Does Prolia (denosumab) increase the healing of fractured bone?

Prolia (Denosumab) Does Not Increase Healing of Fractured Bone

Prolia (denosumab) does not increase the healing of fractured bone and may potentially impair the normal fracture healing process due to its mechanism of action as a potent antiresorptive agent.

Mechanism of Action and Effects on Bone Healing

Denosumab (Prolia) is a human monoclonal antibody that works by:

• Binding to RANKL (receptor activator of nuclear factor kappa-B ligand) 1
• Inhibiting osteoclast formation, function, and survival 2
• Suppressing bone resorption, which is a critical part of the bone remodeling process 3

While denosumab effectively increases bone mineral density (BMD) and reduces fracture risk in osteoporosis patients, its effects on fracture healing are concerning for several reasons:

1. Suppression of bone turnover: The normal fracture healing process requires balanced bone remodeling with both resorption and formation phases. Denosumab's potent suppression of osteoclast activity disrupts this balance.

2. Potential for delayed healing: Antiresorptive medications like denosumab may impair the processes by which stress fractures normally heal 1.

3. Risk of atypical fractures: Long-term use of denosumab has been associated with atypical femoral fractures (AFFs), suggesting impaired bone remodeling 1.

Clinical Evidence and Guidelines

Current guidelines and evidence do not support using denosumab to enhance fracture healing:

• No clinical guidelines recommend denosumab for improving fracture healing 1
• Denosumab is approved for preventing bone loss and reducing fracture risk, not for enhancing fracture healing 2
• Guidelines specifically warn about potential adverse effects on bone healing, including:
  • Atypical femoral fractures with long-term use 1
  • Delayed healing after orthopedic procedures 1

Special Considerations and Risks

When considering denosumab in patients with fractures, be aware of these important issues:

• Rebound effect: Discontinuation of denosumab leads to rapid bone turnover rebound and increased risk of multiple vertebral fractures 1, 4
• Long-term effects: Concerns exist about impaired mineralization of bone and delayed healing after orthopedic procedures 1
• Osteonecrosis risk: Denosumab carries a risk of osteonecrosis of the jaw, particularly with invasive dental procedures 1

Appropriate Uses of Denosumab

While denosumab does not enhance fracture healing, it remains valuable for:

• Treatment of postmenopausal osteoporosis in women at high fracture risk 5
• Prevention of bone loss in patients receiving cancer treatments like androgen deprivation therapy or aromatase inhibitors 1
• Management of osteoporosis in patients with compromised renal function 6

Clinical Recommendations

For patients with fractures:

• Do not use denosumab specifically to enhance fracture healing
• For patients already on denosumab who sustain a fracture:
  • Continue treatment to prevent further bone loss
  • Monitor fracture healing closely
  • Consider temporary suspension if healing appears delayed
• For patients with new fractures considering osteoporosis treatment:
  • Consider alternative therapies if rapid fracture healing is a priority
  • If denosumab is selected for other reasons (e.g., renal impairment), understand it will not accelerate healing

In summary, while denosumab is effective for preventing fractures by increasing bone mineral density, there is no evidence it enhances the healing of existing fractures, and its mechanism of action suggests it may potentially impair normal fracture healing processes.