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Osteoporosis Drugs: Good Medicine or Big Pharma Scam?

A recent story on NPR accused the drug manufacturer Merck of inventing a disease, osteopenia, in order to sell its drug Fosamax. It showed how the definition of what constitutes a disease evolves, and the role that drug companies can play in that evolution.

Osteoporosis is a reduction in bone mineral density that leads to fractures. The most serious are hip fractures, which require surgery, have complications like blood clots, and carry a high mortality. Many of those who survive never walk again. Vertebral fractures are common in the osteoporotic elderly and are responsible for dowager’s hump and loss of height. There is also an increased risk of wrist and rib fractures.

Bone density tends to decrease with age. Postmenopausal women are particularly susceptible to osteoporosis when their production of estrogen declines. The risk is increased in people taking corticosteroids and in people with certain diseases like rheumatoid arthritis. Other risk factors are European or Asian ancestry, smoking, excess alcohol, a family history of fractures, vitamin D deficiency, too much or too little exercise, malnutrition, and low body weight.

When a measurement like bone density varies widely in a population and decreases with age, how can we decide where to draw the line and call it abnormal? When does it become a disease requiring treatment?

For a long time, the diagnosis of osteoporosis depended on the occurrence of a fracture. In 1992 a group of experts convened by the World Health Organization agreed to define osteoporosis as a bone density 2.5 standard deviations below that of an average 30 year old white woman. They defined osteopenia as a bone density one standard deviation below that of an average 30-year-old white woman. The decision to use one standard deviation and 2.5 standard deviations was arbitrary, and it was meant as a tool to measure the emergence of a problem in a population rather than to have precise diagnostic or therapeutic significance for an individual. Nevertheless, these criteria were widely interpreted to mean that half the population has a disease they need to worry about.

Bisphosphonate drugs like Merck’s Fosamax and Sally Field’s beloved Boniva were intended to reduce the risk of fractures in patients with osteoporosis. They are effective in reducing spine fractures and in increasing bone density measurements, but some studies have shown no reduction in non-spine fractures, which are more common, and in the case of hip fractures, more significant. A British Medical Journal article pointed out,

Two thirds of vertebral fractures are subclinical or asymptomatic and may not affect quality of life. As a consequence showing that drugs reduce vertebral fractures may not be as important to patients as it seems.

According to a table published by the USPSTF (US Preventive Services Task Force), among women aged 50-54, 60 women need to be treated to prevent one vertebral fracture and 227 to prevent one hip fracture. Among women aged 65-69, 30 must be treated to prevent one vertebral fracture and 88 must be treated to prevent one hip fracture. Sally is 63: the numbers for her age group are 30 and 121. One wonders if she is aware of these numbers.

These drugs are not benign. To prevent ulceration of the esophagus, for 30 minutes after taking Fosamax patients must avoid eating or drinking anything but plain water; they must not lie down or recline, or take any other medications during that time. Bisphosphonates have been linked to osteonecrosis of the jaw. There are as yet no long-term studies. Case reports suggest the possibility that they might paradoxically increase fractures in the long run. By one estimate, the NNH (Number Needed to Harm) is 16 as measured by discontinuing treatment due to adverse effects.

When Merck started marketing Fosamax, not many women were being screened for osteoporosis because the standard DEXA (dual energy x-ray absorptiometry) test required expensive equipment and was not readily available. They thought if they could increase the rate of diagnosis they could sell more pills. Merck promoted the development of small, less expensive scanners that could be used on a heel or wrist in a doctor’s office. Merck even set up a nonprofit organization called the Bone Measurement Institute, which worked to spread the use of these machines and bring down the price of bone exams. Unfortunately, the results of those scans did not correlate well to the results of the gold standard DEXA scan.

A doctor quoted by NPR said,

The problem with the smaller peripheral machines is that taking a measurement of someone’s heel or forearm isn’t going to tell you what you need to know about the bones in the parts of the body that, if fractured, increase a woman’s risk of death — the hip and spine.

Who should be screened? The USPSTF found that, for women 55 to 59 years of age, the number needed to screen (NNS) over five years was more than 4,000 to prevent one hip fracture and 1,300 to prevent one vertebral fracture. The NNS to prevent one hip fracture over five years declines with age, to 1,856 for women 60 to 64 years of age, 731 for women 65 to 69 years of age, and 143 for women 75 to 79 years of age.

The USPSTF currently recommends that women aged 65 and older be screened routinely for osteoporosis. It recommends that routine screening begin at age 60 for women at increased risk for osteoporotic fractures (there is a handy online FRAX tool for estimating an individual’s risk of osteoporotic fractures). It found insufficient evidence to make any recommendations for younger women or for men. Meanwhile, direct-to-public ultrasound screening companies have jumped on the bandwagon and are offering poor quality osteoporosis screening to men and women of all ages, with innumerable false positives requiring further testing and unnecessary worry.

The results of the scans promoted by Merck were reported either as normal bone density, osteopenia, or osteoporosis. Osteopenia carries only a small increased risk of fractures, but the assumption was that left untreated it would progress to osteoporosis. It is really more of a risk factor for osteoporosis than a disease in its own right. Some women diagnosed with osteopenia may not even have bone loss; they may just be at the low end of normal on a wide spectrum. But osteopenia sounds abnormal, and it sounds like a diagnosis, and it sounds to a lot of people like it needs treating. A new disease was born with a ready-made treatment.

There are other pharmaceutical options for osteoporosis. Estrogens reduce osteoporosis risk but carry too many other risks to be used for that indication alone. Raloxifene is a selective estrogen receptor modifier that has estrogenic effects on bone but anti-estrogenic effects on the uterus and breast. It reduces the risk of vertebral fractures but not other fractures. It increases the risk of thromboembolism and fatal stroke although it does not reduce the overall death rate. Another option is calcitonin, but it is less effective.

Pharmaceutical treatments are not the only option. Weight-bearing exercise, prevention of falls, quitting cigarettes, curtailing alcohol, and ensuring adequate intake of calcium and vitamin D are all beneficial. A recent study showed that higher doses of vitamin D supplements (over 400 IU a day) reduced fractures by 20%.

Merck’s actions may have been misguided, but I don’t see this as a scam. Merck employees were trying to make money for the company, but that doesn’t mean they weren’t also genuinely trying to do the right thing to help patients. They had a product that they thought would prevent fractures and save lives, and they wanted to get it to everyone who could benefit. In their enthusiasm, they overshot and went beyond the science.

The NPR article admitted that there are two sides to this story.

…drug companies produce incredible drugs that can greatly relieve suffering. But one way they profit from those drugs is to extend their use to as many people as possible, which frequently means that medications are used in populations with milder and milder versions of a disease, so that the risks of medicating can come to outweigh the benefits.

