Time will tell.

Recently, I had a new patient who had been inappropriately placed on Fosamax (a bisphosphonate) for a bone density that just barely edged into the osteopenia range. She didn’t like being on it and persuaded her doctor to take her off it after 5 years. Recently, another doctor put her back on it (after 8 years off) because her bone density was about the same (i.e. still osteopenia).
Now, I know that 15 years ago, Fosamax was new and the
drug reps were pushing it hard and everyone thought it was the bee’s knees, so it’s understandable (but not justifiable) for her doctor to have placed her on Fosamax then. Now, however, it’s generic so there’s no drug rep pushing the medication, so why would a physician be prescribing it inappropriately?
Well, despite my
pointing out that this is poor practice by the evidence five years ago, an article on the current evidence of these medications’ lack of benefit with long term use only came out today after FDA presentations about the lack of efficacy.
The risks have been continually underplayed: osteonecrosis of the jaw and atypical fractures. Both of these, like most side effects, are dramatically under-reported. An oral surgeon isn’t going to want it getting out that a patient got osteonecrosis of the jaw, so is going to avoid working on people with risk and downplay what does happen. Meanwhile, atypical fractures aren’t going to get reported simply because the people seeing them (mostly ER docs) are too busy and are just trying to get the patient better. So, the true incidence of these risks is probably dramatically higher than what is reported in the literature.
It’s unfortunate that the real data on risks and lack of benefit of these medications only comes out once the medication goes off patent. We see the same with the PPIs (Prilosec, Nexium, etc): nutritional docs have been pointing out the risks for years, but now that they are off patent, the risks of pneumonia, bone loss, and small intestine bacterial overgrowth are starting to trickle out into the mainstream press.
Could it be that media corporations are hesitant to bite the hand that feeds them? Ever since direct-to-consumer drug advertising started, those advertising dollars have bought silence from the news outlets in addition to interest from patients. Perhaps the for-profit media is only willing to speak ill of a drug once it’s gone generic and the profits have already dried up.

The Fosamax facade is starting to crumble

After years of hints that all the bisphosphonates (medications used for osteoporosis) caused jaw osteonecrosis (destruction of the jaw bone after dental work), a new article shows that the risk of jaw osteonecrosis when the person gets dental surgery who has been on Fosamax is one in 23, or around 4%, 1600 times higher than the 0.0005-0.0025% Merk “estimated” in 2007.
While 4% may not seem like a big number, it seems a lot more problematic when realizing how devastating jaw osteonecrosis can be. The jaw bone near the surgery breaks down, leaving a broken jaw, and it can continue to expand. Any attempt to bridge the gap will cause further destruction, as drilling into the bisphosphonate saturated bone will only trigger more breakdown. With no known way to remove the bisphosphonate from the bone once it’s in there, all the dentist can do is watch helplessly as the jaw falls apart.
Hyperbaric oxygen therapy is the only treatment that has shown any promise in stemming the collapse and even that isn’t stunningly effective.
Understandably, dentists are reluctant to operate on people who may be at risk due to the devastating effects on the patient, and are also reluctant to report it happening due to the devastating effects on their reputation and office. So, the condition is dramatically under-reported. Even with less loaded conditions, 90% are never reported.
Of course, this is on top of the risk of erosions and cancer of the esophagus from these medications.
The companies making the bisphosphonates (Fosamax, Actonel, Boniva, Aredia, Zometa and Reclast) have been attempting to portray these medications as safe and effective for the treatment of osteoporosis as well as attempting to expand the market to include the treatment of osteopenia (milder bone loss). Clearly, if one in 23 of people on the oral form of these medications (the IV form is much worse) will have their jaw disintegrate if they get dental surgery, it’s not safe. Whether it’s effective is open to debate.
When trying to prove that putting their new chemical into people is a good idea, drug companies and the researchers that work for them have a lot of tricks to make the chemical that they’ve dumped a pile of money into producing look good enough to produce the serious return on investment they need. Drug companies like to use intermediate markers rather than outcomes since they are easier and cheaper to measure and easier to game than the real outcomes we care about. With cardiac disease, the outcome we’re concerned about is dying or having a hospitalization, while cholesterol or LDL levels are an intermediate marker that may not translate into the outcomes I mentioned. With bone loss, the real outcome is fractures, while an intermediate marker is bone density. By strapping a lead rod behind your leg, it can look denser to the machine, but it won’t do a thing to reduce fractures. While a medication may increase bone density (remember that density is mass per volume, so heavier bones), it may not actually make them stronger (they can be dense and brittle, or lighter but with just enough give to resist breaking: think glass compared to titanium).
While the drug companies have been doing their typical attempt to brush it all under the rug, they also engaged in their typical pastime of trying to get doctors to prescribe it to people for whom it isn’t indicated. As I
discussed 18 months ago, the evidence doesn’t support the idea that this drug is beneficial for osteopenia. Perhaps the only thing that does support the idea is the money the drug companies spend on lunches for physicians so they can whisper these sweet nothings in their ears.

"Pharmacologic Treatment of Osteopenia Not Usually Indicated"

A recent American Family Physician journal, citing a JAMA article, puts the lie to the idea that people (particularly women) with osteopenia (low bone density) should be on medications. With all the evidence that these medications (like Fosamax or its friends) shouldn't be first-line treatments, why are doctors still prescribing them so quickly? If your doctor pulls out the pad for this, ask them when the last time they saw that drug rep and whether they are pushing the doc to use it as a preventative. This kind of behavior is occurring more and more, so let your doctor know that it's getting so obvious and blatant that even the patients are picking up on it. There are some movement among conventional docs to limit their exposure to drug reps, No Free Lunch for practicing physicians and Pharmfree for medical students. Sadly, the No Free Lunch doesn't turn up any drug-rep free primary care physicians in Ann Arbor (though it does find a pediatrician in Ypsilanti).
Interestingly, the article points out that the
only treatment that has been shown to reduce nonvertebral fracture risk in women with osteopenia is estrogen. Bioidenticals, anyone?