No News Usually Good News: Bisphosphonates (Fosamax)

I was once at a Chinese restaurant and when I opened my fortune cookie at the end of the meal I found no fortune. When I told the waiter, he smiled and said, "no news is good news."
It seems to me, that it least when it comes to reporting on medical news, the media tends to only report on one thing: bad news. Medical headlines are often about a common drug that has now found to be dangerous or what you are eating/doing that will probably kill you. The rare exception tends to be a story about the latest miracle cure (usually with little to no evidence to support it). This is one of the reasons I started this blog: to give a broader, balanced physician's perspective on media headlines; to allay fears or let patients know when they are actually warranted. One of my frustrations with the media has been lack of reporting on additional research after a major story, especially when that research is actually reassuring.

One of the best examples of this has been Avandia. Recently, the media was quick to pick up on a Senate report regarding concerns on the way the company (GSK) and the FDA handled Avandia's safety data. The Avandia story first made headlines in May, 2007 when Dr. Nissen's meta-analysis on Avandia was published the New England Journal which claimed that Avandia increased the risk of heart attack by 43%. However, the media never really covered the RECORD trial, whose results were released in July, 2009 that showed Avandia does not in fact increase heart attacks. Even if they felt it was not necessary to mention the RECORD study in July 2009, it was inexcusable not to mention this when reporting about the recent Senate report, which bashed the drug and it's maker, but failed to mention any of the new, reassuing data.
When I prescribe Avandia to patients, they are still convinced that the drug is dangerous. This is because the media reported the bad news (back in 2007, and more recently with the Senate report), but never the good news. In fact, in response to the Senate report, a group of cardiologist who had been studying this class of medications extensively released their report earlier than planned. This report was extremely reassuring regarding Avandia safety. Yet, there was no mention of this in the press.

The latest example is bone fracture and bisphosphates. I blogged about this last month, when two reports from a medical conference surfaced, and these concerns were given significant media attention, including a Diane Sawyer piece on ABC. The class of drugs is called bisphosphonates and include medications like Fosamax (now available as generic alendronate), Actonel, and Boniva- the drug pitched by celebrity spokesperson Sally Field. These drugs are designed to treat osteoporosis which is a condition where the bones become brittle; but there had been some reports of rare, but serious bone fractures. In my blog post back then, I noted how the FDA was aware of the reports, had looked at the issue, and found no compelling reason to issue a warning. I also noted that most of these fractures occurred in women who had been on bisphosphonates for a long time, and that new evidence suggests five years is enough. After looking into the issue further, I found that there was a population study that suggested there was no link between these medications and dangerous fractures.

Now for the good news! In the current issue of the New England Journal of Medicine, several researchers took this issue head on. They combined the data from large, randomized controlled trials to look for any risk. In the three trials they examined, which included over 14,000 patients, they found no increased risk.

They state, "the occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare, even among women who had been treated with bisphosphonates for as long as 10 years. There was no significant increase in risk associated with bisphosphonate use, but the study was underpowered for definitive conclusions."

This study, along with other information is very reassuring for the millions of women taking these medications, now wondering whether or not they are safe. Why did the media not give this new study even 5% of the attention they gave to some of the initial concerning reports? Why is it that the media reports only when there are concerns about treatment, and virtually never reports about studies that subsequently show that these initial concerns are unfounded? Why does the media feel it can only attract readers/viewers with tales of woe?

Bottom Line: Often you will never hear about good news regarding medical treatments because the media does not cover this information. Ask your doctor, or go online yourself, before completely discounting a recommended medication or treatment due to safety concerns you may have heard about. Regarding bisphosphonates like Fosamax and Boniva, these appear to be safe medications, though I would still not recommend taking for more than 5 years.

Blood sugar, high blood pressure and cholesterol control still important for diabetics.

The secondary findings of the ACCORD trial reported out today, and already the media is buzzing. Though the news was disappointing, the results are not nearly as bad as some of the media headlines are making it out to be. ABC News is reporting: ACCORD Study: Cholesterol, BP Control Does Little Good for Diabetics and MSNBC states that Intense treatment hopes for diabetics dashed. If I were a diabetic, I might think that controlling blood pressure and cholesterol was not important. However, this couldn't be further from the truth.

