One might be convinced it's a glorious week for our aging bones.
The Food and Drug Administration willing, we could soon be lining up for our annual quick infusion of zoledronic acid and, wonder of wonders, within three years, our risk of hip fractures would be reduced by some 40 percent — and our risk of spine fractures even more.
One might be convinced it's a glorious week for our aging bones, but I'm not. And I won't let my patients fall victim to this hype.
The devil is in the details of the Horizon Pivotal Fracture Trial, published in the May 3 issue of the influential New England Journal of Medicine, to much fanfare. This trial received much publicity, as it studied the effect of a bone-protecting treatment that those going through menopause would only have to take once every year.
But the same devil underlies all the hype about the competing pharmaceutical remedies.
Our nation has been taught to fear the consequences of our thinning bones. Women flock to get the mineral density of their bones measured -- older and younger women -- and likely consume pharmaceutical remedies whenever they are told their bones are too thin. They take pills, and often at considerable expense to ward off the horror of fragility fractures of the spine and hips.
The Horizon trial studied nearly 8,000 women, the majority over 70 years old, and all with some evidence of collapsing of a spinal bone, a spinal fragility fracture.
Hence, these women have thin bones that can collapse without unusual trauma — osteoporosis.
They were randomized so that 4,000 were to receive the annual drug infusion for three years. The study was designed to see if the women who received the infusion had fewer hip fractures or less evidence of spinal fragility fracturing. Let's focus on the more severe and more unequivocal hip fractures:
Number of Women Who Suffered a Hip Fracture Despite Receiving the Drug: 52
Number of Women Who Suffered a Hip Fracture Without Receiving the Drug: 88
So, if you infuse the drug every year for three years into 4,000 women, 36 might be spared a fractured hip. That's an absolute difference in hip fracture frequency of less than 1 percent, which is not a number likely to engender so much excitement in the media.
However, the reduction in frequency from 2.5 percent to 1.4 percent on the drug is a reduction that approaches the "40 percent reduction" in the hype I am decrying.
No one, not you or I, not the media or the journals should ever be offered a relative difference without first emphasizing the absolute difference.
What does this mean? Well, let's say you can take a pill that reduces your chance of dying in a year from 40 percent to 20 percent. Let's say there's another pill you can take that reduces your chance of dying in a year from 2 percent to 1 percent.
Both pills reduce your relative risk of dying by 50 percent, but the absolute risk reduction is dramatically different.
Based on the absolute difference with this new drug, I'd have to treat about 100 women for three years to spare one a hip fracture. Before I ask you to ponder whether such a potential benefit is worth it to you, I need you to consider if such a benefit is believable. I do not find it believable for the following reasons:
Small Effects and the Limits of Science
Horizon is a randomized controlled trial. Half of the 8,000 women were randomly chosen to receive the infusions of the drug.