SIR Backs Vertebroplasty Despite Controversial Findings

Kevin McGraw, M.D.	David Kallmes, M.D.
Rachelle Buchbinder, M.D.	Brian F. Stainken, M.D.

Despite two controversial studies indicating that vertebroplasty is no more effective than a sham procedure, the Society of Interventional Radiology (SIR) stands firm in its support of the treatment and stresses the need for further research before making a rush to judgment.

The authors of both studies—which appeared in the August 2009 edition of The New England Journal of Medicine and were the first clinical trials to test vertebroplasty against a placebo—not only agree more that research is needed, they said they believe such clinical trials should have been performed long before now.

"How is it possible that about 200,000 people a year receive a treatment for which we do not have a risk-benefit ratio with any element of certainty?" asked Rachelle Buchbinder, M.D., director of the Monash Department of Clinical Epidemiology at Cabrini Hospital in Malvern, Australia, and lead author of one of the studies. "Only randomized controlled trials with placebo control and blinding can determine the true benefit of treatment."

For its part, SIR contends that vertebroplasty is hugely beneficial to appropriately selected patients and that both NEJM-published studies are not only flawed but run counter to decades of data and patient testimonials documenting the procedure’s effectiveness.

"These two studies had methodological and statistical flaws and one must carefully consider any data that are discordant with the body of literature," said SIR President Brian F. Stainken, M.D. "Hundreds of thousands of patients have greatly benefited from vertebroplasty with almost complete resolution of their pain; tens of thousands dependent on intravenous narcotics have been discharged from the hospital virtually pain- and drug-free following their treatment."

Ten million Americans have osteoporosis, a disease that causes 700,000 vertebral fractures annually, according to the National Osteoporosis Foundation. According to Medicare statistics, the number of vertebroplasty procedures nearly doubled from 2001 to 2005 among Medicare enrollees, from 45 per 100,000 to 87 per 100,000.

Findings Surprise Study Authors

Dr. Buchbinder and colleagues conducted a multicenter, randomized, double-blind placebo-controlled trial with 78 participants who suffered one or two painful unhealed, osteoporotic vertebral fractures in the last year. Participants were randomly assigned to undergo vertebroplasty or a sham procedure. Those assigned to the sham intervention underwent the same procedures as those in the vertebroplasty group up to the insertion of the needle. At that point, the central sharp stylet was replaced with a blunt stylet. To simulate vertebroplasty, the vertebral body was gently tapped and polymethylmethacrylate was prepared so the smell permeated the room.

In the second multicenter trial, David F. Kallmes, M.D., and colleagues in the Investigational Vertebroplasty Safety and Efficacy Trial (INVEST), randomly assigned 131 patients to undergo either vertebroplasty or a simulated procedure similar to the one used by Dr. Buchbinder. Primary outcomes were scores on the modified Roland-Morris Disability Questionnaire (a scale of 0 to 23) and ratings of average pain intensity (on a scale of 0 to 10) during the preceding 24 hours at one month follow-up. Listen In as Dr. Kallmes discusses the impetus for his research.

The number of vertebroplasty procedures nearly doubled from 2001 to 2005 among Medicare enrollees. Image courtesy of the Society of Interventional Radiology.

In Dr. Buchbinder's study, vertebroplasty showed no beneficial effect at one week or one, three or six months after treatment, when compared with a sham procedure. Similarly, researchers found no difference in benefit between vertebroplasty and the sham procedure in Dr. Kallmes' study.

Both authors were surprised by the results. "I had a high confidence that this procedure was benefiting patients," said Dr. Kallmes, an interventional radiologist at the Mayo Clinic in Rochester, Minn., who has performed vertebroplasty for about 15 years and written dozens of papers on the procedure first developed in the mid 1980s. Dr. Kallmes is a 1997 Bracco/RSNA Research Scholar Grant recipient.