The same thing happened when the media first reported that the ACCORD study was stopped.
( See ACCORD and ADVANCE: Good News for Type 2 diabetes...really). This first part of the study was looking at whether or not intense lowering of blood sugar to normal (A1c less than 6%) prevented heart attacks and strokes more than the current standard of care (A1c less than 7%) which had not proven to reduce heart attacks or strokes. The study was stopped early because there were more heart attacks and deaths in the intense group. However, though the media headlines similarly questioned the role of blood sugar control back then, the good news was that the rate of heart attacks and strokes were much lower than expected. In other words, good sugar control in diabetics is likely important in preventing cardiovascular disease; however, intensely lowering blood sugar is probably not a good idea.



What was reported today at the American College of Cardiology meeting was the blood pressure and cholesterol arms of the study. The blood pressure arm similarly looked at getting the blood pressure to normal (120/80) compared to standard care. Again, both groups had fewer heart attacks and strokes than expected. Thus, blood pressure control is important, just not continuing to add medicines until the BP is normal. The cholesterol arm of the study looked at something different. All the patients were given statins, but half were randomized to fenofibrate, a different kind of cholesterol medicine that doesn't affect bad cholesterol too much (LDL), but does raise good cholesterol (HDL) and lowers fats (triglycerides). Unfortunately, there was no difference in heart attacks or strokes in either group. However, when you looked at diabetics with low HDL and high triglycerides, there was an improvement. In other words, unlike statins which should be given to every diabetic, fibrates should be used only in diabetics with low HDL and high triglycerides. Again, this reinforces the importance of cholesterol lowering in diabetics, despite what the headlines may read.

Bottom Line: If you are a diabetic, try and keep your A1c under 7%, and don't take any more medicines (especially insulin) to try to get the A1c any lower. Blood pressure and cholesterol control are also very important. Diabetics should keep the blood pressure under 130/80, but don't need to keep adding medications to get it perfect (under 120/80). All diabetics should take a statin medications (regardless of LDL number), and if your triglycerides are above 200 and HDL is below 35, add a fibrate to the statin.

Stop Fosamax After Five Years

There has been a flurry of news about osteoporosis drugs in the media being dangerous. The class of drugs are called bisphosphonates and include medications like Fosamax (now available as generic alendronate), Actonel, and Boniva- the drug pitched by celebrity spokesperson Sally Field. These drugs are designed to treat osteoporosis which is a condition where the bones become brittle. Osteoporosis is common in older women because estrogen, which decreases after menopause, prevents bones from breaking down. In the past, hormone replacement was the primary treatment and preventative agent for osteoporosis, except the Women's Health Initiative study found hormone replacement to be associated with increase cancer and heart attack. Since that study, bisphosphonates have dramatically increased in use. In fact, there is good data to show that bisphosphonates not only strengthen bones, but can prevent fractures. Fractures of the spine and hip can be extremely debilitating.

However, reports from two recent studies surfaced and have created a media storm, and likely significant confusion for the millions of women that take these drugs. Today, the USA Today reported Long-term use of osteoporosis drugs linked to hip breaks and proud ABC boasted in its headlines: FDA to Investigate Possible Osteoporosis Drug-Femur Fracture Link After ABC News Report . This occurred after a Diane Sawyer story about a physician taking a bisphosphonat, who suffered a femoral fracture by doing nothing more than walking. The femur is the long bone in the leg. It is a strong bone, and rarely fractures, unless there is extreme trauma. Thus, it was surprising when reports surfaced of women similar to the doctor Ms. Sawer interviewed having sudden, non-traumatic fractures of their leg bones.

This is not the first we have heard of these reports. In today's FDA statement in response to the media attention (see FDA Drug Safety Communication: Ongoing safety review of oral bisphosphonates and atypical subtrochanteric femur fractures ) the FDA stated:

"Based on published case reports of atypical subtrochanteric femur fractures occurring in women with osteoporosis using bisphosphonates, FDA, in June 2008, requested information from all bisphosphonate drug manufacturers regarding this potential safety signal. All available case reports and clinical trial data were requested. FDA's review of these data did not show an increase in this risk in women using these medications."


