Category Archives: Osteoporosis

Osteoporosis Drugs – You Got to Know When to Fold ‘Em …

If you are one of the millions of Americans taking a bisphosphonate drug for treatment of bone loss, you’ve most likely worried about what you’ve gotten yourself into.

Earlier this month, the FDA took the highly unusual step of publishing the results of their investigation into reports of atypical fractures of the femur occurring in long term users of drugs like Fosamax (alendronate), Actonel (risedronate), Boniva (ibandronate) and Reclast (zoledronic acid).

Now we have yet another investigation confirming the association of these fractures with bisphosphonate use, and correlating the increasing risk with increasing duration of therapy.

When categorized by duration of treatment, compared with no treatment, the odds ratio for an atypical fracture vs. a classic fracture were 35.1 for less than two years of treatment, 46.9 for two to five years of treatment, 117.1 for five to nine years and 175.7 for more than nine years.

What’s Going On Here? 

How do drugs that are supposed to prevent fractures cause new ones? That’s a good question. And the answer is complicated, so let’s see if I can simplify it.

Think of your bones as a road system that is constantly being remodeled depending on where the traffic is. There’s a large well-funded road crew constantly digging up the old road and replacing it with new road. They work in small sections scattered throughout the system, so as not to disrupt the road’s integrity. The members of the crew that digs up the old road are called the osteoclasts –

 and the ones who fill in and re-pave it are called the osteoblasts.

Now suppose over time, for whatever reason – age, bad weather (underlying medical conditions), lack of road material (vitamin D deficiency, menopause) –  you’ve dug up or lost more roads than you’ve replaced (Osteoporosis).  So you start treatment with a bisphosphonate like Fosamax or Actonel or Boniva. These drugs work by cutting back on the digging crew, but keeping the paving and refilling going in the areas that have already been dug up, thus rapidly bringing miles and miles of untravelable road into good use. Not to mention it’s a nice strong road, becoming mineralized over time. (That’s your bone density increasing.)

The whole thing is working so well that you send almost the entire road crew on a prolonged vacation. (Suppression of bone turnover, which is how bisphosponates work) Now you’re left with a skeleton road crew (pun intended), which, for most folks is still enough to deal with the usual cracks and potholes that appear over time, and can keep the road (your bones) in good working condition. But in some of you (perhaps those who are genetically predisposed) the downsized crew just can’t keep up with the repair work. As time goes on, the structural integrity of your bones becomes weakened. And then one day, for no apparent reason, just during the course of usual activity,  a small crack that the crew hasn’t yet repaired becomes a large crack – and you’ve just fractured your femur.

You don’t have to be on a bisphosphonate for these kind of atypical fractures to occur. Some folks just get them. But taking a bisphosponate increased the chances in predisposed individuals, and that chance increases the longer you take the drug, especially if your bone mass is in the osteopenic or normal range.

Exactly What are the Risks?

The chance that you’ll get one of these atypical spiral fractures while taking bisphosphonates is extremely low –  one study estimates the incidence at about 32 per million users per year, compared with over 10 times that many fractures prevented in the same million users.  So overall, the benefits of these drugs still far outweigh the risks.

However, drilling down into the fracture data reveals that we can do better than just accepting a rare risk in return for a common benefit.

Those who develop atypical fractures appear to be  individuals whose bone mass in the femur is in the normal or osteopenic range, as opposed to those whose hips show osteoporosis. This happens to be the very same group that recent studies suggest may safely stop Fosamax after 5 years without losing the benefits of having been on the drug.

So, if continuing the drog for longer than 5 years adds little benefit but increases risks, even if those risks are rare, it becomes pretty darned obvious what we need to do.  Stop the drug.

Which reminds me of that song from Kenny Rogers – “You got to know when to hold ’em / Know when to fold ’em / Know when to walk away /Know when to run… ” Not that treating osteoporosis is a gamble, but the Gambler’s advice rings eerily true for this class of drugs.

 

When to Fold ‘Em

New data suggest that as long as your bone density is above the osteoporotic range, you can stop taking your bone meds after 5 years.  Continuing the drug past that time only brings added risk without any benefit.

