Spine FACTs

FRACTURE AWARENESS,
CONSIDERATIONS, & TREATMENT

FREE: Fracture Reduction Evaluation Study

Important Safety Information

12 Month Outcomes (The Lancet, 2009) 24 Month Outcomes (JBMR, 2011)

In this largest randomized controlled trial comparing balloon kyphoplasty to non-surgical management (NSM) in patients with osteoporosis, balloon kyphoplasty was shown to be more effective than non-surgical management for the treatment of acute VCFs.

Clinical Outcomes at 12 and 24 Months:

Faster and Sustained Pain Relief

3 times greater pain reduction at 1 week vs non-surgical1 management (NSM)

Significantly better pain relief results were seen at 1 month and maintained for up to 2 years versus NSM.

Pain relief was associated with fewer BKP patients using pain medications through 12 month and opioids through 6 months than NSM patients.

1 Tillman J, Shabe P, Rose M, Elson P, Wülfert E, Ashraf T. Fracture Reduction Evaluation Study 24-month final clinical study report, August 27, 2010. Medtronic Spinal and Biologics Europe BVBA.

Better Quality of Life1

4 times greater improvement in quality of life at 1 month vs NSM

Significantly improved quality of life when averaged across 2 years vs NSM

BKP was superior to non-surgical management when measured by SF-36 PCS at 1 month.

On average through 24 months, BKP patients experienced significantly better quality of life than patients treated non-surgical as measured by EQ-5D and SF-36 PCS.

1 Tillman J, Shabe P, Rose M, Elson P, Wülfert E, Ashraf T. Fracture Reduction Evaluation Study 24-month final clinical study report, August 27, 2010. Medtronic Spinal and Biologics Europe BVBA.

Quicker Return of Mobility

5 fewer days of restricted activity at 1 month compared to baseline

Rapid return to daily activities maintained up to 2 years vs. NSM

BKP patients has an estimated 136 more days of activity over the 24-month period than those receiving non-surgical management

BKP patients had significantly better back function than non-surgical management patients on average through 24-month as measure by Roland-Morris Score.

Greater Patient Satisfaction

BKP patients were significantly more satisfied than those treated non-surgically at all time points through 24 months.

Comparable Safety Results vs. NSM (from FREE24 study)

  • There were similarities in overall frequencies of adverse events and serious adverse events between treatment groups during the 24-month study
  • The kyphoplasty group had 11 patients (7.4%) with new clinical fractures that the investigator considered possibly or probably related to cement
  • There was no statistically significant difference between BKP and NSM in the number of patients with subsequent radiographic fractures or subsequent radiographic adjacent fractures.
  • As reported previously (Wardlaw Lancet 2009), one hematoma SAE at the surgical site was device-related and one exacerbation of a recurrent urinary tract infection SAE (owing to catheterization) occurred within 2 days of surgery and was considered procedure-related.
  • There were two serious adverse events related to bone cement that occurred after 1 year. The patient who had the urinary tract infection (above) also developed spondylitis near the cement in the treated vertebral body 376 days after surgery; biopsy indicated that the bacterium causing the urinary infection was the same as that causing the spondylitis. Another patient had a recurrent fracture of an originally treated level with subsequent anterior migration of the cement. These serious adverse events were uncommon and should be monitored
  • One patient from each treatment group terminated the study early owing to an AE during the 24-month follow-up period.
  • There were 23 deaths, 12 in the kyphoplasty group and 11 in the nonsurgical group. All deaths were considered unrelated to treatment.

