What is the best course of action to reduce fracture risk in a patient with a rising FRAX hip score after a drug holiday?

From the Guidelines

The best course of action to reduce fracture risk in a patient with a rising FRAX hip score after a drug holiday is to resume osteoporosis therapy, specifically restarting the previously effective antiresorptive medication, such as alendronate 70mg weekly, risedronate 35mg weekly, or zoledronic acid 5mg IV annually, as recommended by the American College of Physicians 1.

Key Considerations

• The patient's rising FRAX hip score from 3.2% to 3.5% indicates an increased fracture risk, suggesting the residual protective effect of the previous treatment is waning.
• According to the EULAR/EFORT recommendations, pharmacological treatment should preferably use drugs that have been demonstrated to reduce the risk of vertebral, non-vertebral, and hip fractures, and should be regularly monitored for tolerance and adherence 1.
• Alendronate and risedronate are first-choice agents due to their tolerability, low cost, and extensive clinical experience, while zoledronic acid and denosumab are alternatives for patients with oral intolerance or other specific needs.

Treatment Approach

• Ensure adequate calcium intake (1000-1200mg daily) and vitamin D supplementation (800-1000 IU daily) to support bone health.
• For patients with very high fracture risk, consider switching to a more potent agent like denosumab or an anabolic agent such as teriparatide or romosozumab.
• The decision to resume therapy should be individualized based on the patient's current bone mineral density, fracture history, and risk factors, with regular follow-up to monitor treatment efficacy and potential side effects 1.

From the FDA Drug Label

Use of teriparatide for more than 2 years during a patient's lifetime should only be considered if a patient remains at or has returned to having a high risk for fracture In the Three-Year Study of FIT, fractures of the hip occurred in 22 (2.2%) of 1005 patients on placebo and 11 (1.1%) of 1022 patients on alendronate sodium, p=0.047. The best course of action to reduce fracture risk in a patient with a rising FRAX hip score after a drug holiday is to consider restarting or initiating osteoporosis treatment, such as alendronate, as it has been shown to reduce the incidence of hip fractures by 51% in patients with a history of vertebral fracture 2.

• Key considerations:
  • The patient's increased FRAX hip score indicates a higher risk for fracture.
  • The use of teriparatide for more than 2 years should only be considered if the patient remains at high risk for fracture 3.
  • Alendronate has been shown to reduce the incidence of hip fractures in patients with osteoporosis 2.

From the Research

FRAX Hip Score Increase After Drug Holiday

• The patient's FRAX hip score has increased from 3.2% to 3.5% after a 2-year drug holiday, indicating a rising fracture risk 4.
• This increase in FRAX score suggests that the patient's bone health has deteriorated during the drug holiday, making them more susceptible to fractures.

Treatment Options to Reduce Fracture Risk

• Antiresorptive drugs, such as bisphosphonates and denosumab, can increase bone mineral density and reduce the risk of vertebral, nonvertebral, and hip fractures in postmenopausal women with osteoporosis 5.
• Anabolic therapy with teriparatide has been shown to be superior to bisphosphonates in preventing vertebral and clinical fractures in postmenopausal women with vertebral fracture 5.
• The sclerostin antibody romosozumab has also been shown to increase bone mineral density and reduce the risk of vertebral and nonvertebral fractures in postmenopausal women with osteoporosis 5.

Considerations for Treatment Selection

• The selection of osteoporosis treatment should be individualized and based on factors such as underlying fracture risk, medical comorbidities, medication burden, and fracture risk reduction profiles 6.
• Polypharmacy is associated with worse adherence to pharmacologic therapy, and the treatment selection should take into account the patient's medication regimen 6.
• The use of fracture risk assessment tools, such as FRAX, can help inform treatment decisions and target treatment to those at high risk of fracture 4.

Adjusting FRAX Scores

• The FRAX score can be adjusted based on the dose of glucocorticoids, with higher doses associated with an increased risk of fracture 7.
• However, this adjustment is not directly relevant to the patient's current situation, as there is no mention of glucocorticoid use.

Vitamin D and Fracture Risk

• Serum 25-hydroxy-vitamin D levels have been shown to decrease during teriparatide treatment, but the fracture risk reduction with teriparatide versus risedronate did not significantly differ between patients with sufficient or insufficient 25(OH)D levels at baseline 8.