Spinal Fractures, Osteoporosis
Conditions
Keywords
Vertebroplasty, Crushed Vertebrae, Back Pain, Structurally Unstable Vertebrae, polymethylmethacrylate, INVEST, PMMA, RDQ
Brief summary
Vertebroplasty is a procedure used to stabilize broken vertebrae, the bones that form the spine. This study will evaluate the effectiveness of vertebroplasty for the treatment of fractures due to osteoporosis.
Detailed description
Spontaneous, atraumatic compression fractures due to osteoporosis occur in more than 700,000 patients per year. Pain associated with these fractures may be excruciating, but before the advent of percutaneous vertebroplasty, treatment options were limited. Analgesic medications, bed rest, and bracing have been the mainstays of treatment, but each of these therapies has substantial limitations. Because of the dearth of viable treatment options for osteoporotic vertebral compression fractures, the practice of percutaneous vertebroplasty, which involves injection of polymethylmethacrylate (medical cement) into the fractured vertebra, has disseminated rapidly. However, evidence for the efficacy of percutaneous vertebroplasty is currently limited to uncontrolled, nonblinded, small case studies. Even though high rates of success are reported, with up to 90% of patients achieving substantial pain relief, these case studies have not accounted for numerous important potential biases, including the natural tendency for compression fractures to heal spontaneously, regression toward the mean (wherein patients seek medical attention when pain is maximum), and the placebo effect. This study will examine the clinical efficacy of percutaneous vertebroplasty for treatment of painful osteoporotic vertebral compression fractures. Participants in this study will be randomly assigned to receive either percutaneous vertebroplasty or a sham procedure (placebo control group). Participants may have up to 2 spinal levels treated. Participants will be enrolled in the study for 1 year and will have study visits at entry and Months 1 and 12. There will also be phone visits at Days 1, 2, 3, and 14 and Months 3 and 6. After Month 1, crossover from the placebo group to the vertebroplasty group will be allowed.
Interventions
Placement of polymethylmethacrylate (PMMA) into vertebral compression fracture
PROCEDURESham vertebroplasty
Participants, following local anesthesia with lidocaine and bupivacaine, were given verbal and physical cues such as pressure on the back, but the needle was not placed.
Sponsors
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
National Center for Research Resources (NCRR)
Mayo Clinic
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Confirmed osteoporosis or osteopenia by a referring physician and/or medical history and physical exam OR osteopenia on plain film * Vertebral compression fracture in vertebrae T4 through L5, of less than 1 year old * Pain not responsive to standard medical therapy * Current rating for pain intensity of at least 3 on a scale of 0 to 10
Exclusion criteria
* Evidence or suspicion of malignant tumor or spinal canal compromise * Concomitant hip fracture * Local or systemic infection * Uncorrectable bleeding diatheses * Surgery within the previous 60 days * Lack of access to telephone * Inability to communicate in English * Dementia * Pregnancy * Abnormal renal function or anticipated venography * Conscious sedation is contraindicated for subject
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Back-specific Functional Status Using Roland-Morris Disability Questionnaire (RDQ) Scale at 1 Month | 1 month after procedure | Back-specific functional status using RDQ scale range from 0 (no pain) to 23, with higher scores indicating more severe disability. |
| Patient's Rating of Average Pain at 1 Month | 1 month | Patient's rating of average pain intensity during the preceding 24 hours at 1 month. The rating scale was from 0 to 10, with higher scores indicating more severe pain. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Patient Well-being at 1 Month | Month 1 | Patient well-being was quantified by these tools: Health status outcome using Medical Outcomes Study 36-Item Short-Form General Health Survey (SF-36). Scores on the Medical Outcomes Study 36-Item Short-Form General Health Survey (SF-36), version 2. Subjects completed the SF-36 which consists of 8 sub-scales which are additionally summarized into 2 summary components (physical and mental). The subscales and the summary scales both range from 0 to 100, with (0 = worst imaginable, 100 = best imaginable). Pain Frequency Index, Pain Bothersome Index (scores range from 0-4, higher scores indicating more severe pain). European Quality of Life (QOL) 5 Dimensions (EQ-5D), scale range -0.1 to 1.0; higher scores indicating a better QOL. Study of Osteoporotic Fractures-Activities of Daily Living (SOF ADL6) range from 0 to 18; higher scores = more back-related disability. |
Countries
United States
Participant flow
Recruitment details
Participants were enrolled at five centers in the U.S., five centers in the United Kingdom and one center in Australia.