Big Pharma advertises but it is doctors who write the prescriptions: when drugs are over-prescribed, only the prescribers are to blame. What should doctors do? In the first place, they should be recommending preventive lifestyle changes to all their patients. They should stick to the best science-based practices and evaluate the evidence for themselves rather than being influenced by Sally Field or by Big Pharma propaganda. They should prescribe drug treatments only when fracture risk is significant, when a fracture has already occurred, or when they think bone density is significantly low (still a judgment call). They should explain the gray areas to their patients and involve them in the decision to treat. They should think in terms of number needed to treat and number needed to harm. And they should be aware of the games Big Pharma plays.

Posted in: Pharmaceuticals

Leave a Comment (81) ↓

81 thoughts on “Osteoporosis Drugs: Good Medicine or Big Pharma Scam?

  1. Zoe237 says:

    I heard that story on NPR. Thank you for covering it and presenting a balanced viewpoint. I would probably substitute “greed” for “enthusiasm.” But that’s my admitted bias. Merck has ruined their public image for good. “The games Big Pharma plays” is probably more accurate.

    “They had a product that they thought would prevent fractures and save lives, and they wanted to get it to everyone who could benefit. In their enthusiasm, they overshot and went beyond the science.”

  2. Sam Homola says:

    My wife thanks you–and I thank you–for a very informative and useful article!

  3. “Thank you for covering it and presenting a balanced viewpoint.”

    Ditto. I’ve been watching “osteopenia” commercials for a while, and wondering why they use that term instead of “osteoporosis.” Now I know! I agree with Zoe’s “bias” and more: I think it crosses the line to scam.

    There is an ongoing argument in the health care reform literature pitting market-freedom against strong regulation. It is sometimes discussed here, and I won’t argue one side or the other now, but simply make a plea for consistency: if regulation is what our democracy has chosen, as it seems to have done, then this kind of advertising contradicts that choice. Direct-to-consumer drug advertising makes me cringe: it makes it more difficult and time-consuming to practice medicine with integrity and it inappropriately fuels “Pharma Shill” arguments.

  4. Calli Arcale says:

    Agreed — situations like this are exactly why we need to give the FDA teeth again and prohibit this sort of deceptive health advertising. Patients do need to know what options are available to them, but I would really like it if the only practical venue for most patients were NOT commercial advertising, which is about the least objective source in the world.

  5. DevoutCatalyst says:

    > Direct-to-consumer drug advertising makes me cringe

    The “Cymbalta can help” spots make my skin crawl. Very well produced, using one of the best voice-over artists imaginable. Would like to see them banned along with all the rest.

    A direct-to-physician campaign, posing as an active lifestyle magazine, for a very popular neuroleptic, was unexpected to me as a layperson. Most of you doctors see right through this crap, right?

  6. daedalus2u says:

    Don’t forget nitric oxide as an important anti-osteoporetic pathway

    http://www.ebmonline.org/cgi/content/full/227/2/88

    The primary regulation of bone stiffness is via nitric oxide. When bone is strained, there is movement of fluid in the normal porosity. That moving fluid generates shear, that shear activates nitric oxide synthase (just as shear does in blood vessels). That NO activates the cells that deposit bone mineral and inhibits the cells that resorb bone mineral. The parts of the bone that experience the greatest strain are the ones that generate the most NO, and so have more bone mineral deposited on them.

    That is the mechanism by which load bearing exercise increases bone density. It isn’t the exercise per se, it is the bone strain that generates nitric oxide.

    There have been studies that used nitroglycerine and observed increased bone density. Nitroglycerine isn’t an NO donor, so how it is working isn’t clear. It is probably through NO/NOx, but nitroglycerine has other effects that are not so good. I wouldn’t recommend using nitroglycerin for that. On the other hand, green leafy vegetables have a lot of nitrate in them, and that should help with basal NO levels, and the consumption of nitrate in amounts associated with eating a few hundred grams of lettuce has been shown to increase NO/NOx levels and produce improvements in NO/NOx phsyiology. I am quite sure that would translate into increased because NO is in the pathway and the pathway is already regulating bone density using NO.

  7. lizkat says:

    Wonderfully rational post Harriet! I have been waiting impatiently for someone to point this out. Increasing bone density does not necessarily improve bone health, and may actually do the opposite. I heard about this years ago but the public is still being misled by Sally Field.

    And you are so right in mentioning the non-drug alternatives.

  8. David Gorski says:

    According to a table published by the USPSTF (US Preventive Services Task Force), among women aged 50-54, 60 women need to be treated to prevent one vertebral fracture and 227 to prevent one hip fracture. Among women aged 65-69, 30 must be treated to prevent one vertebral fracture and 88 must be treated to prevent one hip fracture. Sally is 63: the numbers for her age group are 30 and 121. One wonders if she is aware of these numbers.

    Actually, to things in a bit of perspective, the NNTTs for biphosphonates are not out of line with those of other preventative drugs that are widely accepted, such as statins. In fact, compared to statins, an NNTT of 30 to prevent one vertebral fracture is pretty darned good. Given how debilitating osteoporotic vertebral fractures are, I’d say that there’s quite a good justification for using them in the 65-69 year old group. Moreover, 88 needed to prevent one hip fracture is on par with how many people have to be treated with Lipitor, if I recall correctly, to prevent one heart attack in people who haven’t had one before but have risk factors, like hyptertension. Even in patients who have had an MI before or have signs of significant heart disease, the NNTT for statins is in the range of 15-25.

    Another example, hypertension. For severe hypertensives (DBP>115), the NNTT to prevent one stroke is around 30. For less severe hypertensives (90 < DBP < 110), the NNTT to prevent one stroke is around 120.

    It is true that these numbers are not emphasized enough, just as I pointed out in my mammography post that the downsides of mammography and how many women need to be screened to prevent one death from breast cancer at various ages are not sufficiently emphasized. However, every argument you make in this post can be applied to numerous other preventive medications. After all, statins are not entirely benign drugs either.

    Here’s an example from breast cancer that is relevant. Women with early stage breast cancer can be expected to have close to a 90% 10 year survival with surgery alone. Chemotherapy can increase that by around 2-3%, a 20-30% relative benefit but only a benefit that is around 3% (at best) in absolute terms. That means, boiling it down very simply and ignoring a few complexities (such as estrogen receptor status and the use of anti-estrogen therapies), for every 100 women with stage I breast cancer, 90% are cured by surgery, approximately 7% will die of their disease within 10 years no matter what is done, and only 3% (at most) benefit from chemotherapy. In other words, we treat 100 women with cytotoxic chemotherapy in order to save two or three lives. The other 97 or 98 don’t benefit. That produces an NNTT of between 33 and 50.

