What do you think about this reason for treating osteopenia?

Alendronate increases bone density by about 1-2%/year in women with osteopenia or osteoporosis. Post-menopausal women lose bone density at a rate of about 1%/year. So, if a women has osteopenia, and lives long enough, she will most likely eventually develop osteoporosis. If she takes a course of alendronate for 3-5 years, she could expect her bone density to substantially increase.

If her bone density increased by 5% over 5 years, then her bone density will be 10% higher than if she was untreated (assuming normal 1% rate of bone loss ). As she ages and her fracture risk progressively rises, she could expect to have a much lower risk of fracture for the rest of her life than if she was untreated because her bone density is 10% higher.

This sort of primary prevention argument isn’t captured by a NNT for fracture over 5 years, but needs an NNT for life. I’ve heard this same argument used for osteopenia treatment many times (and for other conditions as well).

Another unrelated point, the paragraph on adverse effects is unbalanced. You’ve quoted a NNH for bisphosphonates of 16. This comes from oncology trials where bisphosphonates are used intravenously at much higher, often seemingly industrial, doses. This is not a fair comparison. There are a variety of long term studies of the risk of osteonecrosis of the jaw in osteoporosis- the risk is low, perhaps 1 in 20,000 to 1 in 200,000 patient-years. Correlation or causation has not been determined for the relationship between bisphosphonates and atypical fractures: do bisphosphonates cause atypical fractures or are people who are likely to get atypical fractures given bisphosphonates? Alendronate does have significant side-effects, and the benefits of treatment needs to be weighted against the risk of these adverse effects. I think people reading this paragraph will not take away a balanced view on the risk of adverse effects with alendronate.

As I said, the evidence was strong enough to convince an FDA advisory committee to recommend approving low-dose fluoride as a treatment. http://articles.latimes.com/1995-11-18/news/mn-4706_1_drugs-advisory-committee ( I cannot find FDA records from this pre-web era online ). In other words, the evidence was strong enough to convince the scientific community asked by the FDA to investigate the question to recommend it. So I disagree with your statement that “the evidence is not strong enough to have convinced the scientific community to recommend it.”

Also, a big reason I brought this up is that fluoride is particularly well suited as a preventative treatment in osteopenia if you want to call osteopenia a disease, as it works best before there is lots of bone loss, and because unlike Boniva and Fosimax, which you say “some studies have shown no reduction in non-spine fractures”, you yourself have cited the meta-analysis which shows fluoride HAS demonstrated reduction in non-spine fractures. (Although it is true that “some studies” have show the reverse with high doses of fluoride, which now makes me question your original implications about Fosimax and Boniva. I mean, after all, there are “some studies” that show that drinking water causes stomach cancer and “some studies” that show cigarette smoking is healthy.) Fluoride treatment is also not linked to stroke, heart disease, thromboembolism, hormonal side effects, or much of anything bad if given in a low sustained dosage form.

So I think fluoride deserves a place in your catalog of alternatives to Fosimax and Boniva.

Calli Arcale,

The only patents available on fluoride are patents on dosage forms and those patents can be circumvented. The real issue is that the Big Pharma companies with stronger patents want to protect their profits and have convinced the non-scientific regulators at FDA to continue to block approval after 40 years of study. The FDA is now demanding a 1,000 person 5 year study after at least twice saying (the second time after the first 5 year study was completed) that if a 100 person 5 year study showed safety and efficacy then the treatment would be approved. The FDA also rejected a compromise proposal to grant tentative approval for marketing conditioned on the expanded study being done post-marketing and said study confirming the earlier findings. So it would be prohibitively expensive and once again there would be no guarantee that even with a positive result in the study the treatment would garner approval. This is how the FDA does Big Pharma’s bidding while appearing to be impartial.

The dental fluoride treatments were developed under patents in the 50’s and 60’s if memory serves and are now all generics competing on the same playing field as other consumer products like mouthwash and adhesive bandages.

