There’s a strange paradox that characterises life in the 21st century. Never before in human history (and prehistory) have we been so reliant on the fruits of science to live our everyday lives; and yet there is a growing movement of suspicion and even rejection of the scientific method that has delivered everything that we take for granted as citizens of a developed country.
For example, I’m sitting in an airport gate lounge as I write this post, typing on a laptop and utilising a wi-fi network to access research papers published by scientists working across the globe. I’m looking out over a tarmac swarming with jet aircraft waiting to ferry passengers hundreds to thousands of kilometres in a matter of hours.
None of these phenomena would even exist if it were not for the patient, diligent application of the scientific method, a process of asking questions, forming hypotheses, testing them and analysing the results, summarised concisely in the diagram below:
The scientific method, which had its roots in the 4th century BC teachings of Aristotle, and was refined and codified in the 19th century, is critical to advancing our understanding of everything from how to feed a human for optimal health, to how to get the 77 tonne chunk of metal I’m about to board off the runway so it can deliver me safely to my destination.
One of the reasons it’s so critical is that the truth often contradicts our intuition.
For example, it seems intuitively true that the Earth is flat. It seems intuitively true that a plane is too heavy to take off and could not possibly fly through the air. And it seems intuitively true that a drug or procedure that reduces the risk of a medical condition that is known to reduce life expectancy, must surely reduce the overall risk of dying.
Unfortunately, doctors are just as prone as the general public to making intuitive leaps that lead them to the wrong conclusion, and one of the consequences of this cognitive error is overprescribing drugs and procedures to people who are highly unlikely to benefit from them.
Which brings me (finally, you might be muttering under your breath) to my topic for the day.
According to a meta-analysis published in JAMA Internal Medicine on August 19, 2019, titled Association Between Drug Treatments for Patients With Osteoporosis and Overall Mortality Rates: A Meta-analysis, treatment of people at risk of fractures due to low bone density with bisphosphonates such as alendronate (Fosamax), risedronate (Actonel) and zoledronate (Zometa, Reclast) does not reduce the risk of overall mortality.
(What’s a meta-analysis? It’s a statistical method of combining data from multiple different studies, to increase statistical power [the probability of avoiding missing a true effect of the intervention], improve estimates of the size of the effect and/or to resolve uncertainty when the results of different trials contradict each other. This study analysed data from over 100 000 people who participated in 38 different clinical trials in which they were randomly assigned to take either a bisphosphonate or an inactive placebo.)
Here’s a forest plot of the findings of each study. For bisphosphonates to reduce mortality, the squares for each study, and the diamond representing the summed data, would need to be to the left of the vertical line. But as you can see, this is not the case:
Why does this finding even matter? Because older women (and some men) whose bone mineral density (BMD) is classified in the osteoporotic range, or even the osteopenic range, are frequently pushed to take bisphosphonate drugs to ‘treat’ their ‘condition’, even when their actual risk of fracture is very minimal.
While many people – including doctors, assume that a reduced BMD is a reliable predictor of fracture risk, the science says otherwise, as I’ve previously discussed in my article The great osteoporosis scam.
The poor risk to benefit ratio of bisphosphonate drugs is reflected in a measure known as the ‘number needed to treat’ (NNT), which reflects how many people must take the drug for one of them to experience benefit (in this case, prevention of a fracture that they would otherwise have suffered).
For postmenopausal women who have the expected decline in BMD that occurs with normal aging, but no prior fractures, bisphosphonates offer zero benefits, and a small risk of harm, ruling out the possibility of calculating the NNT.
In postmenopausal women who have already suffered a fracture or have very low bone density, the NNT for hip fracture is 100, meaning that 100 women need to take a bisphosphanate drug to avoid one of them suffering a hip fracture.
Obviously, for that one woman, the benefit is huge, but the other 99 women have been exposed to the significant harms associated with bisphosphonates (including atypical fractures, in which the shaft of the femur [thigh bone] breaks, osteonecrosis of the jaw, gastrointestinal and musculoskeletal side effects, while receiving zero benefits.