    This is one reason why tests such as the Oncotype have so rapidly infiltrated practice. For ER(+) breast cancer, the Oncotype can assign tumors into high risk and low risk categories, the former of which benefit a lot more from chemotherapy and the latter of which benefit very little. For stage I ER(+) cancer we now have a fairly decent tool to determine who does and does not benefit from chemotherapy. We probably need something similar for conditions such as osteoporosis and hypertension–and others for which we recommend preventive medications.

  9. lizkat says:

    I think you missed some of Harriet’s more important points — for example, that these drugs don’t seem to prevent hip fractures, which are much more dangerous for the elderly than other types of fractures. Or that bone which is more dense is not necessarily healthier or stronger.

    As she said, long-term studies have not been done, and it’s possible these drugs do more harm than good.

    Additionally, stopping smoking and excess alcohol, becoming physically active, and improving nutrition — all these might actually do more to improve bone health than the drugs.

    The Sally Field ads specifically state that exercise and nutrition did not work for her, implying that they are less reliable preventative measures than the drugs.

  10. Harriet Hall says:

    I’m not saying any particular NNT justifies or fails to justify treatment. I’ve written about the NNT for statins and other widely used treatments. I think most patients get the false idea that everyone who takes the drugs benefits. I’m only advocating informed consent.

    If you told BP patients the drug had an NNT of 120, some of them might get more motivated about losing weight, smoking cessation, exercise and other lifestyle modifications that might do more good in the long run.

  11. David Gorski says:

    Ah, but what’s the NNTT for those nonpharmacologic interventions?

  12. David Gorski says:

    I think you missed some of Harriet’s more important points — for example, that these drugs don’t seem to prevent hip fractures, which are much more dangerous for the elderly than other types of fractures.

    No, I don’t think so, because that’s not really what Harriet said taken in the context of her whole post. After all, if these drugs didn’t prevent hip fractures, it wouldn’t be possible to calculate an NNTT or the NNTT would be incredibly high, much less in the range of 88. What her post said is that they don’t work as well to prevent hip fractures as they do to prevent vertebral fractures.

    Moreover, what is the NNTT for diet and exercise for these things? I ask this not because I think drugs are better than lifestyle interventions but because a direct comparison demands such figures. If you’re going to argue that only 1 in 88 women from 65-69 have a hip fracture prevented by these drugs and that exercise and diet will do more good then there need to be numbers to compare to.

  13. Sid Offit says:

    Great post. I became interested in this issue while examining the the dairy industry’s relentless effort to get children to consume ever higher amounts of calcium through, not surprisingly, milk and cheese

  14. windriven says:

    I am taken by the willingness of some commenters here to prohibit direct to consumer advertising and to otherwise chastise the pharmaceutical industry for pursuing its interests – which often intersect with our own interests.

    In a perfect world every physician would be up to date on all of the available drugs and therapies. But we don’t live in a perfect world of Novellas and Gorskis and Halls and Crislips. Dr. Crislip prides himself on not having seen a drug rep since before the advent of red clay. That is fine because Dr. Crislip stays closely in touch with both the literature and ID practice community.

    But what about Dr. Schlub on the corner who also hasn’t seen a drug rep in 20 years but who also hasn’t cracked a journal seriously in that time either?

    I am not suggesting that direct to consumer is a great idea. I am suggesting that pharmaceutical (and device) companies will use all available channels to get their messages to the physicians who can prescribe them. Getting consumers to ask their physicians about a given drug or intervention is one available channel.

    We live in an imperfect world with imperfect doctors and imperfect therapies. Remember too that very often a physician is not choosing between a silver bullet and a useless nostrum, s/he is selecting from a field of suboptimal choices. Drug companies will rightly want their choice to be among those considered.

  15. lizkat says:

    “what is the NNTT for diet and exercise for these things?”

    I don’t know but my guess is that it is much lower than for the drugs. And there are no harmful side effects — diet and exercise improve all aspects of health, not just bone strength. It almost goes without saying, and without lots of expensive research, that people who walk very little will have weaker bones. Anyone who lies in bed for a while will lose bone mass, as we know. Sitting in chairs and cars all day is probably not much better.

    So simply walking a couple of miles every day would prevent some of the bone loss that normally results from inactivity.

    How many elderly women would have to sacrifice their inactive lifestyles to prevent one hip fracture? I don’t know, but I don’t imagine it’s all that many. And there are no disadvantages whatsoever, only advantages.

    And if a woman exercises but gets a hip fracture anyway, she will probably be more likely to recover than if she didn’t exercise, since her general healthy will be better.

    And, of course, the same goes for excessive smoking, drinking and junk food. There are no disadvantages in cutting back on these, so the NNT is not really very relevant.

  16. Harriet Hall says:

    David Gorski said, “If you’re going to argue that only 1 in 88 women from 65-69 have a hip fracture prevented by these drugs and that exercise and diet will do more good then there need to be numbers to compare to.”

    That’s not at all what I’m arguing. I’m arguing that women should be given the information on the risk/benefit ratio of any treatment rather than being misled into thinking the treatment is a panacea. Sally Fields sends a panacea message rather than saying this is a drug with pros and cons that only offers partial protection and doesn’t benefit every woman who takes it, and that shouldn’t automatically be prescribed to everyone diagnosed with osteopenia by an arbitrary test.

    The point is not to compare the NNT of drugs to the NNT of non-drug treatments. False dichotomy! The point is that there are non-drug measures with essentially no harmful side effects that can be recommended before, AND ALONG WITH, the drugs. And that have other beneficial effects for other diseases. And that often get forgotten because people fixate on a pill to fix the problem.

  17. Bentham says:

    windriven:
    “But what about Dr. Schlub on the corner who also hasn’t seen a drug rep in 20 years but who also hasn’t cracked a journal seriously in that time either?”

    Dr. Schlub probably needs to pass boards (maintenance of certification every 10 years). Probably won’t do so (at least not in Internal Medicine) without paying attention to what is considered standard evidence-based practice.

  18. Basiorana says:

    windriven, driect-to-consumer advertising rarely results in a patient suggesting a drug and then finding the drug works great for them. Usually Dr. Schlub will just prescribe the pill-of-the-week without attempting to determine if it’s a good idea for the patient, or a good doctor will just prescribe a better alternative. While I support allowing drug companies to, say, run PSAs talking about signs of common illnesses and encouraging patients to talk to their doctor about depression, it’s rarely a good idea to let them decide they NEED Drug X and Drug X will solve their problems.

