What is minimum period of Alendronate to minimise Prolia rebound?

Posted by surefire @surefire, Jan 14 8:33am

I started on Prolia in July 2022 on advice from my doctor that the treatment would be for only 4-5 years and thereafter I could stop. I have taken 3 Prolia injections, the last one in July 2023.

Before my 4th injection in Jan 2024, I started doing a lot of reading and decided that I do not want to be on any osteoporosis drug at all. So, instead of taking my 4th Prolia injection and to minimise the rebound effect from stopping Prolia, I started on a weekly dose of Alendronate.

However, I am really not comfortable taking Alendronate as well and would like to seek any advice/opinion on whether I am stuck with taking Alendronate for the next 6, 12 or even 24 months.

What is the shortest period I can be on Alendronate? Or should I just risk the rebound effect and stop my Alendronate now (I have taken 3 weekly doses so far)?

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@ans

@surefire - Sounds like it's going pretty well with Alendronate , but I will share that when I spoke with Dr. McCormick, because I have had in my past some Gerd issues, he said Actonel would probably be a better rebound drug for me, if I was resistant to take Reclast. good luck!!

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Thanks for sharing! I know that, of the 4 main biphosponates, Dr McCormick's least favoured is Boniva (Ibandronate). Alendronate may aggravate GERD issues so it's out of consideration. I wonder, if you didn't have any GERD issues, which biphosponate would Dr McCormick prescribe as a relay drug?

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@surefire

Yes, I have read that article, thanks. These 2 youtube videos will also be helpful:



From my research, you are likely on the right track as you have only taken 2 shots of Prolia. Dr McCormack in his youtube interview was of the opinion that Reclast would be necessary as a relay drug once you have taken 3 or more shots of Prolia but I have read elsewhere that Alendronate can be used too for up to 2 years of Prolia.

How long have you been on Alendronate and have you had any side-effects?

I know the standard instruction is to keep upright and not eat for 30 mins after Alendronate but I prefer to be cautious and usually do not eat until at least 1.5 to 2 hrs after. Also, I read that during the 30 minutes after taking the tablet, you should drink at least 2 oz of water

On the recommended time-frame for the step-down, I have seen from as low as 6 months to up to 2 years. I think if you can get BTM tests done regularly, they could help give guidance on the best time to stop your Alendronate - this is something I need to explore with my doctor too. Do you have any baseline BTMs to compare with?

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Thanx for the UTube cites. I have a high regard for Cleveland CLinic, but have no idea who this other guy might be. In any event, my own preference for learning is the written word.....I do not absorb info as well when it is given in lecture form. And especially when it is in science-speak.

Nonetheless, these videos have given me some ideas about discussing whether to continue or stop the Alendronate after one year when I see my doctor about it next May.

I too failed to do sufficient research about Prolia before beginning it. I am retired and travel a lot....precise timing of Prolia injection was my biggest concern initially and for that reason alone, Prolia was not a good fit. Of course I was not told anything about the need for exit strategies which would likely have made me more hesitant to start it. Nor told that my DEXA score might not even be low enough to warrant Prolia or that bone-building meds might also be an option...the doctor was simply concerned with how long I had been on Alendronate, never mentioning a possible drug holiday because my DEXA scan put me into osteoporosis territory, (FYI: the doctor who first prescribed Alendronate was a very good doctor of mine for 25 years....my understanding is that he hoped to keep me from slipping into OP after my ovarian cancer treatment eliminated any sliver of natural estrogen production.)

In retrospect, I personally feel that the Prolia recommendation may have been driven by insurance guidelines more than by good medicine. Are you Medicare eligible?

I had no side effects with either Prolia or Alendronate, either pre-Prolia or post.

I hope there is a typo in your post about taking only 2 oz of water after the alendronate. The instructions that came with my meds direct 8oz of water before the med and another 8oz after the med. That may be difficult for some people but not for me as I am familiar with hydrating because I play tennis primarily in hot weather.

As to your concern about the present usefulness of BTM tests if there is no baseline, I too have never had either of these tests. However, there is a reference in the NIH survey material that a European medical society recommends absolute values for both CTX and PNIP in determining 'adequate response' to whatever post-Prolia med is taken.

I will certainly also be taking this up with my doctor in May....of course there was also never any mention about these tests in determining possible treatment options.

You seem very concerned about your situation because you took 3 Prolia injections before transitioning to alendronate at the time when the 4th Prolia was due. I do not see how that is so different from my situation after only 2 Prolia injections. It seems that Prolia's effectiveness is not cumulative and that that is why there is not a lot of flexibility about the timing of each injection. Or am I missing something?