In other words, the FDA knew about this, looked at the data, and didn't find a connection. Nonetheless, today's excitement is over two studies presented yesterday at the 2010 Annual Meeting of the American Academy of Orthopaedic Surgeons (AAOS). In one report (here is the link to the actual study ), researchers obtained bone biopsies from 21 postmenopausal women with femoral fractures; nine who did not take a bisphosphonate and twelve who did. They found some differences in the structure of the bone for the women who had taken a bisphosphonate. Of note, the average duration of bisphosphonate therapy in this study was 8.5 years. The second study was done at Columbia University, where researchers evaluated the bone structure of 111 postmenopausal women with primary osteoporosis, 61 of whom had been taking bisphosphonates for a minimum of four years and 50 controls taking calcium and vitamin D supplements. The study found that during the first four years, there was improvement in bone, but after 4 years, the trend started to reverse, and with longer treatment any gains made were diminished.

It is important to point out that femoral fractures are very rare, whereas osteoporotic fractures of the hip and spine are common, which is why bisphosphonate therapy is so important. However, even though the FDA's review in 2008 found no association, it appears there is a least a signal of a potential harmful type of fracture with the use of these drugs. Most importantly, these harmful effects appear to occur only in patients on long term use of these medications. The patient Diane Sawyer interviewed had been on Fosamax for over 10 years. The good news is that the beneficial effects of 5 years woth of taking a bisphosphonate are seen 5 years after stopping! In a study published in JAMA in 2006, Effects of Continuing or Stopping Alendronate After 5 Years of Treatment , patients who had been taking bisphosphonates for 5 years were randomized to taking 5 more years of a bisphosphonate or stopping. Though there were some decreases in bone structure in those patients that stopped the bisphosphonates, there were no differences in hip and spine fractures in the two groups. In other words, for patient taking bisphosphonates, it appears that after 5 years on the drug, at least a 5 year "holiday" should be taken.

Bottom Line: Osteoporotic fractures are a major source of disability for older women in the US. Bisphosphonates are an effective form of treatment for osteoporosis and can prevent fractures. Whether or not bisphosphonates can cause rare femoral fractures is unclear, but if they do, it appears to occur only after long term use. The real benefits of bisphosphonates are seen in the first 5 years of therapy, and experts are now recommending stopping bisphosphonates after 5 years, which should also diminish if not eliminate the risk for femoral fractures. If you are taking a bisphosphonate, don't stop.....unless you have taken it for 5 years or more, in which case you should discuss with your doctor about stopping the medication. (This goes for you too Sally).

Having health insurance doesn't ensure it will be easy to find a doctor

An excellent article appears in today's Washington Post entitled "Having health insurance doesn't ensure it will be easy to find a doctor," where a young, otherwise healthy and insured woman discusses her extreme difficulty in finding a doctor in Washington, DC who will see her.

"I was just 23, basically healthy and, most important, insured. So I pulled out my computer, looked up the UnitedHealthcare list of pre-approved doctors and started calling. And I got rejected. Again. And again. (Usually after being put on hold for three or four minutes.) "

Next to Massachusetts, D.C. has the largest number of physicians per patients. (The article briefly mentions the lessons Massachusetts has learned about providing health care for everyone without addressing whether there are enough primary care physicians to see them). D.C.'s doctor excess, like Mass., is somewhat exaggerated given that there are several teaching hospitals with more than a few resident physicians. However, there are more than enough docs in D.C. to see patients. The problem is that in addition to not having enough primary care physicians, more and more primary care physicians are not accepting new patients. The article suggests that this is a supply and demand issue, which is true. However, another major factor that the article neglects to mention is that there are many primary care physicians in D.C. gladly accepting new patients. However, they will not take your insurance.

I practice in a large, academic teaching center in D.C. and we stopped taking new patients several years ago. This happened because many of the physicians in D.C. stopped taking insurance, and many of their former patients who were not willing to pay out of pocket to see their former doctor came to our practice (we take virtually every insurance). The problem is that we now have so many patients, they have a very difficult time getting to see us for an appointment.