Participants by arm
| Arm | Count |
|---|---|
| Vertebroplasty Participants will receive percutaneous vertebroplasty | 68 |
| Control Group Participants will receive partial vertebroplasty without PMMA | 63 |
| Total | 131 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First Randomized Intervention | Lost to Follow-up | 1 | 2 |
Baseline characteristics
| Characteristic | Vertebroplasty | Total | Control Group |
|---|---|---|---|
| Age Continuous | 73.4 years STANDARD_DEVIATION 9.4 | 73.84 years STANDARD_DEVIATION 9.48 | 74.3 years STANDARD_DEVIATION 9.6 |
| Average pain intensity during past 24 hours at baseline | 6.9 Units on a scale STANDARD_DEVIATION 2 | 7.02 Units on a scale STANDARD_DEVIATION 1.9 | 7.2 Units on a scale STANDARD_DEVIATION 1.8 |
| EQ-SD Score at baseline | 0.57 Units on a scale STANDARD_DEVIATION 0.18 | 0.55 Units on a scale STANDARD_DEVIATION 0.2 | 0.54 Units on a scale STANDARD_DEVIATION 0.23 |
| Pain Bothersome Index score at baseline | 2.9 Units on a scale STANDARD_DEVIATION 0.7 | 2.98 Units on a scale STANDARD_DEVIATION 0.75 | 3.1 Units on a scale STANDARD_DEVIATION 0.8 |
| Pain Frequency Index Score at baseline | 3.0 Units on a scale STANDARD_DEVIATION 0.8 | 3.04 Units on a scale STANDARD_DEVIATION 0.8 | 3.1 Units on a scale STANDARD_DEVIATION 0.8 |
| RDQ Score at baseline | 16.6 Units on a scale STANDARD_DEVIATION 3.8 | 17.05 Units on a scale STANDARD_DEVIATION 3.98 | 17.5 Units on a scale STANDARD_DEVIATION 4.1 |
| Region of Enrollment Australia | 13 participants | 22 participants | 9 participants |
| Region of Enrollment United Kingdom | 26 participants | 52 participants | 26 participants |
| Region of Enrollment United States | 29 participants | 57 participants | 28 participants |
| Sex: Female, Male Female | 53 Participants | 99 Participants | 46 Participants |
| Sex: Female, Male Male | 15 Participants | 32 Participants | 17 Participants |
| SF-36 score; summary mental component at baseline | 44.8 Units on a scale STANDARD_DEVIATION 11.8 | 43.21 Units on a scale STANDARD_DEVIATION 13.03 | 41.5 Units on a scale STANDARD_DEVIATION 14.1 |
| SF-36 score; summary physical component at baseline | 25.3 Units on a scale STANDARD_DEVIATION 7.8 | 25.3 Units on a scale STANDARD_DEVIATION 7.55 | 25.3 Units on a scale STANDARD_DEVIATION 7.3 |
| SOF-ADL Score at baseline | 10.0 Units on a scale STANDARD_DEVIATION 3.6 | 10.14 Units on a scale STANDARD_DEVIATION 3.23 | 10.3 Units on a scale STANDARD_DEVIATION 2.8 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 68 | 0 / 61 |
| serious Total, serious adverse events | 1 / 68 | 1 / 61 |
Outcome results
Primary
Back-specific Functional Status Using Roland-Morris Disability Questionnaire (RDQ) Scale at 1 Month
Back-specific functional status using RDQ scale range from 0 (no pain) to 23, with higher scores indicating more severe disability.
Time frame: 1 month after procedure
Population: 68 subjects were randomized to undergo vertebroplasty and 63 to undergo the control intervention. All underwent the assigned intervention. One subject in the vertebroplasty group and two subjects in the control group were lost to follow-up before 1 month.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vertebroplasty | Back-specific Functional Status Using Roland-Morris Disability Questionnaire (RDQ) Scale at 1 Month | 12.0 units on a scale | Standard Deviation 6.3 |
| Control Group | Back-specific Functional Status Using Roland-Morris Disability Questionnaire (RDQ) Scale at 1 Month | 13.0 units on a scale | Standard Deviation 6.4 |
Comparison: Between group comparisons, confidence intervals, and P values were calculated with the use of analysis-of-covariance models with adjustment for study group assignment, baseline value of the outcome measure, and study center. Negative treatment effects favor the control procedure, and positive treatment effects favor vertebroplasty.p-value: 0.4995% CI: [-1.3, 2.8]ANCOVA
Primary
Patient's Rating of Average Pain at 1 Month
Patient's rating of average pain intensity during the preceding 24 hours at 1 month. The rating scale was from 0 to 10, with higher scores indicating more severe pain.