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@rjd

Thanx for the UTube cites. I have a high regard for Cleveland CLinic, but have no idea who this other guy might be. In any event, my own preference for learning is the written word.....I do not absorb info as well when it is given in lecture form. And especially when it is in science-speak.

Nonetheless, these videos have given me some ideas about discussing whether to continue or stop the Alendronate after one year when I see my doctor about it next May.

I too failed to do sufficient research about Prolia before beginning it. I am retired and travel a lot....precise timing of Prolia injection was my biggest concern initially and for that reason alone, Prolia was not a good fit. Of course I was not told anything about the need for exit strategies which would likely have made me more hesitant to start it. Nor told that my DEXA score might not even be low enough to warrant Prolia or that bone-building meds might also be an option...the doctor was simply concerned with how long I had been on Alendronate, never mentioning a possible drug holiday because my DEXA scan put me into osteoporosis territory, (FYI: the doctor who first prescribed Alendronate was a very good doctor of mine for 25 years....my understanding is that he hoped to keep me from slipping into OP after my ovarian cancer treatment eliminated any sliver of natural estrogen production.)

In retrospect, I personally feel that the Prolia recommendation may have been driven by insurance guidelines more than by good medicine. Are you Medicare eligible?

I had no side effects with either Prolia or Alendronate, either pre-Prolia or post.

I hope there is a typo in your post about taking only 2 oz of water after the alendronate. The instructions that came with my meds direct 8oz of water before the med and another 8oz after the med. That may be difficult for some people but not for me as I am familiar with hydrating because I play tennis primarily in hot weather.

As to your concern about the present usefulness of BTM tests if there is no baseline, I too have never had either of these tests. However, there is a reference in the NIH survey material that a European medical society recommends absolute values for both CTX and PNIP in determining 'adequate response' to whatever post-Prolia med is taken.

I will certainly also be taking this up with my doctor in May....of course there was also never any mention about these tests in determining possible treatment options.

You seem very concerned about your situation because you took 3 Prolia injections before transitioning to alendronate at the time when the 4th Prolia was due. I do not see how that is so different from my situation after only 2 Prolia injections. It seems that Prolia's effectiveness is not cumulative and that that is why there is not a lot of flexibility about the timing of each injection. Or am I missing something?

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I believe my doctor was not even aware of the need for an exit plan for Prolia as he had assured me that I could switch to oral biphosphonates at any time

My concern with the transition is that the longer one is on Prolia, the harder it is to mitigate the rebound effect. Don't quote me on this but if I remember correctly, Prolia works differently from Alendronate. Unlike Alendronate which kills the osteoclasts (the ones that break down bones), Prolia only puts them into a state of suspension. The longer you are on Prolia, the more of such "suspended osteoclasts" accumulate and once you stop Prolia, the brakes are taken off and these osteoclasts come back with a vengence!

Once you are on Prolia for 2 or more years, Alendronate may not be sufficient and you may need a stronger anti-resorptive like Reclast. And if you are on Prolia for even longer say, 7 years, it may not even be possible to prevent the rebound effect. So basically you would be stuck on Prolia for life which is worrying given that there is safety data for only 10 years

On the liquid intake for Alendronate, it's not a typo. My understanding is that you need to take the tablet with 6-8 oz of water. Other than that, there is no mention of further liquid intake in my Alendronate leaflet. The recommendation for the additional 2oz of water during the 30 min fasting period was in some other material I came across. I have not read anything about needing to take 8+8 oz of water but there certainly wouldn't be any harm (and probably a lot of benefit) in doing that

Oh, do you have the link for the NIH study that mentioned absolute values for BTMs? I have only come across 1 article which states that, if no baseline BTMs are available then we should target the lower half of the relevant reference range (not very helpful as I understand the reference range is very large) - see link below:
https://www.ccjm.org/content/90/1/26

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@surefire

Thanks for sharing! I know that, of the 4 main biphosponates, Dr McCormick's least favoured is Boniva (Ibandronate). Alendronate may aggravate GERD issues so it's out of consideration. I wonder, if you didn't have any GERD issues, which biphosponate would Dr McCormick prescribe as a relay drug?

Jump to this post

@surefire - well, before I told him of my history of some GERD issues he had said my follow up drug would be Alendronate (Fosamax ) . That is what he took as his follow up drug after Forteo. He took Forteo for 2 yrs and Alendronate for one . Hope that helps !!!

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@ans

@surefire - well, before I told him of my history of some GERD issues he had said my follow up drug would be Alendronate (Fosamax ) . That is what he took as his follow up drug after Forteo. He took Forteo for 2 yrs and Alendronate for one . Hope that helps !!!