Because both studies were conducted independently and neither author knew the other’s outcome until publication, both researchers say the nearly identical results strengthen the validity of their findings. "The fact that neither trial found any benefit, yet the size of benefit is supposedly large, means that it is most unlikely we would have missed a treatment benefit," Dr. Buchbinder said. Listen In as Dr. Kallmes discusses Dr. Buchbinder’s study.

Study Populations, Designs are Flawed, SIR Contends

While supporting the role of randomized controlled trials and evidence-based medicine, SIR contends that neither study tells the whole story; potential flaws included small numbers of patients; small percentages of eligible patients actually enrolled; patients with milder degrees of pain and disability being treated and the high rate of crossover from placebo to vertebroplasty in the Kallmes study. Listen in as Dr. Kallmes discusses the placebo effect and crossover results.

In the Kallmes study, patients were allowed to cross over to the other study group after one month. Eight patients in the vertebroplasty group crossed over to the sham procedure whereas 27 in the sham group crossed over to the vertebroplasty group. "The tremendous crossover rate speaks for some obvious benefit of vertebroplasty over sham and is worthy of a future adequately powered analysis to evaluate," said SIR member Kevin McGraw, M.D., section head of interventional radiology at Riverside Interventional Consultants in Columbus, Ohio.

Dr. McGraw also pointed out that Dr. Kallmes and colleagues did not use MR imaging to determine whether a fracture was in fact the cause of the patient's pain. "Theoretically, some patients could have a healed fracture and some other etiology for their acute pain that was not appropriately treated," Dr. McGraw said. He also noted that a physical examination was not performed on patients prior to the procedure.

In Dr. Buchbinder’s study, only 78 of 468 patients screened were enrolled and were randomly assigned to a study group, Dr. McGraw said. "Obviously, selection bias was introduced into the study by enrolling only 16 percent of eligible patients," he said.

Patient selection is the key to the success of vertebroplasty, according to Dr. Stainken. "We believe that the careful use of pre-procedural imaging correlated with a thorough physical examination offers us the best ability to precisely target the level responsible for the pain," he said.

Follow-up Trials Necessary

While SIR contends that results of these trials are discordant with personal experience and more than 15 years of accumulated medical literature espousing the benefits of vertebroplasty, Dr. Kallmes assesses the results differently.

"I wish they had read our study more carefully, since the observed outcomes of immediate, sustained, statistically significant, and clinically relevant improvement—in both groups—were exactly in line with prior studies," Dr. Kallmes said of SIR members. "The treatment arm does work, but we have to ask ourselves why the sham group got so much benefit. That is one of many aspects we need to focus on in future research." Listen In as Dr. Kallmes discusses SIR’s response to his research.

The studies "were read with great scrutiny," according to Dr. McGraw, who also stressed that SIR members don't have a financial motive for criticizing the studies. "My group has one of the largest vertebral augmentation practices in the country," Dr. McGraw said. "If we stopped performing vertebroplasty it would result in a loss of less than 1 percent of our net income."

Although he struggled for years to get his research funded and completed, Dr. Kallmes has submitted multiple grants for future clinical trials testing the efficacy of vertebroplasty. "I am looking for the truth, plain and simple," he said.

Based on the results of these studies, SIR is recommending that radiologists inform patients of the studies’ results during consultation and is encouraging larger clinical trials to address the weaknesses of the research, according to a statement from SIR.

At its annual meeting in March, SIR released the results of VERTOS II, the first methodologically sound randomized controlled trial designed to assess the cost-effectiveness of vertebroplasty compared to conservative therapy in patients with an acute osteoporotic vertebral compression fracture. Results showed that vertebroplasty decreases pain immediately for patients with acute osteoporotic vertebral compression fractures and pain relief is sustained for up to one year.

"We need to work to understand what Dr. Kallmes is seeing, and avoid a rush to judgment," Dr. Stainken said. "The worst thing we can do is harm our patients by denying them a solution."