Are we overdosing Reclast???

I think it is possible that doctors may play a little loose with protocol all the time. Perhaps in an effort to avoid the 'all size fits all' implicit with protocol?

This I learned during chemo for ovarian cancer. My highly regarded gyn onc adjusted dosages. He did not tell me about this until my side effects (peripheral neuropathy) showed that it was a 'nice try but no cigar' and he returned to protocol.

In our subsequent discussions, he indicated that he had judged that because I was in better physical condition (avid tennis player) at the age of 61 years than just about any other of his patients with a similar diagnosis, it was worth a try in light of the high fatality rate (70% in my case) of ovarian cancer. His concern about the neuropathy was how it would affect the quality of whatever life I might have for however long after treatment. The neuropathy slowly subsided.

I have been cancer-free for almost 13 years, still playing tennis and traveling, and believe that it is in large part due to the skill and experience-gained knowledge of this particular doctor. I have tried to do my part with diet and exercise.

Of course, the cancer limits my present choice of osteoporosis treatment....for example, hormones are not an option.

My bottom line? Protocols are important but not set in stone. It seems to me that, in partnership with a good and experienced practitioner, anyone in treatment is still part of trying to figure out what is best for their particular medical situation.

And that is why this forum is so valuable.

Yes. I agree about the one size fits all. I’m about 115 lbs and I am still suffering from horrible side effects of headaches and dizziness. I had the infusion on August 9. And I can’t take prednisone which my doctor recommended for this side effect. It only made it worse! My endocrinologist is still trying to figure out what to do for me. I’m just afraid that it’s not going to go away.

I would rather have a broken bone than this headache and dizziness because this interferes with my thought processes.

@windyshores and @normahorn and all of you responders, thanks for reading these papers and doing some thinking about dosing and side effects. It's encouraged me to dig into this again.
I started this discussion about Reclast dosing out of the excitement I had over finding three papers that shed light on fears those of us have on this and other osteoporosis forums. One of the biggest fears is: am I going to be one of those who have serious side effects with this drug. One of the biggest questions is: are there any ways to reduce the odds of getting those serious side effects?

Personally I have so far dodged the side effects but not the fears. I have had 11 Evenity shots with great success and no significant side effects. So I'm well aware that osteoporosis treatment with meds can go very well. Still, facing the next drug choice I'm once again afraid. Many of us are on this forum due to similar concerns.

The three papers I suggested all offer some valuable information for us. They were not written for the individual patient. They are not written or designed or executed from the concerned patient perspective. But they can be looked at from a concerned patient perspective. Our perspective on this forum I think.

The first two papers more obviously make my point that lower doses of Reclast are just as effective as higher doses. The third paper (2021) at first glance appears to support using a higher dose. I think under scrutiny it actually does the opposite. Consequently, I'm going to focus on the third paper which is the most problematic for my thesis.

The third paper suggests that 4 mg is better than 2 mg of Reclast therefore we should stick to the higher dose (note that standard is 5mg in the US). Ok, so they report that one dose produced a better result in the spine than the other and we're all done, end of discussion. But let's dig deeper and ask what can one see from the patient perspective.

The first thing I noticed (excitedly) when reading and rereading this paper was that the difference in increase in the lumbar spine of those on 4mg was only very slightly better than those on 2 mg. And that for the hip the lower dose was actually better by a larger margin than the larger dose was better for the spine. Sticking with the spine for the moment the difference in the increase in the spine is between 2mg gains 4.86% and 4mg gains 5.35%. So the higher dose increases by less than half a percent (0.46%) more than the lower dose. Or in practical speech you could say a gain of about 5% with either dose.

My immediate thought: you researchers are suggesting that one should double the dose of a very powerful drug in order to get that very slight improvement of a fraction of a percent? The authors of the paper did not say anything in reply to what I was screaming inside my head. They just were not thinking as a patient with real fears of powerful drugs. BTW they do not even discuss that little detail about the hip being better on the lower dose in the paper but you can see it in the charts and tables. Perhaps it was just too inconvenient for what they had decided to prove? So I provide that little bit of neglected data below.

I pulled the numbers below out of their table and added an explanatory comment to the right on each line. Look closely, the hips have actually gain more bone density for the lower dose than the spine does for the higher dose. The "gain" is the difference in g/cm2 on a DXA in the baseline and at 1 year.

