When to take a holiday off bisphosphonates (bone resorption inhibitors)?

From the Guidelines

Bisphosphonate treatment should be stopped after 5 years unless the patient has a strong indication for treatment continuation. This recommendation is based on the current evidence suggesting that increasing the duration of bisphosphonate therapy to longer than 3 to 5 years reduces risk for new vertebral fractures but not risk for other fractures, while also increasing the risk for long-term harms 1.

When considering a holiday from bisphosphonates, several factors should be taken into account, including:

• The patient's baseline risk for fracture, which should be assessed based on individualized evaluation of bone density, history of fractures, response to prior treatments for osteoporosis, and multiple risk factors for fractures 1
• The patient's adherence to recommended treatments and healthy lifestyle modifications, including exercise, and counseling for evaluation and prevention of falls 1
• Adequate calcium and vitamin D intake, which should be part of fracture prevention in all adults with low bone mass or osteoporosis 1

In general, a bisphosphonate holiday may be considered after 3-5 years of therapy, with the duration of the holiday period varying depending on the type of bisphosphonate and the patient's fracture risk. During this period, bone mineral density and fracture risk should be reassessed, and treatment should be resumed if bone mineral density significantly decreases, fracture occurs, or fracture risk increases. However, the most recent and highest quality study suggests that the primary consideration should be to stop treatment after 5 years unless there is a strong indication for continuation 1.

Key considerations for clinicians include:

• Prescribing generic medications whenever possible to reduce costs
• Encouraging adherence to recommended treatments and healthy lifestyle modifications
• Assessing baseline risk for fracture and monitoring for changes in risk during the holiday period
• Being aware of the potential for long-term harms associated with bisphosphonate therapy, such as atypical femur fractures and osteonecrosis of the jaw 1

From the Research

Duration of Bisphosphonate Drug Holidays

• The recommended duration of a drug holiday from bisphosphonates varies, but most studies suggest 2 to 3 years for most patients after long-term bisphosphonate therapy 2, 3.
• The decision to take a holiday from bisphosphonates should be based on individual patient factors, including total bisphosphonate exposure, type of bisphosphonate used, bone mineral density, falls risk, and patient sex and body weight 2.
• For patients at high risk of fracture, continuation of treatment for up to 10 years (oral) or 6 years (intravenous) may be considered, with periodic evaluation 3.
• A drug holiday can be considered in many patients, although high-risk patients may benefit from continued bisphosphonate therapy 4, 5.

Factors Influencing Drug Holiday Duration

• Total bisphosphonate exposure: patients with higher cumulative exposure to bisphosphonates may require longer drug holidays 2.
• Type of bisphosphonate used: different bisphosphonates have varying durations of action and may require different drug holiday durations 2, 6.
• Bone mineral density and falls risk: patients with lower bone mineral density or higher falls risk may require longer treatment durations or shorter drug holidays 2, 3.
• Patient sex and body weight: these factors may influence the duration of bisphosphonate effects and the risk of adverse events 2.

Risks and Benefits of Bisphosphonate Therapy

• Bisphosphonates have demonstrated antifracture efficacy in randomized, placebo-controlled trials, but rare side effects such as atypical femoral fractures and osteonecrosis of the jaw have been reported 6, 3.
• The benefits of bisphosphonate therapy outweigh the risks for most patients, but individual patient factors should be considered when making treatment decisions 5.