One of the strategies used to influence people who have very little chance of benefiting from these drugs to accept the use of them, generally for the rest of their lives, is inculcating fear of the consequences of suffering a broken bone – especially the dreaded ‘hip fracture’, which is actually a fracture of the neck of the femur (thigh bone).
For example, an article in The Conversation cited statistics that:
- 1 in 3 adults aged 50 and over dies within 12 months of suffering a hip fracture;
- Older adults have between 5 and 8 times the risk of dying within 3 months of suffering a hip fracture compared to those without a hip fracture; and
- This increased risk of death persists for almost ten years.”
The increased mortality risk is attributed to trauma; complications of the fracture including such as infections (especially pneumonia), internal bleeding, stroke or heart failure; and an exacerbation of pre-existing health conditions such as heart disease and frailty, caused by immobility after the fracture.
Understandably then, when an older woman undergoes a DEXA scan and is told that her BMD is the osteoporotic range, chances are she’s going to become very fearful, and this fear increases the likelihood that she will submit to taking an bisphosphonate drug, either orally or by injection.
However, as the authors of the JAMA article point out,
“Much of the increased risk for both fracture and mortality may be owing to the patients’ poor health or other factors; thus, it is not clear whether or to what degree mortality following fractures could be reduced by preventing fractures… Studies have estimated that less than 30% of the mortality following hip and vertebral fractures may be attributed to the fracture itself and, therefore, potentially avoidable by preventing the fracture.”
Now, there’s no denying that suffering a hip fracture is a terrible experience. The pain, debility, loss of physical function, increased dependence, decreased social engagement, and deterioration in quality of life take a serious toll. Suffering a hip fracture frequently results in an older person having to leave their home and enter residential aged care, potentially resulting in emotional trauma, social isolation, and in many cases, worse nutrition than they were getting while living at home.
So it’s very counterintuitive that even when bisphosphonate drugs do ’work’ – that is, prevent fractures that would otherwise have occurred – they don’t result in the people who take them living any longer than they would have, had they not taken the drug and ended up suffering a fracture.
Perhaps this is because the NNT for bisphosphonates is so high and the adverse effects, while apparently rare, are potentially severe and even life-threatening. Note also that the author of the NNT review pointed out that initial clinical trials of these drugs lasted only 3-5 years and the incidence of severe adverse reactions increases with greater duration of use.
Given that fracture risk is so poorly correlated with BMD, and is increased by modifiable lifestyle factors (such as smoking and consuming 3 or more standard alcoholic drinks per day), lifestyle-responsive disease conditions (including rheumatoid arthritis and frailty), and medications (such as antihypertensives, sleeping pills and antidepressants) that may become unnecessary if individuals undertake diet and lifestyle change, Lifestyle Medicine interventions should be offered as first line treatments to all individuals who are considered at risk of fracture.
Unlike bisphosphonates, improving one’s diet, getting regular physical activity and smoking cessation – pillars of Lifestyle Medicine – have been shown to reduce mortality.
The decision to take any drug requires a careful weighing of risks and benefits, as well as consideration of alternative courses of action (including doing nothing) and the risks of benefits of each of these options. This is called informed consent, and it’s the cornerstone of my approach to working with clients.
Ultimately, it’s up to each individual to decide whether the likely benefits of a treatment outweigh the risks in their particular case. Doctors and other health care providers have a responsibility to help patients make these decisions by presenting all the data in an unbiased fashion, and avoiding pressuring them to undertake treatments of dubious value to them by using scare tactics.
Studies like the one I’ve summarised in this post are invaluable aids to that decision-making process. The knowledge that taking a bisphosphonate drug won’t actually reduce your risk of dying prematurely, even if it does prevent you from suffering an osteoporosis-related fracture, would likely cause many people to decline the drug and explore fracture-reduction strategies that do reduce the risk of an untimely demise.
Leave A Response