When to Hold ‘Em

If you’re at increased risk for fracture and have been taking your meds for less than 5 years, you may still be getting benefit without significant risk. Remember that these drugs decrease the risk of conventional osteoporotic fractures at over 10 times the rate that they increase the risk of atypical fractures, so don’t throw the baby out with the bathwater.  But make sure you are getting adequate vitamin D, calcium and weight bearing exercise to maximize the benefits you’re getting while you’re still on these drugs. And discuss with your doctor whether its worth considering coming off the drug in the future if your bone mass improves into the osteopenic range.

If you’ve been on these drugs for 5 years or more, but your bone mass is still in the osteoporotic range, you also may still be getting benefit from continuing treatment. Ditto if you’re at high risk for vertebral fractures. You are not in the group at highest risk for atypical fractures, but are in the group at highest risk for the more common type of osteoporotic fractures. Talk to your doctor about the comparative risks of continuing vs stopping treatment. It may not be a straightforward decision, as we don’t have exactly clear guidance on when to stop in everyone.  But at least have the conversation.

Should You Even Be in the Bisphosphonate Game?

Not everyone taking bisphosphonates needed to start them in the first place. Aggressive marketing and disease mongering by Big Pharma initially led to overuse of these drugs for treatment of osteopenia, a condition we now know does not necessarily need to be treated.  With the help of the FRAX fracture risk calculator, we’re now able to determine which patients with osteopenia are at significant fracture risk and require treatment (very few, it turns out) and which ones can be adequately managed with lifestyle, calcium and vitamin D (most).  Talk to your doctor about using FRAX before deciding if treatment is warranted. 

Remember too that bisphosphonates are not the only drugs that treat osteoporosis. Other medications to consider include hormone replacement,  Evista (raloxifene) and injectable terapeptide. Each of these drugs has its own set of risks and benefits, and some work better than others depending on your type and location of bone loss, so a reflex switch from bisphosphonates may not necessarily be the best option. As always, its best to talk with your doctor about what is right for you.

Bottom Line

The optimal duration of bisphosphonates for most individuals appears to be between 3-5 years. Beyond that point, unless there is osteoporosis at the hip or a high spinal fracture risk, there appears to be added risk rather than additional benefit to prolonged use of these medications, and it may be time to consider stopping therapy.

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Resources

 

Bone Density Testing – How Often Should It Be Done?

Not as often as you think, even though Medicare may be willing to pay for it every two years.

Now a new study led by Margaret L. Gourlay, MD, MPH of the University of North Carolina at Chapel Hill School of Medicine finds that women aged 67 years and older with normal bone mineral density scores may not need screening again for 10 years.

“If a woman’s bone density at age 67 is very good, then she doesn’t need to be re-screened in two years or three years, because we’re not likely to see much change,” Gourlay said. “Our study found it would take about 16 years for 10 percent of women in the highest bone density ranges to develop osteoporosis. That was longer than we expected, and it’s great news for this group of women,” Gourlay said. (Via Science News)

The researchers suggest that for T scores > -1.5, repeat testing needn’t be done for 10 years. Women with T scores between -1.5 and -2.0 can be re-screened in 5 years, and those with T scores below -2.0 can have every other year testing as is done now.

To be honest, I’ve been spacing out bone density testing in woman with good baseline scores for some time, but not knowing how long I can go. This is great information for me and for my patients.
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Image from Wikimedia Commons

Vitamin D – New Guidelines from the Institute of Medicine

Taking a lesson from the recent failures of vitamins to live up to their much-hyped potential for disease prevention, the Institute of Medicine is calling for caution in Vitamin D  use, concluding in a recent report that the prevalence of vitamin D deficiency and the health benefits of high dose vitamin D intake have been largely overestimated.

Scientific evidence indicates that calcium and vitamin D play key roles in bone health. The current evidence, however, does not support other benefits for vitamin D or calcium intake. More targeted research should continue. However, the committee emphasizes that, with a few exceptions, all North Americans are receiving enough calcium and vitamin D. Higher levels have not been shown to confer greater benefits, and in fact, they have been linked to other health problems, challenging the concept that “more is better.”

The group concluded that vitamin D intake of 600 IUs daily is sufficient for almost all adults up to age 70, with 800Iu recommended daily for those age 71 and older.

Re-defining normal vitamin D levels

The IOM has redefined normal vitamin 25 OH Vitamin D levels in adults as 20 ng/dL for the overwhelming majority of the population, with no additional benefit seen to having levels above 30 ng/dL, and potential harm when levels are above 50 ng/dL.