    Drug companies should absolutely advertise to doctors as much as possible. That makes sense, provided they aren’t outright bribing them. But advertising to consumers very rarely helps the consumer. Have you noticed most of the advertisements are either for really, really common problems (Lipitor) or, the majority around here, are for subjective conditions based on symptoms (fibromyalgia, depression, restless leg syndrome)? That makes it more dangerous, because the patient can go in to a new (bad) doctor, reel off the symptoms listed in the ad, and get the drug.

    Exceptions, though– over-the-counter meds, birth control, vaccines, etc can be safely advertised, since most of those are consumer-choice, not based on a specific diagnosis. I mostly worry about the psychiatric meds– what a great idea, tell people that if they’re sad they have depression and need meds when the majority of people with “depression” need counseling and maybe some lifestyle changes. It encourages self-diagnosis, which is a BAD idea with psychiatric patients.

  19. DevoutCatalyst says:

    @windriven

    In the case of SSRI’s, does Big Pharma also become Big Placebo? I believe these meds are over-prescribed, with a result no better than homeopathy where they are mis-prescribed.

  20. Basiorana says:

    DevoutCatalyst, SSRIs aren’t placebos, by a long shot. When I’ve been overprescribed SSRIs I am apathetic and my senses dulled. Overprescribing psychiatric meds isn’t anything like homeopathy, it’s dangerous and mind-altering.

  21. windriven says:

    @bentham

    Physicians are like lawyers, plumbers and everyone else. There are many, many fine physicians who take their profession seriously and work hard to stay abreast of rapidly changing technologies. But there are also physicians who don’t. And they have to screw up pretty badly before they forfeit their licenses.

    I presume from your post that you are an internist. And unless you live a cloistered life I would bet that you know more than one of your colleagues whom you wouldn’t trust to treat a dead cat. Those are the few, of course. But the skills and dedication of the entire cohort of internists can be expected to be described by a bell curve. Some will necessarily fall in the bottom quartile.

  22. windriven says:

    @Basiorana

    What you seem to be telling me is that people are too stupid to manage their own affairs. And while there are some who truly can’t for lack of intellectual resources, the vast majority surely can.

    We could of course build a society where people are saved from having to make choices about which messages are true or useful and which are not. But does that in some way develop critical thinking? Does that help build the skills people need to make quality decisions in other aspects of their lives? What real purpose is served?

    It is easy enough to say that we should ban information that we don’t like or don’t agree with. I spent a year and a half living in PR China and I’ve seen that done by the pros. It deforms people in subtle but important ways.

    It is much better, I believe, to encourage people to take some responsibility for their health and for their healthcare decisions. The best situation is an engaged and informed patient working with a trusted and competent physician. But both halves of that equation must be present. Because without an engaged and informed patient isn’t ‘informed consent’ little more than a legal device?

  23. Zoe237 says:

    Dr. Hall:

    “And that often get forgotten because people fixate on a pill to fix the problem.”

    Hmm… liking this website more and more.

    I’d say the practice of pharmaceutical companies who market to physicians who don’t keep up to date on their research is an even more dangerous proposition. But I don’t have a whole heck of a lot more faith in doctors than I do in the general public (which is why I check the literature and USPSTF and make them write “left” on my surgical leg before taking a med or having surgery or a test).

    Good for Dr. Crislip for not seeing a drug rep since before the advent of red clay!

  24. windriven says:

    @Devout Catalyst

    “I believe these meds are over-prescribed”

    So it is your responsibility to have a relationship built on mutual trust and respect with your physician. Problem solved, at least for Devout Catalyst.

  25. Zoe237 says:

    Windriven:

    “I believe these meds are over-prescribed”

    “So it is your responsibility to have a relationship built on mutual trust and respect with your physician. Problem solved, at least for Devout Catalyst.”

    Well, no. Overprescribing and direct to consumer advertising drives up the costs for everyone else. Sounds like a “what’s the harm” argument.

  26. weing says:

    ““what is the NNTT for diet and exercise for these things?”

    I don’t know but my guess is that it is much lower than for the drugs. And there are no harmful side effects — diet and exercise improve all aspects of health, not just bone strength. It almost goes without saying, and without lots of expensive research, that people who walk very little will have weaker bones. ”

    I guess, you suffer from a severe lack of imagination. I’ve had friends (doctors) drop dead while running. Shin splints, stress fractures, muggings just to name a few harmful side effects. I’m sorry, but in my opinion, you do need an NNT and NNH for all these things.

    “In the case of SSRI’s, does Big Pharma also become Big Placebo? I believe these meds are over-prescribed, with a result no better than homeopathy where they are mis-prescribed.”

    Do you have any solid evidence for this?

  27. David Gorski says:

    The point is not to compare the NNT of drugs to the NNT of non-drug treatments. False dichotomy!

    Why is it a false dichotomy? I never actually made a dichotomy and never said that the two couldn’t be used together. From my perspective, consistency in science-based medicine demands that the evidentiary standards be the same, hence my question about NNT for non-drug interventions, which was to me not only a reasonable question but highly relevant given that you seemed to be implying that they could do as much good as the drugs. Moreover, it was you who fixated on NNT in the post; so it was natural for me to wonder what the NNT for the non-drug treatments are, given that you advocated them. Again, I don’t disagree that these drugs are probably overprescribed or with your emphasizing lifestyle interventions, but it appears to me that doing so without having even a ballpark figure of NNT is doing so based more on assumptions than evidence. They may be reasonable assumptions, but I like a bit of evidence added to them, and no one here, you or anyone else, has as yet pointed me to it (and I haven’t had time to do any literature searches myself).

    My point was that if you want to say that these drugs are overprescribed (almost certainly true) and that non-drug treatments should be tried first and are likely to be more beneficial for most women (a point I’m not disagreeing with, by the way, only challenging the way that you made it), then I would still argue that it is just as important to know the NNT for these interventions. I grant you that they would be much harder to figure out than for a pill, but a ballpark figure is important, particularly under real word circumstances. Lifestyle changes are hard. Relatively few people can adhere rigorously to them, and this would likely increase the NNT for such interventions because of poor adherence. In any case, if these non-drug treatments turned out to have an NNT of, say 1000 (I doubt it’s that high, but go with me on this for a minute; it’s an example for the purposes of discussion) to prevent one hip fracture, that would be significantly worse than the drug. True, you could argue a host of other benefits, but not so much for hip fracture. In such a case, it wouldn’t make a lot of sense to expect much benefit from the lifestyle interventions.

