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.
WHAT’S NEW: Trials cast doubt on established procedure
VP has essentially become the standard of care for painful osteoporotic vertebral fractures, bolstered by a long list of methodologically inferior studies that have lent support to the procedure’s efficacy. These 2 studies are the first to incorporate a sham procedure that supports true placebo control. The complete lack of benefit for VP compared with conservative management in these well-done trials calls into question the results of prior reports.
CAVEATS: Sample size, study design
Researchers in both studies had considerable difficulty enrolling patients. Both were multi center trials and enrolled patients over a 4-year period; nonetheless, taken together, only about 200 patients consented. The researchers faced opposition from referring doctors and patients alike, who believed that the possibility of receiving a placebo treatment rather than VP constituted inferior care.
In addition to their relatively small size, these studies enrolled patients with fairly chronic fractures. It has been postulated that VP has a higher likelihood of success with acute fractures, but that was not the focus of these trials. The majority of the fractures in trial participants were not acute (<4 weeks). Neither trial was designed for analysis based on the chronicity of the fracture, and neither found a difference in outcome based on fracture duration.
Because these trials were not designed, or robust enough, for subgroup analysis, we don’t know if there is a population that might benefit (ie, severity of the compression, acuteness of the fracture, or premorbid health, etc). In addition, these results do not apply to the use of VP for other reasons—malignant spinal neoplasms or vertebral hemangiomas, for example.
Finally, it is important to remember that these trials did not strictly compare VP with conservative treatment. The sham treatment may have had significant placebo power that is greater than that of typical conservative treatment.
CHALLENGES TO IMPLEMENTATION: Support for VP is well established
Anecdotal results, established treatment patterns, and numerous low-quality studies support the use of VP for vertebral compression fracture. Medicare and other insurers had reviewed the evidence prior to these 2 trials and agreed to reimburse for the procedure. It remains to be seen whether these 2 trials will be sufficient to overcome these barriers and change practice patterns.
At a minimum, however, it is prudent to reserve VP for patients who have intractable symptoms until further trials are undertaken to determine whether VP really works, and if so, for which patients.
Acknowledgement
The PURLs Surveillance System is supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.
