Voormolen 2007.

Methods	Design: multicentre (three hospitals), two‐arm open‐label randomised controlled trial; control group allowed to cross‐over to vertebroplasty at two weeks Setting: the Netherlands and Belgium Timing: not reported Interventions: percutaneous vertebroplasty or usual care Sample size:a priori sample size calculation not reported Analysis: completers' analysis
Participants	Number of participants Number of participants who were screened is not reported but it is stated that approximately one in four of those screened initially consented to participate 46 participants randomised but 10 did not receive the assigned treatment (6 in the usual care group wanted to receive vertebroplasty and 2 in the vertebroplasty group wanted to be treated with usual care) 38 received treatment (18 treated with vertebroplasty, 16 treated with usual care and 4 unknown) Data were available for 34 participants at 2 weeks (18 for vertebroplasty and 16 for usual care) as 4 participants who were treated with unknown therapy did not complete 2‐week follow‐up and were excluded from the analysis Inclusion criteria Patient age 50 years or older Back pain due to vertebral fracture refractive to medical therapy for at least 6 weeks and no longer than 6 months Focal tenderness on physical examination related to the level of the vertebral fracture Height loss of the vertebral body of a minimum of 15% on plain radiograph of the spine Bone density T‐scores less than ‐2.0, 5 Bone oedema of the affected vertebra on MRI  Exclusion criteria Poor cardio‐pulmonary condition Untreatable coagulopathy Ongoing systemic infection or local infection of the spine (osteomyelitis, spondylodisciitis) Radicular and/or cord compression syndrome Indication of other underlying disease than osteoporosis No informed consent Baseline characteristics Vertebroplasty Mean (range) age: 72 (59 to 84) years; 14 females, 4 males Mean (range) duration of back pain (units not reported, assumed as days): 85 (47 to 138) days Mean (range) number of pre‐existing vertebral compression fractures: 3.3 (1 to 8) at T5 to L5 Mean (range) baseline pain: 7.1 (5 to 9) Mean (range) baseline disability, RMDQ: 15.7 (8 to 22) Mean (range) baseline quality of life, QUALEFFO: 60 (37 to 86) No pain medication: 2 (11%) Paracetamol: 4 (22%) NSAIDs: 6 (33%) Opioids: 6 (33%) Usual care Mean (range) age: 74 (55 to 88) years; 14 females, 2 males Mean (range) duration of back pain (units not reported, assumed as days): 76 (46 to 141) days Mean (range) number of pre‐existing vertebral compression fractures: 3.1 (1 to 8) at T5 to L5 Mean (range) baseline pain: 7.6 (5 to 10) Mean (range) baseline disability,RMDQ: 17.8 (9 to 24) Mean (range) baseline quality of life, QUALEFFO: 67 (38 to 86) No pain medication: 1 (6%) Paracetamol: 7 (44%) NSAIDs: 3 (19%) Opioids: 5 (31%)
Interventions	Vertebroplasty  Percutaneous vertebroplasty was performed under local anaesthesia on a biplane (in 2 hospital departments) or monoplane (in 1 hospital department) angiographic unit. In most cases, a bilateral transpedicular approach was used. Under continuous fluoroscopy, PMMA bone cement (Osteopal V; Biomet Merck, Ried B. Kerzers, Switzerland) was injected manually using 1 mL syringes and 11‐ or 13‐gauge bone biopsy needles (Cook Europe Bjaeverskov, Denmark). Immediately after the percutaneous vertebroplasty, a CT scan with multiplanar reconstructions of the treated levels was performed to assess the cement deposition and to identify possible extra cement leakage or other local complications that might not have been noted under fluoroscopy. Usual care Participants were treated with the following medications, in ascending order. Paracetamol (acetaminophen) Non‐steroidal anti‐inflammatory drugs (NSAIDs) Opioids The dose per day of prescribed analgesics was regulated, and the class of pain medication was adjusted as needed.
Outcomes	Outcomes were reported at 1 day and 2 weeks Outcomes Mean pain on a 0‐ to 10‐point scale ranging from 0 (no pain) to 10 (worst pain in the patient's life) Type of analgesic use (ordinal variable from 0 (no analgesic use) to 3 (use of opioids) Disability: Roland‐Morris Disability Questionnaire (RMDQ), 0 to 23‐point scale, with higher scores indicating worse disability Quality of life: Quality of Life Questionnaire of the European Foundation for Osteoporosis (QUALEFFO), scores range from 0 to 100, with lower scores indicating a better quality of life Adverse events Incident clinical vertebral fractures Outcomes included in this review Mean pain Disability measured by the RMDQ Vertebral fracture‐specific quality of life (QUALEFFO), scores range from 0 to 100, with lower scores indicating a better quality of life) at 2 weeks.
Source of funding	None reported.
Notes	Trial registration: not found. Standard deviations not reported for pain, disability or quality of life in the trial report but were provided by Dr Voormolen. The trial authors report that the original protocol was to follow participants for up to 12 months with outcome assessments at 1 day, 2 weeks and 3, 6, and 12 months. Participants randomised to usual care who still had severe pain after two weeks could cross‐over to receive vertebroplasty. As the majority of participants receiving usual care crossed over to vertebroplasty after two weeks, the authors stopped the study early, and did not collect outcome data beyond two weeks. There were two adjacent incident vertebral fractures in the vertebroplasty group within the two‐week follow‐up period, but it is unclear if there were any incident fractures in the usual care group.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	The method of generating the random sequence was not reported.
Allocation concealment (selection bias)	Unclear risk	An independent central operator allocated participants to treatment but whether or not treatment allocation was concealed is not reported.
Blinding of participants and personnel (performance bias) All outcomes	High risk	Participants and investigators were not blinded to treatment assignment.
Blinding of outcome assessment (detection bias) Self‐reported outcomes (e.g., pain, disability)	High risk	Participants were not blinded to treatment assignment.
Blinding of outcome assessment (detection bias) Objective outcomes (e.g., radiographic outcomes)	High risk	Radiologists were not blinded to treatment assignment.
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Four participants were excluded from the analysis (refused to complete 2‐week follow‐up). The treatment group of these participants is not reported.
Selective reporting (reporting bias)	High risk	Trial protocol is not available. The number of participants with an incident clinical vertebral fracture is only reported for the vertebroplasty group. Measures of variance were not reported for continuous outcomes.
Other bias	Unclear risk	Eight participants withdrew after randomisation as they were not assigned to their preferred treatment (2 in the vertebroplasty group and 6 in the usual care group). The source of funding is not reported.