Evidence map›Paper›PMID 23778906›Full record

SynthesisAnnals of internal medicine2013

Effectiveness and harms of recombinant human bone morphogenetic protein-2 in spine fusion: a systematic review and meta-analysis.

Rongwei Fu, Shelley Selph, Marian McDonagh, Kimberly Peterson, Arpita Tiwari, Roger Chou, Mark Helfand

Abstract readMeta-AnalysisSystematic Review
PubMed Publisher
In one paragraph

Synthesis in Annals of internal medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 201 papers, 12 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
201citing papers in PubMed, 12 pooled it
42.1field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

201 citing papers in PubMed, 12 syntheses or guidelines pooled it, 436 citations in OpenAlex.

  1. Pooled it
  2. Iliac crest bone graft versus cell-based grafts to augment spinal fusion: a systematic review and meta-analysis.European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society · 2024
    Pooled it
  3. Application of rhBMP in spinal fusion surgery: any correlation of cancer incidence? A systematic review and meta-analysis.European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society · 2023
    Pooled it
  4. Pooled it
  5. Efficacy and safety of bone substitutes in lumbar spinal fusion: a systematic review and network meta-analysis of randomized controlled trials.European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society · 2020
    Pooled it
  6. Bone morphogenetic protein in adult spinal deformity surgery: a meta-analysis.European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society · 2017
    Pooled it
  7. Industry sponsorship and research outcome.The Cochrane database of systematic reviews · 2017
    Pooled it
  8. Platelet concentrates in spine fusion: meta-analysis of union rates and complications in controlled trials.European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society · 2016
    Pooled it
  9. Cochrane in CORR1: Steroids for Acute Spinal Cord Injury (Review).Clinical orthopaedics and related research · 2016
    Pooled it
  10. Pooled it
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  12. Pooled it
  13. Trial
  14. Evaluation of an increased strut porosity silicate-substituted calcium phosphate, SiCaP EP, as a synthetic bone graft substitute in spinal fusion surgery: a prospective, open-label study.European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society · 2019
    Trial
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141 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 1 institution in 1 country.

Rongwei FuOregon Health & Science University and Portland Veterans Affairs Medical Center, Portland, OR 97239, USA.
Shelley Selph
Marian McDonagh
Kimberly Peterson
Arpita Tiwari
Roger Chou
Mark Helfand
Oregon Health & Science University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundRecombinant human bone morphogenetic protein-2 (rhBMP-2) is used as a bone graft substitute in spinal fusion, which unites (fuses) bones in the spine. The accuracy and completeness of journal publications of industry-sponsored trials on the effectiveness and harms of rhBMP-2 has been called into question. PURPOSE: To independently assess the effectiveness and harms of rhBMP-2 in spinal fusion and reporting bias in industry-sponsored journal publications. DATA SOURCES: Individual-patient data (IPD) from 17 industry-sponsored studies; related internal documents; and searches of MEDLINE (1996 to August 2012), other databases, and reference lists. STUDY SELECTION: Randomized, controlled trials (RCTs) and cohort studies of rhBMP-2 versus any control and uncontrolled studies of harms. DATA EXTRACTION: Effectiveness outcomes in IPD were recalculated using consistent definitions. Study characteristics and results were abstracted by 1 investigator and confirmed by another. Two investigators independently assessed quality using predefined criteria. DATA SYNTHESIS: Thirteen RCTs and 31 cohort studies were included. For lumbar spine fusion, rhBMP-2 and iliac crest bone graft were similar in overall success, fusion, and other effectiveness measures and in risk for any adverse event, although rates were high across interventions (77% to 93% at 24 months from surgery). For anterior lumbar interbody fusion, rhBMP-2 was associated with nonsignificantly increased risk for retrograde ejaculation and urogenital problems. For anterior cervical spine fusion, rhBMP-2 was associated with increased risk for wound complications and dysphagia. At 24 months, the cancer risk was increased with rhBMP-2 (risk ratio, 3.45 [95% CI, 1.98 to 6.00]), but event rates were low and cancer was heterogeneous. Early journal publications misrepresented the effectiveness and harms through selective reporting, duplicate publication, and underreporting. LIMITATIONS: Outcome assessment was not blinded, and ascertainment of harms in trials was poor. No trials were truly independent of industry sponsorship.

conclusionIn spinal fusion, rhBMP-2 has no proven clinical advantage over bone graft and may be associated with important harms, making it difficult to identify clear indications for rhBMP-2. Earlier disclosure of all relevant data would have better informed clinicians and the public than the initial published trial reports did. PRIMARY FUNDING SOURCE: Yale University and Medtronic.

Indexed as

Conflict of InterestDrug IndustryPublication BiasSpinal FusionBone Morphogenetic Protein 2HumansIliumIncidenceIntervertebral Disc DegenerationNeoplasmsOff-Label UsePublishingRecombinant ProteinsTransforming Growth Factor betaTreatment OutcomeBone Morphogenetic Protein 2recombinant human bone morphogenetic protein-2Recombinant ProteinsTransforming Growth Factor beta

Identifiers

PMID23778906
OpenAlexW2125728570

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.