Nine studies, all published between 2009 and 2011, met the inclusion criteria for this review (Figure 1).
Of the included studies, three were published in general medical journals (The New England Journal of Medicine, Lancet), three in spine research related journals (Spine, Journal of Neurosurgery-Spine), one in a radiological journal (the American Journal of Neuroradiology), and two in osteoporosis/ bone research journals (Osteoporosis International, Journal of Bone and Mineral Research).
Five studies came from Europe, two from Asia, one from the USA, and one from Australia. The total number of citations was between 60 to 561 with a citation density of 9 to 70 per year. One study was declared an industry-sponsored trial [15]. The two studies with the highest number of citations were published by Kallmes et al. [16] and Buchbinder et al. [17] both in the New England Journal of Medicine (NEJM) (Table 1).
Interventions performed
The following objectives were analysed in the included studies: VP/KP versus conservative treatment (n=5), VP versus sham procedures (n=2), VP versus KP (n=1), and different cement formulations for KP (n=1) (Table 1).
Table 1
Summary of overall citation and citation density of included studies.
Rate
|
Study
|
Journal
|
Year
|
Interventions performed
|
Total citations
|
Citation density (Citations/ year)
|
1.
|
Kallmes
et al. [16]
|
NEJM
|
2009
|
VP vs Sham
|
561
|
70
|
2.
|
Buchbinder et al. [17]
|
NEJM
|
2009
|
VP vs Sham
|
554
|
69
|
3.
|
Klazen
et al. [18, 19]
|
Lancet
|
2010
|
VP vs conservative
|
299
|
43
|
4.
|
Rousing
et al. [20]
|
Spine
|
2010
|
VP vs conservative
|
104
|
15
|
5.
|
Liu
et al. [21]
|
Osteoporosis International
|
2010
|
VP vs KP
|
102
|
15
|
6.
|
Farrokhi
et al. [22]
|
Journal Neurosurgery Spine
|
2011
|
VP vs conservative
|
72
|
12
|
7.
|
Boonen et al. [15]
|
JBMR
|
2011
|
KP vs conservative
|
65
|
11
|
8.
|
Blattert et al. [23]
|
Spine
|
2009
|
KP (CaP vs PMMA)
|
62
|
8
|
9.
|
Klazen et al. [19]
|
American Journal
of Neuroradiology
|
2010
|
VP vs conservative
|
60
|
9
|
NEJM = New England Journal of Medicine, JBMR = Journal of Bone and Mineral Research, VP = Vertebroplasty, KP = Kyphoplasty, CaP = Calcium phosphate, PMMA = polymethylmethacrylate
|
Outcome parameter
The absolute use of all outcome parameters was analyzed regarding their type (pain, HRQol,
function and disability, radiographic imaging and others). In total, 23 different outcome parameters were used in the nine analyzed studies. Ten different outcome parameters were used to analyze the HRQol, five different parameters for radiographic imaging, four for disability and function and one for pain (Table 2, Table S1 of supplemental material). Overall the five top used outcome parameters (³ 4 times used) were: Visual analogue scale (VAS-pain; n = 9), European Quality of Life–5 Dimensions (EQ-5D Score; n = 4) and Roland–Morris Disability Questionnaire (RMDQ; n = 4) (Table 2).
Table 2
Publications included in the analysis according to the inclusion criteria.
Study
|
Pain
|
Health-related Quality of Life
|
Disability/ Function
|
Radiographic
|
Other
|
Primary outcome parameter
|
Kallmes
et al. [16]
|
VAS
|
EQ–5D
SF-36 (PCS, MCS), SOF–ADL score, CMI, Pain Frequency and Pain Bothersomeness Indices
|
RMDQ
|
_
|
Opioid use
|
RMDQ
at 1 month
|
Buchbinder et al. [17]
|
VAS (Overall pain* and pain at rest and pain in bed at night)
|
EQ–5D QUALEFFO AQoL
|
RMDQ
|
_
|
_
|
Overall pain at 3 months
|
Klazen
et al. [18, 19]
|
VAS
|
EQ-5D QUALEFFO
|
RMDQ
|
_
|
cost-eff effectiveness
|
Pain at 1
month and 1
year
|
Rousing
et al. [20]
|
VAS
|
SF-36 DPQ
|
Timed Up&Go, MMSE, Barthel, Chair Test
|
plain radiographs (fracture detection)
|
_
|
Not defined
|
Liu
et al. [21]
|
VAS
|
_
|
_
|
VBH, kyphotic wedge angle
|
_
|
Not defined
|
Farrokhi
et al. [22]
|
VAS
|
ODI
|
_
|
VBH and SI, new fractures
|
_
|
Pain and ODI
|
Boonen et al. [15]
|
VAS
|
SF-36 (PCF) EQ-5D
|
RMDQ
|
_
|
patient satisfaction
|
SF-36 (PCF)
at 1 month
|
Blattert et al. [23]
|
VAS
|
_
|
_
|
bisegmental endplate angle on plain radiographs; distribution and texture of cement plugs on 2-mm CT-scans
|
_
|
Not defined
|
Klazen et al. [19]
|
VAS
|
_
|
_
|
New VCFs
|
_
|
New VCFs
|
Citation density (Citations/ year); AQoL = The Assessment of Quality of Life; cons.= conservative treatment; JBMR=Journal of Bone and Mineral Research; KA = Kyphotic angle; KP = kyphoplasty; MRI = Magnetic Resonance Imaging; NEJM = The New England Journal of Medicine; QUALEFFO = Questionnaire of the European Foundation for Osteoporosis; VCF = Vertebral compression fracture; VP = Vertebroplastie; DPQ = Dallas Pain Questionnaire; EQ-5D = European Quality of Life–5 Dimensions; MCS = Mental component score;mmSE = Mini-Mental State Examination ; ODI = Oswestry Disability Index; PCS = Physical component score; RMDQ = Roland–Morris Disability Questionnaire; SF 36 = Short Form 36 General Health Survey; SI = Sagittal index; VBH = Vertebral body height
|
Pain
A Visual or Numeric Rating Scale scale (VAS and NRS respectively) is an easy and widely used instrument for pain measurement [24, 25]. Five of the nine studies defined pain as their primary outcome (Table 2). Furthermore, the pain was measured in every study at least at baseline. In the short term, four of nine studies assessed pain after 1 week. The most frequently used long term time points were 3, 6, and 12 months (Figure 2, Table S1 additional files).
