Alan Cassels is a drug policy researcher at the University of Victoria and a regular contributor to the blog. He is also the author, most recently, of The Cochrane Collaboration: Medicine’s Best-Kept Secret. He tweets as @AKEcassels.
A June 1st story in the New York Times, “Fearing Drugs’ Rare Side Effects, Millions Take Their Chances With Osteoporosis,” raises some provocative questions:
Risks to patients or profit?
The catalyst for this front page story is the apparent decline in the use of bisphosphonate drugs, standard treatments used to prevent osteoporotic fractures, and the concern that patients are being misled about the safety of these drugs. Research shows that rates of bisphosphonate use, post-hip fracture, have “declined significantly from 40.2% in 2002, to 20.5% in 2011.” Such decline would obviously be a concern for two reasons: First, there may be dangers to patients who may be eschewing helpful, important treatments. Secondly, there may be dangers to the profit centers of major drug companies who make bisphosphonates and who are clearly concerned about the public image of these products in the minds of patients and prescribers.
You might wonder which concern gets the most media play.
The quality of the reporting of osteoporosis is a serious issue, given that it remains a controversial classification which some say is a classic example of selling sickness. In this case, selling the ‘risk’ of ‘low’ bone density as a bona fide disease in and of itself, as discussed in the BMJ, has no doubt added to the controversy. Since Fosamax, the first major bisphosphonate to hit the market, arrived just over 20 years ago, it is a good time to consider how well both the drug and the disease is being discussed in mainstream news reporting.
For starters, the safety of the bisphosphonates has always been a concern, even from the earliest days. Fosamax was linked to over 6,000 adverse event reports made to the FDA in 1996, the first full year it was on the market. It had the distinction of being associated with the most reported adverse events that year. The danger most reported was esophageal injury and what followed was stricter recommendations on how to safely take the drug. A number of me-too bisphosphonates arrived over the next few years and the warnings began to pile up. In 2011, two FDA advisory panels recommended stronger warnings on the drugs. At the time, the New York Times said the advice was “prompted by concerns over a relatively small number of long-term users who had suffered unusual thigh fractures or a serious jaw disease.” There was also the concern of longer-term use as FDA staffers said the benefits of the drugs have only been demonstrated for three to five years. There was a lot of news media coverage of the dangers of bones spontaneously breaking, osteonecrosis of the jaw and even kidney failure, yet the degree to which those stories would change patients’ behavior was unknown. Certainly it would be of interest to those who make the drugs and see their markets shrinking, as well as to the organizations and patient groups funded by the manufacturers of bisphosphonates.
Who’s putting out the ‘urgent calls’? ‘Clearly a pattern here’
Among those asking if this most recent New York Times article is an attempt to put some makeup on the declining image of bisphosphonates is Robert J. Davis, PhD– a veteran health journalist and author of The Healthy Skeptic–who’s based in Atlanta, Georgia. He said: “The groups that are pharma funded are the ones putting out ‘urgent calls’ around the safety issue. There is clearly a pattern here, a concerted effort to get the word out.” The groups he’s referring to include the American Society for Bone and Mineral Research, the National Osteoporosis Foundation and the National Bone Health Alliance, all of which receive funding from companies making osteoporosis drugs.
He particularly noted how the story seemed to downplay all the serious safety issues, “barely digging into the FDA warnings. There was no discussion of that.” In his opinion this was a “missed opportunity to talk about the legitimacy of of people’s concerns about the drugs.”
Professor Teppo Järvinen at the University of Helsinki and an expert in the research around osteoporosis echoes those comments. He said that “there are many things about the disease which are absolutely controversial: the drugs are targeting people to prevent hip fractures and while the studies might show some benefit, real-world studies can’t demonstrate any effectiveness of the drugs in preventing hip fractures.” He adds, “they don’t work in men or women over 80 and they can cause pretty serious adverse effects.” (Publisher’s note: you can hear much more from Dr. Järvinen in a podcast discussion we had with him in 2015.)
Trials show that magnitude of benefit is small
A review of all randomized controlled trials of bisphosphonates here found “no statistically significant reduction in hip or wrist fracture for women who have no prior fracture or vertebral compression at baseline. This represents the majority of women presently treated with bisphosphonates, most of whom are presumably being identified by bone mineral density measurements.” And for those women with previous fractures, “the incidence of hip and wrist fracture was decreased by bisphosphonates, however, the absolute magnitude of benefit is small, 1% for hip and 1.3% for wrist, and it is based on a potentially biased subset of randomized patients,” the review found.
Dr. Järvinen told me that there are major errors in even conceiving of osteoporosis as an important risk factor for fractures. “Blaming fractures on ‘bone weakening’, pumping the benefits of the drugs which are non-existent in many patients and downplaying the terrible adverse effects of those drugs” which he says aren’t as rare as many doctors are led to believe does a disservice to the Times’ readers.
It is clear that the very use of bone density as a predictor of fractures is controversial. As this BMJ commentary by Jarvinen and colleagues suggests, it may well be the patient’s age, not their bone density, which is the most relevant predictor of fractures. They note that the “Incidence of hip fracture in women rises 44-fold from the age of 55 to 85, and the effect of ageing is 11-fold greater than that of reduced bone mineral density.”
Sources’ drug company ties not disclosed
One thing that is most curious here is that much of the research and commentary in this story comes from osteoporosis experts who have who ties to drug companies. For example, the medical journal articles cited as news hooks by the Times — the ones “documenting” and “bemoaning” the abandonment of osteoporosis drugs by patients — are co-written by employees of drug companies and those with significant financial ties to drug companies. But those relationships are not mentioned by the Times. And Dr. Paul Miller, who laments the “fear factor” that keeps patients away from osteoporosis drugs, consults for companies that make osteoporosis drugs like Amgen, Lilly, and Merck. But again, Miller’s ties to those companies are not disclosed. Only when the Times quotes experts without current ties to drug companies (though many of these experts do appear to have past ties) does it alert readers that these sources “have no association with the makers of the drugs.”
Do the conflicts of interest matter? They do to Robert Davis. He tells me, “the story basically parrots the pharma industry line (which it is pushing through groups and the doctors it funds) that patients who worry about the drugs’ side effects are being irrational and that by not taking the drugs they ‘take their chances.’”
Perhaps the conflicts result in what Robert Davis thinks are the story’s key limitations: “The story fails to address some key issues such as the limitations of bone density testing; what “high risk” of fracture—the criterion for using the drugs—means exactly; the unknown risks of putting people on these powerful drugs for decades; and the seriousness of an FDA warning, which the drugs carry.”
We should acknowledge that the story did provide a graphic description of what it’s like to experience atypical fractures — from a patient who called the drugs “that wretched, dreadful stuff.” Perhaps coming 1,000 words into a 1,200 word story this comment is arguably too little, too late.
Reporters need to cover these kinds of stories, but they certainly need to do so with a heightened level of skepticism, and talk to more experts who aren’t tied to the drug industry view of treating osteoporosis. In that light, Robert Davis wondered to me, “Are the makers of the drugs trying to reverse declining sales by waging an informational campaign to stop docs and patients from questioning the drugs’ safety?” He adds: “Unfortunately, instead of reporting this angle, the article simply handed industry a giant platform for its propaganda.”
Note: Alan Cassels has written four books, including Selling Sickness with Ray Moynihan, the author of BMJ commentary mentioned in this post. Each of Cassel’s books have covered various aspects of the controversies around osteoporosis, its diagnosis and treatment.