Time frame: 1 month
Population: 68 subjects were randomized to undergo vertebroplasty and 63 to undergo the control intervention. All underwent the assigned intervention. One subject in the vertebroplasty group and two subjects in the control group were lost to follow-up before 1 month.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vertebroplasty | Patient's Rating of Average Pain at 1 Month | 3.9 units on a scale | Standard Deviation 2.9 |
| Control Group | Patient's Rating of Average Pain at 1 Month | 4.6 units on a scale | Standard Deviation 3 |
Comparison: Between group comparisons, confidence intervals, and P values were calculated with the use of analysis-of-covariance models with adjustment for study group assignment, baseline value of the outcome measure, and study center. Negative treatment effects favor the control procedure, and positive treatment effects favor vertebroplasty.p-value: 0.1995% CI: [-0.3, 1.7]ANCOVA
Secondary
Patient Well-being at 1 Month
Patient well-being was quantified by these tools: Health status outcome using Medical Outcomes Study 36-Item Short-Form General Health Survey (SF-36). Scores on the Medical Outcomes Study 36-Item Short-Form General Health Survey (SF-36), version 2. Subjects completed the SF-36 which consists of 8 sub-scales which are additionally summarized into 2 summary components (physical and mental). The subscales and the summary scales both range from 0 to 100, with (0 = worst imaginable, 100 = best imaginable). Pain Frequency Index, Pain Bothersome Index (scores range from 0-4, higher scores indicating more severe pain). European Quality of Life (QOL) 5 Dimensions (EQ-5D), scale range -0.1 to 1.0; higher scores indicating a better QOL. Study of Osteoporotic Fractures-Activities of Daily Living (SOF ADL6) range from 0 to 18; higher scores = more back-related disability.
Time frame: Month 1
Population: 68 subjects were randomized to undergo vertebroplasty and 63 to undergo the control intervention. All underwent the assigned intervention. One subject in the vertebroplasty group and two subjects in the control group were lost to follow-up before 1 month.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vertebroplasty | Patient Well-being at 1 Month | SF-36 summary physical component | 29.7 units on a scale | Standard Deviation 9.6 |
| Vertebroplasty | Patient Well-being at 1 Month | SF-36 summary mental component | 46.9 units on a scale | Standard Deviation 12 |
| Vertebroplasty | Patient Well-being at 1 Month | Pain frequency index score | 2.1 units on a scale | Standard Deviation 1.2 |
| Vertebroplasty | Patient Well-being at 1 Month | Pain bothersome index score | 1.9 units on a scale | Standard Deviation 1.1 |
| Vertebroplasty | Patient Well-being at 1 Month | EQ-5D score | 0.70 units on a scale | Standard Deviation 0.18 |
| Vertebroplasty | Patient Well-being at 1 Month | SOF-ADL score | 7.7 units on a scale | Standard Deviation 3.7 |
| Control Group | Patient Well-being at 1 Month | EQ-5D score | 0.64 units on a scale | Standard Deviation 0.2 |
| Control Group | Patient Well-being at 1 Month | SF-36 summary physical component | 28.7 units on a scale | Standard Deviation 8 |
| Control Group | Patient Well-being at 1 Month | Pain bothersome index score | 2.1 units on a scale | Standard Deviation 1.1 |
| Control Group | Patient Well-being at 1 Month | SF-36 summary mental component | 45.6 units on a scale | Standard Deviation 14.8 |
| Control Group | Patient Well-being at 1 Month | SOF-ADL score | 8.2 units on a scale | Standard Deviation 3.6 |
| Control Group | Patient Well-being at 1 Month | Pain frequency index score | 2.3 units on a scale | Standard Deviation 1.1 |
Comparison: SF-36 Physical Component Summary treatment effectp-value: 0.4595% CI: [-1.7, 3.7]ANCOVA
Comparison: SF-36 Mental Component Summary treatment effectp-value: 0.8395% CI: [-3.7, 4.6]ANCOVA
Comparison: Pain Frequency Index treatment effectp-value: 0.3395% CI: [-0.2, 0.6]ANCOVA
Comparison: Pain Bothersome Index treatment effectp-value: 0.3395% CI: [-0.2, 0.6]ANCOVA
Comparison: EQ-5D Index treatment effectp-value: 0.1395% CI: [-0.01, 0.11]ANCOVA
Comparison: SOF-ADL treatment effectp-value: 0.595% CI: [-0.8, 1.6]ANCOVA