Are we overdosing Reclast???

Posted by awfultruth @awfultruth, Sep 9 5:35pm

Note: I have posted this elsewhere in comments but I don't think it was widely seen so I'm posting this here as it's own discussion.

Now to the point, YES, I think Reclast is being overdosed and that the the large dose given once a year is probably responsible for a lot of the bad side effects some people experience.
There is strong evidence in studies that lower dosages and altered infusion schedules produce very similar results and in one case superior results to the standard 5 mg dose of Reclast.
It becomes clear from studying the papers below that the motivating factors behind the 5mg yearly dose is convenience, patient compliance, money and they claim the greater good for the most people. They do not consider intelligent individualized medicine. Nor do any of these papers report anything other than temporary discomfort as a side effect. None of them seriously consider that a lower dose might be safer.

Before I list the papers supporting my argument that lower doses could be effectively and safely used I want to mention that maybe severe long term side effects are rare events and don't merit this attention. The short term flu like etc reactions are acknowledged but long term life changing side effects don't seem to be well reported for Reclast. I do not know how often or in what percentage of Reclast users these occur. Some reports could be coincidence and not due to Reclast at all. I do not know how to determine how real the threat of long term serious consequences is. So, for the purposes of this post I'm considering the serious long lasting adverse side effects of standard dosing of Reclast to be real, of unknown frequency and something to consider and try to avoid.

Here are three papers showing lower doses work just as well.

The first one compares 3 different doses and shows that 1mg does well, 2.5mg does best and 5mg does ALMOST as well as 2.5 mg. All three were one dose with result at one year.
https://academic.oup.com/jcem/article/97/1/286/2833555...
The second one alters dosing schedules depending on dosage. Combined with the paper above this is great information. They used dosages as small as 0.25mg quarterly with the same result as the large annual dose. It's behind a paywall but you can get a free account and get three free articles a month.
https://www.nejm.org/doi/pdf/10.1056/NEJMoa011807...
The third one compares 2mg to 4mg and concludes that we should stick with 4mg. BUT, if you dig into the details you see that there is reason to rethink their conclusion. Yes there is a tiny advantage to 4mg in the spine BUT there is a tiny advantage to the femur neck and total hip for the 2mg. Hardly what would make me call the 4mg superior and certainly not a significant difference. The difference in the spine is between 2mg gains 4.86% and 4mg gains 5.35%. So a gain of about 5% with either dose. As I said it flips the other way with the hips but they do not consider that even though their study shows it.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8420937/
What also needs to be considered is how often we are dosing Reclast and how the annual dose for osteoporosis may be too frequent and may be putting people at unnecessary risk of long term side effects.
I wanted to list a fourth paper showing that Reclast doesn't usually need to be given annually. That it often lasts as an effective dose for 18-24 months. I'm almost certain I saw a paper on this but I cannot find it now. What would be best IMO is to monitor CTX and only give another infusion when the CTX reaches a level indicating bone turnover is speeding up too much.

Interested in more discussions like this? Go to the Osteoporosis & Bone Health Support Group.

windyshores | @windyshores | Sep 17 5:09pm

In reply to @normahorn "I can handle one dosage of my BP medication but an increase left me in trouble..." + (show)

@normahorn I have had the same experience with multiple meds. I am not saying that dose does not matter all the time, of course.

But I am puzzled that reducing doses on some osteoporosis meds seems to still leave me with such significant side effects. A few of us have wondered if there is an immune component.

By the way I have Klonopin for muscle relaxing. I can tolerate 1/4 thought it makes me sleepy. Imagine a full dose!

njhornung | @normahorn | Sep 17 6:50pm

In reply to @awfultruth "@normahorn hi there. I agree that sample size matters and that this is a smaller study..." + (show)

It seems to me they are pushing the limits of statistical comparison, especially with this being a small study. I would love to know what the results would be if they repeated the BMD readings on the day following the first ones. There is an error associated with each reading although they minimized that by using the same equipment and having only one radiologist for all readings.

Did you look at the graph of BMD over time? Especially look at the std dev limits shown. Side of the barn!!!!

awfultruth | @awfultruth | Sep 17 8:21pm

In reply to @normahorn "It seems to me they are pushing the limits of statistical comparison, especially with this being..." + (show)

@normahorn Hi again.
I take it that the 3rd study bothers you in that the number of patients involved may not be great enough to prove their conclusions. Adding to that we know that DXA's are not nearly as exact as we would like. So, I think I understand your general meaning.
As to what you are talking about specifically with the graph of BMD over time I'm not sure what exactly you mean. I might have to be standing next to you, with you pointing at a blow up of the chart to really get it? Maybe because the chart overwhelms me with numbers?

My biggest problem with the study is the authors interpretation of the data. In the third study the spine is a little better with high dose and the hips are a little better with the low dose. They do some statistical maneuvers I don't understand and declare the spine and the high dose the winner. That's what puts the burr under my saddle.
We both seem to be bothered by such a strong conclusion (high dose Reclast wins) when there are multiple reasons to question that or to at least point out how very little difference in saving bone there is between the two doses. Hope I didn't misconstrue your views. Correct me if I did.

njhornung | @normahorn | Sep 17 8:36pm

Parameters* 2 mg (n=31) 4 mg (n=33) P
Percentage change in LS-BMD 4.86±3.05 5.35±3.73

That translates into percent change of 1.81 to 7.91 for the 2 mg group
and 1.62 to 9.08 for the 4 mg group. And they claim the difference in average of 4.86 and 5.35 is significant. Maybe in the rigorous world of statistics but not in the real world of patients.

awfultruth | @awfultruth | Sep 17 8:54pm

In reply to @normahorn "Parameters* 2 mg (n=31) 4 mg (n=33) P Percentage change in LS-BMD 4.86±3.05 5.35±3.73 That translates..." + (show)

@normahorn I heartily agree! Thanks for clarifying further

windyshores | @windyshores | Sep 17 9:13pm

But we don't know the actual difference in side effects. There needs a way to quantify these: duration, severity. The number of participants who drop out of a study can be an indicator.

gravity3 | @gravity3 | Sep 18 1:07am

Great discussion. Thanks for posting

.very helpful

windyshores | @windyshores | Sep 18 6:13am

I am stopping at 2mg due to side effects, Mainly GI, also increased tinnitus which may calm down. Last time I had pins and needles in hands and feet but that did not recur. We'll see if my hip improves.

mayblin | @mayblin | Sep 18 8:55pm

In reply to @windyshores "I am stopping at 2mg due to side effects, Mainly GI, also increased tinnitus which may..." + (show)

Hi windy, did you have 1mg or 2mg at second infusion? Do you feel the side effects were more tolerable this time? Hope all is well and sending my best wishes!

windyshores | @windyshores | Sep 19 12:12am

In reply to @mayblin "Hi windy, did you have 1mg or 2mg at second infusion? Do you feel the side..." + (show)

I had 1 mg on the second infusion. I did not get a fever but, oddly, I felt sicker. That was the immediate reaction, for the first few days, that did not concern me.

I have a lot of health issues, many of them relevant to how my body reacts to Reclast: kidney disease, afib, lupus, possible scleroderma, GERD/reflux. asthma, neuropathy/paresthesias, "central" vertigo and migraine (from the brain), tinnitus etc. etc. I don't want anyone else to conclude that Reclast will be difficult for them.

Tymlos is the only medication I seem to be able to finish. Thank heavens the titration worked. The study posted about 2mg vs 4mg was reassuring though I would have done the full dose if I could.

I'll get a DEXA in April to see where I am though having several fractures the DEXA usefulness is limited.