The article suggests several solutions to increase the number of primary care physicians including recruiting more primary care oriented students into medical school and funding more residency spots for graduates going into primary care. These are good ideas but will not solve the problem. In a survey we did, we found that only 2% of students going into internal medicine were going into primary care internal medicine. The main reason that they chose not to do primary care was lifestyle. Students perceived primary care physicians as too busy, doing too much paperwork, and undervalued by society. Until this problem is fixed, the primary care crisis will remain. ( See Factors Associated with Medical Students' Career Choice Regarding Internal Medicine: Pay is Not Really One of Them! )

I have previously discussed that the same issue happened with psychiatrists years ago, and this is why we have a two types of psychiatry in the US. The psychiatry that you see on the TV and in the movies only occurs for those patients willing to pay out of pocket for their care. Those who pay for mental health with insurance might see a psychiatrist once a year for a few minutes, but any counselling is done by someone else. Getting an appointment with a mental health professional that accepts your insurance is similarly challenging. (See a piece I wrote for KevinMD called "As psychiatry goes, so will primary care," and How can a psychiatrist write 100,000 prescriptions a year, and why this matters to Primary Care? )

Though I believe it is important to support health care reform, it will do nothing to fix the lack of primary care physicians nor does it address the root cause of the problem (see Why you must support health care reform, even though it won't fix our health care system. ). If you are frustrated by the system, one thing to think about is paying out of pocket to see your primary care physician. Though many doctors who see "cash paying" patients run more of boutique or concierge practice, more and more primary care physicians are seeing patients at more reasonable prices, and just desire to get the insurance middle man out of the picture ( see Insurance Free Medicine )

Update: A related post byDr. Toni Brayer was just posted on KevinMd. Primary care needs to be valued first before it can be saved . I think a lot of us are all saying the same thing.

Should all patients with metabolic syndrome or elevated HgA1c take statins?

Metabolic syndrome is a constellation of factors (increased waist circumference, high blood pressure, elevated fasting glucose, high triglycerides, low hdl) that are associated with increased cardiovascular risk. Metabolic syndrome is often called pre-diabetes both because sugars are high and because metabolic syndrome is related to insulin resistance, the primary mechanism of type 2 diabetes. Diabetes has been generally defined as having a fasting blood sugar of greater than 126, so patients with sugars between 100-125 have also been called pre-diabetics. Like diabetes, we know that metabolic syndrome is associated with increased cardiovascular risk (increased risk for heart attack and stroke). Men with three or more components of metabolic syndrome have more than double the risk for cardiovascular disease, and women with three or more factors have almost six times the risk for cardiovascular disease.

Because diabetes is associated with such a high cardiovascular risk, and because lowering cholesterol with statins in diabetics has proven to reduce these events, current guidelines recommend that virtually all diabetics take a statin, even for those patients with normal cholesterol levels. One question which remains is whether the same should be done for patients with elevated fasting blood sugars and/or metabolic syndrome.

A recent study in the New England Journal called Glycated Hemoglobin, Diabetes, and Cardiovascular Risk in Nondiabetic Adults may give us more reason to consider thinking about using cholesterol lowering agents in patients with elevated blood sugars, even if the cholesterol is normal. The study looked at the relationship of hemoglobin A1c (HbA1c) to development of diabetes and cardiovascular risk. It was not surprising that even high end normal HbA1c's predicted development of diabetes, but what was surprising was that high normal HbA1c was strongly associated with risk for heart attack and stroke.

In the study, patients with an HbA1c of less than 5.0% had 4% relative decreased risk of cardiovascular disease compared to patients with and A1c of 5.0 to 5.5%. However, those with A1c's from 5.5 to 6.0% had a 23% increase, those with A1cs of 6.0 to 6.5% had a 78% increased risk, and those with 6.5% or greater had an almost double risk of cardiovascular disease. This suggest a strong correlation between elevated blood sugar (pre-diabetic patients) and cardiovascular risk.

