If you were diagnosed with osteoporosis four or five years ago, or if your doctor said your bone density was getting dangerously low and you needed medications, you joined a large group of porous-boned individuals. Osteoporosis affects 10 million Americans; another 34 million have osteopenia (low bone mass). A recent article in the May issue of The New England Journal of Medicine titled “Bisphosphonates for Osteoporosis – Where Do We Go From Here?” discusses the timing and length of indicated therapy.  Apparently  more than 150 million prescriptions have been written between 2005 and 2009, some of them by me…

A quick pharmacologic review: bone is a living tissue that is constantly undergoing resorption (micro drilling) and formation (filling of those micro holes). When the drilling exceeds the filling, bone loss occurs. Over time, the bones can become so porous that they can break or, in more medical terms, fracture. The class of medications called  bisphosphnates such as Fosomax, Actonel, Boniva and Reclast stop the drilling allowing the  filling to continue and thus the bone accumulates lost mass. The bisphosphonates are also incorporated into the newly formed bone and can persist there for years through ongoing cycles of bone resorption and deposition. But with long term use, side effects can occur; these include jaw necrosis and abnormal bone formation. The latter, albeit rare, can cause the long bone in the thigh to loose it’s architectural strength and stability and subsequently break with minimal or no trauma. (This is called an atypical femur fracture.)

The FDA recently reviewed the available long term data on bisphosphonates. Overall  all these medications were effective and increased bone density over a period of three to five  years. Continuation of treatment beyond five years was found to maintain the improved bone density in the  most delicate part of the femur (the femur neck) and improved bone mineral density in the lower vertebrae of the spine (the lumbar area). In patients who were switched to placebo after five years of therapy, bone mineral density in the femoral neck decrease “modestly” during the first two years and then stabilized while the lumbar spine bone density continued to increase.

Ultimately, however, it’s not the numbers in the bone scan that count. The endpoint of therapy has to be a significant decrease in fracture rates…and so far the benefits of fracture protection from continued therapy has been inconsistent. The authors of the article note that pooled data from several studies of patients who have received Bisphosphonates therapy for six years or more shows that fracture rates ranged from 9.3 to 10.6% whereas rates for patients switched to placebo after five years was 8.0 to 8.8%. It seems that at least for some patients stopping therapy after five years won’t compromise their bone gain. They may be a subset of patients, however, that are still at increased risk for fracture, especially older patients with a history of fracture and a bone mineral density that remains in the osteoporotic range. These patients may benefit from continued Bisphosphonate therapy.

Bottom line: if you started one of these bisphosphonate medications to prevent or reverse bone loss and your bone density scan is no longer in the osteoporotic range, or if your bone density improved (although still low) and you have had no fractures, you and your doctor may want to consider discontinuing therapy after five years.

I started to write this in an airport lounge on my way to visit family. I’ll probably finish it in a day or two. But leave it to the Danes…they were in no hurry; they took 15 years to complete an exhaustive study of over 1,626,158 women. So reporting what they found in a few paragraphs should be fairly effortless and sans personal excuses. Here we go:

A unique identification number is given to all Danish citizens at birth and to those who have immigrated; then recorded in all public registries. These numbers are also used to provide data on the length of schooling, status of education, vital statistics, and emigration. All public and private Danish hospitals register the diagnostic codes together with the patient’s identification number whenever anyone is admitted and treated or, heaven forbid, die. And to add to this ” big brother ” scenario, the country maintains a Register of Medicinal Products Statistics which is updated daily, and provides information about filled prescriptions for oral contraceptives and other types of hormonal contraception. Finally, information about smoking habits is currently available for 480,223 women.

Obviously the Danes are statically in a phenomenal position to answer questions about the use of hormonal contraception and a possible correlation to the risk of major, life-threatening complications, such as stroke and heart attack.