An urgent call for more research

The insitute is calling for urgently needed research to further define what, if any, role vitamin D may play beyond maintenance of bone health in normal individuals. Until then, caution is advised.

My take

As a clinician, I find the IOM report reassuring and helpful, since until now it seems as if everyone I screen has been vitamin D deficient, and I have been truly wondering how this could be in a population that is overall healthy, and at least here in NYC, getting some sun exposure every day.

Aiming for levels above 20 ng/dL, I suspect most of my patients will not need to take much more vit D than I am already recommending on a daily basis. I will certainly be backing off on treating those with Vitamin D levels already in the low-to-mid 20’s, which seems to be where most of my patients live.

A group I will still be screening and treating for Vitamin D deficiency are those with bone loss. Some of these individuals are older and have Vitamin D levels significantly below 20 ng/dL, which may be how they ended up with bone loss in the first place. For these individuals, I’ll continue my practice of prescribing short periods of high weekly dose D to get them up into normal ranges, then backing off to standard recommended doses.

Vitamin D Reduces Fractures

Vitamin D, if taken regularly and in doses higher than 400 IU daily, reduces fractures by up to 20% in older adults. So say researchers in a meta-analysis published in this month’s Archives on Internal Medicine.

Previous studies on the efficacy of vitamin D in preventing fractures have shown conflicting results, with some finding a benefits and others not. A team of Swiss and American researchers hypothesized that this variability in effect might be because some studies used too low a dose of Vitamin D and others did not accurately measure whether subjects even took the Vitamin D they were given. (We call that adnerence to therapy.) In addition, many previous studies did not control for baseline vitamin D levels or measure whether levels were actually increased with therapy.

In a complicated but nicely done meta-analysis, these researchers culled the cream of the crop of randomized clinical trails of vitamin D supplementation and fracture risk. Only studies that used higher doses of vitamin D, measured blood levels of Vitamin D and assessed subjects’ adherence to therapy were included in the analysis. The researchers compared fracture risk according to vitamin D dose and levels.

What they discovered was that doses of vitamin D of 400 IU daily were not effective in preventing fracture. Higher doses were – to the tune of a 20% reduction in non-vertebral fractures and an 18% reduction in vertebral fractures in individuals over age 65. (This is actually something that has been suspected for some time now, and in fact the current recommended daily dose of Vitamin D is 800 IU daily, with some saying that we should increase that further to 1200 IU daily.)

In support of the effect, fracture reduction was related to vitamin D levels, with higher levels showing greater reduction, up to a level of 112 nmol/ml (about 40 ng/ml). The benefits of vitamin D were seen irrespective of calcium supplementation.

The researchers recommend that future studies of Vitamin D and fracture risk use higher doses and longer duration of therapy, and measure both adherence to therapy and serum levels of vitamin D.

Take Home Message

Vitamin D indeed appears to be effective in reducing fracture risks, provided you adhere to your treatment and take over 400 IU daily. I’d recommend 800 IU daily. (And 1200 IU won’t hurt you…)

I’ve been measuring vitamin D levels in my patients with low bone mass, and have been not surprised to find that most of them are deficient. I love that I have an intervention for them that is both safe and inexpensive.
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Prevention of Nonvertebral Fractures With Oral Vitamin D and Dose Dependency. A Meta-analysis of Randomized Controlled Trials. Heike A. Bischoff-Ferrari, DrPH; Walter C. Willett, DrPH; John B. Wong, MD; Andreas E. Stuck, MD; Hannes B. Staehelin, MD; E. John Orav, PhD; Anna Thoma, MD; Douglas P. Kiel, MD; Jana Henschkowski, MD. Arch Intern Med. 2009;169(6):551-561.

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11/30/10 UPDATE

New IOM guidelines recommend vitamin D intake of 600 IU daily for adults up to age 70, and 800 IU daily for those age 71 and older.

Using the FRAX in Clinical Practice

This post is in response to Jane Brody’s recent NY Times article on the FRAX fracture risk calculator. FRAX is a clinical decision tool devised by the World Health Organization that allows physicians to account for the myriad of risk factors, including bone density, to determine a patient’s risk for osteoporotic fracture.