In the most recent updates to the ADA guidlines published in the January 2010 edition of Diabetes Care, the ADA now defines diabetes as patients with an A1c of >6.5%, and those patients with A1c's between 5.7–6.4% have been included in a category of increased risk for future diabetes. Thus, the last group in the recent study would now be considered to already have diabetes.

This study also made me think of the JUPITER trial. The JUPITER trial is a controversial trial which I have blogged about before (see Jupiter is Out, and the News is Good! and Crestor: Get Ready to Ask Your Doctor for the CRP Test). It showed that patients with relatively normal cholesterol levels, but high levels of CRP benefited from taking 20mg of Crestor. Crestor now has an FDA indication for primary prevention of heart disease.

Interestingly in the JUPITER study, 41% of patients had the metabolic syndrome. The median A1c was 5.7 (interquartile range was 5.4-5.9). This means that about half the patients in the study had an extra 23% increase for cardiovascular disease based on A1c alone, and about 25% of patients had a 78% additional risk or higher (with the new ADA definition, there was probably not an insignificant number of patients in the JUPITER study that had an A1c above 6.5% that would now be considered to be diabetic and should have been on a statin). The reason I bring up JUPITER is because we now have a primary prevention trial in which a substantial number of patients had metabolic syndrome or elevated sugar, and this trial showed that statins were beneficial.

Thus, there are compelling arguments that can be made to suggest that patients with either metabolic syndrome or an elevated HgA1c should be on a statin (similar to diabetics) regardless of their cholesterol number.

However........
1. In order to definitively make this case, you would need a large, randomized clinical trial of patients with metabolic syndrome (or A1c's between 5.5 and 6.5) and normal cholesterol, randomized to statin or no statin. I am hopeful that the NIH or some drug company is planning on doing this.
2. In a subgroup analysis of the JUPITER trial, the investigators looked to see whether metabolic syndrome was a factor in those patients that benefited from Crestor and didn't find a statistically significant difference. It appears that CRP levels and not sugar levels is what made the difference.
3. Though the presence of metabolic syndrome does predict cardiovascular disease, it predicts diabetes much better, and the Framingham risk score is a much better predictor of cardiovascular disease (see Metabolic Syndrome vs Framingham Risk Score for Prediction of Coronary Heart Disease, Stroke, and Type 2 Diabetes Mellitus )

Bottom Line: Elevated HgA1c levels and metabolic syndrome substantially increase risk for cardiovascular disease, and there are compelling reasons to consider statin therapy in these patients, though conclusive data is lacking. As per the new ADA guidelines, patients at risk for diabetes should be screened with a HgA1c, and if it is greater than 6.5%, these patients are now considered diabetic and should receive a statin.

Since the Framingham risk calculation is still the best predictor for cardiovascular risk, a reasonable approach might be to adjust the Framingham score for patients with HgA1c's between 5.5% and 6.5%. Currently, patients with a Framingham risk of greater than 10% are considered for more aggressive LDL goals (which usually means they need a statin). Based on the numbers from the recent New England Journal study, for patients with A1c's from 5.5 to 6.0%, more aggressive goals should be considered when these patients have a Framingham score of 8% (instead of 10%), and for those with A1cs of 6.0 to 6.5%, more aggressive goals should be considered for a Framingham score above 6%.

Why Barack Obama should come clean about his smoking and what he can do to quit

As a physician I believe that your personal health should be private. I can certainly understand why the American people would want the right to know about a potential presidential candidate's health prior to an election. However, afterwards, the health of a President, unless life threatening should probably remain private. That said, the President recently had a complete physical and the results of that physical are now public. In addition to knowing the President's blood pressure and cholesterol numbers, we now also know according to a New York Time's report (President in ‘Excellent Health,’ Routine Checkup Finds) that President Barack Obama continues to smoke. Though I still believe that health should be a private matter for patients, even if that patient happens to be the President, since our President has chosen to reveal his health information, I think that he should officially come clean about how much he smokes. According to the New York Times report, all we know is that he doesn't smoke on a daily basis, but rather smokes infrequently. In June, the President was quoted as saying, “Have I fallen off the wagon sometimes? Yes. Am I a daily smoker, a constant smoker? No.”

