Had this topic been discussed 18 months ago, there would have been little or no controversy as to the beneficial role of cement augmentation for the management of painful osteoporotic and malignant pathological fractures of the spine. On the basis of an overwhelmingly positive clinical experience of dramatic pain relief, and supported by many large prospective case series and even a prospective comparative cohort study,1 most physicians believed that vertebroplasty and/or kyphoplasty offered clear benefit over non-operative treatment of painful osteoporotic fractures. However, since the publication of two separate randomised controlled trials (RCTs) in the August 2009 edition of the New England Journal of Medicine,2,3 the entire landscape of care for this condition has changed; providers are faced with a seemingly baffling disconnect between the previous evidence and this latest ‘highest quality’ data.
So what was so different about these studies?
The two prospective RCTs, enrolling a total of 209 patients, were the first Level I studies to compare vertebroplasty with placebo. Buchbinder et al2 included patients with subacute fractures (nine weeks since injury), where after the surgery all participants received usual care according to the discretion of the treating physician. Kallmes et al3 included chronic fractures (18 weeks) and patients were allowed to cross over to the alternative treatment after one month. Neither study found a significant difference in pain, function or quality of life between vertebroplasty and placebo.
Many criticisms have been levelled at these studies, including lack of statistical power, failure to include all or even sufficient eligible patients, treatment group crossover, failure to analyse fracture type subgroups, failure to include patients with high pain scores, failure to differentiate acute from chronic fractures and surgeon and patient bias inherent in consenting to a sham procedure. However, with the bewildering number of subsequent editorials, letters, author responses and finally governmental, insurance carrier (in the United States) and professional body statements, both Level I studies appear to have weathered the inevitable storm.
Action and reaction
In October 2009, a mere two months after the two publications in the New England Journal of Medicine, the North American Spine Society (NASS) issued a statement in response to the professional and media frenzy that ensued.4 In this thoughtful and thought-provoking analysis they highlighted a number of key methodological concerns regarding both studies. They suggested that the actual findings of these studies were not surprising, nor that dissimilar to previous data, but that the conclusions drawn by the authors were inappropriate.4 They cautioned that the data from these two studies must be considered carefully and thoughtfully, and that more practical conclusions should be made based on a thorough and systematic review of all of the literature, in order to better define the subgroup of patients for which vertebroplasty might be most appropriate.
In September 2010 The American Academy of Orthopedic Surgeons (AAOS) issued a Guideline and Evidence Report on the various treatment options for painful osteoporotic fractures.5 As a result of the rigour and thoroughness of the literature analysis, this report is an excellent reference source for this topic.
In summary, the AAOS issued a strong recommendation against vertebroplasty, and a weak recommendation for kyphoplasty, in the management of painful osteoporotic vertebral fractures. The reason for the clear distinction in recommendation between the two seemingly ‘similar’ procedures is very important.
The strong recommendation against vertebroplasty was based on the two recent Level I studies2,3 and the only three Level II studies,6-8 all of which failed to show any clinically meaningful benefit of vertebroplasty, even in the short-term. No Level III or IV evidence was even considered in the analysis.
In October 2010, in response to the AAOS guidelines, the NASS made a statement. They said the guidelines ‘appear to have been developed in an appropriate and transparent manner. The recommendations offered may be applied to the populations that were the basis of the studies reviewed at the time. However, it is the policy of NASS to restrict comment to the validity of the process by which other organizations develop evidence-based guidelines’.9 NASS have suggested that updated guidelines be developed after a finite time interval or when additional high-level studies have been published with different conclusions or if additional studies are published examining a different population.
These apparent conflicting statements from NASS and the AAOS create another disconnect for the bewildered clinician to consider. One current popular model of ‘evidence-based medicine’ comprises three components: best available literature, patient preference and expert opinion. With respect to cement augmentation for insufficiency fractures of the spine, whose opinion do we consider most expert? NASS? AAOS? And how do we decide what to tell the patient? After all, isn’t a patient’s preference significantly impacted by the opinion of their individual clinician expert?
With particular respect to the evidence supporting a weak recommendation in favour of kyphoplasty, two Level II studies have compared kyphoplasty alongside conservative treatment.10,11 Wardlaw et al10 studied patients with subacute fractures, and found clinically important benefits in pain at one week and one month, with possibly important effects at three and six months. There was no clinically important benefit in pain at 12 months. The study also found clinically important benefits in physical function at one, three and six months.10 Clinically important improvement in quality of life was present at one month, and possibly at three, six, and 12 months. Grafe et al11 investigated all patients aged > one year with fractures, raising the question as to whether the fracture was responsible for all of the pain. There was however a statistically significant and possibly clinically important improvement in pain at three, six and 12 months.
