What management is recommended for fractures in patients taking Denosumab (denosumab)?

From the Guidelines

Patients experiencing fractures while on denosumab should continue their denosumab treatment as scheduled and undergo standard fracture management, including immobilization, pain control, and possibly orthopedic intervention, while maintaining or optimizing calcium and vitamin D supplementation. The management of fractures in patients taking denosumab involves a multifaceted approach that prioritizes the patient's bone health and minimizes the risk of further fractures. According to the most recent and highest quality study 1, it is crucial not to discontinue denosumab without medical guidance due to the risk of rebound bone loss and increased fracture risk.

Key Considerations

• Standard fracture management, including immobilization and pain control with acetaminophen or NSAIDs if appropriate, should be initiated promptly.
• Calcium (1000-1200 mg daily) and vitamin D (800-1000 IU daily) supplementation should be maintained or optimized to support bone health.
• The healthcare provider may consider adding an anabolic agent like teriparatide (Forteo) or romosozumab (Evenity) to promote fracture healing, especially for complex fractures or if this is a repeat fracture while on therapy.
• Fractures while on denosumab may indicate inadequate response to therapy, poor medication adherence, or the presence of other factors affecting bone health that require evaluation, such as vitamin D deficiency, secondary causes of osteoporosis, or high fall risk that needs addressing.

Discontinuation of Denosumab

Discontinuation of denosumab should be done under medical guidance, and consideration should be given to initiating bisphosphonate therapy to reduce or prevent the rebound increase in bone resorption and potential excess risk for vertebral fractures, as suggested by the study 1. The optimal bisphosphonate regimen post-denosumab is currently unknown, but many osteoporosis clinicians use a single 4- or 5-mg treatment of zoledronate.

Overall Management

The overall management of fractures in patients taking denosumab requires careful consideration of the patient's bone health, the risk of further fractures, and the potential consequences of discontinuing denosumab. By prioritizing the patient's morbidity, mortality, and quality of life, healthcare providers can develop an effective management plan that addresses the patient's unique needs and minimizes the risk of adverse outcomes.

From the FDA Drug Label

Atypical low energy or low trauma fractures of the shaft have been reported in patients receiving Prolia [see Adverse Reactions (6. 1)]. These fractures can occur anywhere in the femoral shaft from just below the lesser trochanter to above the supracondylar flare and are transverse or short oblique in orientation without evidence of comminution. During Prolia treatment, patients should be advised to report new or unusual thigh, hip, or groin pain. Any patient who presents with thigh or groin pain should be suspected of having an atypical fracture and should be evaluated to rule out an incomplete femur fracture Patient presenting with an atypical femur fracture should also be assessed for symptoms and signs of fracture in the contralateral limb. Interruption of Prolia therapy should be considered, pending a benefit-risk assessment, on an individual basis.

For patients taking Denosumab (denosumab) who experience fractures, the recommended management includes:

• Evaluation: Evaluate the patient to rule out an incomplete femur fracture if they present with thigh or groin pain.
• Assessment: Assess the patient for symptoms and signs of fracture in the contralateral limb if an atypical femur fracture is suspected.
• Interruption of therapy: Consider interrupting Denosumab (denosumab) therapy, pending a benefit-risk assessment, on an individual basis 2.

From the Research

Management of Fractures in Patients Taking Denosumab

• The management of fractures in patients taking denosumab is crucial to prevent further bone loss and fractures 3, 4, 5, 6.
• Studies have shown that discontinuation of denosumab can lead to rapid bone loss and increased risk of multiple vertebral fractures 3, 4, 5, 6.
• Patients who have sustained rebound-associated vertebral fractures (RAVFs) after denosumab discontinuation may benefit from treatment with antiosteoporotic medications such as denosumab, teriparatide, zoledronate, or a combination of denosumab and teriparatide 5.
• However, reinstitution of denosumab treatment may not completely eliminate the risk of new RAVFs, and the rebound of bone turnover may not be the sole mechanism to explain this phenomenon 6.
• Adherence to denosumab treatment is crucial for patients who are initiated with denosumab, as discontinuation is associated with a significantly increased risk of subsequent fractures and mortality 4.

Treatment Options

• Denosumab: can be effective in preventing further bone loss and fractures in patients who have sustained RAVFs 5.
• Teriparatide: can be effective in increasing bone mineral density (BMD) and preventing further fractures in patients who have sustained RAVFs 5.
• Zoledronate: can be effective in preserving BMD and preventing further fractures in patients who have sustained RAVFs, although it may not be as effective as denosumab or teriparatide in increasing BMD 5.
• Combination of denosumab and teriparatide: may be effective in increasing BMD and preventing further fractures in patients who have sustained RAVFs 5.

Considerations

• Patients who are at high risk of fracture should continue denosumab therapy for up to 10 years or be switched to an alternative treatment 3.
• Patients who are at low risk of fracture may be able to discontinue denosumab after 5 years, but should be considered for bisphosphonate therapy to reduce or prevent the rebound increase in bone turnover 3.
• The optimal bisphosphonate regimen post-denosumab is currently unknown, and continuation of denosumab can also be considered until results from ongoing trials become available 3.