    I suspect we’re close to on the same page here. I was simply pointing out an area in your post where you appeared to be proceeding on an assumption for which you didn’t appear to have much evidence, and the impression you left me that you thought these NNTs for biphosphonates were ridiculously high. That was the only reason I pointed out that the NNT’s presented for anti-osteoporosis drugs are not much different from the NNTs for a lot of other preventative measures for other diseases, including incredibly common ones conditions like hypertension.

    But, hey, what do I know? I’m just a dumb surgeon. Worse, I’m a pharma shill. :-)

  28. Basiorana says:

    @windriven: Of course the majority of us can manage our own affairs. And we do so by ignoring the ads, and simply talking to our doctors about symptoms and getting REAL medical advice. Or, if we’re REALLY good at managing our own affairs, we might read up some journal articles about different medicines, compare trials, then talk to our doctors about them once we have real information.

    However, the majority are not the targets of these ads. The targets are the elderly, the mentally ill/depressed, those with little or no critical thinking skills, the mentally disabled and hypochondriacs. A minority, but a vulnerable minority that are easily preyed on. To them, ads are the ultimate barriers to informed consent– they give them preconceived notions about their health and the medication that may or may not be accurate, so they don’t listen to their doctors and thus don’t receive real information.

    I believe that if you can’t independently go out and purchase a thing without permission of a third party, it shouldn’t be advertised to you. You can’t buy a tank without government permission, so tanks shouldn’t be advertised on TV. You can’t buy Cymbalta without a doctor’s permission, so Cymbalta shouldn’t be advertised on TV. Most of us won’t care because we ignore or mock those ads anyway, but it WILL help the few people this does affect, while easing the burden on doctors who won’t have to sit there explaining to an 80 year old woman that she doesn’t actually need Viagra no matter what the TV says.

  29. windriven says:

    @Zoe

    “Well, no. Overprescribing and direct to consumer advertising drives up the costs for everyone else. Sounds like a “what’s the harm” argument.”

    Oh pul-eaze. The price is determined by what the market will bear, not by the cost of advertising. We do not live in a ‘cost plus’ economy, we live in a market economy.

  30. windriven says:

    @Basiorana

    “The targets are the elderly, the mentally ill/depressed, those with little or no critical thinking skills, the mentally disabled and hypochondriacs.”

    Huh???

    Lipitor
    Viagra
    Ambien
    I’ve forgotten the name of the allergy one.

    These aren’t aimed at aged, mentally ill, morons. And each and every one of these requires a physician’s prescription. Have you so little confidence in MDs that you believe they can’t tell if their patient is an aged, mentally ill moron? Do you believe they just don’t care and write the script for grins?

    I think if you explored carefully you’d find that the marketing concept behind direct to consumer is to get the patient to work the drug into their conversations with their physicians. “Hey doc, I have high cholesterol, would Lipitor be a good thing for me to take?”

  31. weing says:

    Regarding osteoporosis and osteopenia, I think Harriet has the correct approach. Inform the patient and let her/him decide. My problem with the drugs is that they are not as effective as I would like. I would prefer an NNT in the single digits. I would not want to experience a compression fracture before starting these medications. The diagnosis is not that cut and dry either. The DEXA may give a score of -1.6, but when I review the measurements of the individual vertebrae, L2 may be -2.7 and the rest in the osteopenia range. When a vertebra collapses, its density increases also. I see compression fractures and no osteoporosis by DEXA.

  32. weing says:

    “while easing the burden on doctors who won’t have to sit there explaining to an 80 year old woman that she doesn’t actually need Viagra no matter what the TV says.”

    That’s funny. I saw a patient like that today and she was taking sildenafil three times a day. But it was for pulmonary hypertension.

  33. Zoe237 says:

    windriven:

    “Well, no. Overprescribing and direct to consumer advertising drives up the costs for everyone else. Sounds like a “what’s the harm” argument.”

    “Oh pul-eaze. The price is determined by what the market will bear, not by the cost of advertising. We do not live in a ‘cost plus’ economy, we live in a market economy.”

    Oh pul-eaze yourself. Overprescribing and direct to consumer advertising drives up demand, which drives up cost. It also drives up the cost of health insurance. The same can be said of any unnecessary medical intervention. “What the market will bear” is a direct reflection of demand. Now if people want a drug that’s not shown to better than a cheaper drug (or placebo), then they ought to pay for it out of pocket.

  34. Harriet Hall says:

    I think there may have been a bit of a misunderstanding. I do not think that non-drug treatments for osteoporosis are anywhere near as effective as bisphosphonates, although I was unable to find NNTs for them. I am strongly in favor of using the drugs for the indications I listed in the last paragraph.

    When I said that other lifestyle modifications might do more good in the long run, I was referring to Dr. Gorski’s BP example where the NNT to prevent a stroke was 120. In that case there are several other modifiable risk factors for stroke besides BP. If a patient stopped smoking, lost weight, controlled blood sugar, exercised, etc. it is likely that all those actions would do more good in the long run than the BP pill because they would reduce morbidity and mortality from other conditions, not just strokes.

    The point about comparing NNTs is well taken. We can’t just consider the risk/benefits of the drug in question, but we must consider the risk/benefits of all the alternatives including no treatment at all. And we must use good judgment and a bit of guesswork because the numbers are derived from populations and don’t necessarily apply to the individual.

  35. windriven says:

    @Zoe

    “Now if people want a drug that’s not shown to better than a cheaper drug (or placebo), then they ought to pay for it out of pocket.”

    Now there is something on which you and I are in complete agreement. But that is a rather different thing from banning direct to consumer advertising or dictating what people should or shouldn’t be able to obtain.

  36. Fifi says:

    windriven – “It is easy enough to say that we should ban information that we don’t like or don’t agree with. I spent a year and a half living in PR China and I’ve seen that done by the pros. It deforms people in subtle but important ways.”

    Advertising isn’t information, it’s propaganda designed to manipulate people to buy a product (in fact, it often obscures facts/information). It isn’t informing patients, it’s selling to consumers – it’s specifically designed to seduce, manipulate and convince someone they very much need that specific product to be happy/sexy/loved/healthy/rich/fill in the need (be it toothpaste, a car or “the purple pill” being sold). Direct to consumer advertising by drug companies was banned for many years (and still isn’t legal in some countries) and it was only allowed after intense lobbying by a consortium of pharmaceutical companies (Big Pharma that makes brand name drugs, not pharmaceutical companies that make generic versions of pharmaceuticals once patents have expired – these two parts of the pharmaceutical industry tend to be at odds with each other). The fact that people in the US are treated like consumers and not patients is exploitative and not in the best interest of the patient or the doctor, or the patient/doctor relationship. Certainly patients should be able to exercise informed choice, direct-to-consumer advertising actually interferes with informed choice by attempting to manipulate people and turn them into consumers of products rather than people to be cared and who take care of themselves.

