NIHR Signal Cement injections to treat spinal compression fractures from osteoporosis can reduce short term pain

Published on 13 December 2016

Injecting cement into osteoporotic spinal fractures within six weeks reduces pain in the first few months and disability six months later. The trial was undertaken in people aged over 60 years and compared the one-off injection to a simulated dummy procedure.

The procedure, called vertebroplasty, aims to stabilise the collapsed vertebra and prevent further collapse.

This trial of 120 older people, average age of 80 years, found that vertebroplasty reduced disability and improved quality of life compared with placebo. Initially, at two weeks, pain scores were better with vertebroplasty, but there was no difference in pain between the groups at three to six months later.

NICE recommends vertebroplasty only for people who have an unhealed fracture and severe pain after conservative management with bed rest and painkillers. NICE do not specify how soon after the fracture this can be offered.

Fractures take on average six weeks to heal. At present in the UK, people are unlikely to be offered vertebroplasty within the six week timescale of participants in this study. Additionally, the procedure is only available in some centres.

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Why was this study needed?

Worldwide, an estimated 1.4 million people with osteoporosis experience vertebral fractures. Most osteoporotic vertebral fractures are treated conservatively with painkillers, bed rest and mobility exercises as function improves. However, painkillers and prolonged bed rest can both have adverse effects in older people.

Vertebroplasty involves injecting special cement into the broken vertebrae to relieve pain and strengthen the bone to prevent future fractures. A common approach is to use vertebroplasty only in people who continue to experience pain several months after sustaining a fracture, to allow time for the fracture to heal of its own accord.

Two randomised controlled trials from 2009 suggest that vertebroplasty has limited benefit in patients with osteoporotic fractures sustained up to 12 months previously. However, more recent open label trials have indicated that the procedure might be effective if used sooner after the fracture occurs. These researchers wanted to test the potential benefits in a carefully designed randomised trial.

What did this study do?

This randomised controlled trial recruited people older than 60 years from four centres in Sydney, Australia. Participants had one or two recent vertebral fractures of less than 6 weeks duration. They also had severe back pain that they rated 7 or more out of 10 (where 0 is no pain and 10 maximum pain; average 8.6). This was a selected group and many patients with less pain and other medical conditions were excluded from the study.

The 61 people (average 80.5 years) were randomly assigned to the intervention group underwent vertebroplasty with injection of polymethylmethacrylate. The 59 people assigned to the placebo group were sedated and underwent a sham procedure designed to simulate vertebroplasty.

The main outcome measure was pain at 14 days after the procedure scored on a validated scale. Disability and quality of life were secondary outcome measures.

What did it find?

  • At 14 days after the procedure, twice as many people in the vertebroplasty group than in the placebo group reported that their pain was less than 4 out of 10 in severity (44% versus 21%). At six months these proportions were 69% and 47%, suggesting a further 25% had a later response.
  • Most benefit in pain seemed to come within the first few months, without much relapse to pre-treatment levels.  There was no difference in Visual Analogue Scale (VAS) pain scores or reduction in pain scores between the groups from three to six months. By six months the VAS score was 23 out of 100 in the vertebroplasty group compared to 34 in the placebo group (95% confidence interval [CI] 0 to 23).
  • Disability at six months had reduced by more among people in the vertebroplasty group than in those in the placebo group (average reduction on the 24-point Roland-Morris Disability Questionnaire [RDQ] 11.7 versus 7.4; mean difference 4.2, 95% CI 1.6 to 6.9). This means that the average score for people in the vertebroplasty group at six months was 7.8 out of 24 compared to 12.4 for the placebo group.
  • Vertebroplasty also improved quality of life at six months compared with placebo (average score on the Quality of Life Questionnaire of the European Foundation for Osteoporosis [QAULEFFO] 38 out of 100 versus 45 out of 100; mean difference 7, 95% CI 1 to 13).
  • Two people in the vertebroplasty group (3%) had serious adverse events related to the procedure, and two people in the placebo group (3%) had serious adverse events related to the fracture.

What does current guidance say on this issue?

NICE technology appraisal guidance on percutaneous vertebroplasty from 2013 recommends percutaneous vertebroplasty as an option for treating osteoporotic vertebral compression fractures only in people:

  • who have severe ongoing pain after a recent, unhealed vertebral fracture despite optimal pain management and
  • in whom the pain has been confirmed to be at the level of the fracture by physical examination and imaging.

The timing of vertebroplasty after a fracture is left to clinical judgement.

What are the implications?

This study supports the NICE recommendation to consider vertebroplasty in people with severe pain, despite optimal pain management, from a recent unhealed vertebral fracture. The study was quite small and received an unrestricted research grant from the manufacturer of a vertebroplasty kit. Other kits are available.

This study showed that vertebroplasty was effective in older people with severe pain, more than half of whom were hospitalised indicating severe disability. In this population group hospital stay was reduced by 5.5 days, suggesting there may be potential savings from wider adoption of the procedure. In some centres vertebroplasty is performed as an outpatient procedure which has further cost savings.

