In an 85‑year‑old woman who has been receiving denosumab (Prolia) for approximately 11 years and is tolerating it well, should therapy be continued long‑term?

Should Prolia Be Continued After 11 Years in an 85-Year-Old Woman?

Yes, continue denosumab (Prolia) indefinitely in this 85-year-old patient who is tolerating it well, as discontinuation poses a severe risk of rebound multiple vertebral fractures that far outweighs the risks of continued therapy. 1, 2

Critical Understanding: Denosumab Cannot Be Safely Stopped

Unlike bisphosphonates, denosumab does not incorporate into bone matrix and its effects reverse rapidly upon discontinuation. 3 This creates a unique and dangerous situation:

• Rebound bone turnover occurs within 7-19 months after the last dose, with bone mineral density returning to pretreatment values within 18 months 2
• Multiple vertebral fractures have been reported in clinical trials and case series, occurring as early as 7 months (average 19 months) after stopping denosumab 3, 2
• Prior vertebral fracture is a predictor of multiple vertebral fractures after discontinuation 2
• The risk of rebound fractures appears to increase with longer treatment duration, making your patient's 11-year history particularly concerning if stopped 4

Evidence Supporting Long-Term Continuation Beyond 10 Years

The FREEDOM trial extension studies demonstrate sustained efficacy and safety through 10 years of continuous treatment, with evidence supporting continuation beyond this timeframe: 1, 5

• Vertebral fracture reduction of 68%, hip fracture reduction of 40%, and nonvertebral fracture reduction of 20% are maintained with long-term therapy 1, 6
• Continuous BMD increases are observed throughout 10 years of treatment, with no plateau effect 7, 5
• For patients with persistent high fracture risk after 10 years (which includes most 85-year-olds), guidelines support indefinite continuation 1

Safety Profile in Elderly Patients

Your patient's advanced age (85 years) actually strengthens the case for continuation rather than stopping:

• No dose adjustments based on age are required for denosumab 3
• Denosumab is particularly appropriate for elderly patients with potential renal impairment, as it is not cleared through the kidneys 1
• The absolute risks of serious complications remain low even with extended treatment 3

Rare but Serious Adverse Events to Monitor:

• Osteonecrosis of the jaw (ONJ): Risk increases to approximately 5% after 3 years, but remains manageable with good oral hygiene and avoiding invasive dental procedures 3, 2
• Atypical femoral fractures: Absolute risk remains low at 3.2-50 cases per 100,000 person-years, though may increase to 100 per 100,000 with long-term use 3
• Serious infections: Slightly increased risk requiring prompt medical attention for cellulitis, urinary tract infections, or endocarditis 2
• Hypocalcemia: Ensure adequate calcium (≥1000 mg daily) and vitamin D (≥800 IU daily) supplementation 3, 6

What If Discontinuation Becomes Necessary?

If denosumab must be stopped for any medical reason, immediate transition to high-dose bisphosphonate therapy is mandatory: 3, 1

• Administer zoledronic acid 5 mg IV within 6-7 months of the last denosumab dose 3, 2
• This is the most commonly recommended approach, though optimal bisphosphonate regimen post-denosumab remains under investigation 3
• Never allow a treatment gap or apply bisphosphonate "drug holiday" concepts to denosumab—the pharmacology is fundamentally different 1

Monitoring Recommendations for Continued Therapy

• Serum calcium monitoring regularly, particularly given denosumab's stronger hypocalcemic effect compared to bisphosphonates 3, 2
• Dental examination annually to assess for early signs of ONJ (jaw pain, swelling, loose teeth, non-healing sores) 3, 1, 2
• Clinical assessment for new thigh, hip, or groin pain that could indicate atypical femoral fracture 1, 2
• BMD reassessment at 1-2 year intervals for clinical documentation, though not required before each dose authorization 1
• Monitor for signs of serious infection (fever, cellulitis, severe abdominal pain, urinary symptoms) requiring prompt medical attention 1, 2

Common Pitfall to Avoid

The most critical error would be discontinuing denosumab without immediate bisphosphonate transition, which can result in catastrophic multiple vertebral fractures. 1, 2 The rebound effect is more severe with longer treatment duration, making your patient's 11-year history particularly high-risk for this complication if stopped abruptly. 4