    To compare regulating the advertising of drugs to censorship in China is hyperbolic and totally misunderstands and misrepresents what advertising actually is and is intended to do.

  37. Annalise says:

    I’m going to go with scam.

    In order to get a reduction on my health insurance rate, I had to fill out a health questionnaire through a separate company.

    I told them I smoke and rarely drink milk.

    They told me I needed to get a bone-density test.

    I’m 24 and 160lbs. I had told them that in the questionnaire, too.

  38. weing says:

    “Advertising isn’t information, it’s propaganda designed to manipulate people to buy a product (in fact, it often obscures facts/information).”

    Now that sounds like propaganda. Advertising can be both.

  39. DevoutCatalyst says:

    I love you, windriven. Anti-depressant television spots are a multiple-times daily affirmation that this stuff works, coupled with a subtle guilt trip, plus a self-diagnosis component/crib sheet on how to get a script from your doctor. Getting an SSRI prescription is child’s play. Dr. Kramer says we can become better than normal. Are people listening to Prozac or listening to placebo?

  40. lizkat says:

    “I’ve had friends (doctors) drop dead while running. Shin splints, stress fractures, muggings just to name a few harmful side effects. I’m sorry, but in my opinion, you do need an NNT and NNH for all these things.”

    First of all, I said walking, not running. Walking in daylight in a safe area has minimal dangers and tremendous health advantages. Never doing any physical activity at all is often deadly, in many different ways. No pill can compensate for such an unhealthy and unnatural lifestyle.

  41. lizkat says:

    “The point is that there are non-drug measures with essentially no harmful side effects that can be recommended before, AND ALONG WITH, the drugs. And that have other beneficial effects for other diseases. And that often get forgotten because people fixate on a pill to fix the problem.”

    Harriet is right.

    “If a patient stopped smoking, lost weight, controlled blood sugar, exercised, etc. it is likely that all those actions would do more good in the long run than the BP pill because they would reduce morbidity and mortality from other conditions, not just strokes.”

    In addition, the patient would not suffer from drug side effects.

  42. weing says:

    “First of all, I said walking, not running. Walking in daylight in a safe area has minimal dangers and tremendous health advantages.”

    I agree. But, I can’t prove it without data.

  43. lizkat says:

    “I can’t prove it without data.”

    Yes, it would be nice to have data on this, and on everything. But for right now, we should tell women to walk every day to prevent osteoporosis, and to ignore Sally.

  44. Harriet Hall says:

    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

  45. Fifi says:

    lizkat – “First of all, I said walking, not running. Walking in daylight in a safe area has minimal dangers and tremendous health advantages. Never doing any physical activity at all is often deadly, in many different ways. No pill can compensate for such an unhealthy and unnatural lifestyle.”

    Well said. There are certainly good enough studies that show the benefits of weight bearing and other exercise for women’s health as we age. Also, YOUNG women should be being taught what they need to do to ensure good health in later life. Not only is exercise essential for physical health, it’s also essential for mental health and has been shown to be preventative for cancer. It’s just weird for anyone to argue against it! Clearly people who can’t exercise for some reason are in a different category regarding healthcare in general.

    Anecdotes about the dangers of running don’t really mean much anyway since we don’t know how obsessive the runner was, if he/she was adequately replenishing minerals and fluids (not doing so can certainly trigger a heart attack), etc. Besides, most running injuries (heart attacks aside) are caused by poor form and fancy running shoes and not the simple, and natural, act of running.

  46. windriven says:

    @Fifi

    “To compare regulating the advertising of drugs to censorship in China is hyperbolic and totally misunderstands and misrepresents what advertising actually is and is intended to do.”

    Does regulating equal banning, comrade?

    Advertising is a form of communication. It may be hyperbolic. It may even be false. But it is still communication – speech if you want to frame it in constitutional terms.

    In this country we have the FTC and, where pharmaceuticals and medical devices are concerned, the FDA and these agencies assure, among other things, that the claims made – including advertising claims – are true.

    That, by definition, is regulating the advertising of drugs.

  47. windriven says:

    @Devout Catalyst

    “Anti-depressant television spots are a multiple-times daily affirmation that this stuff works”

    I wouldn’t know. I don’t own a television.

    But let’s say that you are correct. Are you suggesting that physicians are so weak-willed that they will not have a conversation with their patients about these drugs and their suitability or unsuitability? Are you suggesting that they would risk their livelihoods by just writing scripts willy-nilly for anyone who asks for a psychotropic pharmaceutical?

    Maybe if you are Elvis Presley.

  48. Tim Kreider says:

    Re: NNT discussion

    Is it apples-to-apples to compare NNT for treating a disease (depression) to NNT for preventing an adverse outcome (fractures)? I would expect higher NNTs for preventative measures in general, so I think the comparison between bisphosphonates and statins more useful.

    If the NNT for exercise includes poor compliance, then I’d like to know if the NNT of the pill accounts for real-world compliance (i.e. use outside a controlled trial) before directly comparing them. I have learned lately that taking a pill every day for the rest of your life is not particularly easy, particularly for pills with onerous requirements (don’t eat or lie down after taking, etc.) or annoying side effects.

  49. weing says:

    “Anecdotes about the dangers of running don’t really mean much anyway since we don’t know how obsessive the runner was, if he/she was adequately replenishing minerals and fluids (not doing so can certainly trigger a heart attack), etc. Besides, most running injuries (heart attacks aside) are caused by poor form and fancy running shoes and not the simple, and natural, act of running.”

    Anecdotes only mean that further studies are needed. I think it’s hypocritical to demand that drugs be subject to a level of scrutiny and required to meet safety standards that lifestyle recommendations are exempt from just because we all think that these things are good for us.

  50. JerryM says:

    Marketing to doctors isn’t all that advisable either.

    There was a consumer program that followed drug reps on rounds to family doctors here in .nl. Their behavioural tactics were devious, and the doctors often had no clue what was going on.

    This film apparently is now part of the course for students.

    Isn’t there be a centralized system, where a doctor could look for a drug for disease X, and have the results of a dedicated panel of doctors reviewing the available drugs for that particular disease? That way they don’t need to read every new article, and the drug companies can market to the panel, and they can collectively resist to temptation.

  51. Risk factors: a significant, but under-recognized, risk factor is sunlight exposure. Bone density has been shown to be low in those with less sunlight, shown to be variable according to season, and shown to respond to sunlight exposure intervention in institutionalized elderly. Physicians rarely assess sunlight exposure, and few physicians, including geriatricians, know what amount of sunlight is optimal. Few know that you can measure the sun exposure with a 35 dollar watch-like device (used to monitor over-exposure to UV to prevent sunburn in certain situations). People: this is totally overlooked, and is not rocket science. It does take an effort to ignore what the drug rep is spoon-feeding you.

