Resurrection of evidence for vertebroplasty?

Although over 500 articles have been published in the last 5 years on vertebroplasty, a fundamental question remains—is vertebroplasty a safe and eff ective procedure to reduce pain and disability for patients with vertebral compression fractures? Initial enthusiasm for vertebroplasty was driven by clinician experience and meta-analysis of large observational series showing patient benefi t. This enthusiasm was dampened after publication of two randomised controlled trials (RCTs) in the New England Journal of Medicine, which showed no statistically signifi cant benefi t to performing vertebroplasty compared with a placebo procedure. Although there were legitimate criticisms of these two trials, their highly publicised nature led to a marked reduction in the use of the procedure in the USA, and removal of public funding for vertebroplasty in Australia. Subsequent open-label RCTs compared vertebroplasty with optimum medical management for osteoporotic fractures. These trials all showed consistent statistically signifi cant benefi t from vertebroplasty, and better refl ected the real-world comparator that we use in clinical practice. This fi nding led to endorsement in 2013 of vertebroplasty for osteoporotic fractures by the National Institute for Health and Care Excellence that advises the National Health Service of England and Wales and by many international medical societies. Nonetheless, over this time of continuing scientifi c discourse, many patients and caregivers were unable to access vertebroplasty as a potential treatment option. In The Lancet, William Clark and colleagues report the VAPOUR trial, a thoughtful and important multicentre, masked, placebo-controlled RCT to assess the effi cacy of vertebroplasty in the subgroup of patients with recent (<6 weeks) vertebral compression fractures causing severe pain (Numeric Rating Scale [NRS] score of ≥7 out of 10). The trial recruited 120 patients; 61 patients were randomly assigned to vertebroplasty and 59 to a placebo procedure (subcutaneous local anaesthetic infi ltration). The primary outcome was the proportion of patients achieving an NRS score of less than 4 at 14 days post-treatment. A signifi cantly greater proportion of patients in the vertebroplasty group achieved the primary outcome compared with the control group (44% vs 21%; between-group diff erence 23 percentage points, 95% CI 6–39; p=0·011). This treatment advantage persisted at all timepoints to 6 months. Moreover, there were also statistically signifi cant reductions in Roland-Morris Disability Questionnaire scores from 1 month to 6 months posttreatment. VAPOUR was diff erent from other studies in a number of respects. First, VAPOUR included earlier treatment of vertebral compression fractures compared with previous masked RCTs, and focused on patients with severe pain (NRS ≥7). Second, the placebo group was diff erent, and closer to a true sham procedure. In the previous masked RCTs, the sham procedure involved periosteal local anaesthetic infi ltration, an active control, which could have provided pain relief particularly for patients with more chronic fractures and secondary mechanical pain. The authors used subcutaneous local anaesthetic infi ltration followed by medical management, thus providing a better comparator more akin to conservative therapy. Additionally, VAPOUR showed that medical management is not always benign, and can also be associated with risk—two patients in the control group developed spinal cord compression from further collapse and retropulsion of their vertebral compression fractures. Third, the major benefi t was driven by fractures in the thoracolumbar (T11 to L2) segment. In this subgroup, 61% of the vertebroplasty group achieved the primary outcome compared with 13% of the control group (between-group diff erence 48 percentage points, 95% CI 27–68). The authors hypothesise that this segment is subject to increased dynamic weight-bearing load and thus there is potentially greater benefi t from restoration of structural integrity after vertebroplasty. Fourth, there was at least a 30% greater vertebral height preservation from 6-month radiographs in the vertebroplasty group without increase in additional vertebral fractures. Finally, 57% of patients enrolled were hospital inpatients, and the median duration of hospital stay was reduced by 5·5 days in the vertebroplasty group. Although there was no cost-eff ectiveness analysis in VAPOUR, such marked reduction in hospital stay will presumably translate to overall health-care cost saving, even when accounting for procedural costs. Published Online August 17, 2016 http://dx.doi.org/10.1016/ S0140-6736(16)31356-3