Should an older adult with a history of osteoporosis continue taking bisphosphonates (e.g. alendronate, risedronate, or zoledronic acid) if their Dual-Energy X-ray Absorptiometry (DEXA) scan results continue to improve?

Should You Continue Bisphosphonates if DEXA Scans Continue to Improve?

No, you should not automatically continue bisphosphonates beyond 5 years simply because DEXA scans are improving—instead, reassess fracture risk and strongly consider a drug holiday unless you remain at very high risk for fractures. 1

Standard Treatment Duration and Reassessment

The American College of Physicians strongly recommends 5 years as the standard treatment duration for bisphosphonates, after which treatment should be stopped unless the patient has very high fracture risk. 1 This recommendation is based on high-certainty evidence that:

• Extending treatment beyond 5 years reduces only vertebral fractures, NOT hip or other non-vertebral fractures, while simultaneously increasing the risk of rare but serious long-term harms. 2, 1
• 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. 1
• Fracture reduction benefits occur even without BMD increases, so improving DEXA scans alone are not an indication to continue therapy indefinitely. 1

Increasing Risks Beyond 5 Years

The primary disadvantages of continuing bisphosphonates beyond 5 years are increased risks of osteonecrosis of the jaw (ONJ) and atypical femoral fractures (AFF). 2

Specific Long-Term Harms:

• ONJ incidence increases with duration, with risk escalating beyond 5 years, particularly after recent dental surgery or extraction. 2
• AFF risk increases significantly after 5 years, escalating sharply beyond 8 years (from 1.78 per 100,000 person-years to 113 per 100,000 person-years with exposure greater than 8 years). 1
• The incidence of AFF is 3.0-9.8 cases per 100,000 patient-years overall, with Asian patients facing up to 8 times higher risk than White patients. 1

Risk Stratification Algorithm for Continuation vs. Drug Holiday

HIGH-RISK PATIENTS (Continue Treatment Beyond 5 Years):

Continue bisphosphonates if the patient has ANY of the following: 1, 3, 4

• Previous hip or vertebral fractures (before or during treatment)
• Multiple non-spine fractures
• Hip BMD T-score ≤ -2.5 despite 5 years of treatment
• Age >80 years
• Ongoing glucocorticoid use (≥7.5 mg prednisone daily)
• Fracture occurring after ≥18 months of bisphosphonate treatment (consider switching to another medication class rather than continuing bisphosphonates) 5
• Significant bone loss (≥10% per year) despite bisphosphonate therapy (consider switching to another medication class) 5

LOW-TO-MODERATE RISK PATIENTS (Consider Drug Holiday):

Initiate a drug holiday if the patient has ALL of the following: 1, 3

• No fractures before or during therapy
• Hip BMD T-score > -2.5 after treatment
• No ongoing glucocorticoid use
• Age <80 years
• No multiple risk factors for fracture

Suggested Drug Holiday Duration by Agent:

• Alendronate: 3-5 years 3
• Risedronate: 1-2 years 3
• Zoledronic acid: 3-6 years 3

Monitoring During Drug Holiday

Do NOT perform routine BMD monitoring during the initial 5-year treatment period. 1 However, during a drug holiday: 1, 3

• Reassess fracture risk regularly for new fractures, changes in risk profile, and BMD changes (particularly femoral neck T-score)
• Resume bisphosphonate therapy if:
  • 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 continue bisphosphonates indefinitely without reassessing risk-benefit—this exposes patients to unnecessary rare adverse events without proven additional benefit in low-risk individuals. 1
• Complete all dental work before initiating or continuing bisphosphonate therapy to reduce ONJ risk, as the most consistent risk factor for ONJ is recent dental surgery or extraction. 2, 1
• Never discontinue denosumab without immediately starting bisphosphonate therapy within 6 months, as denosumab discontinuation causes rebound vertebral fractures. 1, 3
• Ensure adequate calcium (1000-1200 mg/day) and vitamin D (800 IU/day) supplementation throughout treatment and during drug holidays. 1

When to Consider Switching (Not Just Continuing)

If you remain at high risk after 5 years, consider switching to denosumab rather than continuing bisphosphonates in these specific scenarios: 1

• Renal impairment (creatinine clearance <60 ml/min)
• Cancer-related bone disease (breast cancer, prostate cancer, multiple myeloma)
• Fractures despite adequate bisphosphonate treatment

However, for most patients with improving DEXA scans and no high-risk features, a drug holiday is the most appropriate next step after 5 years of bisphosphonate therapy. 1, 3