What is the best course of action for an older postmenopausal woman with osteoporosis, currently on alendronate (bisphosphonate), whose T-scores are worsening?

Management of Worsening T-Scores on Alendronate

For a postmenopausal woman with worsening T-scores despite alendronate therapy, reassess fracture risk and consider either continuing alendronate beyond 5 years if she has high-risk features (previous hip/vertebral fractures, T-score ≤ -2.5, or multiple fractures), or switch to denosumab if she has very high ongoing fracture risk, renal impairment, or demonstrated treatment failure. 1

Initial Assessment and Risk Stratification

Determine if this represents true treatment failure or expected variation:

• Worsening T-scores do not automatically indicate treatment failure, as fracture reduction occurs even without BMD increases in patients on bisphosphonates 1, 2
• The American College of Physicians recommends against routine BMD monitoring during the initial 5-year treatment period for this exact reason 1
• However, significant bone loss (≥10% per year) despite bisphosphonate therapy defines very high fracture risk and warrants intervention change 1

Assess treatment duration:

• If she has been on alendronate for <5 years, continue current therapy as this is the standard treatment duration 1
• If she has been on alendronate for ≥5 years, proceed with risk stratification below 1

Risk Stratification After 5 Years of Alendronate

High-risk features requiring continued or intensified therapy include: 1

• Previous hip or vertebral fractures during treatment
• Multiple non-spine fractures
• Hip BMD T-score ≤ -2.5 despite treatment
• Age >80 years
• Ongoing glucocorticoid use (≥7.5 mg prednisone daily)
• Significant bone loss (≥10% per year) on therapy

If high-risk features are present:

• Continue alendronate beyond 5 years, as extending treatment reduces vertebral fractures (though not other fracture types) 1
• The FLEX trial showed only modest increases in clinical vertebral fractures (5.3% vs 2.4%) when alendronate was discontinued after 5 years, with no difference in non-vertebral or hip fractures 1

When to Switch to Alternative Therapy

Switch to denosumab 60 mg subcutaneously every 6 months if: 1, 2

• Creatinine clearance <60 mL/min (alendronate contraindicated if CrCl <35 mL/min) 3, 4
• Very high fracture risk features as defined above, particularly if fracture occurred after ≥18 months of bisphosphonate treatment 1
• Demonstrated treatment failure with significant BMD decline despite adequate compliance and supplementation 1

Denosumab shows greater BMD increases than bisphosphonates (3.5% vs 2.6% at the hip), though this doesn't necessarily translate to superior fracture outcomes in patients already treated with bisphosphonates 1

Critical warning: Never discontinue denosumab without immediately starting bisphosphonate therapy within 6 months, as rebound vertebral fractures occur with denosumab cessation 1, 2

Consider Anabolic Therapy for Very High-Risk Patients

Teriparatide or romosozumab should be considered over continuing antiresorptive therapy if: 1

• Multiple vertebral fractures present
• Fracture occurred after ≥18 months of adequate bisphosphonate treatment
• T-score ≤ -3.0 with additional risk factors
• Significant bone loss (≥10% per year) despite bisphosphonate therapy

The American College of Rheumatology conditionally recommends anabolic agents over antiresorptive agents for patients meeting these very high-risk criteria 1

Essential Concurrent Measures

Verify adequate supplementation and compliance:

• Calcium 1000-1200 mg/day and vitamin D 800 IU/day are mandatory throughout treatment 1, 4
• Inadequate supplementation reduces treatment efficacy and may explain apparent treatment failure 4
• Check serum 25(OH)D levels; target ≥30 ng/mL for optimal bone health 4
• If 25(OH)D <30 ng/mL, give ergocalciferol 50,000 IU weekly for 8 weeks, then recheck 4

Confirm proper alendronate administration:

• Must be taken with full glass of water (6-8 ounces), remain upright for at least 30 minutes, avoid food/drink during this period 1
• Poor compliance or improper administration may explain lack of response 3

Long-Term Safety Considerations

If continuing alendronate beyond 5 years, counsel about increased risks:

• Osteonecrosis of the jaw risk increases with duration beyond 5 years (incidence <1 case per 100,000 person-years with osteoporosis dosing) 1
• Atypical femoral fractures occur at 3.0-9.8 cases per 100,000 patient-years, with risk escalating sharply beyond 8 years 1
• Complete dental work before continuing therapy to reduce osteonecrosis risk 1

The risk-benefit ratio remains favorable: An estimated 162 osteoporosis-related fractures are prevented for every one atypical femoral fracture associated with antiresorptive medication 1

Common Pitfalls to Avoid

• Do not automatically switch therapy based solely on BMD changes without assessing clinical fracture risk and compliance 1, 2
• Do not initiate a drug holiday in high-risk patients (previous fractures, T-score ≤ -2.5, age >80, glucocorticoid use) 1
• Do not switch to denosumab without counseling about mandatory transition back to bisphosphonates if it must ever be discontinued 1, 2
• Do not overlook inadequate calcium/vitamin D supplementation as the cause of apparent treatment failure 4