The procedure was performed within three weeks of the fracture on average. At present in the UK, people are unlikely to be offered vertebroplasty within three weeks. If this were to become a treatment option at an earlier stage, more people in the UK would become eligible and cost effectiveness analysis could be useful to see if a change in guidance would be good value for money.

Citation and Funding

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. Lancet. 2016;388(10052):1408–16.

The study was funded by an unrestricted research grant from CareFusion Corporation, which makes the vertebroplasty kit used in this study.

Bibliography

Hirschemail JA, Chandra RV. Resurrection of evidence for vertebroplasty? Lancet. 2016 (forthcoming).

Johnell O, Kanis JA. An estimate of the worldwide prevalence and disability associated with osteoporotic fractures. Osteoporos Int. 2006;17(12):1726–33.

NHS Choices. Osteoporosis. London: Department of Health; 2016.

NICE. Percutaneous vertebroplasty and percutaneous balloon kyphoplasty for treating osteoporotic vertebral compression fractures. TA279. London: National Institute for Health and Care Excellence; 2013.

Why was this study needed?

Worldwide, an estimated 1.4 million people with osteoporosis experience vertebral fractures. Most osteoporotic vertebral fractures are treated conservatively with painkillers, bed rest and mobility exercises as function improves. However, painkillers and prolonged bed rest can both have adverse effects in older people.

Vertebroplasty involves injecting special cement into the broken vertebrae to relieve pain and strengthen the bone to prevent future fractures. A common approach is to use vertebroplasty only in people who continue to experience pain several months after sustaining a fracture, to allow time for the fracture to heal of its own accord.

Two randomised controlled trials from 2009 suggest that vertebroplasty has limited benefit in patients with osteoporotic fractures sustained up to 12 months previously. However, more recent open label trials have indicated that the procedure might be effective if used sooner after the fracture occurs. These researchers wanted to test the potential benefits in a carefully designed randomised trial.

What did this study do?

This randomised controlled trial recruited people older than 60 years from four centres in Sydney, Australia. Participants had one or two recent vertebral fractures of less than 6 weeks duration. They also had severe back pain that they rated 7 or more out of 10 (where 0 is no pain and 10 maximum pain; average 8.6). This was a selected group and many patients with less pain and other medical conditions were excluded from the study.

The 61 people (average 80.5 years) were randomly assigned to the intervention group underwent vertebroplasty with injection of polymethylmethacrylate. The 59 people assigned to the placebo group were sedated and underwent a sham procedure designed to simulate vertebroplasty.

The main outcome measure was pain at 14 days after the procedure scored on a validated scale. Disability and quality of life were secondary outcome measures.

What did it find?

  • At 14 days after the procedure, twice as many people in the vertebroplasty group than in the placebo group reported that their pain was less than 4 out of 10 in severity (44% versus 21%). At six months these proportions were 69% and 47%, suggesting a further 25% had a later response.
  • Most benefit in pain seemed to come within the first few months, without much relapse to pre-treatment levels.  There was no difference in Visual Analogue Scale (VAS) pain scores or reduction in pain scores between the groups from three to six months. By six months the VAS score was 23 out of 100 in the vertebroplasty group compared to 34 in the placebo group (95% confidence interval [CI] 0 to 23).
  • Disability at six months had reduced by more among people in the vertebroplasty group than in those in the placebo group (average reduction on the 24-point Roland-Morris Disability Questionnaire [RDQ] 11.7 versus 7.4; mean difference 4.2, 95% CI 1.6 to 6.9). This means that the average score for people in the vertebroplasty group at six months was 7.8 out of 24 compared to 12.4 for the placebo group.
  • Vertebroplasty also improved quality of life at six months compared with placebo (average score on the Quality of Life Questionnaire of the European Foundation for Osteoporosis [QAULEFFO] 38 out of 100 versus 45 out of 100; mean difference 7, 95% CI 1 to 13).
  • Two people in the vertebroplasty group (3%) had serious adverse events related to the procedure, and two people in the placebo group (3%) had serious adverse events related to the fracture.

What does current guidance say on this issue?

NICE technology appraisal guidance on percutaneous vertebroplasty from 2013 recommends percutaneous vertebroplasty as an option for treating osteoporotic vertebral compression fractures only in people:

  • who have severe ongoing pain after a recent, unhealed vertebral fracture despite optimal pain management and
  • in whom the pain has been confirmed to be at the level of the fracture by physical examination and imaging.

The timing of vertebroplasty after a fracture is left to clinical judgement.

What are the implications?

This study supports the NICE recommendation to consider vertebroplasty in people with severe pain, despite optimal pain management, from a recent unhealed vertebral fracture. The study was quite small and received an unrestricted research grant from the manufacturer of a vertebroplasty kit. Other kits are available.

This study showed that vertebroplasty was effective in older people with severe pain, more than half of whom were hospitalised indicating severe disability. In this population group hospital stay was reduced by 5.5 days, suggesting there may be potential savings from wider adoption of the procedure. In some centres vertebroplasty is performed as an outpatient procedure which has further cost savings.

