Preserving Bones with Bisphosphonates: Should You Avoid NSAIDs?

Preserving Bones with Bisphosphonates: Should You Avoid NSAIDs?
Worst Pills Best Pills Newsletter article July, 2010

Evidence is emerging that suggests a possible interaction between nonsteroidal anti-inflammatory drugs (NSAIDs) and a class of osteopo rosis drugs called bisphosphonates. Patients need to be alert to the fact that the combination can result in an increased risk of ulcers and other gastrointestinal side effects.

The bisphospho nates examined included alendronate (FOSAMAX), etidronate (DIDR­ONEL), ibandronate (BONIVA) and risedronate (ACTONEL) combined with NSAIDs such as ibuprofen (ADVIL) and naproxen (ALEVE).

In this article, we present the conflicting evidence and offer some practical advice on what the cautious drug user should do.

Evidence of danger

One randomized study in 26 healthy subjects looked for stomach ulcers in people who were given three short-term (10-day) treatments with alendronate, naproxen, and both together. Subjects were given all treatments with a one-to four-week washout between each. Eight percent of the people who took alendronate alone developed a stomach ulcer, and 12 percent of patients who took naproxen alone also developed a stomach ulcer. The study found that 38 percent of patients who took the two drugs together developed a stomach ulcer. There was a dramatic increase in the risk of stomach ulcers, demonstrating what is called syner gism between the two drugs (the total damage from being greater than the sum of the individual damages).

A larger study examined the medical records of 242 patients receiving NSAID therapy for rheumatoid arthritis over a three-month period and found that 31 percent of patients receiving bisphospho nates along with their NSAID therapy had gastrointestinal ulcers, compared to 17 percent in those who received NSAIDs alone.

The mechanism by which this in creased damage occurs appears to be that each of the drugs causes irrita tion to the lining of the gastrointesti nal tract in different ways, that are at least additive with one another.

Other Studies

There are three studies that fail to find this increased ulcer damage from the combination of bispho sphonates and NSAIDs, but they suffer from several flaws.

Among those were the different designs of the studies, different kinds of patients involved, and the fact that some of the patients were on anti-ulcer medications (which may reduce the risk). In addition, whereas the two positive studies actually looked for ulcers, two of the three nega tive ones relied on the reporting of adverse events by patients rather than actually looking into the gastrointes tinal tract using endoscopy.

Of the three negative studies, two were paid for by Merck, the maker of alendronate, and were potentially subject to bias. One of the Merck studies and the other negative study were published in Alimentary Phar macology and Therapeutics, a journal owned by Wiley-Blackwell, whose mission statement includes: “pre mier provider of publications for the global pharmaceutical industry.”

What You Can Do

Taking all of the evidence together, it appears likely that patients who take bisphosphonates and NSAIDs at the same time have an increased risk of gastrointestinal ulcers as opposed to taking either drug alone.

Whether the combined use of these drugs also increases other types of adverse gastrointestinal events is not established. The avail able data do not support such a con nection, but a trend toward increased gastrointestinal bleeding was noted in one study.

There are no official warnings against the combined use of bis phosphonates and NSAIDs. Your prescriber may have considered the benefit versus risk and may advise you to take both types of drugs.

Never take NSAIDs unless you truly need them. In addition to the possibility of increasing the gastroin testinal toxicity of bisphosphonates, NSAIDs can cause gastrointestinal toxicity on their own, as well as worsen the risk of heart failure and hypertension. They also can cause lithium or methotrexate toxicity and increase the risk of bleeding for patients who are taking warfarin. Finallly, overuse can cause kidney disease, especially in people who already have kidney problems.

If you are taking bisphosphonates and/or NSAIDs, check with your doctor at the first sign of gastrointes tinal symptoms.

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10 replies. Join the discussion

No shock here - both drugs have warnings about gastrointestinal problems, so combining them seems dubious to say the least. Perhaps consider switching doctors or getting another opinion if you are taking bisphosphonates since the risks are beginning to look like they are outweighing the risks.

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But what about other routes of administration ? Since Boniva can be administered via a Quarterly IV ... and my own opinion is that this route is always the better option.... does not this eliminate the interaction/ or co-morbidity on the gut ?

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Yes, IV bisphosphonates are better regarding stomach upset and damage but still can be a side effect. Other side effects of injectables are much worse.

Here is a list of side effects I found listed for IV administered Boniva:

Headache, stomach upset, flu-like symptoms (e.g., fever, chills, tiredness, joint/muscle ache), or injection site reactions (e.g., redness, swelling) may occur. If any of these effects persist or worsen, notify your doctor or pharmacist promptly.

Here is another list of side effects from another site for IV Boniva:

Side effects may include diarrhea, pain in the arms or legs, or upset stomach. Tell your doctor and dentist about all the medicines you take. Tell them if you develop jaw problems (especially following a dental procedure) or severe bone, joint, and/or muscle pain. Your doctor may also recommend a calcium and vitamin D supplement.

IV administered bisphosphonates are thought to be more damaging to bone in that jaw osteonecrosis is more prevalent in these groups. There are times when that risk seems reasonable such as breast cancer that has metastasized to bone. Two women I know who had BC were in this situation and did get ON of the jaw. However, in their cases it did seem help prevent and heal fractures.

