Prolia: Suppressing Bone Resorption
Osteoporosis medications can be confusing. It can feel overwhelming to understand why a medication is being recommended for you, weigh the pros and cons, and decide whether taking it is the right choice.
One question that I think you need to ask before starting any osteoporosis medication is this:
“How do I come off of it?”
This isn’t a question you need for most medications. But it is essential when starting treatment for osteopenia or osteoporosis.
Why?
Because some medications — like Prolia — cannot be stopped abruptly without a plan in place to avoid rebound bone loss.
What Is Prolia (Denosumab), and How Does It Work?
Prolia (generic name: denosumab) is an osteoporosis medication approved in 2010. Unlike bisphosphonates, it does not bind to bone. Instead, Prolia works by interfering with a molecule called RANKL. When this protein is disrupted, your body has difficulty activating osteoclasts, the cells that break down bone.
When the RANKL protein isn’t able to do its job, fewer osteoclasts can form, and those that already exist become less active. The result?
Bone resorption slows down dramatically.
Here’s what this means for you:
Your bone density increases over time
Your fracture risk decreases
IMPORTANT TO KNOW - The effect lasts only as long as you continue taking Prolia
How Prolia is given:
Prolia is an injection you get every 6 months.
It is often prescribed to women who:
Have a high risk of fracture
Cannot tolerate oral bisphosphonates
Have significant bone density loss
Have mild to moderate kidney issues (Prolia is not cleared by your kidneys like bisphosphonates, and is maybe a better choice if you have kidney problems)
Prolia is very effective at suppressing bone breakdown. But, because it works differently from other medications, it requires a specific plan if/when you want to stop getting the injections.
How Long Do You Take Prolia?
Prolia is meant for long-term use. Unlike bisphosphonates, which may be taken for 3-5 years followed by a drug holiday, Prolia works only while it is in your system — and its effects wear off quickly if your injections are delayed or stopped.
Recommended schedule:
One injection every 6 months
No more than 7 months between doses (this is important)
Prolia begins losing its effect around the 6-month mark. If you wait too long between doses, bone breakdown increases rapidly, and bone density can drop faster than before you started the medication.
Why Prolia is a long-term medication
Prolia does not bind to bone the way bisphosphonates do.
This means:
There is no residual protection after you stop getting your injection
There is no ability to take a drug holiday
The medication works only while you continue the injections
Many women stay on Prolia for years — sometimes indefinitely — as long as it remains effective and side effects are minimal.
What Happens When You Stop Prolia (And Why This Matters)
If Prolia is stopped without starting another medication, several things can happen:
Rapid bone loss (within 12–24 months)
Increased risk of vertebral fractures, including multiple vertebral fractures occurring close together
This is called rebound bone loss. The medication is not the problem — the gap in treatment is.
Why this happens
Prolia suppresses osteoclast activity (remember, it interferes with RANKL) for about 6 months. When it wears off, your body briefly “overshoots,” and bone breakdown speeds up before going back to baseline. If you don’t do something to control this rebound, your bone density can drop quickly.
How to prevent rebound bone loss
If you stop taking Prolia (for any reason), you must transition to another antiresorptive medication to protect your bones.
This usually means:
A bisphosphonate
Zoledronic acid (Reclast) – one IV dose
Alendronate (Fosamax) – oral weekly dosing
These medications will most likely be started about 6 months after your last Prolia injection
This follow-up medication slows down bone breakdown again and helps maintain the bone you gained while on Prolia.
Key Takeaway
You can safely stop Prolia, but only with a transition plan in place.
It is not a medication you simply “come off” without a next step.
A note about dental work. It is important to let your dentist know you are on Prolia before scheduling any dental work. Your team will help time your medication around the dental work for the best outcome.
With the right follow-up medication, Prolia can safely and effectively reduce your fracture risk. I hope this overview helps you feel more prepared to discuss your options with your physician and make an informed decision.
And, if you have questions about how exercise fits into your medication plan, or how to safely build strength alongside these treatments, I’m always here to help you navigate it. Join my next Strong Women, Strong Bones Jumpstart to gain a solid base and get started.
Andrea Trombley PT
One more thing…… I encourage you to watch this 4-minute video from the Kendler study, Denosumab in the Treatment of Osteoporosis: 10 Years Later: A Narrative Review, cited below, if you are starting Prolia or any of the newly approved Denosumab medications.
References
Bone HG, Wagman RB, Brandi ML, Brown JP, Chapurlat R, Cummings SR, Czerwiński E, Fahrleitner-Pammer A, Kendler DL, Lippuner K, Reginster JY, Roux C, Malouf J, Bradley MN, Daizadeh NS, Wang A, Dakin P, Pannacciulli N, Dempster DW, Papapoulos S. 10 years of denosumab treatment in postmenopausal women with osteoporosis: results from the phase 3 randomised FREEDOM trial and open-label extension. Lancet Diabetes Endocrinol. 2017 Jul;5(7):513-523. doi: 10.1016/S2213-8587(17)30138-9. Epub 2017 May 22. PMID: 28546097.
Cummings SR, Ferrari S, Eastell R, Gilchrist N, Jensen JB, McClung M, Roux C, Törring O, Valter I, Wang AT, Brown JP. Vertebral Fractures After Discontinuation of Denosumab: A Post Hoc Analysis of the Randomized Placebo-Controlled FREEDOM Trial and Its Extension. J Bone Miner Res. 2018 Feb;33(2):190-198. doi: 10.1002/jbmr.3337. Epub 2017 Nov 22. PMID: 29105841.
Drugs.com. Denosumab. https://www.drugs.com/denosumab.html
Kendler DL, Cosman F, Stad RK, Ferrari S. Denosumab in the Treatment of Osteoporosis: 10 Years Later: A Narrative Review. Adv Ther. 2022 Jan;39(1):58-74. doi: 10.1007/s12325-021-01936-y. Epub 2021 Nov 11. PMID: 34762286; PMCID: PMC8799550.
Ono T, Hayashi M, Sasaki F, Nakashima T. RANKL biology: bone metabolism, the immune system, and beyond. Inflamm Regen. 2020 Feb 7;40:2. doi: 10.1186/s41232-019-0111-3. PMID: 32047573; PMCID: PMC7006158.
Ouyang H, Yang F, Wei W, Wang W. Effectiveness of Sequential Treatment with Zoledronic Acid Following Discontinuation of Denosumab in Osteoporosis: A Narrative Review. Drug Des Devel Ther. 2025 Nov 9;19:10013-10031. doi: 10.2147/DDDT.S549062. PMID: 41244713; PMCID: PMC12615142.