Tobacco smoke in the US is an important matter. It is currently the single leading cause of preventable death and accounts for billions of dollars in health care costs. Given our current health care crisis, including the escalating costs of health care, I think it would be important for the President to discuss the burden of tobacco in this country as well as his own struggle in quitting cigarette smoking.

Now as far as what the President can do, a lot depends on how much he smokes. My guess is that he probably smokes a few cigarettes a few days a week during stressful times. If this is the case, then withdrawal is likely a minimal concern, and his nicotine consumption is probably just reinforcing this very bad habit. If that is the case, stress management techniques are probably the best way to quit. I advise patients who smoke only a few cigarettes a day to think about what else they can do to manage their stress besides smoking. For example, taking a walk, reading a book, meditation, prayer, etc. Something that is relaxing and reduces stress. Certainly our President is under a lot of stress and one can understand why he would need some sort of stress relieving activity. Smoking cigarettes is obviously not the best way to reduce stress.

If the President does smoke more than just a few cigarettes a day, the current guidelines recommend that most patients benefit from pharmacotherapy (medication). Nicotine replacement in the form of lozenges, gum or the patch have been effective in doubling quit rates. Even more effective than nicotine replacement are pills, specifically buproprion or Chantix (Varenicline). Recently there's been some concern about safety issues regarding Chantix, ( see More FDA warnings should not be cause for worry. and Where's the Good News about Chantix? ) initially brought up by the FDA. However, these safety concerns have not seemed to have panned out, and more recent studies seem to indicate that Chantix is very safe given certain precautions, specifically worsening of mental conditions. Patients using any form of a medication should be aware that quitting cigarettes (with or without medication) can worsen underlying mental health conditions, such as depression or anxiety.

In addition, I have blogged previously about Electronic Cigarettes , which I have received a number of comments (also see More on Electronic Cigarettes or E-cigs ). I think those who responded are mostly e-cigarette users that have misunderstood my objections to e-cigarettes. My objection is not that I am opposed to the existence of electronic cigarette. It's more that e-cigarettes are not regulated, so 1) their safety cannot be completely ascertained and 2) they are being promoted as a smoking cessation treatment, which they have not proven to do. E-cigarettes are likely a healthier alternative to tobacco smoke, but should be regulated by the FDA since they do contain nicotine. I'm also bothered that electronic cigarettes are sold in our shopping malls, and can potentially be purchased by children. Electronic cigarettes are probably less carcinogenic, than tobacco cigarettes. However, nicotine itself has unhealthy effects, and the goal of smoking cessation should be getting off nicotine completely. All of the treatments for smoking cessation such as the patch and the gum and even the pills are only supposed to be used for short periods of time, usually three months to no more than 6 months. Electronic cigarettes might be safer replacement for tobacco cigarettes, but are not designed to get patients off of nicotine. Generally, most of the nicotine replacement products work by giving patients a continuous supply of nicotine, and eventually weaning that level down once the patient has been off tobacco cigarettes for a few weeks. For example, with the nicotine gum or lozenge, you don't take a piece of gum every time you crave a cigarette. Rather, you use the gum continuously throughout the day, starting with about 15 pieces per day eventually decreasing the number. Theoretically, the electronic cigarette could be used in that manner, but by just replacing a tobacco cigarette, you are not addressing the behavioral issues related to smoking cessation. So, while I believe that electronic cigarettes may be safe, I also believe they should be regulated by the FDA and should not (until proven) be used or promoted as smoking cessation agents.


The President could also call 1-800 QUIT NOW. This is a 24/7 support line designed to help patients quit tobacco products. It is free and fully funded by money from this tobacco settlements. This program can be used use in conjunction with treatment from your health care provider as well as with medication, nicotine replacement and other smoking cessation techniques.


Bottom Line: While I do believe the President's health is a personal matter, since he has come out admitting that he is still smoking cigarettes despite his promises to our First Lady, I believe that he should admit to exactly how much he still smokes as well as further discuss his own personal struggles with his addiction. This will hopeful bring additional attention to the problem of cigarette smoking, which remains the single leading cause of preventable death in our country.