Osteoporosis risks vs. benefits of osteoporosis drugs — spinning the numbers
When it comes to osteoporosis, most patients and their practitioners are primarily concerned with fractures. The thinking behind bisphosphonates was that if we could halt the bone breakdown process and make bones denser, we could prevent them from breaking. Most of the ads you see will tell you this is the case. But on taking a closer look, the numbers don’t seem so hot.
What’s disappointing to me is the way numbers from studies can be manipulated to exaggerate treatment benefits. Allow me to give you an example. When the manufacturers of Fosamax say that the drug can reduce fractures by up to 50% in high-risk women, what they are referring to are results of a 2004 study showing relative risk reduction among women who, as a group, are already highly likely to fracture before they are even selected for the study. Most people don’t have time to analyze study results in detail, but these reveal that out of thousands of high-risk postmenopausal women (those with osteoporotic bone density and a history of previous fracture), about twice as many (2.2%) of the placebo group will fracture as those taking the drug (1.1%). Because 1.1% indeed is half of 2.2%, the drug’s manufacturer can advertise that the drug reduces hip fractures by 50% — which is the relative risk reduction (that is, a comparison of the number of people who fractured in both groups). But let’s not forget that both groups contained many more people who did not fracture at all, and if you include them in your comparison, you get what’s called the absolute risk reduction — a paltry 1.1% (2.2 minus 1.1) — in those taking Fosamax compared to those not taking anything.
A 2008 review of more than 40 years’ worth of data on more than 12,000 women using alendronate — that’s a lot of data — shows that overall, there was a mere 1-2% absolute risk reduction with its use. Co-opting this science, direct-to-consumer marketing continues to play up the 45-50% relative risk reduction figures. Yes, relative risk reduction can be a useful tool for researchers, and of value to a healthcare provider when determining absolute risk reduction. But any good biostatistician will tell you that it does not seem to be as useful a measure for patients or families when choosing a method of treatment!
Another detail we don’t hear from the drug companies is that fracture-reduction benefit of these drugs is largely for secondary prevention — that is, when bone density is already osteoporotic and/or there has been an existing fracture. There is much less benefit in primary prevention, where bone density is not osteoporotic and there have been no previous fractures. In women with osteopenia, some research even suggests increased rates of certain types of fracture with prolonged use! In fact, these drugs are not recommended at all for primary prevention, yet women who are not at elevated risk for fracture are among the largest target audience of direct-to-consumer advertising for bone drugs.
Possible adverse side effects associated with osteoporosis medications (bisphosphonates)
- Ulcers of the esophagus
- Upper GI irritation
- Irregular heartbeat
- Fractures of the femur
- Low calcium in the blood
- Skin rash
- Joint, bone, and muscle pain
- Jaw bone decay (osteonecrosis) (rare)
- Increased parathyroid hormone (PTH)
If patients knew the reality of these numbers and the dangerous side effects that come with taking bisphosphonates (see chart at left), I’m sure they would reconsider the merits of taking a prescription for low bone density for the rest of their days. This information is hard to find, and many practitioners don’t have the time to analyze the statistics of each and every study that comes across their desk.
I would advise patients to ask their providers what the absolute risk reduction is for a drug before taking it. Or you can also ask about the number needed to treat (NNT). This figure gives you a sense of how many people would have to take the medication for one person to receive a benefit, and the lower the NNT, the better the chance that the drug will benefit you. For example, the above information tells us that Fosamax reduces fracture risk by about 1% (absolute risk reduction), so 100 people would have to be treated for one to benefit from fracture risk — the NNT is 100, in this case. In essence, the NNT is telling us that for every single person who is benefitting from these drugs, 99 more are getting no benefit at all!
The business behind bone density drugs
Unfortunately, the ads we see on television for various osteoporosis drugs don’t mention how small the benefits really are, or how serious the side effects can be. As the Baby Boomers begin to grow older, pharmaceutical companies have a market larger than ever before for bisphosphonates, and they aren’t stopping at much to capitalize on it. In fact, this large aging population is part of the reason it looks like osteoporosis has become an epidemic in this country. In reality, US hip fracture rates have gone down since the late 1960’s in women and since the early 1990’s in men, despite an aging population. Because of the large number of aging Baby Boomers, the actual number of fractures can seem overwhelming, even though the rate is decreasing.
It’s true that such a large group of people getting older, possibly fracturing, and taking up hospital beds will represent a burden to society. This is partially why drug companies want to find a solution, but the other part — as I’m sure you can imagine — has to do with profits. In 2006, at least $2 billion was spent on Fosamax alone. Drug companies are pushing hard for direct consumer advertising to encourage women to get bone density tests, in the hopes they’ll then be treated for low bone density.
In an article on leveraging the potential osteoporosis market, a contributing editor to Medical Marketing and Media writes, “In the United States, 95–100% of women who are screened and diagnosed with osteoporosis receive treatment.” He goes on to advise drug companies to “drive diagnosis rates” by sponsoring traveling DEXA scans in shopping malls, clubs for the elderly, and community events.
The DEXA scan was developed in the early 1980’s as a way to quantify bone density, but unfortunately it doesn’t reveal much about the actual strength of bone. Patients are given a T-score that compares their bone to that of a healthy 20- to 30-year-old, then told they have osteopenia or osteoporosis! The Z-score, which compares your bone density to that of other men or women in your age group, is more helpful for tracking your bone density over time, but still not great at predicting risk. The reality is there are many factors that go into predicting fracture risk, and bone density is just part of the whole picture. It clearly works in the interest of pharmaceutical companies to compare your T-score to a young person’s, but you should know that while a machine may categorize you as osteopenic or even osteoporotic, you may never fracture a bone in your life. And the odds are with you — most people don’t fracture their bones, even if they are at high risk.
The Surgeon General’s advice — work with nature
In one sense, I agree with pharmaceutical companies: prevention is best. But I don’t agree with their approach to prevention. Pharmaceutical medications, in my opinion, don’t work with your body. They work by suppressing or fooling it into doing something it wouldn’t do naturally. I know that in certain circumstances, bisphosphonates can be helpful, but for the most part they should remain a last resort.
In 2004, the Surgeon General studied osteoporosis in the United States and wrote a report over 330 pages long on the best ways to promote bone health and prevent osteoporosis and fracture. His advice, in essence, is to work with nature.
He provides an osteoporosis pyramid for prevention and treatment that starts with nutrition, physical activity, and fall prevention at the base. The second tier involves assessing and treating the underlying causes of compromised bone health. The very tip of the pyramid, and the last resort, is pharmacotherapy. The bottom line is that your bones are meant to last a lifetime. In most cases they don’t need drugs to keep them strong or prevent fracture. There are many, many natural ways to support your bones with proper bone nutrition and, many times, simple lifestyle changes to prevent osteopenia, osteoporosis, and needless fracture.
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