My concern continues to be that women are put on these drugs without a full assessment - lab tests, resolving digestive disorders etc. Also, borderline osteoporosis need not be a major problem. Exercise and nutrition alone can turn the tide - but is does take work.

Here is a list of side effects I found listed:

Headache, stomach upset, flu-like symptoms (e.g., fever, chills, tiredness, joint/muscle ache), or injection site reactions (e.g., redness, swelling) may occur.

Note the statement below regarding the doctor judges that the benefits out weigh the risk - not all docs agree that the vast majority of people ultimately benefit from these drugs.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

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True but there are times when the IV route is the only choice, you state , "your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects". To clarify your statement, first no physician should be giving the right to prescribe any medication to any individual without their consent. Hence both physician and patient must together examine the cost and benefit of any drug. True, there is an "agency" problem here to use the business model - but this is another issue.

My own problem was that I could not tolerate any of the Oral medications for my "incidental" diagnosis of Osteoporosis in 2002. Weighing the emerging pros and cons of "Zometa" (now marketed as "ReClast") , I refused to take this drug given "off label" for Osteoporosis. Instead my choice after detailed review of the literature was AREDIA IV and than on to BONIVA IV ( I scored a point here when I alerted my physician at a highly regarded "center of excellence" that this IV route was in Clinical Trials) when this too became available. Side effects of the drugs diminished progressivly during my three years of treatment to none. My DEXA scores have shown likewise a reversal to Osteopenia/ normative status. I am now on a drug holiday and I am very aware of the "Jaw Death" issue as I may have gum grafting done in the near future. But this is a part of the Cost/ Benefit equation that I referred too. Sadly, it appears that many on this forum are still using the judgement of the physician as the sole basis for their decision making.

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It takes a very long time to study the diagnosis of osteoporosis, what it means and what to do about it. I am still confused and I read research papers every day. I agree with you that patients need to be informed but that is easier said than done.

Reversal of osteoporosis to osteopenia may or may not be a good thing. Early Fluoride treatments looked good too in the beginning - nice increase in bone density but years later women began to fracture because the quality was so poor.

You landed on one aspect of my post that is important and I wholeheartedly agree that women need to educate themselves as much as possible. It is difficult however for laypeople to appreciate the significance of a study and whether or not the study is a good one.

I am very confident that my opinion regarding that most people who are on meds do not need them. When possible I lean toward bio-identical hormones before the other meds. If I had a -3.5 and surely a -4 I would take Forteo and would not take a bisphosphonate of any kind before or after. There are those who cannot take Forteo and for them meds make since. But again I see patients who have severe loss without proper work-up. Anyone with a -3 and above I am thinking parathyroid tumor until it is absolutely ruled out. Sometimes I will redo the lab 6 or more times because it can be normal and 4 out of 6 are high - patients have no idea about this level of thinking that should go into a case.

Let's say that someone has gluten intolerance or parathyroid tumor and it is not discovered - they still will have the issue. A doctor needs to spend significant time analyzing, assessing, thinking and have a very clear knowledge of nutrition and digestive issues.

Each patient needs to be treated individually and that is a rarety today. You have a symtom it is treated. Last night I read that an astonishing 23% of people over the age of 45 are on statin medications. We are not suffering from a statin drug deficiency we are suffering from the notion that often doctors have a knee-jerk reaction and treat the symptoms rather than looking to find a cause and eradicating the cause first if possible.

Patients too want the easy way out - just give me a pill to fix the problem doc.

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As far as the long term impact on my reversal, that is of course the million dollar question . But to date no lose of height and no further issues with my experimental drug regime - for that is exactly what it was. You have furthermore pointed out the American love affair with drugs; that is, the mythology that what ever we do to our selves there is a "purple pill" to fix it ! Not only has the public bought into this but as well the overtaxed physician. And the pharmaceuticals are entirely willing to satisfy this demand if the money is right and it is indeed so !

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Thanks for the lively discussion and your wisdom. Just to dispel yet another myth. The number one reason why we lose height is not due to fracture - it is because the discs between our vertebrae decrease in size and dry out as we age, or due to injury - the end result of that process is osteoarthrosis and when inflamed it is osteoarthritis (itis means inflamed). One can easily see this - you are taller in the morning, right after getting up. Measure again in the afternoon and you will be shorter. During the night the disks imbibe with fluid to the extent that they are able. I am a full inch taller in the morning but then, I am a young 61 years old.

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Amazing info on height!

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I am 61 years old with osteoporosis in my femur neck and osteopenia in the femur head and the lower back. I have been on Boniva since November. I have High Blood Pressure and have taken a baby aspirin (81 mg) daily for a number of years. I also have a hiatus hernia leading to lots of acid reflux so I am on Prilosec and have been for a few years. My question is: Should I stop the aspirin? Is it still recommended for certain adults to take a daily baby aspirin (81mg)? By the way, I also have Asthma and take ADVAIR so that is also complicating my calcium balance. Treatment for one disease complicates the others. Very difficult to figure it all out.

My Doctor is in the States. I live on the equator in Africa. I work at a hospital but not one that can do many tests and certainly no tests that I need for osteo.

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The aspirin was probably prescribed to protect you from the development of a clot. That is still common here in the states.

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