08/05/09 Two new studies have concluded that a common repair for spinal compression fractures in people who have osteoporosis offers no more benefit than a sham injection and may carry serious risks, experts said Wednesday.
The studies, which were published in The New England Journal of Medicine, were the first clinical trials to test a popular and expensive procedure called vertebroplasty against a placebo, and many experts said they were stunned by the results, which showed that patients got equal amounts of modest pain relief whether they got vertebroplasty, where bone cement is pumped into broken vertebrae, or a dummy injection.
David F. Kallmes, MD, an interventional radiologist at the Mayo Clinic in Rochester, Minn., who led one of the studies, said he thought something was wrong with the data when he finally learned the results.
“I just really couldn’t believe it when they told me,” Dr. Kallmes said in an interview. (In double-blinded clinical trials, neither researchers nor patients are allowed to know who is getting the investigational treatment or the placebo.)
Dr. Kallmes said he was relieved to learn that a team of Australian researchers had gotten roughly the same results in a similar study.
“I think both trials show that vertebroplasty is no better than a sham procedure for either improving pain, function or quality of life,” said Rachelle Buchbinder, PhD, a rheumatologist and director of the Department of Clinical Epidemiology at Cabrini Hospital in Malverne, Australia.
“I don’t think there’s any benefit of having a vertebroplasty and there are potential risks, and they haven’t really been fully elucidated to date,” Dr. Buchbinder added.
In her study, which enrolled 78 patients with spine fractures, one participant who received the cement developed a serious bone infection called osteomyelitis.
And previous research has suggested that bone cement may increase the risk for fractures in adjacent vertebrae because it changes the way the spine is able to absorb shock.
Still, other experts said that while they found the studies to be rigorous and well designed, the results were tough to reconcile with personal experience.
“I have seen patients come into the O.R. in so much pain that they could not walk,” says Scott Boden, MD, director of the Emory Spine Center in Atlanta, who was not involved in either study. “They get the cement and two minutes later they are walking out the door. It’s that fast.”
Such cases have convinced many in the medical community that the procedure works, and Dr. Boden said he believes the procedure may still have benefit for certain kinds of patients, particularly in those who have recent fractures.
During the past six years, the number of vertebroplasty procedures performed in the United States has doubled, according to Medicare data, from 4.3 to 8.9 procedures for every 1,000 persons, though questions and worries about the risks remained.
And vertebroplasty is expensive. The total cost is usually around $5,000 when the cost of an MRI scan is included.
So in 2002, Dr. Kallmes convinced the National Institute of Arthritis and Musculoskeletal and Skin Diseases, or NIAMS, part of the National Institutes of Health, to give him money to compare vertebroplasty to a placebo.
Researchers rarely test surgical procedures, even minimally-invasive ones, against a placebo because unlike drug studies, where it’s possible to hand out harmless sugar pills, placebo surgeries involve breaking the skin, a move that can be ethically dicey because it opens the door to infections and other kinds of dangerous complications.
Dr. Kallmes also didn’t want to leave patients in pain if they got the dummy injection, so he told all study participants that they could get the other intervention if they had not experienced adequate relief after 30 days.
He eventually enrolled 131 patients who were randomly assigned to receive either the bone cement or a dummy injection of short-acting painkillers.
Study investigators took great pains to make patients who got the dummy injection believe they were getting the real thing, including opening a container of the bone cement so the distinctive smell, something like nail polish remover, would waft through the air.
And each month, as he submitted his data, he said he half expected someone would call and tell him to cancel the study, something that happens when results show overwhelming benefit, or danger, early on.
But the call never came.
In the final analysis, patients in both the placebo group and the treatment group reported that on a scale from 1 to 10, their pain dropped by an average of about three points after 30 days, whether they got the bone cement or not.
The Australian study, which was very similar, had almost the same results.
“The placebo effect, I don’t think, can be underestimated,” said Dr. Buchbinder.
“Especially for an invasive procedure, people have a higher expectation that they will benefit. They put themselves on the line if they have to have an invasive procedure, so they really have to buy into it and I think that really heightens the placebo response.”
Dr. Buchbinder said that after the study, she received a visit from a grateful patient who had been flown to the hospital by air ambulance because the fracture in his back was so painful.
He was enrolled in the study, and after the procedure, his pain was so much better than he was able to drive home.
Curious, Dr. Buchbinder looked up his number to see which treatment he’d gotten.
He had gotten the placebo.
Whether his own belief was enough to blunt his pain, or whether the fracture may have healed on its own, as many do, is anyone’s guess, Dr. Buchbinder said.
“Unless you do rigorous studies, no matter how amazing it looks in these instances, I don’t think you actually can know unless you’ve done the studies,” she said.