    Also: lighter body weight: while this may translate into lower t scores and z scores, it may not indicate pathological level of bone density; if you are 100 pounds, you may not need the same bone density as a woman who is 200 pounds. Think back to the MCAT for the definition of “force.” As weight increases, a woman would exert geometrically increasing stress on her skeleton if running, falling, etc. I have looked at some risk studies, but have not seen risk of falls, or risk of hip fracture, analyzed by body weight. Thus, this moderator has not been elucidated, although it would be very easy. People: this is totally overlooked, and is not rocket science. It does take an effort to ignore what the drug rep is spoon-feeding you.

  52. weing says:

    JerryM,

    Uptodate and Medical Letter are like that. I prefer Uptodate. Expensive but worth it, in my opinion.

  53. weing says:

    “As weight increases, a woman would exert geometrically increasing stress on her skeleton if running, falling, etc. I have looked at some risk studies, but have not seen risk of falls, or risk of hip fracture, analyzed by body weight.”

    I recall reading something about this a few years ago and the winners were the overweight. The bone mass increases in order to support that weight, so that when you get into the postmenopausal state you have a much greater store of calcium in your bones. There is also the cushioning effect of the fat when she falls on the floor. I’ll try and find the references.

  54. Fifi says:

    medsvstherapy – “Risk factors: a significant, but under-recognized, risk factor is sunlight exposure. Bone density has been shown to be low in those with less sunlight, shown to be variable according to season, and shown to respond to sunlight exposure intervention in institutionalized elderly.”

    Thanks for posting this, yet another reason why vitamin D supplementation is so very important when one either lives in the North or don’t get to see the sun very often. Or, if one can manage it, a vacation in the sun to break up the winter.

    weing – “Anecdotes only mean that further studies are needed. I think it’s hypocritical to demand that drugs be subject to a level of scrutiny and required to meet safety standards that lifestyle recommendations are exempt from just because we all think that these things are good for us.”

    Actually, there’s been a lot of research into the effects of exercise on health in the aging and elderly done here in Canada and into exercise and osteoporosis all over the world. It’s one of the benefits of having universal healthcare, these kinds of studies get funded. It’s a bit sad that you seem so unaware of them and seem so influenced by the fact that a doctor you know had a heart attack while running (when no one was actually recommending anyone run a marathon or even jog).

    Of course, we need to define whether we’re talking about prevention or treatment of osteoporosis if we’re going to define the appropriate level and intensity of exercise (muscle strength and balance are also crucial factors in regards to falling and breaking bones). I seriously can’t believe you’re trying to argue against exercise and are so unaware of the research done in this area (not only in regards to osteoporosis but also other age related health issues). Are you just being contrarian? Do you not exercise yourself? Do you not inform your patients about the importance of exercise and diet in maintaining good health?

  55. weing says:

    I work out 45 minutes to an hour, 7 days a week. Yes, I do recommend exercise as I believe it has benefits and studies do seem to show that. I am just not convinced how much of a benefit. I also think that the risks of exercise have not been looked at to a sufficient degree. I refuse to believe that anything is risk free.

  56. Fifi says:

    Fair enough weing but there have been lots of studies on exercise in the aging and elderly, particularly vis a vis osteoporosis. (There’s been a lot of publicly funded research on this in Canada, universal healthcare combined with an aging population makes it worthwhile to do here.) Sure the research is generally focused on determining whether there are benefits or not but obviously if there were negative consequences these would show up too. Nobody is asking you to believe that anything is risk free – that’s something going on in your own head. Perhaps due to the heart attack someone you knew had jogging (apparently the fact that he was a doctor is also important to you, perhaps it personalizes the death?). Obviously, like anything else, it’s about appropriate exercise for the individual in question – which is perhaps something best prescribed by a specialist. There is a whole field of medicine – sports medicine – that deals with exercise and injury due to exercise. These things do get studied despite what you seem to believe!

    “Founded in 1970, the Canadian Academy of Sport Medicine (CASM) is a not-for-profit organization of physicians committed to excellence in the practice of medicine as it applies to all aspects of physical activity.

    Our mission is to forge a strong, collective voice for sport medicine in Canada; to be a leader in advancing the art and science of sport medicine including health promotion and disease prevention, for the benefit of all Canadians through programs of advocacy, education, research and service.”

  57. Fifi says:

    Also, I think it’s ridiculous that you seem to think there’s some prejudice against drugs and that pharmaceuticals are being treated unfairly next to exercise. Considering that most research into exercise is done in the public interest and most research into drugs is done by the pharmaceutical companies selling them (who have repeatedly shown themselves untrustworthy and happy to fudge the science when profitable), it seems quite reasonable to be more circumspect when it comes to the drugs (particularly ones still under patent). There really is no profit to be made from recommending someone talk a 30 minute walk or swim every day, or even much to be made from recommending yoga or lifting light weights. It’s why this kind of research is generally done in the public interest. (Though there is a benefit/profit from citizens being healthy in a country with universal healthcare, which is why you see more public sport facilities and promotion of exercise and healthy diet in countries with universal healthcare.) It’s a shame that you seem to be up on the drug research but not on the research into exercise, particularly since you seem to think exercising is worthwhile for yourself. Nobody here is proposing that exercise is magic, just that it’s part of maintaining basic health.

  58. weing says:

    “Sure the research is generally focused on determining whether there are benefits or not but obviously if there were negative consequences these would show up too.”

    I’m not sure I agree with that. If you don’t look for something, you may not see it. I don’t think pharmaceutical companies have that approach.

    “Nobody is asking you to believe that anything is risk free – that’s something going on in your own head.”

    Maybe you are right. I just got the impression from several posters here that only drugs have adverse effects.

  59. weing says:

    Oh, I am aware of the research. That’s why I exercise.

  60. lizkat says:

    “Yes, I do recommend exercise as I believe it has benefits and studies do seem to show that. I am just not convinced how much of a benefit. ”

    We should not think of exercise as an intervention or a medical treatment. We should think of the LACK of exercise as abnormal, unhealthy, and the main cause of many supposedly age-related diseases.

    Walking is the simplest and easiest, and quite possibly the best, way to avoid extreme inactivity.

    It is not so much that exercise is beneficial, it’s really that extreme lack of exercise, over a period of years, is harmful. Even deadly.

    (Too much exercise might be just as deadly as the complete lack.)

    weing it is surprising, and disconcerting, that you are not aware of the extreme dangers of the modern inactive lifestyle.