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Thank you, that was very helpful.

I wonder if you can share how many doses of Prolia you took before transitioning to Actonel? Also, did Dr McCormick mention how long you need to take Actonel or is he suggesting using something like BTM readings to determine the right time to stop? Thank you and best wishes for your good health

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@surefire

Thank you, that was very helpful.

I wonder if you can share how many doses of Prolia you took before transitioning to Actonel? Also, did Dr McCormick mention how long you need to take Actonel or is he suggesting using something like BTM readings to determine the right time to stop? Thank you and best wishes for your good health

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@surefire - I actually haven’t taken any drugs for osteoporosis to date . When I met to see what path McCormick felt was viable for me that’s what he recommended. Forteo 2 years , mostly likely Actonel for 1 year. I think he may have first said Reclast as follow up and I said I was a bit leery of that med, then he offered Fosamax , but when I mentioned a bit of GERD history he said Actonel would be better. Though I have read that Actonel can be a bit reactive if you have GERD. I also told him I my goal was NOT to be meds forever/ long term. And his response was you could do what I did 2 years Forteo , followed by one year Actonel as a substitute for Fosamax ( which he did).Hope that clears it up. I mean I could probably try Reclast. The thing that scares me is it’s obviously a big dose since it covers soo much time before the next dose. If you have issues, in my mind , you’re kind of stuck there with just hope that it decreases overtime.
But I understand it is a more potent maintainer. Good luck to you and all out there making these decisions!!!

REPLY
@surefire

I believe my doctor was not even aware of the need for an exit plan for Prolia as he had assured me that I could switch to oral biphosphonates at any time

My concern with the transition is that the longer one is on Prolia, the harder it is to mitigate the rebound effect. Don't quote me on this but if I remember correctly, Prolia works differently from Alendronate. Unlike Alendronate which kills the osteoclasts (the ones that break down bones), Prolia only puts them into a state of suspension. The longer you are on Prolia, the more of such "suspended osteoclasts" accumulate and once you stop Prolia, the brakes are taken off and these osteoclasts come back with a vengence!

Once you are on Prolia for 2 or more years, Alendronate may not be sufficient and you may need a stronger anti-resorptive like Reclast. And if you are on Prolia for even longer say, 7 years, it may not even be possible to prevent the rebound effect. So basically you would be stuck on Prolia for life which is worrying given that there is safety data for only 10 years

On the liquid intake for Alendronate, it's not a typo. My understanding is that you need to take the tablet with 6-8 oz of water. Other than that, there is no mention of further liquid intake in my Alendronate leaflet. The recommendation for the additional 2oz of water during the 30 min fasting period was in some other material I came across. I have not read anything about needing to take 8+8 oz of water but there certainly wouldn't be any harm (and probably a lot of benefit) in doing that

Oh, do you have the link for the NIH study that mentioned absolute values for BTMs? I have only come across 1 article which states that, if no baseline BTMs are available then we should target the lower half of the relevant reference range (not very helpful as I understand the reference range is very large) - see link below:
https://www.ccjm.org/content/90/1/26

Jump to this post

The link to the NIH survey was the one I gave you previously and you indicated you already had that essay.

The following is quoted from a portion of that publication , summarizing what various countries are recommending. It is the last sentence that provide BTM targets for 'an adequate response'

"The European Calcified Tissue Society (ECTS) provided the most updated guidance on the issue. Guidance for denosumab discontinuation is stratified according to the duration of use and individual fracture risk [39]. Individuals with high fracture risk treated with denosumab for more than 2.5 years should continue denosumab for up to 10 years or alternatively switch to zoledronic acid starting 6 months after the last denosumab injection and monitor BTMs 3 and 6 months later, and a repeat dose should be considered if BTMs are persistently elevated. Alternatively, zoledronic acid should be given at 6 and 12 months after the last denosumab injection if BTMs are not available. Oral bisphosphonates for 12 to 24 months can be used in place of zoledronic acid. Conversely, individuals with low fracture risk treated with denosumab for less than 2.5 years may be switched to 1 to 2 years of oral bisphosphonates or zoledronic acid with close monitoring of BTMs and BMD. BTM targets of CTX < 280 ng/L or P1NP < 35 µg/L were specified as targets for an adequate response."

Hope you find this helpful.