Intense activity superior endplate L1 vertebra with associated mild anterior wedging. Intense uptake sacrococcygeal junction. Mild to moderate uptake right L2/L3 facet joint. Superficial uptake overlying the left greater trochanter. Moderate activity at the sympyhis pubis is associated CT evidence of osteitis and mild activity at the adductor tendon insertions.
COMNMENT:
1. Recent crush fracture superior endplate L1 vertebra. Recent sacrococcygeal fracture. Normal activity within the ribs.
2. Mild/moderate facet joint arthrosis right L2/L3.
3. Left trochanteric enthesopathy/bursitis. Bilateral adductor enthesopathy/osteitis pubis.
Prof. has suggested that Vertebroplasty might be helpful as an answer to my associated pain. I also sustained two fractures of the coccyx. I was absolutely shocked to discover that the procedure alone will cost $3000.00 as it is not covered by my or any Health Fund in Australia. I have been in my Health Fund for 31 years. These days I pay approx $2,500 per annum for the privilege of contributing to my Health Fund.
I can draw the money out of my depleting Superannuation but I'm also terrified of an adverse outcome if I proceed with a Vertebroplasty. Could I please hear from those patients who have had this procedure.
My concern is I was supposed to have verpoplasy/kynoplasty today, October 21st. According to my neurosurgeon it will help restore the fractured vertebra to its original strength and I could get up and do my usual routine, although with caution. Blood test results showed though that I have a low platelet count. Hence, I was referred to a hematologist; I'll meet with him on October 26th.
Today I got a copy of the non-certification for the request for the procedure. It came from a peer review conducted by Workers Compensation. And I read the not-so-good things about the vertebroplasty. The doctor who issued the non-certification of the request for the procedure based his review on investigative studies.
Now, after reading more about the procedure, I found out that certain studies could not really be valid nor reliable because of the wrong method of selecting the samples. Like most of those studies did not include certain people like my case. They did not include those who have had very recent vertebrae fractures like 6 to 10 weeks. And that if they had included that group in the investigative tests, they would have come up with better results, and therefore, recommend this non-invasive procedure.
I am really at a loss whether I should join the appeal in favor of the procedure or not.
By the way, I am 77 years old and was injured on the job as a caregiver.
Hope to hear from you soon. Thank you.
My compression fracture is now 4 years old.Is there any point in having 1 of these procedures at this late date?,
This article is a rush to judgement on "science based medicine" without applying scientific technique in appraising the studies. Verebroplasty is usually applied (in Australia) to the exquisitely painful subgroup of acute osteoporotic fractures when the pain cannot be adequately controlled by oral medication. These elderly folks find themselves incapacitated and often hospitalized unable to cope. They cannot sleep, find the pain unbearable and can talk of suicide. They may have bowel or cerebral complications from the narcotic medications. Traditionally they had up to 6 weeks in hospital. Now they have 2 days and a vertebroplasty and go home. The technique can only be truly effective on un-united fractures. In this setting it provides internal fixation of the fracture fragments and ameliorates pain. Acute fracture fixation is well recognized to reduce acute fracture pain elsewhere in the skeleton.
Both of these studies have incorrect patient selection with back pain for up to one year. These fractures unite in 6 weeks - to inject them at 6 months defies logic and, of course, can only have placebo effect. Kallmes et al excluded all inpatients from the study due to local logistics. This is the group most likely to benefit. It is unfortunate that the authors did not mention this in the manuscript. Furthermore, 4 weeks medical therapy was mandated prior to the "outpatient" vertebroplasty. Thus. the subacute fracture group has been completely removed from Kallmes et al.
Buchbinder et al could not recruit (aimed to recruit 200) and required 4.4 years in Melbourne, a city of 4 million people to recruit 78 patients. Two of the four hospitals (The Alfred and Monash) dropped out having done 5 vertebroplasty trial patients between them. They were concerned by the ethics of the study. Only 23 patients in Buchbinder et al had pain less than 6 weeks - too few for statistical analysis. 68% of patients were performed in one centre (Cabrini Hospital) by one radiologist who had no input into patient selection. These patients were selected by the principle author who therefore had control over the outcome of the study.
In both studies 70% of patients refused enrolment and were not followed. This alone makes the studies meaningless and makes a mockery of the hallowed concept of sham surgical studies.
What amazes me, a physician who has performed 2,000 vertebroplasties almost exclusively on subacute osteoporotic fractures is the ease with which these second rate studies have been accepted. They have inappropriate patient selection, terrible recruitment and selection bias with the majority not followed.
This is not surprising with Buchbinder et al where the first four authors are physicians who have never performed a single vertebroplasty. The craft group (IR) who practice the procedure were effectively locked out of patient selection.
If the authors apply the same patient selection principles to appendicectomy (right iliac fossa pain for up to one year) then they can collectively prove that appendicectomy also does not work better than a sham.
The VertosII study in Europe has recruited 200 patients with pain less than 6 weeks. The results of this study will be far more meaningful than either of these sham studies for one good reason – appropriate patient selection.
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