And this is what they did in a recent study published in the New England Medical Journal. But before I get to their data on hormonal contraceptives I should point out three other facts that were “discovered”. First, women with the highest level of education had half as many thrombotic strokes (caused by a clot blocking an artery in the brain) and one third as many myocardial infarctions (heart attacks) as women with the lowest level of education. Second, the rates of thrombotic stroke and myocardial infarction were increased by factors of 20 and 100, respectively, in the oldest group (45 to 49 years) as compared to the youngest age group (15 to 19 years). And thirdly, the not-at-all-surprising fact was that for women who smoked, the relative risks of thrombotic stroke and myocardial infarction were 1.57 and 3.62 compared to women who did not. (Just in case you don’t remember what that means…and I’ll use the latter number…women who smoked were more than three and a half times more likely to have a heart attack, simply due to smoking!)

Now the rest of the study results: Women who used the pill with an estrogen called ethinyl estradiol ( which is the estrogen used in most combined estrogen and progestin birth control pills) at levels between 30 and 40 micrograms (considered low dose pills) were found to have a risk of arterial thrombosis that caused a stroke or a heart attack that was 1.3 to 2.3 times higher than the risk among nonusers; and women who used pills with a lower ethinyl estradiol dose of 20 micrograms (termed very low dose pills) had a risk that was 0.9 to 1.7 times higher than that of nonusers.

And here is where I want the lawyers to pay attention: the type of progestin in the birth control pill made a very small difference in these risks. That means that the first, second and third generations of progestins were similar in their risk ratios when it came to arterial thrombosis. The latter includes the third generation progestin called drosperinine which has been maligned in pills such as Yasmin and Yaz.

None of the progestin-only products, including the progestin-releasing IUD increased the risk of stroke or heart attack, but the authors stated that the numbers of these products used were rather small and analysis less accurate. On the other hand, risk was increased over three fold for thrombotic stroke among women who used the contraceptive patch and nearly two and a half times among those who used the vaginal ring. The number of heart attacks was too low to provide reliable estimates.

Now before anyone totally freaks over these numbers know that out of the 1,626,158 million women followed for up to 15 years (which in person years was14,251,063) only 3311 women had thrombotic strokes and 1725 had myocardial infarctions. So the overall risk was very low. And when you take a rare occurrence and state that the risk is doubled or tripled it is still extremely rare.

Bottom line: The lowest amount of estrogen in a birth control pill is associated with the least risk. The type of progestin doesn’t make a significant difference in risk, and altogether these types of serious risks are extremely rare. Blood pressure, family history and the risks associated with pregnancy should be considered when birth control choices are made.

I routinely read the section in JAMA that gives quick news updates. (But just so you know, I also scan the journal for relevant articles.) This last week one of the updates made me use my most favorite sentence: “I told you so…”.

Researchers analyzed data from 193,083 adults who received the shingles vaccine between 2007 and 2008. They were all 50 or older.. The only “adverse” event that they found that had occurred was a small increase in redness, swelling, and/or tenderness at the injection site. And no increase was seen in stroke, heart attack, meningitis, encephalitis, or Bell’s palsy. I recommended the shingles vaccine for everyone over 60 two years ago (see my archived article titled “Out, Out Damn Pox“) but that recommendation has been “down-aged” to 50.

So if you or a family member has not received it, get thee to a pharmacy or a physician who carries the vaccine. We have to assume that virtually all Americans who are 50 or over have had chicken pox. And once you’ve had it the virus it stays in your system forever! As we get older and/or develop diseases that stress our immune system, the virus can reappear and spread along a nerve root to form extremely painful lesions that may last for months. And even when those lesions fade, the irritated nerve can continue to cause severe pain. The shingles vaccine can significantly diminish the chance of this occurring, so frankly it’s a no brainer (or a no “never”).

Before I begin my usual reporting on published studies, I want to thank those of you who emailed or wrote to me with condolences on the death of my father. A friend who attended his funeral felt that I had omitted one of his most salient traits in the short eulogy I posted last week. My father was a true feminist. He had two daughters and felt that they could choose any career that they wanted, even in the then male – dominated fields of math and science. A generation (or 2) later we are still encouraging gender equality in these fields while it also appears (I have to add this) that our reproductive rights have been brought into question. So thank you Daddy…. your push for science education paid off…even if (in his world of theoretic physics) it led to “just” medicine. I will always be grateful.

Now onto the question of calcium supplementation: As soon as the article published in the British Medical Journal Heart was brought to everyone’s attention by the media, patients called my office asking “Should I continue to take my calcium supplements?”

