When to take a holiday from Prolia (denosumab)?

From the Guidelines

Consult with your healthcare provider before taking a break from Prolia (denosumab), as temporary discontinuation is not recommended due to the risk of rebound bone loss and increased fracture risk. The pharmacokinetics of denosumab argue against intermittent treatments, and studies in osteoporosis patients have shown a rapid rebound in bone turnover after denosumab is stopped, associated with an increase in vertebral fractures 1. If a break is necessary for dental procedures or other medical reasons, it should be carefully planned with your doctor, taking into account your last injection and individualized fracture risk. Your doctor might recommend alternative osteoporosis medications during any break to prevent rapid bone loss. When Prolia is discontinued, another antiresorptive medication (like a bisphosphonate) is often prescribed to maintain bone density, as denosumab should not be stopped abruptly, given its reversible mechanism of action 1.

Some key considerations for taking a holiday off Prolia include:

• The timing of the break, which would depend on your last injection, as Prolia is typically given every 6 months
• The need for careful planning with your doctor to minimize the risk of rebound bone loss and increased fracture risk
• The potential for alternative osteoporosis medications to be prescribed during the break
• The importance of individualizing the decision to pause treatment based on your fracture risk, treatment history, and specific medical circumstances
• The need to avoid invasive dental procedures during therapy if possible, and to receive a comprehensive dental examination and appropriate preventive dentistry before bone-modifying therapy 1.

Never stop Prolia without medical guidance, as the medication's effects on bone remodeling can lead to significant bone density loss within months of missing a scheduled dose. It is essential to weigh the benefits and risks of taking a break from Prolia and to make an informed decision with your healthcare provider.

From the FDA Drug Label

Advise patients not to interrupt Prolia therapy without talking to their physician [see Warnings and Precautions (5. 6)]. The FDA drug label does not provide specific guidance on when to take a holiday off Prolia. However, it advises patients not to interrupt Prolia therapy without talking to their physician. If a dose of Prolia is missed, the injection should be administered as soon as convenient, and thereafter, schedule injections every 6 months from the date of the last injection 2.

From the Research

Holiday Duration for Prolia (Denosumab)

• The optimal duration of a "drug holiday" from denosumab has not been established, but existing data suggest that a decision to discontinue therapy should be based on regular reassessment of bone mineral density and fracture risk 3.
• For patients considered at high fracture risk, denosumab therapy should either be continued for up to 10 years or switched to an alternative treatment 3.
• For patients at low risk, a decision to discontinue denosumab could be made after 5 years, but bisphosphonate therapy should be considered to reduce or prevent the rebound increase in bone turnover 3.

Comparison with Bisphosphonates

• Denosumab increased bone mineral density (BMD) more than bisphosphonates at 12 and 24 months at the lumbar spine, total hip, and femoral neck 4.
• There was no difference in fracture end point at 12 months, but denosumab had a lower osteoporotic fracture incidence than alendronate at 24 months 4.
• The optimal length of a "drug holiday" for bisphosphonates has been suggested to be up to 5 years with alendronate, 3 years with zoledronate, and 1 year with risedronate 5, 6.

Considerations for Discontinuation

• Discontinuation of denosumab may lead to an increased risk of multiple vertebral fractures due to a rebound increase in bone resorption 3.
• Clinicians and patients should be aware of this potential risk, and a re-evaluation should be performed after 5 years of denosumab treatment 3.
• Bisphosphonate therapy should be considered after discontinuation of denosumab to reduce or prevent the rebound increase in bone turnover, although the optimal bisphosphonate regimen post-denosumab is currently unknown 3.