Farrokhi 2011

Methods	Design: two‐arm open‐label randomised controlled trial; control group allowed to cross‐over into vertebroplasty group from one month (cross‐overs < 2 months = 4, < 6 months = 3, <12 months = 3, < 36 months = 10) Setting: Iran Timing: Sept 2004 to Jan 2009 Interventions: percutaneous vertebroplasty or usual care Sample size:a priori sample size calculation not reported Analysis: reported an intention‐to‐treat analysis
Participants	Number of participants 105 screened for eligibility 23 excluded (20 did not meet inclusion criteria and 2 declined to participate) 82 patients were randomised (40 to vertebroplasty and 42 to usual care) Data for 82 (40 (100%) for vertebroplasty and 42 (100%) for usual care) available at 6‐month follow‐up but 3 (7%) participants assigned to usual care received vertebroplasty before the 6‐month follow‐up Data for 76 (37 (93%) for vertebroplasty and 39 (93%) for usual care) available at the final 36‐month follow‐up but 10 (24%) participants assigned to usual care received vertebroplasty before the 36‐month follow‐up Inclusion criteria Severe back pain refractory to analgesic medication (analgesics or NSAIDs) for at least 4 weeks and no longer than 1 year Vertebral compression fracture with 10%–70% loss of vertebral body height on X‐ray of the spine Focal tenderness on physical examination at the level of vertebral fracture Vacuum phenomenon or bone marrow oedema of the vertebral fracture on MRI Osteoporosis (T‐score less than ‐2.5) on bone densitometry Exclusion criteria Uncorrected coagulopathy Local or systemic infection Secondary osteoporosis Inability to give informed consent Impaired cardio‐pulmonary function Dementia Posterior wall defect of the vertebral body on CT imaging Spinal cancer Traumatic fracture Neurological complications Baseline characteristics Vertebroplasty group: Mean (range) age: 72 (59 to 90) years; 30 female:10 male Duration (range) of back pain: 30 (6 to 54) weeks Previous vertebral fractures: 50 Mean (SD) baseline pain score: 7.2 (1.7) Initial pain medication‐ paracetamol (acetaminophen) and codeine: 30 (75%); NSAIDs: 20 (50%) Usual care group: Mean (range) age: 74 (55 to 87) years; 30 female:12 male Duration (range) of back pain: 27 (4 to 50) weeks Previous vertebral fractures: 56 Mean (SD) baseline pain score: 8.4 (1.6) Initial pain medication‐ paracetamol (acetaminophen) and codeine: 30 (71%); NSAIDs: 32 (76%)
Interventions	Percutaneous vertebroplasty performed by neurosurgeons; usual care ('optimal medical therapy') delivered by a physician. Vertebroplasty Induction of conscious sedation (a combination of IV fentanyl and midazolam) in 10 (25%) participants and general anaesthesia in 30 (75%) participants. Patients were placed prone and single‐plane C‐arm equipment was used. Using sterile techniques, an 11‐gauge needle was inserted into the vertebral body via a unilateral parapedicular approach in 35 (87.5%) patients and via a bilateral transpedicular approach in 5 (12.5%) patients. A bilateral transpedicular approach was used only if there was inadequate instillation of cement with the unilateral approach under fluoroscopy. A polymethylmethacrylate mixture was injected into the vertebral body. Following the procedure, the patient remained supine in bed. During cement injection, fluoroscopic monitoring with a C‐arm unit was used in both planes. It is not stated whether or not participants in the vertebroplasty group could also receive analgesia and/or treatment of osteoporosis. Usual care The usual care group was prescribed 250 mg acetaminophen with codeine twice daily, 400 mg ibuprofen twice a day, 1000 mg calcium daily, 400 IU vitamin D daily, 70 mg alendronate orally once weekly, and 200 IU calcitonin daily. Analgesia could be increased by the treating physician as needed. Cross‐over to vertebroplasty was permitted after 1 month. Follow‐up care A change in lifestyle and physical treatment (undefined) was also suggested to participants in both groups.
Outcomes	Outcomes were reported at 1 week, and 2, 6, 12, 24 and 36 months after treatment Primary outcomes Mean pain in previous 24 hours, measured on a 1 to (no pain) to 10 (excruciating pain) VAS scale. Mean disability, measured by the Oswestry Low Back Disability Index (ODI), 0 to 100 scale (0 is no disability) Secondary outcomes Ability to walk after one day Incidence of new symptomatic vertebral fractures (at 24 months) Radiographic measurement of vertebral body height (VBH, mm); and correction of spinal deformity (sagittal index, degrees) at 2, 6, 12, 24 and 36 months. Adverse events Outcomes included in this review Mean pain Disability as measured by the ODI Incidence of new symptomatic vertebral fractures Adverse events
Source of funding	The Vice‐chancellor for research affairs of Shiraz University of Medical Sciences and Apadana Tajhizgostar Co. (distributor of medical devices) provided grant support.
Notes	Trial registered retrospectively on 11 Oct 2009 at www.irct.ir, number IRCT138804252193N1. All participants in the control group were permitted to undergo vertebroplasty after 1 month; 4 crossed over before 2 months, 3 before 6 months, 3 before 12 months and 10 before 36 months (total cross‐over 20/42 (47.6%)). We included the 2‐month follow‐up data in the 3‐month analyses/meta‐analyses. The trialists report epidural cement leakage in one participant receiving vertebroplasty, and no cases of venous emboli or infection. It is not reported if any adverse events occurred with usual care.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Generated by computerised random number generator
Allocation concealment (selection bias)	Low risk	The treatment assignment was kept in sealed envelopes. It is not explicitly reported who prepared and opened the envelopes, but it is likely that allocation was concealed and the neurosurgeon (performing vertebroplasty) and the physician (administering usual care) had no role in allocation.
Blinding of participants and personnel (performance bias) All outcomes	High risk	Participants were unblinded; the treating clinicians were unaware of the other treatment group
Blinding of outcome assessment (detection bias) Self‐reported outcomes (e.g., pain, disability)	High risk	Participants self‐assessed pain and disability and were unblinded.
Blinding of outcome assessment (detection bias) Objective outcomes (e.g., radiographic outcomes)	High risk	It is not stated who assessed the imaging outcomes. It is unlikely that they were blinded to treatment assignment as vertebroplasty cement is opaque and will be detected on imaging.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Loss to follow‐up was small and equal across groups (3/40 participants in the vertebroplasty group and 3/42 participants in the usual care group at the final 36 month follow‐up).
Selective reporting (reporting bias)	Unclear risk	Unclear if any additional outcomes were measured and not reported; e.g., incident fracture is not listed in the methods as an outcome but data are reported in the results for the 2‐year (but not end of study) follow‐up.
Other bias	Low risk	None apparent