Now about 20 years into the practice of medicine, I have evolved from what they call an “early adopter” of new drugs, through a time of cautious use of new drugs, to what I am now – highly skeptical of most new medications and suspicious of Big Pharma, medical thought leaders and anyone else trying to “educate” me about a disease. I am also disappointed in my medical societies for failing to cut the ties between themselves and industry, but hopeful that we are slowly but finally starting to emerge from of an era of industry-dominated health care and into a time of patient-centered medicine.

Case in point – Treatment of Bone Loss.

I used to prescribe a fair amount of medication for treatment of bone loss, having fallen victim, I am ashamed to say, to the Big Pharma’s commandeering of medical education on Osteoporosis, with all the so-called experts telling us all that Osteopenia was a treatable medical condition rather than an arbitrary research category. (The story is one that should go into the Hall of Shame for medicine, and I encourage you to follow the link to NPR’s fabulous article about it.)

These days, I prescribe meds much less often for bone loss. With the help of the FRAX fracture risk calculator, I’m able to determine which of my patients with osteopenia are at significant fracture risk and require treatment (very few, it turns out) and which ones can be adequately managed with lifestyle, calcium and vitamin D (most).

I’ve been using FRAX for almost two years now, and find it to be an extremely helpful and objective tool. With it, I can calculate a person’s risk for fracture in the next 10 years. Then, using the WHO or National Osteoporosis Foundation guidelines for treatment, I treat only those with risks high enough to warrant medication. (I’ve also been screening for and treating vitamin D deficiency in a large number of women, giving me a non-pharmacologic treatment option for bone loss that is welcome by my patients.)

FRAX is not an entirely perfect tool. For instance, FRAX does not account for high risk medication other than steroids. For women taking drugs such as aromatase inhibitors, therefore, I fudge the FRAX by checking off the “steroid use” box. It’s not a perfect fix, but it’s not a bad one, either. Another fracture risk assessment tool called QFracture is under investigation as an alternative that may address some of FRAX’s limitations.

Despite its limitations, FRAX is a more than adequate tool in my clinical practice. I find sitting down with my patients and doing the FRAX together serves as great education for them and brings us together into the realm of joint decision making. I do the FRAX with them when they come in to have a vitamin D level checked – that’s a test I do routinely in women with low bone mass before deciding on any course of management. The FRAX only takes a few minutes to do, and my patients can take a print out of the results home along with their bone density results.

My major issue with the FRAX is that it seems to be a proprietary site. The FRAX tool is not integrated with any medical record system that I know of, which means I have to head to the FRAX site every time and enter information that already resides in my chart. This, I believe, limits use of the FRAX use and I would encourage the WHO to find ways to integrate FRAX into online EMR systems. Integrating FRAX results into bone density reports would also go a long way to increasing the use of this important clinical decision making tool. (I believe the NOF has made recommendations to radiology practices on how this should be done.)

By the way, in the NY Times article, Jane Brody describes FRAX as a “controversial” tool. I have not seen any controversy over its use. The National Osteoporosis Foundation appears to have embraced FRAX (actually, it was from them that I first learned about FRAX). The controversy lies in deciding if and when to treat bone loss. Like the mammogram controversy, the question is one of balancing potential harm (in this case, side effects of medication) with benefit ( lowering of fracture risk).

Fosamax – Can You Stop After 5 Years?

Stopping aledronate (Fosamax) after 5 years of use may be a reasonable option for many women using this osteoporosis-fighting drug, according to a research study published this week in the Journal of the American Medical Association.

In this multicenter study, which was funded by Fosamax manufacturer, Merck, and designed jointly by both Merck and non-Merck investigators, women who had been using Fosamax for 5 years were randomly assigned to continue aledronate for another 5 years, to continue for 5 years at a lower dose, or to take a placebo for 5 years.

Not surprisingly, stopping aledronate after 5 years led to a decline in bone mineral density at both the hip and the spine, and bone turnover increased. The loss of bone, though significant, was small, so that bone densities five years later were still higher than they were when aledronate was first started.

Women who stopped aledronate after 5 years did not have an increase in the rate of new non-vertebral fractures.

However, there was a significantly higher risk of vertebral fractures in women who stopped aledronate.

The protection provided by continuing aledronate beyond 5 years was evident among women whose T scores (measured at the hip) were below -2.0 at baseline and in women who had a prior risk of fracture. For women whose baseline bone density was above -2.0, the risk for fracture was the same whether or not they stopped or continued aledronate.

