Consternation and questions about two vertebroplasty trials
Confronted with the unexpected results of two trials of vertebroplasty,1,2 physicians are feeling some consternation, We had thought that percutaneous vertebroplasty helps patients with osteoporosis who sustain a painful vertebral insufficiency fracture. However, the trials found it to be no better than a sham procedure in terms of relieving pain.
How will these findings affect our practice? Should we abandon this popular procedure? Or are there other considerations that may mitigate these negative findings? And what should we tell our patients?
700,000 FRACTURES PER YEAR
Vertebral insufficiency fractures are the most common type of fracture in patients with osteoporosis. Every year in the United States, about 700,000 of them occur.
Nearly two-thirds are asymptomatic. The other one-third typically present with the acute onset of localized pain.
Vertebral insufficiency fractures often lead to chronic pain, impair the ability to walk and to perform daily activities, and accentuate thoracic kyphosis, which in turn can lead to pulmonary restrictive disease, and they raise the risk of death. Also, a patient who has a vertebral insufficiency fracture has a 20% risk of sustaining a new one within 1 year.3
Whether symptomatic or asymptomatic, finding a vertebral insufficiency fracture should prompt one to consider drug therapy for osteoporosis. In addition, until now, a patient who presented with the acute onset of back pain and whose evaluation revealed a vertebral insufficiency fracture would also be considered for a vertebral augmentation procedure, either vertebroplasty or kyphoplasty, to relieve the pain.
Vertebroplasty involves injecting polymethylmethacrylate cement percutaneously into the affected vertebral body. Kyphoplasty, a similar procedure, uses a balloon to create a cavity in the fractured vertebral body. After the balloon is withdrawn, the cavity is filled with cement.
TWO RANDOMIZED TRIALS OF SHAM VS REAL VERTEBROPLASTY
Two teams, Kallmes et al2 and Buchbinder et al,1 independently performed randomized controlled trials to see if vertebroplasty really relieves pain as well as has been reported in open studies, case series, and nonrandomized trials.4–7
In both trials, patients were randomized to undergo either sham vertebroplasty or real vertebroplasty. The sham procedure closely approximated the real procedure, including inserting a needle, infiltrating a local anesthetic, bupivacaine (Marcaine), into the periosteum of the posterior lamina1 or the pedicle of the target vertebrae,2 and opening a vial of polymethylmethacrylate so that the patient would smell the product.
Inclusion criteria
Patients in both trials had to have evidence of a recent (acute) or nonhealed vertebral insufficiency fracture.
Pain was the primary outcome measured
In both trials, the investigators assessed the patients’ pain at baseline and again at several specified intervals, using validated tools.
Kallmes et al assessed pain intensity and functional measures at 1 month (the primary outcome measured), and also at 3, 14, and 90 days and at 1 year.
Buchbinder et al assessed pain at 1 week and at 1, 3, and 6 months. The primary outcome measured was pain at 3 months. Secondary outcomes included quality-of-life measures, pain at rest, and pain at night.
Surprising results
In both trials, the mean pain scores were better than at baseline at all time points after the procedure in both the real-procedure and the sham-procedure groups. Moreover, the effect did not differ between the two treatment groups in either study.
QUESTIONS COMPLICATE THE ISSUE
These two trials should make us consider whether this intervention is warranted. We should, however, also consider some limitations of these studies that raise questions about how the conclusions should or should not alter practice.
Does local anesthetic continue to relieve pain?
In both the sham and the real procedure, the bupivacaine injection may have helped relieve pain to some extent afterward, as its anesthetic effect may last longer than we would expect from its 3-hour half-life. The effect could certainly have contributed to improvements in pain levels at the earlier time points after the procedure.
Was there selection bias?
Both studies were highly rigorous and were done at hospitals that had extensive experience with vertebroplasty. However, they may have harbored selection bias, as many more patients were screened than were randomized.
Buchbinder et al1 screened 468 patients. Of these, 30% declined to participate, and another 53% did not meet the eligibility criteria. In the end, only 78 patients were randomized.
Kallmes et al2 screened 1,813 patients, 300 of whom declined and 1,382 of whom were excluded, leaving 131 patients to be randomized. The reasons for exclusion were not specifically reported in many cases.
In both studies, it would be interesting to know how many of those who declined proceeded to undergo a vertebral augmentation procedure.