2 mg 0.35 gain in LS (g/cm2) 4 mg 0.37 gain so higher dose is 0.02 better in LS

2 mg 0.012 gain in FN 4 mg 0.08 gain so lower dose is 0.04 better in FN

2 mg 0.09 gain in TH 4 mg 0.07 gain so lower dose is 0.02 better in TH

SO IN REALITY THE BENEFITS ARE ALMOST IDENTICAL BUT SLIGHTLY BETTER FOR THE LOWER DOSE. YET THEY CONCLUDE THE LARGER DOSE IS SUPERIOR AND THEY IGNORE THE SMALLER DOSE'S BIGGER WIN AT THE HIPS. JUST BIZARRE.

Ok, so now if we take it from the patient perspective I would say that from this study I can take half my dosage (forget for the moment that it's 4mg and not 5mg as the standard) and get virtually the same benefit and probably improve my odds quite a bit of not having reactions or reactions that are as bad or long lasting.
To Be Continued

Continued From Above
However, as windyshores has pointed out in this thread, this study says there is no difference in side effects between 2mg and 4mg. Oh darn, there's no point in pursuing the lower dose. I give up. Just shoot me!

Wait. Let's take the patient perspective again. A determined patient's perspective that is.
Can we trust that the study got the adverse effects part right? I have my doubts. First the increase in bone density is measured by DXAs before and after. The machine prints a report, you get the numbers, a nice 5% increase that works great. The increases in bone density seem pretty reliable but how about side effects, how do they measure that?

No machine does that for those researchers. It's much more subjective, much harder to quantify and we know historically that the side effects part of studies has failed so many times. Think of Vioxx, Accutane, Thalidomide and many many other drugs that had to be withdrawn. Think of "our own meds," Prolia and Fosamax. How long did it take for the medical establishment to notice that Prolia can cause multiple fractures when you stop taking it? I checked on Prolia, looks like it was 6 years after it's approval that the first papers appeared considering the multiple fracture dangers. Six years after that my excellent internal medicine doctor still seemed unaware of the problem. And someone having 6 vertebrae collapse after they missed a Prolia shot by 3 months, that shouldn't be that hard to notice, right? How long before they noticed or considered important the damaged digestive tract that can happen from taking Fosamax? Not to mention, how many decades of trials using only males were done before someone suggested maybe smaller females with different bodies should be a part of medical trials. There also seems to be is a bias against facing up to long term side effects and even accepting that the drug could be responsible.

So evaluating side effects does seem to be difficult and the obvious historical failure for pharmaceutical makers to get it right seems to verify that. The difficulty and the history are generating a little bit of distrust on my part about the accuracy of the side effects section of many studies.
OTH can we trust the dire reports of long term serious side effects that appear on this and other forums from those taking Reclast? Perhaps it is only a very small percentage of people who get the really bad effects? Maybe their adverse effects are just coincidence and not related to Reclast at all? That is a huge discussion and I for one do not know the answers.

The accepted and reported data for Reclast seems to be that some percentage get various adverse reactions including flu like effects for 3 to 5 to 7 days. In the 3rd study "a total of 30 (43%) patients developed APR ... . Pyrexia was seen in 24%, whereas flu-like illness was seen in 13% of the participants". So 43% had an acute phase reaction of some sort, 24% had fever and 13% had flu like symptoms. They further state "None of our patients developed any significant adverse effects such as deterioration in renal function, atrial fibrillation, symptomatic hypocalcemia, or ocular inflammation."
So they were supposedly looking for long term effects but were they considering all the possibilities. I don't seem severe chronic pain listed for instance.

As for those reporting serious long term life changing symptoms from a shot of Reclast I have found only one paper discussing that kind of "adverse event". For this thread I'm just going to stick with 1. many people have pretty unpleasant side effects for 3 to 5 to 7 days - that's accepted as fact. 2. Based on the self reporting in various forums I'm also going to consider it likely that some unknown percentage of people have seriously bad long term effects from Reclast. I wish I knew how often these bad things happen. I don't. Maybe they almost never occur, but even if they occur only in a small percentage of people I want to do my best to avoid them.

I think many, if not most of us, know first hand of instances of discounted side effects that the doctors or studies just disregard in one way or another. For me I think of my brother-in-law who was diagnosed with high cholesterol and prescribed a statin. He was at the time an avid bicycler and hiker. He could do 15-20 mile one day hikes on steep mountain trails. Two weeks on statins and he had severe muscle pain that took two years to resolve. During that time he could only do moderate excursions with a lot of pain. To this day modern medicine acts as if muscle problems from statins are a minor problem usually resolving right after you stop the statin and happening to very few people. Some experts and studies argue that the "alleged" muscle pain is caused by reading that others have had muscle pain. Oh really! One's reading habits and one's foolish impressionable mind causes those years of pain. My brother-in-law will be really glad to know that.

