What are the criteria for postmenopausal women or older adults with a history of osteoporotic fractures and taking Alendronate (bisphosphonate) for 5 years or more to switch to Prolia (denosumab) and when should they see their provider?

When to Switch from Alendronate to Prolia After 5+ Years

After 5 years of alendronate therapy, most postmenopausal women with osteoporotic fractures should consider a drug holiday rather than automatically switching to Prolia (denosumab), unless they have specific high-risk features that warrant continued treatment. 1, 2

Risk Stratification After 5 Years of Alendronate

Patients Who Should Continue Treatment (Consider Prolia)

High-risk patients who should NOT take a drug holiday and may benefit from switching to Prolia include those with: 2

• Previous hip or vertebral fractures occurring during alendronate treatment 2
• Multiple non-spine fractures 2
• Hip BMD T-score ≤ -2.5 despite 5 years of treatment 2
• Age >80 years 2
• Ongoing glucocorticoid use ≥7.5 mg prednisone daily 2
• Significant bone loss (≥10% per year) despite bisphosphonate therapy 2
• Creatinine clearance <60 mL/min (denosumab preferred due to renal safety) 2, 3

Patients Eligible for Drug Holiday (Do NOT Switch)

Patients without high-risk features can safely discontinue alendronate for 3-5 years if they have: 2, 4

• No fractures before or during the 5-year treatment period 2, 4
• Hip BMD T-score > -2.5 after treatment 2
• No ongoing glucocorticoid use 2
• Age <80 years without multiple risk factors 2

The FLEX trial demonstrated that women discontinuing 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, supporting drug holidays in appropriate patients. 2, 5

Specific Indications for Switching to Prolia

FDA-Approved Criteria

Prolia is indicated for postmenopausal women with osteoporosis at high risk for fracture, defined as: 3

• History of osteoporotic fracture 3
• Multiple risk factors for fracture 3
• Patients who have failed or are intolerant to other available osteoporosis therapy 3

Clinical Scenarios Favoring Prolia Over Continued Alendronate

Switch to Prolia when: 2, 6

• Renal impairment with CrCl <60 mL/min (denosumab does not require renal dose adjustment) 2
• Gastrointestinal intolerance to oral bisphosphonates 3, 6
• Poor adherence to oral bisphosphonate dosing requirements 2
• Cancer-related bone disease (breast cancer, prostate cancer, multiple myeloma) 2
• Fracture occurring despite adequate bisphosphonate treatment 2

Denosumab shows greater BMD increases than bisphosphonates (3.5% vs 2.6% for alendronate at the hip), though this does not necessarily translate to superior fracture outcomes in patients already treated with bisphosphonates. 2

When to See Your Provider

Immediate Evaluation Required

Contact your provider immediately if you experience: 7

• New fracture or bone pain (may indicate treatment failure) 2
• Unusual thigh, hip, or groin pain (possible atypical femoral fracture) 7
• Jaw pain, swelling, numbness, loose teeth, or non-healing mouth sores (possible osteonecrosis of the jaw) 7
• Signs of serious infection (fever, chills, severe abdominal pain, urinary symptoms) 7
• Severe bone, joint, or muscle pain 7

Scheduled Provider Visits

See your provider at these intervals: 2, 7

• At 5 years of alendronate treatment for fracture risk reassessment and treatment decision (continue, switch, or drug holiday) 2
• Every 6 months if starting Prolia for administration of injections 3
• Every 1-2 years during treatment for clinical assessment (not necessarily BMD monitoring) 2, 7
• Before any dental procedures while on Prolia to minimize osteonecrosis of the jaw risk 7
• If considering stopping Prolia to arrange immediate transition to bisphosphonate therapy within 6 months 2, 7, 4

Critical Warnings About Prolia

Never Discontinue Prolia Without Transition Therapy

Denosumab fundamentally differs from bisphosphonates—it CANNOT be safely discontinued without immediate replacement therapy. 2, 7, 4

• Stopping Prolia causes rapid rebound bone turnover with high risk of multiple vertebral fractures 2, 4
• Bisphosphonate therapy (such as zoledronate) MUST be initiated within 6 months of last Prolia dose 2, 7, 4
• Drug holidays are NOT recommended for denosumab (unlike bisphosphonates) 2, 4

Required Monitoring on Prolia

Essential monitoring includes: 7

• Calcium and vitamin D levels before starting (correct deficiencies to prevent hypocalcemia) 7, 3
• Dental examination before initiating therapy 7
• Adequate supplementation with calcium ≥1000 mg daily and vitamin D ≥400-800 IU daily 7, 3
• Clinical assessment for infections, skin reactions, and musculoskeletal pain 7

Common Pitfalls to Avoid

Do not automatically switch to Prolia after 5 years without reassessing fracture risk—many patients can safely take a drug holiday, avoiding unnecessary exposure to a medication that cannot be safely discontinued. 2

Do not apply bisphosphonate drug holiday concepts to denosumab—the pharmacology is fundamentally different and requires continuous treatment or immediate transition therapy. 2, 4

Do not start Prolia in patients with poor dental health or planned dental procedures—complete all dental work before initiating therapy. 7

Do not forget to ensure adequate calcium and vitamin D supplementation—this is mandatory throughout treatment to prevent hypocalcemia, especially in patients with renal impairment. 7, 3