What are the disadvantages of continuing bisphosphonates (bone resorption inhibitors) for longer than 5 years?

Disadvantages of Continuing Bisphosphonates Beyond 5 Years

The primary disadvantages of continuing bisphosphonates beyond 5 years are increased risks of osteonecrosis of the jaw and atypical femoral fractures, with observational data showing these rare but serious adverse events occur more frequently with longer treatment duration, particularly after 5 years of therapy. 1

Specific Long-Term Harms

Osteonecrosis of the Jaw (ONJ)

• Incidence increases with duration: While extremely rare in osteoporosis treatment schedules (0% to 0.5% with oral bisphosphonates), risk escalates with extended treatment beyond 5 years 1
• The most consistent risk factor is recent dental surgery or extraction 1
• Monthly IV bisphosphonate schedules (used in cancer) show higher rates than osteoporosis dosing schedules (every 6 months), which have 0% to 1% incidence 1

Atypical Femoral Fractures

• Risk increases with cumulative dose and duration: These subtrochanteric fractures are paradoxical, occurring despite treatment intended to prevent fractures 1
• Observational studies demonstrate higher risk after longer treatment duration, particularly beyond 5 years 1
• While rare, these events represent a concerning pattern of unusual fracture location and morphology 2, 3

Oversuppression of Bone Turnover

• Chronic suppression of bone remodeling may prevent repair of microdamage to bone architecture 1
• This paradoxically could compromise bone strength despite increased bone mineral density 1
• The long-term skeletal consequences of prolonged remodeling suppression remain incompletely understood 4

Limited Additional Fracture Benefit

Vertebral Fractures Only

• Extending treatment beyond 5 years reduces vertebral fractures but NOT other fracture types 1
• After 3-5 years of treatment, continuation versus discontinuation reduced radiographic and clinical vertebral fractures but not nonvertebral fractures 3
• This limited benefit profile must be weighed against increasing harm risks 1

Residual Anti-Fracture Effect After Discontinuation

• Bisphosphonates accumulate in bone and continue to provide fracture protection for 1-2 years after stopping 4, 3
• Studies with alendronate and zoledronate show persisting antifracture efficacy during drug holidays 4, 5
• This residual effect reduces the urgency of continuous long-term therapy for many patients 4

Guideline-Based Recommendations

The 5-Year Decision Point

• The American College of Physicians explicitly states that clinicians should consider stopping bisphosphonate treatment after 5 years unless the patient has strong indication for continuation 1
• This recommendation balances the modest benefit (vertebral fractures only) against increased long-term harms 1

Risk Stratification for Continuation

• High-risk patients (prior fractures, very low BMD, glucocorticoid use) may warrant continuation to 7-10 years 1, 6
• Moderate-risk patients should generally stop at 5 years with reassessment 1
• Low-risk patients may stop even earlier (3-5 years) and take extended drug holidays 4, 7

Treatment Failure Considerations

• Patients who fracture after ≥18 months of bisphosphonate therapy or experience significant BMD decline (≥10%/year) should switch to another medication class rather than continue bisphosphonates 1, 6
• This indicates the bisphosphonate is no longer providing adequate benefit 1

Clinical Pitfalls to Avoid

Continuing Without Reassessment

• The decision to continue beyond 5 years must be individualized based on fracture risk, medication type, and half-life in bone 1
• Simply continuing indefinitely without reassessing risk-benefit is inappropriate 1

Ignoring Dental Health

• All patients on long-term bisphosphonates require oral examination and good oral hygiene 1
• Invasive dental procedures should be completed before initiating therapy or carefully timed during treatment 1

Not Considering Drug Holidays

• For patients at mild-to-moderate risk, a drug holiday after 5 years allows bone to maintain some protection while reducing exposure to rare harms 4, 5
• Drug holidays of 2-3 years are recommended for most patients after 5 years of therapy 5, 7