I'm not recounting this to enter a debate about statins but rather to say that while sometimes you may very reasonably question a persons reported side effects - other times you "just know", they did this and this happened and the thing they did caused it. For some reason the medical world may try to talk you out of it. I don't personally know anyone who has had severe side effects from Reclast (I don't know anyone taking it even) but I'm not tossing out the accounts on the forums of those who believe they are suffering because of Reclast.

To Be Continued

Continued From Above

What about common sense and the idea that the dose does not have an effect on the side effects? The third study reports that side effects are the same with half dose or full dose. Interestingly, looking at the charts and tables you see they actually report the side effects are slightly worse with the lower dose (I'm not going to even try to discuss that one).

Is it logical that a half dose or a quarter dose would have the same side effects as the larger dose? When does the world work that way? The saying that the dose makes the poison is pretty apt in this case. I'm going to go with simple logic and common sense on this one.

If a much smaller dose of Reclast produces roughly the same benefit I'm going to go with the smaller dose as it is logically much less likely to produce harm than a larger dose. If I'm wrong in my logic and half a bottle of wine produces just as bad a hangover as a full bottle of wine, well I've lost nothing because I've had the same fun at the party and the same hangover. But if simple logic and common sense is right, I would have less of a hangover from the half bottle of wine. Translated to taking Reclast, with the lower dose I might dodge chronic bone pain for the next 2 years completely or at least it may be less intense.

Wrapping up, two of the three studies I cited clearly show that various smaller doses and dosing schedules work just as well as the larger dose. The third study with a bit of digging shows the same, despite the authors reaching a different conclusion (and an erroneous one as shown by their own data). So lower doses work just as well in all these studies. What about adverse events (side effects)? Some of the studies claim side effects are the same whether low dose or high dose. I offer logical, common senseical and historical reasons to doubt that conclusion. For myself I want to increase my odds for safety as best I can in this complex puzzle of medications for osteoporosis. I think lower doses improve my odds with Reclast.

You missed a point. I don't recall the same size but when dealing with small differences, one needs to make sure that are statistically significant. If the sample size were on the order of 100, would a different group of 100 have the same results or maybe reversed even. If the study involved 10,000 people, I would trust the results to be more reflective of reality.

@awfultruth I noted the fact that hip did better on 2mg then 4mg, and wonder why. My hip is much worse than spine so that caught my eye. (The third study was stopped because of a stastically significant difference in favor of 4mg, as I recall.)

As for side effects with lower vs higher dose, many side effects are not "dose dependent" in medicine, just as some sensitivities and allergies are not "dose dependent." If a person has anaphylaxis with chocolate, it doesn't matter how much is ingested. Ditto with celiac and gluten (I know this from my daughter).

I originally was limited to Forteo as an option (before Tymlos came on the market). I did a tricky thing to get a 10% dose. I shot the entire dose into a sterile cup, then used my kid's insulin syringe to measure it, then shot out 90% of the dose and injected the remaining 10%. I had the exact same reaction that I had with the full dose. (I also went to an immunologist who tried to desensitize me with smaller doses and declared my immune system had "gone awry." I was puzzled but happy that titrating Tymlos worked.

I have had low doses of every med at this point (except Prolia, which I won't take) and had side effects with every one. Of course I accept fever with Reclast (even at 20% dose) but there are also effects for me like pins and needles, GI issues/reflux, and we'll see what else.

I think that for folks like me (lupus, previous cancer, afib, high antibodies for scleroderma, central vertigo, central migraines, history of Lyme etc.etc.) that our bodies react strongly to very small amounts of medications and the appearance, at least, may be that these reactions have more to do with our immune system reacting to a foreign subtance and less to the actual dose.

Of course, as we well know, noone in medicine seems to know much about any of this, not for lack of trying, but lack of research and most research is still going to take time. Factors like convenience for the medical system, access to infusion centers, patient compliance and of course money are probably determining dose. Amgen probably did not want to make a whole system for production of two different dosing pens for instance. I am skeptical of everyone and everybody to be honest.

Now what do we do if we react to most medications offered in such a way that makes them intolerable? I am very willing to suffer side effects that are even barely tolerable but some are just no. Is the choice more fractures? I am up to 7 as I have written many times before. I lifted just a few books and my back is killing me.

Bottom line: If half doses are what are tolerable and full dose is not tolerable, then we should be able to have half dose. Insurance, without a medical reason, may insist first that we try full dose. Insurance is a whole other problem. They don't want to pay for infusion center/staff/infusion multiple times a year.

I can handle one dosage of my BP medication but an increase left me in trouble for weeks after dropping back down.

@normahorn hi there. I agree that sample size matters and that this is a smaller study but I'm not sure what you are referring to in this case?