There have also been three Level II studies directly comparing kyphoplasty to vertebroplasty.12-14 In general, kyphoplasty has been shown to be at least equivalent and inconsistently superior to vertebroplasty for short- and long-term pain relief. These studies have been inconsistent in design and outcome and so had little impact on the final recommendation made by the AAOS.
When considering the technical similarities between kyphoplasty and vertebroplasty and the uniquely different AAOS recommendations for their use, several points deserve reiteration. The benefit of vertebroplasty over sham is clearly in doubt. Both procedures have previously been compared to similar control groups with kyphoplasty being consistently superior. The direct comparison between vertebroplasty and kyphoplasty shows a clinically important advantage in critical outcomes for kyphoplasty at durations up to two years.
To date there have been no Level I studies, comparing kyphoplasty to placebo, similar to either of the recent NEJM vertebroplasty studies. Given the similarities between the procedures, does the same fate await kyphoplasty, with the inevitable publication of a placebo controlled RCT?
This article was originally published in the Canadian Orthopaedic Association’s COA Bulletin #92, Spring 2011 edition.
1. Alvarez L, Alcaraz M, Pérez-Higueras A, et al. Percutaneous vertebroplasty functional improvement in patients with osteoporotic compression fractures. Spine (Phila Pa 1976) 2006;31:1113-18.
2. Buchbinder R, Osborne RH, Ebeling PR, et al. A randomized trial of vertebroplasty for painful osteoporotic vertebral fractures. N Engl J Med 2009;361:557-68.
3. Kallmes DF, Comstock BA, Heagerty PJ, et al. A randomized trial of vertebroplasty for osteoporotic spinal fractures. N Engl J Med 2009;361:569-79.
4. No authors listed. North American Spine Society. Newly Released Vertebroplasty RCTs: A Tale of Two Trials. http://www.spine.org/Documents/NASSComment_on_Vertebroplasty.pdf (date last accessed 5 November 2012).[[bibmisc]]
5. No authors listed. American Academy of Orthopaedic Surgeons. The treatment of symptomatic osteoporotic spinal compression fractures: guideline and evidence report. http://www.aaos.org/research/guidelines/SCFguideline.pdf (date last accessed 5 November 2012).[[bibmisc]]
6. Rousing R, Andersen MO, Jespersen SM, Thomsen K, Lauritsen J. Percutaneous vertebroplasty compared to conservative treatment in patients with painful acute or subacute osteoporotic vertebral fractures: three-months follow-up in a clinical randomized study. Spine (Phila Pa 1976) 2009;34:1349-54.
7. Voormolen MH, Mali WP, Lohle PN, 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 Am J Neuroradiol 2007;28:555-60.
8. Diamond TH, Bryant C, Browne L, Clark WA. Clinical outcomes after acute osteoporotic vertebral fractures: a 2-year non-randomized trial comparing percutaneous vertebroplasty with conservative therapy. Med J Aust 2006;184:113-17.
9. No authors listed. North American Spine Society Statement on Vertebroplasty Guidelines. http://www.spine.org/Pages/ConsumerHealth/NewsAndPublicRelations/NewsReleases/2010/pressrelease_101410.aspx (date last accessed 5 November 2012).[[bibmisc]]
10. Wardlaw D, Cummings SR, Van MJ, et al. Efficacy and safety of balloon kyphoplasty compared with non-surgical care for vertebral compression fracture (FREE): a randomized controlled trial. Lancet 2009;373:1016-24.
11. Grafe IA, Da FK, Hillmeier J, et al. Reduction of pain and fracture incidence after kyphoplasty: 1-year outcomes of a prospective controlled trial of patients with primary osteoporosis. Osteoporos Int 2005;16:2005-12.
12. Grohs JG, Matzner M, Trieb K, Krepler P. Minimal invasive stabilization of osteoporotic vertebral fractures: a prospective nonrandomized comparison of vertebroplasty and balloon kyphoplasty. J Spinal Disord Tech 2005;18:238-42.
13. Liu JT, Liao WJ, Tan WC, et al. Balloon kyphoplasty versus vertebroplasty for treatment of osteoporotic vertebral compression fracture: a prospective, comparative, and randomized clinical study. Osteoporos Int 2010;21:359-64.
14. De Negri P, Tirri T, Paternoster G, Modano P. Treatment of painful osteoporotic or traumatic vertebral compression fractures by percutaneous vertebral augmentation procedures: a nonrandomized comparison between vertebroplasty and kyphoplasty. Clin J Pain 2007;23:425-30.