Vertebroplasty Evidence Reversal

Percutaneous vertebroplasty — injection of polymethylmethacrylate cement into collapsed vertebral bodies — was introduced in the late 1980s and rapidly adopted based on compelling open-label studies showing dramatic pain relief. Uncontrolled case series reported pain improvement in 80-90% of patients, and the procedure spread globally as an apparently effective treatment for painful osteoporotic vertebral compression fractures. The rapid diffusion occurred without randomized evidence, driven by patient demand and impressive anecdotal results. However, the lack of placebo or sham controls left uncertainty about whether the observed benefits reflected true treatment effects or a combination of natural history, regression to the mean, and the powerful placebo effect of an invasive procedure.

In 2009, two landmark sham-controlled RCTs published simultaneously in the New England Journal of Medicine delivered a seismic shock to the field. The Buchbinder trial (Australian) randomized 78 patients to vertebroplasty or a sham procedure (local anesthetic to periosteum without cement injection) and found no significant difference in pain or disability at any time point up to 6 months. The Kallmes (INVEST) trial randomized 131 patients to vertebroplasty or sham and similarly found no difference in pain or disability through 1 month. Both trials demonstrated that the impressive improvements seen in open-label studies were attributable to placebo effects and natural history rather than the cement injection itself. These trials represent one of the most dramatic evidence reversals in modern medicine, challenging a procedure performed hundreds of thousands of times annually.

The controversy did not end with the 2009 sham trials. The VERTOS-IV trial (2018) — another sham-controlled RCT of 180 patients with acute fractures (<9 weeks) — confirmed no benefit of vertebroplasty over sham, reinforcing the negative findings. However, the VAPOUR trial (2016, Australia) introduced nuance by randomizing 120 patients with acute fractures (<6 weeks) and severe pain to vertebroplasty versus sham, finding significantly greater pain reduction with vertebroplasty at 14 days. The VAPOUR authors argued that patient selection (acute fractures, severe pain, bone marrow edema on MRI) and technique differences explained the discrepant results. This created an ongoing and polarized debate: proponents argue that vertebroplasty works in carefully selected acute fractures, while skeptics note that the weight of sham-controlled evidence is overwhelmingly negative.

Guidelines have diverged significantly in response to the conflicting evidence. The American Society of Bone and Mineral Research (ASBMR) task force recommended against vertebroplasty for osteoporotic compression fractures based on the weight of sham-controlled evidence. NICE guidelines in the UK similarly recommend against vertebroplasty. However, cardiovascular and interventional radiology societies have maintained more favorable positions, arguing for selective use in acute fractures with imaging confirmation of edema. The AO Spine Knowledge Forum recommends against routine vertebroplasty but acknowledges potential benefit in selected acute fractures failing conservative management.

Vertebroplasty remains one of the most contentious topics in musculoskeletal medicine. The procedure continues to be performed widely in many countries despite the predominantly negative sham-controlled evidence, illustrating the difficulty of de-implementing established practices. Some clinicians advocate a risk-stratified approach, reserving the procedure for patients with acute fractures (<6 weeks), severe pain, MRI-confirmed bone marrow edema, and failure of conservative management — the population that showed benefit in VAPOUR. Others argue that even VAPOUR's modest short-term benefit does not justify ongoing use. Kyphoplasty (balloon-assisted vertebroplasty) faces similar scrutiny, with the FREE trial showing benefit over nonsurgical management but no sham-controlled evidence. This topic stands as a case study in evidence reversal, the power of placebo in procedural medicine, and the challenges of changing clinical practice in the face of contradictory evidence.