What to do if bone mineral density (BMD) decreases during a bisphosphonate (e.g. alendronate, risedronate) holiday?

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Last updated: June 18, 2025View editorial policy

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From the Guidelines

If bone mineral density decreases during a bisphosphonate holiday, consider restarting bisphosphonate therapy, especially if the decrease is significant or if the patient has developed a new fracture. The decision to restart therapy should be individualized and based on baseline risk for fractures, type of medication and its half-life in bone, benefits, and harms 1. For most patients, resuming the original bisphosphonate (alendronate 70mg weekly or risedronate 35mg weekly) is appropriate. Some key points to consider when deciding on the course of action include:

  • The patient's baseline risk for fractures
  • The type of medication and its half-life in bone
  • The benefits and harms of restarting therapy
  • The presence of any new fractures or significant decrease in bone mineral density Treatment should generally continue for another 3-5 years before reassessing for another potential holiday. In high-risk patients with multiple risk factors or previous fractures, consider adding or switching to a more potent agent such as zoledronic acid 5mg IV yearly or denosumab 60mg subcutaneously every 6 months 1. After restarting therapy, monitor BMD again in 1-2 years to ensure stabilization or improvement. The rationale for restarting therapy is that a significant BMD decrease during a holiday suggests the protective effects of the stored bisphosphonate in bone have diminished, and the patient's fracture risk is likely increasing. Bisphosphonates work by inhibiting osteoclast activity and reducing bone turnover, and resuming therapy will help restore this protective effect. Calcium (1000-1200mg daily) and vitamin D (800-1000 IU daily) supplementation should be continued throughout this process 1.

From the Research

BMD Decrease During Bisphosphonate Holiday

If bone mineral density (BMD) decreases during a bisphosphonate holiday, several factors should be considered:

  • The duration of the bisphosphonate holiday and the patient's fracture risk 2, 3
  • The type of bisphosphonate used and its pharmacokinetics 3
  • The patient's overall health and medical history 4, 5

Management Options

Management options for patients with decreasing BMD during a bisphosphonate holiday may include:

  • Re-initiation of bisphosphonate therapy, especially for patients at high risk of fracture 4, 2
  • Transition to a different osteoporosis treatment, such as denosumab, which has been shown to increase BMD and reduce bone turnover compared to monthly oral bisphosphonates 6
  • Close monitoring of BMD and fracture risk to determine the best course of treatment 3

Considerations for Bisphosphonate Holiday

When considering a bisphosphonate holiday, the following should be taken into account:

  • The benefits of continuing bisphosphonate therapy, including reduced fracture risk, may outweigh the risks for patients with high fracture risk 4, 2
  • The concept of a drug holiday is based on the idea that bisphosphonates continue to exert an antiresorptive effect for a period of time after dosing is discontinued, allowing for a temporary break in treatment while still maintaining some level of fracture protection 4, 3
  • The duration of the bisphosphonate holiday should be individualized based on the patient's fracture risk and the pharmacokinetics of the bisphosphonate used 3

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Long-term use of bisphosphonates in osteoporosis.

The Journal of clinical endocrinology and metabolism, 2010

Research

Denosumab significantly increases bone mineral density and reduces bone turnover compared with monthly oral ibandronate and risedronate in postmenopausal women who remained at higher risk for fracture despite previous suboptimal treatment with an oral bisphosphonate.

Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA, 2014

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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