The article was based on a prospective study of approximately 24,000 men and women in Germany who were between the ages of 35 and 64. The participants answered questions about their diet, dietary calcium and use of supplements and/or calcium only supplements during the 11-year study period. The brands and quantities of supplements were not identified. A self-administered questionnaire was used to assess consumption of 148 food items. From the latter, the amount of dietary calcium intake was calculated. And, of course, dairy foods were the main sources of dietary calcium. The participants were also asked if they had taken vitamin/mineral supplements in the last 4 weeks prior to the survey or if they took calcium only. They were then divided in four groups (or quartiles) depending on dietary calcium intake (high or low), use of multiple supplements or calcium only.

The authors reported that total dairy or non dairy calcium intake did not have a statistically significant association with cardiovascular risk except for a “likely” reduction of heart attack associated with a higher dairy calcium intake. But the study also suggested that heart attack risk might be “substantially” increased by calcium supplements. Those who took only calcium supplements were, in their calculations twice as like to suffer heart attacks as those who didn’t take any calcium supplements.

They also stated that a higher calcium intake was associated with favorable factors, including younger age, higher likelihood of having a university degree and being physically active, less likelihood of being overweight or obese, an average shorter time of having smoked and lower lifetime alcohol consumption. Compared with non-users, users of calcium supplements were more likely to be women, physically more active and less likely to be overweight/ obese. However, users of calcium supplements were older, had an overall lower educational level and a longer duration of smoking. (So this means that they had additional factors that could contribute to heart attacks.) There was one more issue that I found concerning when I read the article; and that had to do with the actual low number of participants who took the calcium- only supplements; just 3.6% of all the study participants. Moreover there was no indication of dose or type of calcium supplements that were taken.

Having come to my own “this is not sufficient” conclusion while reading the article, I also agree with the official one offered by the president of the National Osteoporosis Foundation (NOF): “While the benefit’s of calcium to bone health are well documented, this study’s findings are inconclusive.” The organization feels that more research is needed to better understand the potential relationship between calcium supplements and heart attack and that individuals should continue to meet their daily calcium needs from food sources first, and not (based on this article), discontinue calcium supplements.

Remember, everyday we “use up” calcium through our body’s metabolism, excretion (urine and feces) and sweating. In order to keep the calcium level stable in our blood and tissues, we either have to intake what is lost or get it from our internal calcium storage… our bones. Based on a huge amount of clinical data the current NOF recommendation for daily calcium intake is 1,000 mg daily for women under age 50 and 1200 mg for women over the age of 50.

There is no doubt that that best way to get your calcium (or any of the other vitamins and minerals on the food and pharmacy shelves) is though nutrition. The food with the most calcium will be dairy-based. So go for that milk, yogurt and cheese but make sure it’s low or non-fat. You can also get calcium in fortified juices and soy milk. Finally, don’t forget the green vegetables such as kale, broccoli and spinach. If you want to figure out how much you are getting in your packaged products just look at the table of nutrition facts….it will tell you the percentage of calcium in a portion. Know that this is calculated from a daily requirement of 1000mg. (Somehow the manufacturers forgot that many of us are over 50 and need more.) So 30 % will mean 300 mg. Just spend a day or two figuring out what you usually eat and how much calcium you are getting. That’s what I do. If at the end of the day I didn’t have that yogurt or milk (in my latte) I add it on at night or the next morning. And remember, we can’t absorb more than 600 mg at a time with most of the supplements (slow release may be the exception)….so don’t try to get it all at once.

We don’t have to become stooped, little old ladies who are in pain, or immobilized. And although calcium and vitamin D are not going to reverse osteoporosis, sufficient amounts will help prevent bone loss.

Greetings Patients and Friends, I will not have the usual medical related article this week.

Last Saturday my father passed away peacefully. He was 92.

Israel Sentizky was a brilliant physicist, violinist and most importantly a devoted husband and phenomenal father. He taught me advanced math (before I was emotionally advanced enough to appreciate it) and spent hours driving his two daughters to daily dance classes in NYC. When asked how long he wanted to live, he replied “Long enough to take care of my wife.” She passed away in January… My sister, his grandchildren and I will always miss him.

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