Abstract

Vertebral fractures are often painful and lead to reduced quality of life and disability. We compared the efficacy and safety of balloon kyphoplasty to nonsurgical therapy over 24 months in patients with acute painful fractures. Adults with one to three vertebral fractures were randomized within 3 months from onset of pain to undergo kyphoplasty (n = 149) or nonsurgical therapy (n = 151). Quality of life, function, disability, and pain were assessed over 24 months. Kyphoplasty was associated with greater improvements in Short-Form 36 (SF-36) Physical Component Summary (PCS) scores when averaged across the 24-month follow-up period compared with nonsurgical therapy [overall treatment effect 3.24 points, 95% confidence interval (CI) 1.47-5.01, p = .0004]; the treatment difference remained statistically significant at 6 months (3.39 points, 95% CI 1.13-5.64, p = .003) but not at 12 months (1.70 points, 95% CI -0.59 to 3.98, p = .15) or 24 months (1.68 points, 95% CI -0.63 to 3.99, p = .15). Greater improvement in back pain was observed over 24 months for kyphoplasty (overall treatment effect -1.49 points, 95% CI -1.88 to -1.10, p < .0001); the difference between groups remained statistically significant at 24 months (-0.80 points, 95% CI -1.39 to -0.20, p = .009). There were two device-related serious adverse events in the second year that occurred at index vertebrae (a spondylitis and an anterior cement migration). There was no statistically significant difference between groups in the number of patients (47.5% for kyphoplasty, 44.1% for control) with new radiographic vertebral fractures; fewer fractures occurred (~18%) within the second year. Compared with nonsurgical management, kyphoplasty rapidly reduces pain and improves function, disability, and quality of life without increasing the risk of additional vertebral fractures. The differences from nonsurgical management are statistically significant when averaged across 24 months. Most outcomes are not statistically different at 24 months, but the reduction in back pain remains statistically significant at all time points.

Background

Every year an estimated 1.4 million vertebral compression fractures worldwide that cause pain, disability and diminished quality of life [1,2] come to clinical attention [3]. In the FREE study, balloon kyphoplasty was shown to be more effective than non-surgical management (NSM) for the treatment of acute VCFs.

Consequences of VCFs

  • Spinal deformity caused by VCFs is associated with a series of clinical consequences which are independent of acute fracture pain:
    • Chronic, debilitating pain [4-7]
    • Decreased lung function (VC, FEV1) [7-9]
    • Impaired physical function [2,4,7,10,11]
    • Impaired gait or poor balance [5,12,13]
    • Early satiety, gastric distress [4]
    • Sleep disorders [4]
    • Decreased Activities of Daily Living (ADL) [2,4,5]
    • Increased dependence on family members and friends [5]
    • Clinical anxiety and/or depression [4,5]
    • Future fracture risk [14-18]

Treatments for VCFs:

  • Non-surgical care such as pain medication, physical therapy, back bracing, walking aids, and bed rest
  • Surgical treatment, such as balloon kyphoplasty

Study Objective

  • This study comparing balloon kyphoplasty to non-surgical care for the treatment of acute VCFs was conducted to test the hypothesis that balloon kyphoplasty would result in increased improvement in quality of life.

Study Design

Randomized Controlled Trial

  • Patients (300) were randomly assigned by computer-generated sequence to either balloon kyphoplasty (n=149) or non-surgical care* (n=151).
  • Investigators referred all participants in both groups for treatment with calcium and vitamin D supplements and antiresorptive or anabolic agents.
    *Non-surgical group received analgesics, bed rest, back braces, physiotherapy, rehabilitation programs, and walking aids according to standard practices of participating hospitals.

Participating Centers

  • 21 European sites
  • 8 countries (Germany, France, Sweden, The United Kingdom, Italy, Austria, The Netherlands and Belgium)

Patient Inclusion

  • 1-3 vertebral fractures between T5 and L5
  • At least 1 fracture with edema on MRI
  • At least 1 fracture with ≥ 15% loss of vertebral body height on X-ray
  • Fracture(s) caused by osteopenia due to primary or secondary osteoporosis, multiple myeloma, or osteolytic metastatic tumors
  • Back pain score ≥ 4 (on a scale of 0=no pain to 10=worst pain imaginable)

Patient Exclusion

  • Patient age ≤ 21 years
  • Fracture age > than 3 months
  • Previous vertebroplasty
  • Pedicle fracture
  • Neurological deficit
  • Radicular pain
  • Spinal canal narrowing
  • Spinal cord compression
  • History of back disability unrelated to VCFs
  • Dementia
  • Non-ambulatory prior to VCFs
  • High-energy traumatic fractures

Follow-up

  • Follow-up at 1, 3, 6, 12, and 24 months

Endpoints

Balloon kyphoplasty was shown to be more effective than non-surgical management for the treatment of acute VCFs.

