Trial Results Raise Doubts About Vertebroplasty

Allison Gandey

August 07, 2009

August 7, 2009 — Two new clinical trials have shown that control-group patients experienced similar improvements to those treated with vertebroplasty for osteoporotic vertebral fractures.

The trials, published in the August 6 issue of the New England Journal of Medicine, are the first randomized controlled studies of the procedure, which has been growing in popularity for about a decade and is already widely in use.

The results have unleashed a media frenzy, with news stories questioning practice and prompting discussions about inappropriate costs. The trial findings are also fast becoming a hot-button topic in the debate on healthcare reform, and many specialists are worried that all this attention will prompt people to abandon the procedure instead of encouraging further study.

Lead investigator David Kallmes, MD, from the Mayo Clinic in Rochester, Minnesota, suggests that lack of study was the problem in the first place. "Let's conduct a thought experiment," he said during an interview. "What would have happened if at the University of Virginia, instead of conducting that first case series of 30 patients, which I was involved with, we had done this trial of more than 100 patients back in 1997?" Dr. Kallmes wonders if vertebroplasty would have ever taken off the way it did.

Randomized Controlled Trials

Lead investigator of the second trial, Rachelle Buchbinder, PhD, from Monash University in Malvern, Australia, raised similar concerns to Medscape Neurology. "There have been numerous examples of treatments that have looked promising in noncomparative studies but have subsequently been shown to be no better than placebo, a sham procedure, or standard care."

Dr. Buchbinder cites arthroscopy for osteoarthritis of the knee, bone marrow transplantation for breast cancer, embryonic neurons for severe Parkinson's disease, and from her own work, shock-wave therapy for plantar fasciitis. She suggests that each of these looked promising early on, but didn't do well after rigorous study.

It had previously been argued that performing a randomized placebo-controlled trial of vertebroplasty is unnecessary and unethical in light of the published results of numerous studies that suggest a benefit. But Dr. Buchbinder said that the take-home message from her trial is that vertebroplasty was no better than a sham procedure for improving pain, function, and quality of life after an osteoporotic spinal fracture.

"Both treatment groups improved by about the same amount," she said. "In view of the known potential adverse effects and no benefit, vertebroplasty should not be used in clinical practice."

Adverse events were infrequent in these trials; however, complications, such as soft-tissue damage and nerve-root pain and compression, have been associated with bone-cement leaks. Rarely reported complications include pulmonary embolism, respiratory, cardiac failure, and death.

In an accompanying editorial, James Weinstein, DO, from the Dartmouth-Hitchcock Medical Center in Hanover, New Hampshire, says these 2 trials could be practice altering. "The results may change vertebroplasty from a procedure that is virtually always considered to be successful to one that is considered no better than placebo."

Practice Altering

In the Investigational Vertebroplasty Safety and Efficacy Trial (INVEST), researchers studied 131 patients with painful osteoporotic vertebral compression fractures. Participants were randomly assigned to undergo either vertebroplasty or a simulated procedure without cement.

The primary outcomes were scores on the modified Roland-Morris Disability Questionnaire and, at 1 month, patients' ratings of average pain intensity during the preceding 24 hours.

Patients were allowed to crossover to the other study group after a month. The researchers report they permitted this because both physicians and patients were reluctant to accept a longer period.

Investigators found no significant difference between the vertebroplasty group and the control group in disability score (0.7; 95% confidence interval [CI], –1.3 to 2.8; = .49) or pain rating (0.7; 95% CI, –0.3 to 1.7, = .19). Patients in both study groups showed immediate improvement in pain and disability after the procedure, and this improvement was sustained at 1 month.

"We actually showed what everyone else has shown," Dr. Kallmes told Medscape Neurology. "There is a treatment effect. The problem is that we also showed there is an effect in the control group, and that is where the message becomes confusing. I hope this will encourage further study."

Similar Results

In the second trial, Dr. Buchbinder and her team looked at 78 patients with painful osteoporotic vertebral fractures. Patients were randomly assigned to undergo vertebroplasty or a sham procedure. The primary outcome was overall pain (on a scale of 0 to 10) at 3 months.

The mean reductions in the score for pain in the vertebroplasty and control groups at 3 months were 2.6 ± 2.9 and 1.9 ± 3.3, respectively. The adjusted between-group difference was 0.6 (95% CI, 0.7 to 1.8).

Investigators observed similar improvements in both groups with respect to pain at night, pain at rest, physical functioning, quality of life, and perceived improvement.

The researchers conclude that vertebroplasty did not result in a significant advantage in any measured outcome at any time point.

Despite the consistent findings, Dr. Kallmes said he's not ready to abandon vertebroplasty. "I still perform the procedure," he said. "These studies have raised many questions and I tell patients the truth and we discuss the potential risks and benefits." Dr. Kallmes said he tries to get these patients into clinical trials so that additional data can be accrued.

"Patients are often in excruciating pain and have no other options; this procedure is easy to do." Dr. Kallmes said there used to be strict criteria for augmentation procedures to be considered. There was never a systematic approach, but he said it was understood that augmentation should only be considered in a subset of patients and this should probably continue to be the case. New studies should help inform who these patients might be.

More Study Needed

"I think that if some individuals still believe there is a place for vertebroplasty, it is their responsibility to conduct an appropriately designed study to prove it," Dr. Buchbinder said.

She added that critics may argue the trialists didn't include patients who were likely to benefit, but the inclusion criteria and baseline characteristics are very similar to those in previous studies.

Dr. Buchbinder suggests that previous studies of vertebroplasty probably overestimated the treatment effect by failing to take into account the natural history of painful vertebral fractures, which tend to improve over time. She also points to a possible placebo effect and regression to the mean.

This isn't the first time investigators have urged caution. As previously reported by Medscape Neurology, teams such as the one led by Paul Hulme from the ME Muller Institute for Surgical Technology and Biomechanics in Bern, Switzerland, have articulated concern about a lack of quality evidence (Spine. 2006;31:1983-2001).

Dr. Hulme oversaw a systematic review of 69 clinical studies of vertebroplasty and kyphoplasty. His group concluded that "the problem with stating definitely that vertebroplasty and kyphoplasty are safe and effective procedures is the lack of comparative, blinded, randomized clinical trials." Dr. Hulme called for standardized evaluative methods.

"Given the increasing use, limited benefit, and potential risk, how often should vertebroplasty be performed?" Dr. Weinstein asked in his editorial. "When best evidence suggests a toss-up between treatment options and no benefit, informed patient choice is essential. When faced with several choices for which the evidence is less than clear, patients and doctors must thoroughly review the options together."

Dr. Kallmes' study was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Kallmes reports that he has received consulting fees from Zelos Therapeutics and grant support from ArthroCare, Stryker, Cardinal, and Cook. Dr. Buchbinder's study was supported by the National Health and Medical Research Council of Australia, Arthritis Australia, the Cabrini Education and Research Institute, and Cook Australia. Dr. Buchbinder is the recipient of a National Health and Medical Research Council Practitioner Fellowship.

N Engl J Med. 361:557-579. Abstract

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