Other measures of pain were the Pain Frequency and Pain Bothersomeness Indices each measured on a 0 to 4-point scale, with higher scores indicating more severe pain [11]. This questionnaire was used by only one study at baseline and one month follow up, making it the least frequently used questionnaire (Figure 4, Table S1 additional file).
Health-related Quality of Life (HRQoL)
Numerous questionnaires are available for recording HRQoL. In the nine studies analyzed, a total of five different instruments were used.
The European Quality of Life–5 Dimensions (EQ–5D) scale (scale from 0 to 1, where 1 indicates perfect health) is a commonly used questionnaire that is also free of charge [26–28]. Five of the nine studies collected the EQ-5D at baseline, while four studies had also collected follow-up data (Figure 3, Table S1 additional file).
The Short Form 36 General Health Survey (SF 36) [29, 30] is also a well-known and commonly used measure to assess HRQoL. It averages the items of each subscale to generate a score ranging from 0 to 100, with a lower score representing greater disability [31]. In addition, the SF-36 has a physical and mental component score (PCS and MCS, respectively). Overall, the SF-36 was obtained at baseline and follow-up in three of the nine RCTs, but at different time points. (Figure 3, Table S1 additional file).
The Questionnaire of the European Foundation for Osteoporosis (QUALEFFO) is a 41-item questionnaire specifically related to vertebral fractures and osteoporosis (scores range from 0 to 100, with lower scores indicating better quality of life) [32]. This questionnaire was used in two clinical trials [17, 18] (Figure 3, Table S1 additional file).
There were additionally two other questionnaires used to measure HRQoL. One is the Assessment of Quality of Life (AQoL) questionnaire, which is a well-validated instrument sensitive to changes in the elderly and frail (scores range from 0 to 1, with 1 indicating perfect health) [33]. The other one was the Study of Osteoporotic Fractures-Activities of Daily Living (SOF-ADL) questionnaire, an easily obtained index to assess frailty [34]. However, these two questionnaires were only collected by one study, and the SOF-ADL was only collected once at baseline (Figure 3, Table S1 additional file).
Disability and Function
Four different instruments were used to assess disability and function in the nine studies analyzed.
The Roland-Morris Disability Questionnaire (RMDQ) is a widely used measure to assess health status in low back pain. It is designed to assess only physical disability due to low back pain [35] (scores range from 0 to 23, with higher numbers indicating worse physical function). Originally, the scale assessed 12 categories with 24 items [36], with the modified version including 23 items covering domains of daily living [31]. The RMDQ was used as a baseline measure by almost half of the RCTs analyzed (four of nine studies). Regarding follow-up measurements, the time points ranged from one day to two months. Three studies chose the same time points, after one and six months, for follow-up (Figure 4, Table S1 additional file).
The Oswestry Disability Index (ODI) was developed in 1976 in a specialized referral clinic with a large number of patients with chronic low back pain [37]. This scale is a functional measure of HrQOL, which includes six items in 10 dimensions [38]. However, the ODI was only collected in one of nine studies [22] (Figure 4, Table S1 additional file).
The Dallas Pain Questionnaire (DPQ) measures four categories (16-items) of impairment of daily living due to chronic low back pain (0% is no pain and 100% is constant pain) [31, 39]. The DPQ was used in only one study and at baseline and three-month follow-up [20] (Figure 4, Table S1 additional file).
Radiographic imaging
In all studies, VCFs were confirmed by radiological imaging. However, only seven of the nine studies analyzed performed initial imaging by spinal MRI. All follow-up examinations were performed using conventional radiographs. The most common outcome described was the occurrence of a new VCF (six of nine RCTs) and the kyphotic angle above the VCF (two of nine RCTs). Also, vertebral body height was measured and reported in three of the nine studies. However, the time points varied between studies. New VCFs were most frequently reported at three and 24 months, whereas kyphotic angle was most frequently measured at 12 months (Figure 5, Table S1 additional file).
Others
In addition, other outcome measures were used in the highly cited RCTs analyzed. In addition to the patient-reported outcomes described above, opioid use was the most commonly described outcome parameter (four of nine studies) (Figure 6, Table S1 additional file).