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PubMed This is a summary of 14 peer-reviewed journal articles Updated
Endocrinology

Drug Holidays and the Risks of Stopping Treatment

At a Glance

A drug holiday from osteoporosis medication may be safe if you take bisphosphonates, as they stay in your bones for years. However, never stop taking denosumab (Prolia) without a transition plan, as it causes a dangerous rebound effect leading to rapid bone loss and spinal fractures.

Managing osteoporosis often involves long-term medication, and you may eventually hear the term “drug holiday.” While the idea of taking a break from medication sounds appealing, it is a clinical decision that must be made with extreme caution. The safety of a treatment break depends entirely on which medication you are taking and your individual risk level.

Bisphosphonates: The “Stay-In-Bone” Medications

Bisphosphonates, such as alendronate (Fosamax) or zoledronic acid (Reclast), work by binding to the surface of your bones. Because they stay “stuck” in the bone tissue for a long time, they continue to provide protection even after you stop taking them [1].

For patients whose bone density has stabilized through treatment and who are now at low-to-moderate risk of fracture, a doctor may consider a drug holiday:

  • Oral Bisphosphonates: Usually considered after 5 years of consistent treatment [1][2].
  • IV Bisphosphonates: Usually considered after 3 years of treatment [1][2].

During a holiday, your doctor will monitor you closely using DXA scans or blood tests called bone turnover markers (like CTX) to see if your bone loss is restarting [3][4]. If your bone density drops significantly, the “holiday” ends, and treatment begins again [4].

Denosumab (Prolia): The “No-Holiday” Medication

Unlike bisphosphonates, denosumab (Prolia) does not stay in your bones. It is a monoclonal antibody that circulates in your blood to block bone-breaking cells [5]. As soon as the drug leaves your system—usually about six months after your last injection—its protective effect disappears completely.

WARNING: Never stop denosumab without a medical transition plan. Stopping denosumab cold-turkey triggers a dangerous rebound effect [6]:

  1. Rapid Bone Loss: Your body experiences a sudden surge in bone-breaking activity, leading to a quick loss of all the bone density you gained while on the drug [6][7].
  2. Rebound Fractures: This surge significantly increases the risk of multiple vertebral (spinal) fractures, which can occur within just months of a missed dose [8][9]. About 1 in 14 patients who stop without a follow-up plan may experience these fractures [10].

The “Relay” Strategy

Because of the rebound risk, denosumab is increasingly viewed as a long-term commitment. If it must be stopped (for example, due to side effects), you cannot simply take a “holiday.” Instead, you must use a relay medication [8].

A relay involves transitioning to a bisphosphonate (like zoledronic acid) exactly when your next denosumab injection was scheduled to occur (usually 6 months after your last shot). This “catches” the bone before the rebound effect can start, locking in the gains you made and protecting your spine from sudden fractures [11][12].

Who Should Not Take a Holiday?

If you remain at very high risk for a fracture—meaning you have a very low T-score (below -3.0) or have had a recent fracture—a drug holiday is generally not recommended [13][14]. In these cases, osteoporosis is treated as a chronic condition that requires continuous management to keep your skeleton stable [13].

Common questions in this guide

Is it safe to take a drug holiday from my osteoporosis medication?
Whether it is safe depends on your medication and your individual fracture risk. Patients on bisphosphonates for 3 to 5 years with low-to-moderate risk may safely take a break. However, patients on denosumab or those at high risk for fractures should not take a drug holiday.
What happens if I stop taking Prolia (denosumab)?
Stopping Prolia without a medical transition plan triggers a dangerous rebound effect. Your body experiences a sudden surge in bone-breaking activity, which can lead to rapid bone loss and multiple spinal fractures within just a few months.
How do I safely stop taking Prolia?
To safely stop Prolia, you must use a 'relay strategy' managed by your doctor. This involves transitioning to a bisphosphonate exactly when your next Prolia injection was scheduled to occur in order to prevent sudden bone loss and protect your spine.
Will I lose bone density if I take a break from bisphosphonates?
Bisphosphonates like Fosamax and Reclast bind to your bones and continue to provide protection even after you stop taking them. During a drug holiday, your doctor will monitor your bone density with DXA scans or blood tests to ensure you are not losing bone.
What should I do if I miss a dose of my osteoporosis medication?
You should contact your doctor right away to discuss your options. Missing a dose of certain medications like Prolia by even a few weeks can leave your bones unprotected and trigger rapid bone loss.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.Is my current fracture risk low enough to safely consider a drug holiday from my bisphosphonate?
  2. 2.If we start a drug holiday, how often will we monitor my bone density (DXA) or bone turnover markers (like CTX) to ensure I am still protected?
  3. 3.Since I am on Prolia (denosumab), what is our exact plan if I ever need to stop this medication to avoid the 'rebound effect'?
  4. 4.Which 'relay medication' would you recommend to transition me off denosumab when the time comes?
  5. 5.If I miss a dose of my medication by even a few weeks, what should I do immediately to protect my bones?