It should be reassuring to Fosamax users to know that no excess in adverse events occurred in the 10 year Fosamax use group, and no cases of osteonecrosis of the jaw were reported in the over 1000 Fosamax users in this study. There were also few differences in outcomes when the 5mg and 10 mg Fosamax doses were compared.

Understanding the results

Bone is a living tissue, undergoing constant reformation via a delicate balance between the breakdown of old bone by osteoclasts and the formation of new bone by osteoblasts. If bone breakdown exceeds bone formation, bone loss results.

Fosamax is one of a class of drugs called bisphosphonates. These drugs bind to the bone to cause the aptosis (cell death) of osteoclasts. This shifts the balance of bone turnover in favor of new bone formation.

Bisphosphonates bind very tightly to bone and can remain there for up to ten years. During this time, they continue to increase bone density and prevent fractures. Although no adverse effect of prolonged use has been reported, concerns remain, particularly in light of recent reports about osteopnecrosis of the jaw in bisphosphonate users. Interest has been growing to find ways to limit bisphosphonate use to shorter periods of time. This study was done in order to determine if Fosamax use could be limited to 5 years and still be effective.

Bottom Line

If you have been taking aledronate for 5 years, and your hip T score is above -2.0, it appears that you can stop your aledronate for 5 years without increasing your fracture risk. Women with certain medical conditions or at increased risk for fracture may do best to stay with with their medciation, so talk to your doctor to see if this applies to you.

If your hip T score is less than -2.0, then stopping aledronate will not increase you chance of a hip fracture over the next 5 years, but your risk of spinal fracture will increase. This increased risk is small and should be weighed against the risks of continuing the drug. Talk to your doctor about your options. If you are at high risk for fracture, it is probably advisable to continue taking you medication. A a one to two year drug holiday might be a good compromise between stopping your medication altogether and staying on it continuously. You could also consider lowering the dose.

If you do stay on bisphonsphonates for 10 years or more, be reassured that to date, long term use has not been found to increase the risk for adverse events.

Do these results with aledronate apply to other bisphosphonates, in particular, risedronate or Actonel? We have no data, but Actonel has a similar mechanism of action and duration of action to Fosamax, so it may not be unreasonable to expect similar results. Again, talk to your doctor.

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Patient information about osteoporosis from the National Osteoporosis Foundation and from The Hospital for Special Surgery.

Physician’s Guide to the Prevention and Treatment of Osteoporosis. This great resource from the NOF is downloadable and free with registration.

Category: Second Opinions

Pasta con le Sarde ala Chita Rivera

pasta and chita 2

In a recent post, in which I basically trashed the recent research on Calium supplements, I noted that the current recommendation is for women to get the majority of their calcium intake from food sources. I decided to take my own advice and made Pasta with Sardines, a classic Sicilian dish. Sardines are a great source of calcium – 4 oz has 300 mg of elemental calcium, a full 1/3-1/4 of the daily recommended requirement for most women.

I planned to make this dish on Saturday, hoping for an early dinner and a nice evening at home with my family. Late that afternoon, all plans for a leisurely dinner were quashed. Around 4 pm, we found out that Chita Rivera’s show “The Dancer’s Life” was going to close in 2 days, which made our tickets for Tuesday night obsolete. My husband had rushed to the box office to see if he could get tickets for the closing night show on Sunday. He returned instead at 5:15 with 4 tickets for that very night! Fine, we figured we’d eat a rushed dinner at 6:30 or so, and still have time to get to the theater at 8. We set to work together in the kitchen, my husband cutting up the veggies while I deboned the sardines.

About halfway through our preparations, the phone rang. My younger daughter’s friend was calling to see why my daughter wasn’t at her house for the special sleepover they had planned (and that we had thought was the following weekend). Now we had an extra ticket! Calls were frantically made to find a friend of my older daughter to accompany us to see Chita. My husband took my younger daughter to the sleepover while I finished the sauce and put it in the fridge to hold. By then it was past 7.

My older daughter’s friend’s father graciously drove us all to the theater. In usual New York fashion, we got stuck in traffic at 54th and 6th. So we jumped out of the car and ran through the freezing night the remaining 6 blocks to the theater, cursing ourselves for not taking the subway, stopping only to warm ourselves on a subway grate (now we knew why the homeless slept there.) We just made the curtain.