The issue of fluoridated water affecting the dosage of supplementation is indeed an issue. The target dosage for osteoporosis treatment is in the 5-10mg/day range whereas a quart of fluoridated drinking water has 1mg of fluoride. This does mean some care needs to be exercised, but it is not an unreasonable burden on doctor or patient.

The issue of children whose teeth are still developing getting too much fluoride, leading to fluorosis of the teeth, is different that the issue of adults getting too much fluoride causing bone defects. Children can have problems with less than 0.1 mg/kg/day which for bottle fed infants can easily lead to problems, especially of the well water is higher than the supplementation standard of 1mg per liter.

That does raise another question for me: how much significance would flouridated water have in determining the correct dose? It’s already an issue for dentists — some areas have so much flouride in the well water that not only is flouridation not required, but some people are actually getting too much. I’m guessing you wouldn’t want to use as much (or, perhaps, any) in those populations.

I stated the overall results of the meta-analysis correctly. I just didn’t list the subgroup results. I agree that there is evidence supporting the use of low dose fluoride, but it is not strong enough to have convinced the scientific community to recommend it. I question your interpretation of why it has not been adopted. There is a patented version of fluoride that could well generate profits. I think it is a question of strength of evidence rather than of economics.

You misstated (and apparently misunderstood) the results of the meta-analysis. The last sentence of the abstract is “However, in subgroup analyses a low fluoride dose (< or =20 mg/day of fluoride equivalents) was associated with a SIGNIFICANT REDUCTION in fracture risk." (emphasis added) Several other sentences in the abstract point out the specific reductions demonstrated for low fluoride doses. I encourage you to read the whole paper, not just the negative parts.

The concerns you stated were concerns from the 1990's which have been addressed by later studies. It is correct that early studies of fluoride for osteoporosis showed that at the (higher) doses studied fluoride leads to mineralization defects which cause structural weakness of the bone despite its higher density. It turns out getting the dosage right was difficult for researchers, in part because fluoride accumulates in the bones which can lead the bones themselves to later becoming a source of fluoride in the bloodstream. However, these problems were worked out in later studies. You can read more about it here: http://www.mfp-fluoride.com/overview.html

Fluoride remains valuable in that it is one of the few options for stimulating bone formation (as opposed to slowing bone loss, which is what most osteoporosis treatments do), has a well understood safety profile, is very safe at effective dosages, and is cheap. Unfortunately, the fact that it is cheap (already generic) is the biggest obstacle to it being adopted. It has mainly fallen out of favor because no one is going to make any money making it and now that there are other FDA approved treatments it no longer has the urgency from non-profit sectors to get it approved as the first and only treatment for osteoporosis.

This is just one of many examples of how our current health care system disfavors cheap treatments over expensive ones. It's a shame.

Fluoride has fallen out of favor as a treatment for osteoporosis because it is less effective, there are concerns about toxicity, and it may even increase the risk of certain types of fracture.

Read about the scientific evidence supporting MFP-Fluoride as a treatment for osteoporosis at http://www.mfp-fluoride.com/

“To put the bisphosphonate NNTs into perspective, a study just published in JAMA found these NNTs for antidepressant drugs:

16 in mild-to-moderate depression
11 in severe depression
4 in very severe depression”

Is it fair to compare the NNTs for preventative drugs with those for therapeutic drugs?

Thanks for a very interesting article. Another way of looking at it is from a population viewpoint. While individuals with osteoporosis by bone density criteria are at high risk of fracture, they make up only a minority of the population, and are vastly outnumbered by those with osteopenia. Individually, people with osteopenia are at lower risk of fracture, but as a group, they have more osteoporotic fractures than those with osteoporosis, because there are many more people with osteopenia. Since the population burden of osteoporotic fractures largely lies in people with osteopenia, unless fracture prevention strategies are targeted at this group, there won’t be a meaningful reduction in the total burden of osteoporotic fractures. The strategy you advocate of waiting until people fracture or their bone density is low before offering treatment is not going to reduce osteoporotic fractures in the population.

