Commenting on the 2 reports in the New England Journal of Medicine, James N. Weinstein, DO, said, “[T]he results may change vertebroplasty from a procedure that is virtually always considered to be successful to one that is considered no better than placebo.”3
In the first study, Rachelle Buchbinder, PhD, and colleagues in Australia report 6-month follow-up data for 35 patients randomized to vertebroplasty and 36 randomized to a sham placebo procedure. Both groups had infiltration of the skin overlying the left pedicle of the fracture site and infiltration of the periosteum of the posterior lamina with anesthetic, and incision in the skin.
The vertebroplasty group then had insertion of a 13-gauge needle placed posterolaterally to the eye of the pedicle and guided through the pedicle into the anterior part of the fractured vertebral body, with injection of about 3 ml of prepared polymethylmetacrylate (PMMA). The control group had the same procedure up to insertion of the 13-gauge needle to rest on the lamina. To simulate vertebroplasty the vertebra was gently tapped with a blunt stylet and PMMA was prepared so that its characteristic smell was apparent in the room.
The primary endpoint was overall pain score at 1 week, 1 month, 3 months, and 6 months. Secondary endpoints included quality of life and pain at rest.
Dr. Buchbinder found no significant differences between groups at any time point, with both groups reporting modest reductions in pain sores and improvements in physical functioning and quality of life. “The observed differences between groups were smaller than the minimal clinically important differences for all outcomes,” the researchers wrote.
“It has been argued that performing a randomized, placebo-controlled trial of vertebroplasty is unnecessary and unethical in view of the published results of numerous studies that suggest a benefit of vertebroplasty. Our results show—not for the first time—the hazards of relying on the results of uncontrolled or poorly controlled studies to assess treatment efficacy,” Dr. Buchbinder said.
The researchers concluded that their findings “call into question the use of vertebroplasty” for patients with recent osteoporotic fractures.
In the second study David F. Kallmes, MD, and colleagues from the Investigational Vertebroplasty Safety and Efficacy Trial (INVEST) reached similar conclusions. Using treatment and control procedures similar to those in the Buchbinder study, the INVEST researchers compared back-pain intensity at 1 month (the primary outcome) and at 3, 14, and 90 days. Secondary outcomes included pain frequency and pain “bothersomeness,” as well as quality of life and use of opioid medications. The multinational, multicenter study included 68 patients randomized to vertebroplasty and 63 randomized to the control group. Both groups had substantial and similar improvements in pain and back-related disability at 3 days after the procedure and maintained at 1 month. They did not differ significantly.
“Patients in the 2 study groups showed immediate improvement in pain and disability after the procedure, and this improvement was sustained at 1 month. These results suggest that factors aside from the instillation of PMMA may have accounted for the observed clinical improvement after vertebroplasty. Such factors may include the effect of local anesthesia, as well as nonspecific effects, such as expectations of pain relief (the so-called placebo effect), the natural history of the fracture, and regression toward the mean,” Dr. Kalmes said.
Dr. Kalmes notes that because the INVEST study permitted crossover, the researchers could not determine the long-term efficacy of vertebroplasty.
Translating research into practice: Vertebroplasty for osteoporotic fractures
In his commentary, Dr. Weinstein noted that the number of vertebroplasties performed in the US has doubled in the past 6 years, from 4.3 to 8.9 per 1000 persons, at a cost of more than $2500 per procedure.
Like Dr Kalmes, Dr. Weinstein also raised the question of whether the placebo procedure was actually an active treatment, since it involved injection of a short-acting analgesic into the bony periosteum, which contains nociceptive fibers that make the area sensitive to manipulation.
Dr. Weinstein argued for discussing this data fully with patients contemplating vertebroplasty. “Physicians typically underestimate patients' desires for information,” he said. He joined Drs. Buchbinder and Kalmes in supporting additional research, despite the high cost of such trials.
“Americans prize advances in technology. However, if in major medical challenges, such as osteoporotic vertebral compression fractures, the alternative is to pay the cost of perpetual uncertainty, we need to support the research necessary to provide sufficient efficacy and safety information for patients to make a truly informed choice,” Dr. Weinstein said.
References
1. Buchbinder R, Osborne RH, Ebeling PR, et al. Randomized trial of vertebroplasty for painful osteoporotic vertebral fractures. NEJM 2009;361:557-68.
2. Kallmes DF, Comstock BA, Heagerty PJ, et al. A randomized trial of vertebroplasty for osteoporotic spinal fractures. NEJM 2009;361:569-79.
3. Weinstein JN. Balancing science and informed choice in decisions about vertebroplasty (editorial). NEJM 2009;361:619-621.
PubMed: Related Articles