The INVEST trial: Limited added utility of vertebroplasty versus sham surgery [Classics Series]

1. Vertebroplasty does not reduce pain or pain-related disability in patients with osteoporotic compression vertebral body fractures when compared to sham surgery after 1 month.

Original Date of Publication: August 2009

This study summary is an excerpt from the book 2 Minute Medicine’s The Classics in Medicine: Summaries of the Landmark Trials, 2e (The Classics Series).

Study Rundown: Osteoporotic fractures of vertebral bodies are often associated with pain and have historically been treated medically, including a combination physical therapy and pain management. These fractures are often a source of pain and disability for patients, and those who fail medical management may require hospitalization or extended care. Percutaneous vertebroplasty, which involves injecting medical cement (polymethylmethacrylate, or PMMA) into the fractured vertebral body, has typically been the next line of therapy in patients who have failed medical management. However, the efficacy of vertebroplasty in relieving pain in osteoporotic fractures has been limited to small case series and nonrandomized controlled studies. Prior to 2009, the best evidence of its efficacy was an open randomized trial involving 34 patients. Despite limited evidence, public institutions have recommended reimbursement for these procedures, which has led to increases in vertebroplasty volume.

The Investigational Vertebroplasty Safety and Efficacy Trial (INVEST) compared the efficacy of PMMA in patients with painful osteoporotic fractures against a sham procedure. The results of this trial showed no significant difference between groups in either the modified Roland-Morris Disability Questionnaire (RDQ) or in their pain scores after intervention, measured both at 24 hours and 1 month after intervention. These results suggest that there is no added beneficial effect in pain reduction or disability in patients undergoing vertebroplasty for osteoporotic compression fractures. A similar randomized controlled study published concurrently also examined vertebroplasty versus sham surgery, and found no beneficial effect of vertebroplasty at 1 week and up to 6 months after intervention. A Cochrane review confirmed these results in 2015, and concluded that there was not enough evidence to support vertebroplasty for the treatment of osteoporotic vertebral fractures.

Please click to read study in NEJM

In-Depth [randomized controlled trial]: This prospective trial was conducted at 11 centers across the United States, United Kingdom, and Australia. These sites were chosen because they had established vertebroplasty practices, and a total of 1813 patients were screened for enrollment. Inclusion criteria included patients over the age of 50 that had one to three vertebral body compression fractures (between T4-L5 vertebral bodies) less than one year old who had failed medical therapy. Key exclusion criteria included evidence/suspicion of neoplasm in the target vertebral body, significant retropulsion of bony fragments, underlying hip fracture, active infection, and incorrigible bleeding diathesis. The main outcome measures were the modified RDQ and patients’ rating of average back pain intensity during the preceding 24 hours on a 10-point scale. The minimal amount of change to be clinically significant was 30% in both pain intensity and RDQ. Patients were measured at various points up to one year after intervention, including 3, 14, and 90 days. The vertebroplasty interventionalists had performed a mean of 250 procedures (range of 50-800). All patients who were included in the study underwent fluoroscopically guided infiltration of skin and subcutaneous tissue with lidocaine and infiltration of the pedicle periosteum of the target vertebrae with bupivacaine. Patients were then randomized to either full vertebroplasty or the sham intervention (control procedure). Patients undergoing vertebroplasty had PMMA infused until it reached the posterior aspect of the vertebral body or it entered a paravertebral space. Patients were allowed to cross over to the other procedure 1 month or later after the intervention.

A total of 131 patients with similar baseline characteristics were enrolled between June 2004 and August 2008, with 68 patients who underwent vertebroplasty and 63 who underwent the control sham procedure. There was no significant difference between both groups with regards to either of the primary outcomes at one month. The mean RDQ score (± SD) in the vertebroplasty group was 12.0±6.3 versus 13.0±6.4 in the control group (adjusted treatment effect: 0.7; 95%CI -1.3-2.8; P = 0.49). The mean pain-intensity rating was 3.9±2.9 in the vertebroplasty group and 4.6±3.0 in the control group (adjusted treatment effect: 0.7; 95%CI -0.3-1.7; P = 0.19). Both groups had similar improvement in back related disability 3 days after intervention, which was maintained at 1 month. At 3 months, 9 patients in the vertebroplasty group and 32 patients in the control group had crossed over and underwent the alternative procedure (p < 0.001).

Kallmes DF, Comstock BA, Heagerty PJ, Turner JA, Wilson DJ, Diamond TH, et al. A Randomized Trial of Vertebroplasty for Osteoporotic Spinal Fractures. New England Journal of Medicine. 2009 Aug 6;361(6):569–79.

Additional Review:

Buchbinder R, Osborne RH, Ebeling PR, Wark JD, Mitchell P, Wriedt C, et al. A Randomized Trial of Vertebroplasty for Painful Osteoporotic Vertebral Fractures. New England Journal of Medicine. 2009 Aug 6;361(6):557–68.

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