We returned after the show to cook the pasta and eat our dinner, in relaxed European style, at 10:30 pm. Luckily, the sauce kept beautifully.

Was it worth all the running around? You bet. Chita was amazing! Singing and dancing for 2 hours at the age of 72! And do you know that her left leg was broken in 12 places in an automobile accident in 1986? Now that’s a woman who must get enough calcium!

Pasta con le Sarde

Most recipes for Pasta con Sarde (and there are probably as many recipes as there are cooks in Sicily) call for anywhere from 1 to 3 8-10 oz. cans of sardines in oil. The recipe on which I based this dish comes from Mario Batali, who calls for 3 pounds of whole fresh sardines! I like sardines, but not that much, so I used about 9 ounces. If I make this again, I will also add a can of anchovies in oil.

2 lbs fennel bulbs, greens removed and reserved, bulb cut into sticks.
9 oz whole fresh sardines
flour, for coating
1-1/2cups extra-virgin olive oil
2 medium onions, minced
3 cloves garlic, minced
1 (28 oz) can whole tomatoes with juice, pulsed a few times on the food processor to chop
3 tbsp pine nuts, lightly toasted
3 tbsp raisins, soaked in a little white wine
salt and pepper to taste
7 saffron strands
1 lb dried bucatini (also called perciatelli, basically thick spaghetti with a hollow center)

In a hot skillet, add olive oil and saute fennel until caramelized. (Next time I’ll add the onions at this step and carmelize them too. )

Remove the heads of the sardines and pull out the backbones and entrails. (You don’t need to do this if you decide to use canned sardines instead.) Select a few sardines for garnish. Chop the rest of the sardines for the sauce, set aside.

Season the flour with salt and pepper, and dredge the selected unchopped sardines in it. Heat 1/2 cup olive oil in a small saucepan until it starts to smoke. Cook the flour-coated sardines in the oil until a light golden brown, about 1 minute on each side. Using a slotted spoon, remove the sardines from the pan and set them aside to drain on a paper towel.

In the skillet with the caramelized fennel, add the onions and cook about a minute. Add the garlic and cook a bit. Add raisins, tomatoes, pine nuts and saffron. Season, to taste, with salt and pepper. Bring the sauce briefly to a boil and then lower to a simmer. Add the reserved sardines and cook, stirring occasionally with a wooden spoon, until the sardines have broken into pieces and are thoroughly mixed into the sauce, about 10 to15 minutes. If the sauce appears too thick at this point, add a little of the pasta cooking water.

Bring 6 quarts of water and 2 tablespoons of salt to a rolling boil. Add the bucatini and cook until tender but still al dente. Drain the cooked pasta into a large serving bowl, add 3/4 of the sauce and stir to combine. Top with the remaining sauce and the fried sardines.

This pasta tastes best if allowed to sit for several minutes, soaking up the flavors of the sauce, before it is served. Keep the pasta covered during this waiting period, then garnish with reserved fennel fronds.

Category: Food, Second Opinions

Calcium Confusion From the WHI

In yet another media “bombshell” from the Women’s Health Initiative and the New England Journal, we are now being told that calcium isn’t as good as we thought in preventing fractures. (See study here.) Moreover, women who take calcium supplements have higher rates of kidney stones than women who don’t. And once again, the media is off and running…

No problem. I can handle this one with my hands tied behind my back…aiebpqiwuy756435yh 46ty2w4… Oh, sorry, I forgot that I can’t type with my nose. Let me get my other shoe off, I’ll use my toes. Okay, are you ready? ‘Cause here we go…

First, let’s talk about the intervention studied by the WHI : Approximately 36,300 women nationwide were randomly assigned to placebo or 1000 mg/day elemental calcium combined with 400 IUs/day of vitamin D. The primary outcome was osteoporotic hip and other bone fractures, with colon cancer as a major secondary outcome. Overall, women assigned to take calcium supplements had no less osteoporotic fractures than those taking placebos.

What???? Oh, wait. I understand. When they looked at women who actually took the pills as advised, there was a 29% reduction in fractures.

So, what they seem to be saying is this – telling women to take calcium and vitamin D doesn’t prevent fractures. Sort of like telling my kids to brush their teeth to prevent cavities – it only works if they actually do it. OK, I’ll buy that.

