No more vertebroplasty for acute vertebral compression fractures?BMJ 2018; 361 doi: https://doi.org/10.1136/bmj.k1756 (Published 09 May 2018) Cite this as: BMJ 2018;361:k1756
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This editorial cites the VERTOS4 trial (1) as proof of lack of efficacy for vertebroplasty in acute, painful osteoporotic fractures but, inexplicably, has ignored the VAPOUR trial (2) which showed vertebroplasty superior to placebo when reserved for patients with more severe symptoms and earlier time of intervention, including hospital inpatients.
VAPOUR is the only blinded trial to enrol patients who had unplanned hospital admission due to acute osteoporotic vertebral fractures (57% of VAPOUR enrolment). Vertebroplasty occurred a mean 6 days following hospital admission, after a failed trial of medical therapy. These inpatients were excluded in the three other blinded trials (1,3,4). At time of admission they usually have fractures less than 2 weeks duration, severe osteoporosis, severe functional disability and other co-morbidities. The combination of symptoms and opiate analgesia can result in a dire clinical situation for this fragile patient group with delirium, constipation, loss of confidence ambulating and loss of condition. Hospitalisation may be prolonged, (mean duration of 20 days for the placebo group of the inpatient cohort in the VAPOUR trial). Vertebroplasty reduced hospital stay by 6 days compared to placebo. There is no information or advice on the role of vertebroplasty in managing hospitalised inpatients in this editorial.
VAPOUR is the only blinded trial to have required severe pain, (defined as NRS ≥7 /10), for enrolment. The other three trials (3,4,1) had lesser pain thresholds for inclusion - 3/10, not stated and 5/10 respectively. Only 34% of patients in VERTOS4 were using strong opiates at the time of randomisation compared to 90% opiate intake in VAPOUR.
VAPOUR performed vertebroplasty much earlier than the other blinded trials. Mean fracture duration at time of vertebroplasty was 2.8 weeks in VAPOUR compared to 6.1weeks (VERTOS4), 11.7 weeks (4) and 16 weeks (3). VAPOUR sub-group analysis showed the benefits of vertebroplasty were concentrated in patients with fractures not more than three weeks duration. 80% of patients in VAPOUR had fractures of 3 weeks duration or less at time of vertebroplasty whereas VERTOS4 had an interquartile range of fracture duration of 29-52 days, well beyond three weeks.
The recent COCHRANE vertebroplasty review (5) is referenced as further proof that vertebroplasty does not work, but the authors of the Cochrane review failed to acknowledge the positive findings of VAPOUR, with no mention of the primary end-point. They drew conclusions from meta-analysis of the blinded evidence without exploring the reasons for the positive outcomes in the VAPOUR trial versus the negative findings in their own trials (3,4) and in VERTOS4. All patients in VERTOS4 were included in a Cochrane meta-analysis of fractures less than 6 weeks duration, whereas less than 50% of the VERTOS4 patients had fractures of this duration at time of vertebroplasty. Meta-analysis of the VAPOUR trial with the other blinded trials has little meaning anyway, given the differences between the trials as described above.
Vertebroplasty is effective in the management of patients with severe pain due to vertebral compression fractures less than 6 weeks duration, when analgesic medication cannot provide adequate symptomatic control. It should be performed early, preferably before the fracture is 4 weeks in duration. The editorial states that ”even those patients with severe pain normally improve within six weeks” but this does not hold for patients with uncontrolled pain despite analgesic therapy. Most placebo group patients in the VAPOUR trial still had moderate or severe pain at 6 months and 76% were still using analgesics. The vertebroplasty group derived clinically important benefits at all time points.
1. Firanescu C, Lohle PN, de Vries J, et al. A randomised sham controlled trial of vertebroplasty for painful acute osteoporotic vertebral fractures (VERTOS IV). Trials. 2011;12:93. doi:10.1186/1745-6215-12-93.4
3. Clark W, Bird P, Gonski P, et al. Safety and efficacy of vertebroplasty for acute painful osteoporotic fractures (VAPOUR): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet2016;388:1408-16. doi:10.1016/S0140-6736(16)31341-1
3. Kallmes DF, Comstock BA, Heagerty PJ, et al. A randomized trial of vertebroplasty for osteoporotic spinal fractures. N Engl J Med2009;361:569-79. doi:10.1056/NEJMoa0900563 pmid:19657122
4. Buchbinder R, Osborne RH, Ebeling PR, et al. A randomized trial of vertebroplasty for painful osteoporotic vertebral fractures. N Engl J Med2009;361:557-68. doi:10.1056/NEJMoa0900429 pmid:19657121
5. Buchbinder R, Johnston RV, Rischin KJ et al. Percutaneous vertebroplasty for osteoporotic vertebral compression fracture. Cochrane Database of Systematic Reviews 2018;4: CD006349. doi: 10.1002/14651858.CD006349.pub3. 29618171
Competing interests: I am an author of the VAPOUR trial