If you were going to intervene in osteopenia, what should a strategy involve? Lifestyle modifications? They have pretty modest effects on bone density, and I don’t think their ability to prevent fractures has been studied. But, it seems pretty optimistic to think that strategies based on lifestyle will have a big effect on fractures. Bisphosphonates? There are few studies assessing fracture prevention in groups who do not osteoporosis. The effect on bone density in people with osteopenia seems to be the same as people with osteoporosis, so it seems more hopeful that they will prevent fractures, when the studies are eventually done.

The argument about not treating people at low-moderate risk surely doesn’t just apply to osteopenia, but could also be applied to most conditions where treatment is given to try and prevent specific adverse outcomes or complications, eg hypertension, lipid disorders, diabetes, vascular disease etc etc. In all these cases, primary prevention, (preventing events in individuals who haven’t had an event already), is much more difficult and always has much higher NNTs than secondary prevention, where individuals have already had events and therefore identified themselves at high risk. I would be very interested in whether you feel the same about treating low-moderate risk individuals with these conditions as you do about people with osteopenia?

Just as the prophet used to say “Trust in God, but tie your camel first.” I tell patients, when indicated, that their active lifestyle is fine, but they still need the medications the I prescribe for them.

Of course. The point of eating well and exercising is to have a better quality of life both now and in the future, not to avoid death (for anyone who lives in reality, anyway). Being healthy often does lead to living longer but there’s not much point, from my perspective, in simply extending life for the sake of extending life if there’s no real living of life going on (though, in some cases, pharmaceutical companies and some doctors do tend to promote unreasonably heroic life saving and life extension via using their products even when there’s incredibly poor quality of life). So far we have no way to avoid death, despite how both Big Pharma and Big sCAM market to Boomers who are terrified of aging and death. (Not that there isn’t also a HUGE investment being made into researching pharmaceutical ways to achieve immortality, Big Pharma is after this demographic just as hard and heavy as Big sCAM and there’s often overlap here with this demographic grasping at any magic straw that’s put on the market. As well as also selling magic happiness in a pill.)

Perky Skeptic – No, winter is a Big Parka/Snowsuit scam. I believe they’re working hand in hand with Big Gym and Big Public Pool to conspire against you getting a workout or to workout indoors. Just as long as there’s someone to blame for inactivity and a pill you can take instead of doing something….it’s not just people into woo who love magic pills and potions!

Exactly how you tell them can make a big difference. If you say, for example, “Walking 5 miles a day might help prevent diabetes, heart disease, cancer and arthritis, but of course we are not absolutely sure of that. I advise you to do it. However, if it turns out that you lack the necessary willpower, we have many pharmaceutical alternatives that do nearly as good a job. In some cases, even better.”

If that is what you tell your patients, or something similar, then they will completely ignore your advice to walk.

A patient who has been almost completely inactive for 20 or more years, for example, finds any kind of activity painful and exhausting. They don’t know how bad they feel, because they have been feeling bad for so long.

So of course they will take the pill instead. They don’t understand how serious their decision to remain inactive will be. They don’t understand the extent of the potential pros or cons.

And I would not tell an out of shape middle aged person to suddenly start walking 5 miles every day. Many don’t have the time, for one thing (unless they give up TV and most never will).

I would just tell them to walk 15 minutes before going to work, or something like that. If they eventually start to like it, they can do more.

I just strongly suspect you are not giving them the whole message, and that they will not take your advice seriously.

I tell my patients to walk at least 5 miles a day.

Living forever is not my goal. My goal is to improve my odds of avoiding high blood pressure, dementia, depression, type 2 diabetes, heart disease, stroke, cancer, arthritis, etc. — all those disease that are assumed to be the inevitable results of normal aging.

Is there no advantage, in your opinion, in feeling good while alive? Is it all about living as long as possible, regardless of how you feel?

If something as simple and easy and enjoyable as walking every day can help prevent all those miseries, then why not do it?

This applies to parents looking out for there kids. It doesn’t mean they are stupid, it means they are human.

@lizkat – even if you exercise regularly you will die~

Just sayin.

Where did you ever get that idea?