The battle over the treatment of patients with a painful osteoporotic vertebral fracture is hotting up nicely. On one side, the protagonists of vertebroplasty are carrying out a considerable number of these procedures and claiming significant, prolonged pain relief for their patients: on the other, the evidence-based medicine brigade can find no evidence that the procedure has anything other than a placebo effect.
In their instructional review, Muijs, van Erkel and Dijkstra consider the place of percutaneous vertebroplasty in the 15% of patients who fail to respond to 12 weeks of conservative treatment. In its favour, they cite Eck et al1 who, in 2008, reported a meta-analysis of the literature to date and found a mean, statistically significant, improvement of 5.68 (SD+/-1.24) in post-operative VAS level. More recently, however, two randomised controlled studies were published in the New England Journal of Medicine (the Australian2 and INVEST3 studies) which cast doubt on its efficacy.
In the midst of this debate, the potential for causing harm should not be overlooked. Eck et al reported a 17.9% risk of new fracture, usually at an adjacent level, after vertebroplasty and a 19.7% risk of cement leak. Complications may be catastrophic and are usually related to leakage of large volumes of cement.
The indications for the procedure, whether effective or not, are now fairly clear. Patients with an osteoporotic fracture with more than 15% loss of anterior vertebral height, severe pain which is unresponsive to all reasonable modalities of conservative treatment, tenderness over spinous process of the fractured vertebra and bone marrow oedema on MRI imaging with fat suppression may be considered for treatment. It is the timing of this treatment that raises a number of issues. In the literature to date patients have been treated as early as one week after their fracture and as late as 12 months. Of the major randomised studies, The Vertos ll study5 only included patients with back pain for six weeks or less, the Australian2 and INVEST3 studies included patients with back pain for up to a year. The Vertos ll study showed that vertebroplasty gave greater pain relief than conservative treatment and concluded that the pain relief is immediate, sustained for at least a year, and is significantly greater than that achieved with conservative treatment. The Australian and INVEST studies concluded that vertebroplasty conferred no additional benefit over placebo or sham treatment.
These studies are not really comparable as they clearly study different populations. Given that the pain of an osteoporotic vertebral fracture will probably settle within 12 weeks in 85% of patients, it seems paradoxical to study a group in which the pain has been present for less than six weeks. Similarly, is it reasonable to study groups of patients who have been in pain for anything between a few weeks and a year?
One further piece of evidence should be considered. Since the article by Muijs et al was accepted for publication, the authors of the Australian and INVEST studies have combined their findings in a meta-analysis to try to identify any subgroups which would benefit from vertebroplasty6. They have concentrated on patients with fractures of recent onset (<6 weeks) and patients in severe pain and have still failed to show any benefit from vertebroplasty over placebo.
Muijs et al are certainly correct in concluding that indisputable evidence in favour or against the effectiveness of percutaneous vertebroplasty is still lacking and that further studies are needed. When these are planned, not only should the inclusion and exclusion criteria be crystal clear but the investigators should undoubtedly narrow down the population studied by duration of symptoms: perhaps 3 to 6 months would be sensible in the first instance. Otherwise, how are we to know if we should advise vertebroplasty, and if so, who to treat and when?
1. Eck, JC Nachtigall D, Humphreys SC, Hodges SD. Comparison of vertebroplasty and balloon kyphoplasty for treatment of vertebral compression fractures: a meta-analysis of the literature. Spine J 2008;8:488-97.
2. Buchbinder R, Osborne RH, Ebeling PR, Wark JD, Mitchell P, Wriedt C, Graves S, Staples MP, Murphy B. A randomized trial of vertebroplasty for painful osteoporotic vertebral fractures. N Engl J Med 2009;361:557-68.
3. Kallmes D, Comstock B, Heagerty P, Turner J, et al. A randomized trial of vertebroplasty for osteoporotic spinal fractures. N Engl J Med 2009;361:569.
4. Voormolen MHJ, Mali WPTM, Lohle PNM, Fransen H, Lampmann LEH, et al. Percutaneous vertebroplasty compared with optimal pain medication treatment: short-term clinical outcome of patients with subacute or chronic painful osteoporotic vertebral compression fractures. The VERTOS study. AJNR American Journal of Neuroradiology. 2007;28:555-60.
5. Klazen CA, Lohle PN, de Vries J, Jansen FH, Tielbeek AV, et al. Vertebroplasty versus conservative treatment in acute osteoporotic vertebral compression fractures (Vertos II): an open-label randomised trial. Lancet 2010;376: 1085-92.
6. Staples MP , Kallmes DF, Comstock BA, Jarvik JG, Osborne RH , et al. Effectiveness of vertebroplasty using individual patient data from two randomised placebo controlled trials: meta-analysis. BMJ 2011;343:d3952 doi: 10.1136/bmj.d3952.
Associate Editor, Journal of Bone & Joint Surgery (British Volume)