Vertebroplasty offers no clear advantages over placebo treatment in two new studies

Both trials were praised for being well-designed but criticized for discounting surgeries that work well.

Two controversial studies — the first randomized controlled investigations of vertebroplasty to use double-blinding to compare results to simulated vertebroplasty techniques — found similar pain improvement with vertebroplasty and control procedures at short-term follow-up.

Investigators for both multicenter studies, published in The New England Journal of Medicine, enrolled 209 patients who met usual vertebroplasty indications.

“Our findings demonstrate once again the importance of establishing the efficacy of new procedures in well-conducted and appropriately designed clinical trials before widespread promotion and adoption into clinical practice,” said Rachelle Buchbinder, PhD, MBBS (Hons), who led the first study. It included 78 patients treated at four Australian centers and demonstrated no advantage of vertebroplasty up to 6 months postsurgery over control surgery.

David F. Kallmes, MD, and colleagues at eight centers in the United States, United Kingdom and Australia enrolled 131 patients in the second study, seeking to understand the role of cement injection in vertebroplasty for altering pain-related dysfunction related to one to three osteoporotic vertebral fractures. They reported immediate and similar improvements in disability in both groups at 1-month postop and comparable pain resolution.

Placebo effect

Vertebroplasty has been performed for years, but “there were no research results to prove whether the efficacy of the treatment relates to the cement injections, patient expectations or other factors,” Kallmes said in a press release. “The cement is a permanent medical implant, and there is some concern it places patients at future risk for additional spinal fractures.”

Harry J. Cloft, MD, PhD, who enrolled patients in the second study, told Orthopaedics Today Europe that a placebo effect could have factored into their results.

“While we cannot say for sure why patients in both groups got better, we feel pretty confident it did not have anything to do with the cement,” he said.

Selection bias

In a statement to Orthopaedics Today Europe, Max Aebi, MD, DHC, FRCSC, and Thomas H. Zweig, MD, at the MEM Research Center, University of Bern, discussed how these findings have affected spine surgeons.

“[Buchbinder’s] article has created quite significant turmoil in the spinal world,” especially among those who have seen patients in extreme pain from osteoporotic vertebral fractures become mostly pain-free within hours of vertebroplasty, they said.

Buchbinder responded that while this may be the perception, similar responses were observed in the control groups in both trials.

Aebi and Zweig also said the study suffered from a small population base. They noted that 78 patients were included from a possible 468 patients, with just 38 patients undergoing vertebroplasty, resulting in 9.5 cases performed per center over 54 months — fewer than 0.6 cases per month.

“As the authors state themselves … there can be anticipated significant selection bias since more than 30% of eligible patients declined to participate,” Aebi and Zweig wrote. However, Buchbinder told Orthopaedics Today Europe that this does not in any way “diminish the internal validity of the trial.”

Also, less cement than usual was injected — 2.8 ml ± 1.2 ml. “We can almost conclude that the cement injection was another level of sham operation,” Aebi and Zweig said. Buchbinder said that there is no evidence of a dose response in the literature.

To reduce confusion among patients, physicians and insurers about vertebroplasty’s efficacy, Aebi and Zweig recommended establishing national registers of the procedure.

Stephan W.J. Becker, MD, of Vienna, lauded the studies’ design and protocol and accepted its noted shortcomings. The fact they met the thresholds to be published in The New England Journal of Medicine indicates their quality, he said.

However, he acknowledged that experience and some studies have shown vertebroplasty gets patients out of bed sooner and acts more rapidly than conservative care. Consequently, Becker said he will continue performing vertebroplasty for now due to the immediate pain relief it provides.

He also questioned if the control groups truly underwent sham surgery, since the local anesthesia used in the studies is a widely recognized pain treatment, even though they are the first recognized sham studies in spine surgery, he said.

Buchbinder responded that a small amount of local anesthetic placed in the skin and subcutaneous tissue “is extremely unlikely to have produced any therapeutic effect, particularly for outcomes measured at 1 week and beyond.”

Becker added, “I think [the studies] point out we really do not understand the mechanisms going on in the vertebrae, and that the nerve endings play a more dominant role than thought.”

For more information:

• Max Aebi, MD, DHC, FRCSC, e-mail: max.aebi@memcenter.unibe.ch, and Thomas H. Zweig, MD, e-mail: tzweig@memcenter.unibe.ch, can be reached at University of Bern, MEM Research Center, Stauffacher Str. 78, CH-3014 Bern, Switzerland; +41-31-337-8922.
• Stephan W.J. Becker, MD, can be reached at Orthopaedic Hospital Vienna-Speising, Speisinger Str. 109, Vienna 1130, Austria; +43-801-82-0; e-mail: stephan.becker@oss.at.
• Rachelle Buchbinder, PhD, MBBS (Hons), can be reached at Cabrini Medical Centre, 183 Wattletree Rd., Malvern, VIC 3144, Australia; +613-9508-1652; e-mail: rachelle.buchbinder@med.monash.edu.au. Her study was supported by the National Health and Medical Research Council of Australia, Arthritis Australia, Cabrini Education and Research Institute and Cook Australia.
• David F. Kallmes, MD, e-mail: kallmes.david@mayo.edu, and Harry J. Cloft, MD, PhD, e-mail: cloft.harry@mayo.edu, can be reached at the Mayo Clinic. 200 First St. SW, Rochester, MN 55905, U.S.A.; +1-507-284-2511. Their study was funded by the U.S. National Institutes of Health.

References:

• Buchbinder R, Osborne RH, Ebeling PR, et al. A randomized trial of vertebroplasty for painful osteoporotic vertebral fractures. N Engl J Med. 2009; 361:557-568.
• Kallmes DF, Comstock BA, Heagerty PJ, et al. A randomized trial of vertebroplasty for osteoporotic spinal fractures. N Engl J Med. 2009; 361:569-579.