What is the best course of action to manage osteoporosis in a 74-year-old female patient with worsening bone density despite being on Prolia (denosumab) since 2022?

Management of Worsening Osteoporosis Despite Denosumab Treatment

The patient should be switched from Prolia (denosumab) to an anabolic agent such as teriparatide or another PTH/PTHrP analog due to treatment failure evidenced by significant worsening of femoral neck T-score despite 3 years of denosumab therapy.

Assessment of Current Status

The patient shows clear evidence of treatment failure with denosumab:

• Left femur neck T-score has worsened from -2.70 (2021) to -3.30 (2025)
• Total femur T-score has worsened from -2.10 (2021) to -2.60 (2025)
• Only the lumbar spine shows improvement from -2.50 (2021) to -1.80 (2025)

This pattern indicates:

• Continued bone loss at critical fracture sites despite 3 years of denosumab therapy
• The patient is now at very high fracture risk with a femoral neck T-score below -3.0

Treatment Algorithm

Step 1: Confirm adherence to current therapy

• Verify the patient has been receiving denosumab injections every 6 months without delays
• Confirm adequate calcium (1,000-1,200 mg/day) and vitamin D (600-800 IU/day) supplementation 1

Step 2: Evaluate for secondary causes of bone loss

• Check laboratory parameters including:
  • Complete blood count
  • Comprehensive metabolic panel
  • Thyroid-stimulating hormone
  • 25-hydroxyvitamin D level
  • Consider parathyroid hormone level 2

Step 3: Implement treatment change based on fracture risk

The patient is at very high fracture risk based on:

• Age >70 years
• Severe osteoporosis (T-score ≤ -3.0 at femoral neck)
• Failure of first-line therapy (denosumab)

For patients at very high fracture risk, anabolic therapy is preferred over continuing antiresorptive therapy:

• Anabolic agents (PTH/PTHrP analogs) are conditionally recommended over antiresorptive agents (bisphosphonates or denosumab) for patients with very high fracture risk 1
• For patients who have had a suboptimal response to antiresorptive therapy, switching to an anabolic agent is recommended 2

Specific Treatment Recommendations

1. Primary recommendation: Switch to an anabolic agent (teriparatide or other PTH/PTHrP analog)

   • Anabolic agents stimulate bone formation rather than just inhibiting resorption
   • This approach is supported for patients with very high fracture risk or those failing antiresorptive therapy 1, 2

2. Alternative if anabolic therapy is not feasible:

   • Consider switching to intravenous bisphosphonate (zoledronic acid)
   • This may provide better adherence and potentially better efficacy than denosumab in this case 1

3. Important considerations for medication transition:

   • When switching from denosumab to an anabolic agent, there may be transient bone loss at the hip and spine 1
   • After completing the course of anabolic therapy (typically 18-24 months), the patient should transition to an antiresorptive agent to maintain gains 1

Lifestyle Modifications

In addition to pharmacologic therapy:

• Ensure adequate calcium intake (1,000-1,200 mg/day) and vitamin D (600-800 IU/day)
• Recommend weight-bearing and resistance training exercises
• Advise smoking cessation if applicable
• Limit alcohol consumption to 1-2 drinks per day 1

Monitoring Recommendations

• Repeat BMD testing after 1 year of anabolic therapy to assess response 2
• Monitor for potential side effects of anabolic therapy
• Reassess fracture risk annually
• Perform vertebral fracture assessment or spine X-rays to evaluate for asymptomatic vertebral fractures 2

Important Cautions

1. Never discontinue denosumab without follow-up therapy

   • Abrupt discontinuation of denosumab leads to rapid bone loss and increased vertebral fracture risk 3
   • The rebound effect after denosumab discontinuation can cause multiple vertebral fractures in up to 20% of patients 3

2. Sequential therapy planning is essential

   • After completing the course of anabolic therapy, transition to an antiresorptive agent 1
   • This sequential approach helps maintain bone gains and prevent rebound bone loss 1

3. Recognize limitations of BMD monitoring alone

   • Most fragility fractures occur in patients with BMD T-scores higher than -2.5 2
   • The presence of significant bone loss despite therapy indicates treatment failure regardless of absolute T-score values