoledronic acid. 2, 3

• After this initial period, all patients must have their need for continued therapy re-evaluated on a periodic basis, as the optimal duration of use has not been definitively determined. 2

• Patients at low risk for fracture should be considered for drug discontinuation after 3 to 5 years of use. 2

Risk Stratification After Initial Treatment Period

High-risk patients who should continue therapy beyond 5 years include: 1, 3

• Patients with previous hip or vertebral fractures during or before treatment
• Multiple non-spine fractures
• Hip T-score ≤ -2.5 despite treatment
• Age >80 years
• Ongoing glucocorticoid use ≥7.5 mg/day prednisone
• Patients who fracture while on therapy

Low-to-moderate risk patients eligible for drug holiday include: 1, 3

• No previous hip or vertebral fractures during treatment
• Hip T-score > -2.5 after treatment
• Stable or improved bone density
• No new fractures during treatment period

Drug Holiday Guidelines

• For alendronate and risedronate, drug holidays of 2-3 years are appropriate for low-to-moderate risk patients after 5 years of treatment. 3, 4

• For zoledronic acid, drug holidays can be considered after 3 years of treatment in appropriate patients. 3

• High-risk patients should be treated for up to 10 years with oral bisphosphonates or 6 years with intravenous zoledronic acid, with periodic evaluation. 3

• The risk of atypical femoral fractures increases significantly after 5 years of treatment, escalating sharply beyond 8 years, with risk rising from 1.78 per 100,000 person-years to 113 per 100,000 person-years with exposure greater than 8 years. 1

DEXA Monitoring Frequency

Do NOT perform routine BMD monitoring during the initial 5-year treatment period, as fracture reduction occurs even without BMD increases. 1

During a drug holiday, reassess patients regularly: 1, 4

• Clinical assessment for new fractures annually
• DEXA scan every 1-3 years during drug holiday to monitor for significant bone loss
• Particular attention to femoral neck T-score changes

Resume bisphosphonate therapy if: 1

• A new fracture occurs during the holiday
• Fracture risk increases significantly based on clinical assessment
• BMD declines substantially (femoral neck T-score ≤ -2.5)

Special Populations and Considerations

Glucocorticoid-induced osteoporosis: 5, 6

• Patients receiving prednisone ≥7.5 mg/day for ≥3 months should start bisphosphonates if they have moderate-to-high fracture risk
• Continue treatment for the duration of glucocorticoid therapy or up to 5 years, whichever is shorter
• Very high-dose glucocorticoids (≥30 mg/day) warrant immediate treatment regardless of bone density

Multiple myeloma patients: 5

• Administer bisphosphonates monthly for 2 years
• At 2 years, seriously consider stopping in patients with responsive or stable disease
• Resume upon relapse with new-onset skeletal-related events

Critical Safety Monitoring

Renal function monitoring: 5

• Monitor serum creatinine before each dose
• Withhold bisphosphonate if serum creatinine increases by >0.5 mg/dL or >1.0 mg/dL above baseline
• Resume when creatinine returns to within 10% of baseline

Other monitoring parameters: 5

• Evaluate for albuminuria every 3-6 months during pamidronate or zoledronic acid therapy
• Discontinue if unexplained albuminuria ≥500 mg/24 hours occurs
• Monitor serum calcium, electrolytes, phosphate, magnesium, and hemoglobin regularly

Dental evaluation: 1

• Complete all necessary dental work before initiating or continuing bisphosphonate therapy
• Osteonecrosis of the jaw risk increases with cumulative exposure, particularly beyond 5 years total treatment

Common Pitfalls to Avoid

• Never 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. 1

• Never discontinue denosumab without immediately starting bisphosphonate therapy within 6 months, as rebound vertebral fractures can occur. 1

• Do not use DEXA monitoring as the primary decision tool during the initial 5 years, as clinical fracture reduction is the goal, not BMD improvement. 1

• Asian patients face up to 8 times higher risk for atypical femoral fractures (595 versus 109 per 100,000 person-years in non-Hispanic white women), requiring more cautious consideration of treatment duration. 1