The statisticians don’t like to hear this. They prefer the purity of an intent to treat analysis, where the only valid comparison is what goup study participants were assigned to, not what they actually did. As a clinician, I alswys have trouble with intent to treat analysis – I tend to want to drill down and find out why. I would argue that this is as valid as the intent to treat.

A benefit was also seen to calcium supplementation in the over-60-years-old crowd. Gee, that makes sense too. I wouldn’t expect to see a big difference in fractures in the under 60 crowd, because that group doesn’t get many fractures. And if someone in that age group is breaking her hip, I’d have a strong suspicion there’s something else going on other than just age. Like maybe anorexia or smoking or an overactive parathyroid gland or malabsorption, to name a few possibilities. No amount of calcium is going to fix that. Hmm…So far, it sounds like calcium is doing exactly what I’d expect it to do.

But that’s not what CBS News says. Their headline? “Calcium, Vitamin D Assumptions Shaken.” Why? Because the big groups analysis showed no benefit to calcium, that’s why. And do you know why? Because the women who received placebo were allowed to take calcium and vitamin D supplements on their own! That’s right. Here it is, right out of the WHI press release: “Since participants were not restricted from taking personal calcium or vitamin D supplements, they had a relatively high calcium and vitamin D intake at enrollment and intake rose even higher during the trial so the impact of study supplementation may have been muted.”

What the researchers are telling you is that since they didn’t control the very intervention they were studying, their results might not be right.

Oh, and one more confounding issue. They also did not restrict the use of Fosamax-type drugs in either group, so about 15% of women ended up on these fracture-preventing meds during the course of the study. This means that most likely the women at risk for fractures in both groups were already taking a more effective medication than just calcium and vitamin D.

Are you getting all this?

Now, let’s talk some more about the WHI’s intervention – namely, giving all women the same dose of calcium, regardless of what amounts they may have been getting in their diet.

You know what? This is not the way we doctors recommend that women take calcium.

Here’s the recommendation of the National Osteoporois Foundation and the American College of Obstetricians and Gynecolgists: “Food is the best source of calcium; however, most Americans do not have enough calcium in their diets. Fortunately, calcium-fortified foods and calcium supplements can fill the gap, ensuring that the daily calcium requirement is met. The amount needed from a supplement depends on how much calcium is consumed from food sources.”

Hmm…I don’t see any recommendation that every woman be given 1000 mg of calium as a supplement daily. Gee, I wonder what might happen if women were to take calcium supplements without taking into account their dietary sources? Maybe they’ll get too much calcium. And what can too much calcium cause? (Let’s shout it out together, shall we?) KIDNEY STONES!

Oh, wait, wait… I forgot to tell you about the vitamin D dose studied – 400 IU daily. Unfortunately, it’s too low. The current recommendation is 800 IU daily. (And not 600 IU as the NY Times says.)

Quick take

And there you have it, folks. The WHI researchers designed an intervention that doesn’t match current medical recommendations, failed to adequately control the intervention they were studying, and then used their results to question the very medical recommendations they didn’t follow. Yet despite this, they did manage to get some results that make sense if you understand what really happened.

Fortunately, Gina Kolata at the New York Times understands it. Here’s her headline: “Big Study Finds No Clear Benefit of Calcium Pills”. That just clears it all up for everyone, doesn’t it? And this from Forbes: “Calcium, Vitamin D Won’t Protect Older Women From Fracture.” The fact that it was the older women who actually did show a benefit is irrelevant to the headline. No wonder we’re all confused.

Here are the current recommendations for calcium and vitamin D (click here). I wouldn’t change a thing.

Mrs. O’Leary Milking Daisy by Norman Rockwell
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Comment : define_me
February 16, 2006
Maybe I should aim to get my first publication with the New England Journal of Medicine…hehehe

Comment: Anonymous
February 17, 2006
Between the calcium and fat study, the headlines should read: Impossible to do prospective food study; massive waste of money and time. Conclusion: retrospective food studies, or even large population studies (Japanese on traditional diet v. American diet) are clearly the best information we’ll get—and far cheaper.) I’m not even going to think how many children could be fed and vaccinated, or how much prenatal nutrition could be paid for with the 415 million from the fat study…

Comment: Guinness_Girl
February 17, 2006
That’s all I have to say. Wow