Questions For You

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References

References (14)
  1. 1

    "Holidays" for osteoporosis drugs: A case-based approach.

    Anagnostis P, Paschou SA, Kenanidis E, et al.

    Case reports in women's health 2019; (23()):e00127 doi:10.1016/j.crwh.2019.e00127.

    PMID: 31431887
  2. 2

    Clinical Practice. Postmenopausal Osteoporosis.

    Black DM, Rosen CJ

    The New England journal of medicine 2016; (374(3)):254-62 doi:10.1056/NEJMcp1513724.

    PMID: 26789873
  3. 3

    Can bone turnover markers help to define the suitability and duration of bisphosphonate drug holidays?

    Statham L, Abdy S, Aspray TJ

    Drugs in context 2020; (9()) doi:10.7573/dic.2020-1-3.

    PMID: 32426015
  4. 4

    To repeat or not to repeat? Measuring bone mineral density during anti-resorptive therapy or a drug holiday.

    Khan TS, Sinha P, Rosen H

    Cleveland Clinic journal of medicine 2023; (90(3)):173-180 doi:10.3949/ccjm.90a.22071.

    PMID: 36858618
  5. 5

    Updated guidelines in the treatment of myeloma bone disease in 2025: consensus statement by the Medical and Scientific Advisory Group of Australia (MSAG) to Myeloma Australia.

    Yong A, Vandyke K, Augustson B, et al.

    Expert review of hematology 2026; (19(2)):133-142 doi:10.1080/17474086.2025.2574716.

    PMID: 41082262
  6. 6

    Effects of denosumab treatment on the expression of receptor activator of nuclear kappa-B ligand (RANKL) and TNF-receptor TNFRSF9 after total hip arthroplasty-results from a randomized placebo-controlled clinical trial.

    Sköld C, Kultima K, Freyhult E, et al.

    Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA 2022; (33(9)):1-8 doi:10.1007/s00198-022-06423-w.

    PMID: 35608639
  7. 7

    Significant bone loss after stopping long-term denosumab treatment: a post FREEDOM study.

    Zanchetta MB, Boailchuk J, Massari F, et al.

    Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA 2018; (29(1)):41-47 doi:10.1007/s00198-017-4242-6.

    PMID: 28975362
  8. 8

    Stopping Denosumab.

    Lamy O, Stoll D, Aubry-Rozier B, Rodriguez EG

    Current osteoporosis reports 2019; (17(1)):8-15 doi:10.1007/s11914-019-00502-4.

    PMID: 30659428
  9. 9

    Denosumab: A Review in Postmenopausal Osteoporosis.

    Deeks ED

    Drugs & aging 2018; (35(2)):163-173 doi:10.1007/s40266-018-0525-7.

    PMID: 29435849
  10. 10

    Prevention and Management of Denosumab Discontinuation Rebound Fractures.

    Jain S

    Endocrinology and metabolism clinics of North America 2024; (53(4)):559-583 doi:10.1016/j.ecl.2024.08.002.

    PMID: 39448137
  11. 11

    Vertebral Fractures After Discontinuation of Denosumab: A Post Hoc Analysis of the Randomized Placebo-Controlled FREEDOM Trial and Its Extension.

    Cummings SR, Ferrari S, Eastell R, et al.

    Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 2018; (33(2)):190-198 doi:10.1002/jbmr.3337.

    PMID: 29105841
  12. 12

    [Multiple Vertebral Fractures after Denosumab Discontinuation: How to Avoid Them?]

    Lamy O, Gonzalez Rodriguez E, Stoll D, et al.

    Praxis 2018; (107(12)):649-654 doi:10.1024/1661-8157/a002997.

    PMID: 29871576
  13. 13

    Fracture risk following intermission of osteoporosis therapy.

    Dennison EM, Cooper C, Kanis JA, et al.

    Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA 2019; (30(9)):1733-1743 doi:10.1007/s00198-019-05002-w.

    PMID: 31175404
  14. 14

    Bisphosphonate drug holidays.

    Nayak S, Greenspan SL

    Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA 2019; (30(12)):2525 doi:10.1007/s00198-019-05107-2.

    PMID: 31616961

This page is for informational purposes only and does not replace professional medical advice. Never stop or delay your osteoporosis medication without first consulting your prescribing physician.

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