Primary Endpoint

  • SF-36 PCS (Physical Component Summary) (scaled 0-100) [19]
  • The difference in change from baseline at 1 month
  • Validated global quality of life measure, weighted on physical abilities
  • Normal range for people over the age of 65 is 8-59 points [19]

Secondary Endpoints

  • Quality of Life
    • SF-36 subscales (scaled 0-100) [20]
    • EQ-5D (EuroQol-5 Domain) health outcome questionnaire (scaled 0-1) [21]
  • Back Function & Mobility
    • Roland-Morris back function disability questionnaire (scaled 0-24) [22]
    • Reduced activity days due to back pain during the previous 14 days [3]
  • Back Pain
    • Back pain score (scaled 0-10) [23]
    • Narcotic analgesic use (percent of patients taking opioids)
  • Adverse Events (device- and procedure-related)
    • All adverse events and serious adverse events, defined per IOS 14155, were reported; investigators assessed whether they were device- or procedure-related.
  • Radiographic assessments (Van Meirhaeghe J, et al. Spine 38(12), p. 971-983.)
  • Economic data (Resultant publications are Strom OI 2010 and Fritzell Spine 2011)

Glossary

SF-36 PCS (Physical Component Summary)
The SF-36 PCS is a complex, standardized, Quality of Life (QOL) aggregate that summarizes the scores of the eight (8) SF-36 subscales but with a strong emphasis (weighting) on the four (4) physical scales: physical function, role physical, bodily pain, and general health. The SF-36 PCS is scaled from 0-100. Normal range for people over the age of 65 is 8-59 points. [19]
SF-36 Subscale
The SF-36 is a validated, multi-purpose, self-reported, short-form health survey that assesses a patient's Quality of Life (QOL) using 36 questions. The questionnaire is comprised of eight (8) subscales which are divided into four (4) physical components: physical function, role physical, bodily pain, general health; and four (4) mental components: vitality, social function, role emotional, mental health. Each sub-scale is scaled from 0-100. [19]
EQ-5D (EuroQol 5 domain) Health Outcome Questionnaire
EQ-5D is a validated Quality of Life (QOL) measure used extensively in Europe. It is a descriptive system of health-related quality of life states consisting of five (5) dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression), each of which can have one of three responses (no problems, some or moderate problems, extreme problems). EQ-5D is scored on a 0-1 scale, where 0=death and 1=perfect health. [21]
Roland-Morris Disability Questionnaire (RMDQ)
The Roland-Morris Disability Questionnaire is a measurement of back function. The questionnaire lists of 24 standard sentences that describe activities related to back pain. Patients select sentences they think describe their condition on that day. This scale is from 0 to 24, where 0=no disability and 24=most severe disability. [22]
Reduced Activity Days
The number of days, within the past 2 weeks, patients reported spending greater than half the day in bed because of back pain. [3]
Back Pain Score
Self-rated back pain (average pain in the past week) on a 0 -10 scale, where 0= no pain and 10= worst pain imaginable. [23]
Narcotic Analgesic Use
Percentage of patient taking opioid drugs to control back pain.
Treatment (Treatment p-value)
The "Treatment" p-value in this study relates to the average treatment effect difference between the groups during the year.
Treatment x Visit (Treatment by visit p-value)
The "Treatment x Visit" p-value in this study relates to a time-related change of the treatment difference between groups. It compares whether the treatment effect between the groups was consistent at the follow-up visits.
Minimally Clinically Important Difference (MCID)
MCID means the smallest improvement (change) in an outcome that is considered to be clinically meaningful.

Boonen S, Van Meirhaeghe J, Bastian L, Cummings SR, Ranstam J,Tillman JB, Eastell R, Talmadge K, Wardlaw D. J Bone Min Res. Epub 2011 Feb 17; 26(7):1627-1637.

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