    Yes, junk food is also a factor. But the extreme inactivity of the average middle-aged American probably accounts for as much or more of the obesity and type 2 diabetes epidemic.

  61. Fifi says:

    weing – “I’m not sure I agree with that. If you don’t look for something, you may not see it. I don’t think pharmaceutical companies have that approach.”

    Well I was talking about research done in the public interest, which does result in unexpected results sometimes, which get reported. There’s no incentive to fudge the results (for the most part, I’m not discounting foul play or human nefarious totally, it just usually gets uncovered by other researchers when they try to duplicate results). I agree that pharmaceutical companies often seem to be looking for a particular positive result. However, they also very consciously, with full awareness, repress negative results. It’s not that they don’t see them, they see them and then hide them so they can pretend that the negative results don’t exist.

    “I just got the impression from several posters here that only drugs have adverse effects.”

    This is the problem with these kinds of discussions devolving into Big Pharma vs Big sCAM, people feel they need to take sides and get defensive. It’s unfortunate because it DOES start to make doctors look like they’re aligned with Big Pharma and see pills as the solution, when that’s not often actually the case (for the pills or the doctor, treatment of depression is the most alarming example of this). The reality is that science done in the public good tends to be better science than industry funded science – certainly in terms of public safety and concern for actual people (and certainly in the case of unprofitable preventative interventions). I know this often gets caught up in politics and peoples’ personal economic/political ideologies – particularly in the US where public science is seen as “socialism” and has become a battleground for the private interests of Big Pharma and Big sCAM, and a means of splitting and manipulating the electorate via religion. Unfortunately the amount of propaganda and repeated talking points from both sides means that this stops being a conversation about reality and becomes one about ideology (or people just reacting to triggers). The only winners in this are Big sCAM and Big Pharma – who both promote this false debate to sell their wares – doctors and patients both lose when they get caught up in what is essentially a marketing strategy dressed up as ideology. (Marketing is about creating emotional attachment to a product, attaching an ideology is one way to do this.)

    Weing, I appreciate you having this discussion with me and I do understand just how under assault doctors can feel by Big sCAM propaganda and the general distrust of doctors it’s created (so as to get people to trust sCAM artists, well intentioned though some CAM practitioners may be). However, let’s not throw the preventative medicine baby out with the bathwater or let Big sCAM steal her away. I’m pretty sure we agree that we need good science around this. It seems to me that will only come via increased funding and protection of public science (and keeping the greedy grubby hands of both Big Pharma and Big sCAM out of positions of power in science, and give it back to those doing public science). I’m quite honestly worried about the future of public science after seeing what’s gone on in the US and is being done in Canada (and I don’t see the Democrats/Liberals being much better really, they’ll reach across the aisle to support industry lobbyists and their own mercenary interests). What I see happening is my freedom to make an informed choice being eroded and the dismantling/perversion of public bodies that were intended to serve the public interest in favor of serving industry using taxpayer dollars. This isn’t about Left vs Right for me – since both have been seduced into the fake Big Pharma vs Big sCAM debate – it’s about science and reality-based thinking vs pseudoscience and the promotion of propaganda/marketing based unrealities as a replacement for reality. Neither doctors or patients can make a reality based decision if they’ve only got propaganda to base that decision upon (and even with good impartial science there are still risks since obviously we don’t know everything and we’re all an N of 1). Nothing is risk free, however we can minimize risks if we’re at least dealing with the best evidence we have at this point in time.

  62. weing says:

    “weing it is surprising, and disconcerting, that you are not aware of the extreme dangers of the modern inactive lifestyle.”

    Where did you ever get that idea?

  63. Geekoid says:

    Consumer advertising of medications needs to be banned.
    When people hear about a problem and it’s symptoms they tend to start thinking they have those symptoms, and when the doctors talks to them, they give bad information to the doctor. GIGO.
    If they are given the same medication, but under a generic name, people will sometime complain about the symptoms they think they have until the get the drug that’s been pounded into there head as the ‘cure’.

    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.

  64. lizkat says:

    “even if you exercise regularly you will die”

    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?

  65. weing says:

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

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

  66. I think winter is a Big Pharma scam. I was walking a good three miles a day until it got bloody cold.

  67. lizkat says:

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

    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.

  68. Fifi says:

    Geekoid – “even if you exercise regularly you will die”

    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!

  69. Fifi says:

    I’m with Lizkat on this one. Why are you handing out exactly the same advice to all your patients if you’re worried about exercise being dangerous? Aren’t you doing a risk assessment and prescribing appropriate activity for their individual level of ability and circumstance? And aren’t you even considering the patient’s ability to adhere to what you prescribe? Saying “walk five miles a day” isn’t really doing this and it’s certainly going to be less attractive than taking a pill, particularly when a doctor thinks the risks of exercise and taking a pill are more or less equivalent.

  70. Fifi says:

    Geekoid – I think most practicing GPs will agree with you about direct-to-consumer advertising (notice it’s to consumers not patients!). You make an excellent point about patients repeating symptoms they’ve seen on TV (though most advertising lists such a broad and vague list of “symptoms” that normal life has been pathologized). Feeling like your life isn’t perfect? Ask about the purple pill!

  71. weing says:

    The point is nothing is risk free. Most of my patients don’t like to take medications anyway and when I explain to my pre-diabetic patients that simply walking half an hour a day is better than any medication at preventing onset of diabetes and avoidance of more meds, they appreciate it. Please give me some credit as to knowing how much exercise to recommend to someone who has led the couch potato life for years! I also tell patients that death is a hunter, so present a moving target. Doesn’t mean they’ll live forever, but they’ll make it difficult for the grim reaper.

    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.

  72. lizkat says:

    Well weing you are starting to sound reasonable. What happened?

  73. Reviewer 3 says:

    Hi Harriet,

    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?

  74. BillyJoe says:

    Harriet,

    “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?

  75. fluoride says:

    Please don’t forget about MFP-Fluoride as a treatment for Osteoporosis. It was recommended for approval by the FDA’s advisory board but Big Pharma got it killed.

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

  76. Harriet Hall says:

    A recent meta-analysis showed that fluoride treatment does not reduce the risk of hip or spine fractures.
    http://www.ncbi.nlm.nih.gov/pubmed/17701094?itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum&ordinalpos=2

    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.

  77. fluoride says:

    Harriet,

    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.

  78. Harriet Hall says:

    fluoride,

    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.

  79. Calli Arcale says:

    Well, the inability to patent flouride sure hasn’t slowed down the dental health industry….or the companies which supply materials to cities to flouridate their water, or the companies which make bottled flouridated water for children.

    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.

  80. fluoride says:

    Harriet,

    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.

  81. Reviewer 3 says:

    Harriet,

    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.

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