Both INVEST (the Kallmes study)1
and the Buchbinder study2
were blinded, randomized, placebo-controlled trials of VP. INVEST, performed at 11 sites in the United States, United Kingdom, and Australia, enrolled 131 patients. The Buchbinder study enrolled 78 patients at 4 sites in Australia. Both enrolled patients with painful osteoporotic fractures of less than 1 year’s duration. Exclusions for both trials included a suspicion of neoplasm in the vertebral body, substantial retropulsion of bony fragments, medical conditions that would preclude surgery, and an inability to obtain consent or conduct follow-up.
Participants in both trials had similar baseline characteristics: They were primarily Caucasian and female, with an average age in the mid-70s. The average pain intensity at enrollment was about 7 on a 0- to 10-point visual analog scale (VAS). The average time since the fracture causing the pain was 4 to 5 months in INVEST and about 2 months in the Buchbinder study. Both trials used appropriate randomization, blinding, and intention-to-treat analysis.
Blinding featured sham procedures. In both studies, the researchers used elaborate measures to ensure blinding: The control patients were prepped in the fluoroscopy suite as if they were about to undergo VP. They received local anesthesia down to the periosteum of the vertebra. The PMMA was opened and mixed in the room to allow its distinctive smell to permeate. Patients also received verbal and physical cues that simulated the procedure, and spinal images were obtained.
INVEST used pain and disability at 1 month as the primary end points. There was minimal difference in pain intensity (3.9 on VAS for the VP group, vs 4.6 for the controls). There was also little difference in back pain-related disability at 1 month, with scores on the Roland Morris Disability scale decreasing (from a baseline of 16.6 for the VP group and 17.5 for the control group) to 12 and 13, respectively (P=.49). Nor were there any statistically significant differences in pain or disability at earlier intervals (the researchers compared the scores of the VP and control groups at 3 days and 14 days.) The authors also looked at 7 other measures of pain and functioning and found no significant differences in any of them at the end of 1 month.
To encourage enrollment, patients in the INVEST trial were allowed to cross over after 1 month. At that time, 12% of those in the VP group and 43% of those in the control group took advantage of this provision and had the alternate “procedure.” Both groups of cross-over patients had more pain than those who did not make the switch. Although both of these groups showed improvement at the 3-month mark, they still had higher pain levels than their counterparts who did not cross over.
The Buchbinder study used overall pain on a 10-point VAS at 3 months as its primary end point. The researchers also recorded 7 other measurements and assessed participants at 1 week, 1 month, 3 months, and 6 months. At 3 months, there was no significant difference in the change in pain scores between the treatment and placebo groups: Mean pain scores for those who underwent VP decreased from 7.4 to 5.1, while the placebo group’s average pain scores went from 7.1 to 5.4. Similarly, there was no difference between the treatment and placebo groups in the change in pain scores at 1 week or 6 months—and no difference between the groups at any time for the other 7 measures of pain and function.