The procedure was performed within three weeks of the fracture on average. At present in the UK, people are unlikely to be offered vertebroplasty within three weeks. If this were to become a treatment option at an earlier stage, more people in the UK would become eligible and cost effectiveness analysis could be useful to see if a change in guidance would be good value for money.

Citation and Funding

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. Lancet. 2016;388(10052):1408–16.

The study was funded by an unrestricted research grant from CareFusion Corporation, which makes the vertebroplasty kit used in this study.

Bibliography

Hirschemail JA, Chandra RV. Resurrection of evidence for vertebroplasty? Lancet. 2016 (forthcoming).

Johnell O, Kanis JA. An estimate of the worldwide prevalence and disability associated with osteoporotic fractures. Osteoporos Int. 2006;17(12):1726–33.

NHS Choices. Osteoporosis. London: Department of Health; 2016.

NICE. Percutaneous vertebroplasty and percutaneous balloon kyphoplasty for treating osteoporotic vertebral compression fractures. TA279. London: National Institute for Health and Care Excellence; 2013.

Safety and efficacy of vertebroplasty for acute painful osteoporotic fractures (VAPOUR): a multicentre, randomised, double-blind, placebo-controlled trial

Published on 22 August 2016

Clark, W.,Bird, P.,Gonski, P.,Diamond, T. H.,Smerdely, P.,McNeil, H. P.,Schlaphoff, G.,Bryant, C.,Barnes, E.,Gebski, V.

Lancet , 2016

BACKGROUND: We hypothesised that vertebroplasty provides effective analgesia for patients with poorly controlled pain and osteoporotic spinal fractures of less than 6 weeks' duration. The effectiveness of vertebroplasty, using an adequate vertebral fill technique, in fractures of less than 6 weeks' duration has not been specifically assessed by previously published masked trials. METHODS: This was a multicentre, randomised, double-blind, placebo-controlled trial of vertebroplasty in four hospitals in Sydney, Australia. We recruited patients with one or two osteoporotic vertebral fractures of less than 6 weeks' duration and Numeric Rated Scale (NRS) back pain greater than or equal to 7 out of 10. We used an automated telephone randomisation service provided by the National Health and Medical Research Council to assign patients (1:1; stratified according to age, degree of vertebral compression, trauma, corticosteroid use, and hospital) to either vertebroplasty or placebo, immediately before the procedure. Patients received conscious sedation. Vertebroplasty was done with the adequate vertebral fill technique and the placebo procedure with simulated vertebroplasty. Follow-up was for 6 months. Outcome assessors and patients were masked to treatment allocation. The primary outcome was the proportion of patients with NRS pain below 4 out of 10 at 14 days post-intervention in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT01482793. FINDINGS: Between Nov 4, 2011, and Dec 5, 2014, 120 patients were enrolled. 61 patients were randomly assigned to vertebroplasty and 59 to placebo. 24 (44%) patients in the vertebroplasty group and 12 (21%) in the control group had an NRS pain score below 4 out of 10 at 14 days (between-group difference 23 percentage points, 95% CI 6-39; p=0.011). Three patients in each group died from causes judged unrelated to the procedure. There were two serious adverse events in each group, related to the procedure (vertebroplasty group) and the fracture (control group). INTERPRETATION: Vertebroplasty is superior to placebo intervention for pain reduction in patients with acute osteoporotic spinal fractures of less than 6 weeks' in duration. These findings will allow patients with acute painful fractures to have an additional means of pain management that is known to be effective. FUNDING: Education grant from CareFusion Corporation.

The Visual Analogue Scale (VAS) is a measurement of pain that uses a horizontal line of 100mm, with “no pain” at one end and “very severe pain” at the other. The person makes a mark along the line to indicate how much pain they are in, which will be from 0 (no pain) to 100 (maximum pain imaginable).

The Roland-Morris Disability Questionnaire (RDQ) is a specific questionnaire to measure disability associated with low back pain. It consists of 24 statements such as “Because of my back pain, I get dressed with help from someone else” and “I find it difficult to get out of a chair because of my back”. Each statement that applies is checked off, creating a score from 0 (no disability) to 24 (maximum disability).

The Quality of Life Questionnaire of the European Foundation for Osteoporosis (QAULEFFO) covers five domains: pain, physical function, social function, general health perception and mental function. The scoring system is complicated, with total score ranging from 0 to 100. Lower scores indicate better quality of life.

Expert commentary

NICE recommends percutaneous vertebroplasty, and percutaneous balloon kyphoplasty without stenting, as options for treating osteoporotic vertebral compression fractures. These approaches should be used in people who have severe on-going pain after a recent, unhealed vertebral fracture despite optimal pain management and in who the pain has been confirmed to be at the level of the fracture by physical examination and imaging. However, despite this guidance, few centres across the UK offer such an intervention. Instead patients are managed sub optimally with bed rest and analgesia.

This study adds further evidence to support the guidance and change the way these patients are managed across the UK.

Opinder Sahota, Professor of Orthogeriatric Medicine & Consultant Physician, QMC, Nottingham University Hospitals NHS Trust