When to switch from Prolia (denosumab) to an alternative osteoporosis treatment?

When to Switch from Prolia (Denosumab)

Switch from Prolia when treatment failure occurs (new fracture ≥12 months after starting therapy or significant BMD loss >10%/year after 1 year), when discontinuing glucocorticoids with persistent high fracture risk, or when severe adverse events develop—and critically, always transition to an alternative antiresorptive therapy (bisphosphonate or other agent) within 6-7 months of the last Prolia dose to prevent rebound vertebral fractures. 1, 2

Treatment Failure Scenarios Requiring Switch

Fracture on Therapy

• Switch to another osteoporosis medication class if a new osteoporotic fracture occurs ≥12 months after initiating Prolia therapy 1
• Alternative options include PTH/PTHrP (teriparatide), oral or IV bisphosphonates, or romosozumab depending on fracture risk level 1
• For glucocorticoid-induced osteoporosis specifically, switching from denosumab to PTH/PTHrP may lead to transient bone losses in hip and spine and is not recommended; however, PTH/PTHrP followed by denosumab leads to continued BMD increases 1

Significant BMD Decline

• Switch if significant BMD loss occurs (≥10% per year or greater than the least significant change per DXA machine) after 1-2 years of treatment 1
• This indicates inadequate therapeutic response requiring alternative therapy 1

Discontinuation of Glucocorticoids

High Fracture Risk Persists

• For adults ≥40 years discontinuing glucocorticoid therapy who continue to be at high fracture risk (BMD T-score ≤-2.5 or history of fragility fracture occurring after ≥12 months of therapy), continue current osteoporosis therapy or switch to another medication class 1

Low Fracture Risk After Glucocorticoid Cessation

• Stop Prolia if fracture risk is assessed to be low at the time of glucocorticoid discontinuation (no new fragility fracture and current BMD T-score ≥-2.5) 1
• However, sequential therapy with a bisphosphonate is strongly recommended after stopping denosumab regardless of fracture risk status 1

Mandatory Adverse Event-Related Switching

Multiple Vertebral Fractures Risk After Discontinuation

• The most critical reason to plan switching: Prolia discontinuation without transition therapy causes rebound bone loss and increased risk of multiple vertebral fractures starting as early as 7 months (average 19 months) after the last dose 2
• Patients must be transitioned to an alternative antiresorptive therapy (bisphosphonate preferred) beginning 6-7 months after the last Prolia dose 1, 2
• Prior vertebral fracture is a predictor of multiple vertebral fractures after discontinuation 2

Osteonecrosis of the Jaw (ONJ)

• Consider discontinuing Prolia if ONJ develops, based on individual benefit-risk assessment 2
• Patients suspected of having or who develop ONJ should receive care by a dentist or oral surgeon 2
• Extensive dental surgery to treat ONJ may exacerbate the condition 2

Atypical Femoral Fractures

• Interrupt Prolia therapy if atypical subtrochanteric or diaphyseal femoral fracture occurs, pending individual benefit-risk assessment 2
• Patients should be advised to report new or unusual thigh, hip, or groin pain during treatment 2
• Assess contralateral limb for symptoms and signs of fracture 2

Serious Infections

• Consider discontinuing if severe infections develop, including cellulitis, endocarditis, or serious skin/abdominal/urinary tract infections requiring hospitalization 2
• Patients on concomitant immunosuppressant agents or with impaired immune systems are at increased risk 2

Severe Dermatologic Reactions

• Consider discontinuing if severe dermatitis, eczema, or rashes develop 2

Severe Musculoskeletal Pain

• Consider discontinuing if severe and occasionally incapacitating bone, joint, and/or muscle pain develops 2

Special Population Considerations

Renal Disease

• Denosumab is preferred over bisphosphonates in patients with renal disease (GFR <35 mL/min) 1
• However, if switching is needed, bisphosphonates may be contraindicated in severe renal impairment 1

Solid Organ Transplant Recipients

• For adults with solid organ transplants, GFR ≥35 mL/min, and no evidence of chronic kidney disease-mineral and bone disorder, treatment decisions should be based on individual patient factors 1
• Expert evaluation is conditionally recommended for renal transplant recipients 1

Critical Transition Protocol

Sequential Therapy Requirements

• Bisphosphonates (oral or IV) should be started 6-7 months after the last Prolia dose to prevent rebound vertebral fractures 1
• Unlike bisphosphonates and raloxifene which can be discontinued without sequential therapy, denosumab, PTH/PTHrP, and romosozumab require transition to anti-resorptive therapy 1
• The best formulation and duration of sequential treatment after denosumab remains unclear but is strongly recommended 1

Monitoring During Transition

• Bone turnover increases above pretreatment values 9 months after the last Prolia dose, then returns to pretreatment values 24 months after 2
• BMD returns to pretreatment values within 18 months after the last injection 2

Common Pitfalls to Avoid

• Never discontinue Prolia without planning sequential antiresorptive therapy—this is the most dangerous error and leads to rebound vertebral fractures 1, 2
• Do not switch from denosumab to PTH/PTHrP as this may lead to transient bone losses 1
• Do not delay switching when treatment failure is evident (new fracture or significant BMD loss) 1
• Ensure calcium and vitamin D supplementation is adequate before and during any transition 3
• Correct hypocalcemia before starting any alternative therapy, particularly bisphosphonates or continuing denosumab 3