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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.

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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?

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.