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@ans

@surefire - I actually haven’t taken any drugs for osteoporosis to date . When I met to see what path McCormick felt was viable for me that’s what he recommended. Forteo 2 years , mostly likely Actonel for 1 year. I think he may have first said Reclast as follow up and I said I was a bit leery of that med, then he offered Fosamax , but when I mentioned a bit of GERD history he said Actonel would be better. Though I have read that Actonel can be a bit reactive if you have GERD. I also told him I my goal was NOT to be meds forever/ long term. And his response was you could do what I did 2 years Forteo , followed by one year Actonel as a substitute for Fosamax ( which he did).Hope that clears it up. I mean I could probably try Reclast. The thing that scares me is it’s obviously a big dose since it covers soo much time before the next dose. If you have issues, in my mind , you’re kind of stuck there with just hope that it decreases overtime.
But I understand it is a more potent maintainer. Good luck to you and all out there making these decisions!!!

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Thank you for responding and clarifying. I wish i had done what you are doing now - researching your options before commiting - as i would never have started on Prolia at all and would have put in more effort on a non-drug treatment.

Anabolics like Forteo and Tymlos seem like a more logical choice to me as initial treatment as anti-resorptives only keep old bones and not build new bones. And while Dexa scans may show positive results with anti-resorptives, there's concern that the denser bones may actually be more brittle.

Anabolics do also come with side-effects and risks so ultimately it's a risk-benefit assessment. I also completely agree with you on your thoughts on Reclast

Good luck and best wishes!

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@rjd

The link to the NIH survey was the one I gave you previously and you indicated you already had that essay.

The following is quoted from a portion of that publication , summarizing what various countries are recommending. It is the last sentence that provide BTM targets for 'an adequate response'

"The European Calcified Tissue Society (ECTS) provided the most updated guidance on the issue. Guidance for denosumab discontinuation is stratified according to the duration of use and individual fracture risk [39]. Individuals with high fracture risk treated with denosumab for more than 2.5 years should continue denosumab for up to 10 years or alternatively switch to zoledronic acid starting 6 months after the last denosumab injection and monitor BTMs 3 and 6 months later, and a repeat dose should be considered if BTMs are persistently elevated. Alternatively, zoledronic acid should be given at 6 and 12 months after the last denosumab injection if BTMs are not available. Oral bisphosphonates for 12 to 24 months can be used in place of zoledronic acid. Conversely, individuals with low fracture risk treated with denosumab for less than 2.5 years may be switched to 1 to 2 years of oral bisphosphonates or zoledronic acid with close monitoring of BTMs and BMD. BTM targets of CTX < 280 ng/L or P1NP < 35 µg/L were specified as targets for an adequate response."

Hope you find this helpful.

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Thank you for your response.

I came across the following study which touches on the same subject:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4162466/
Following is an extract from the article:
"The lower part of the premenopausal reference intervals have been previously proposed as a target for treatment. This range was 0.05–0.19 ng ml−1 for CTX, 15.0–38.1 nmol bone collagen equivalent (BCE) per mmol Cr for NTX, 4.2–30.1 ng ml−1 for PINP, 5.2–9.8 ng ml−1 for bone ALP and 8.8–17.9 for osteocalcin."

The units used are a bit different from those in your reference so will have to try to reconcile the numbers

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@proliamistake

the rebound effect from prolia is compression fractures and more unfortunately you just ca;t stop prolia without taking something read up on prolia and you will see. what else you can take i really do not know but it would be nice if the drs knew. i had a severe reaaction to my 1st shot of prolia and when i asked my dr what do i do he said i don't know made me feel real happy i have posted mu ordeal with prolia which has been horrible after not taking another shot i had 2 compression fractures since and for dome reason developed ra can't tell you why because no one knows but i can say before prolia i was relatively pretty healthy. my ra dr did say it could be possible the prolia caused the ra but he said we will never know i posted under prolia mistake and boy what a mistake it was i now have a little high glucose reading from the medication so i could get diabetes and the list just goes on and on very depressing to say the least i see no light at the end of this tunnel just more heartache and pain

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Just read your post from January re: Prolia reactions. I too was talked into Prolia by 3 Doctors-giving me scare tactics that I would have fractures and need my bones cemented back. TERRIBLE!! I am entering my 5 th month of Prolia with tons of side effects-namely flu like symptoms for one week after initial dose, cracking of joints doing yoga, bleeding inflamed gums (Which I NEVER HAD) water retention and the list goes on and on BUT most importantly I was NEVER informed that I could not go off Prolia cold turkey. At least I only have one injection but that too I can have spinal fractures. I am in exceptional physical shape-75 -exercise about 14 hours a week and my readings are not horrible--2.9 is the worst -everything about normal. Shame on the Doctors for not giving full disclosure of the side effects and the rebound effect if not followed up with another shot. My Doc wants me to go on actonel after this. And by he way the Prolia injection is $2,400 a shot. Good money for all involved.

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