title: Systematic review of biochemical biomarkers for neck and upper-extremity musculoskeletal disorders.
abstract: OBJECTIVE
  This study systematically summarizes biochemical biomarker research in non-traumatic musculoskeletal disorders (MSD). Two research questions guided the review: (i) Are there biochemical markers associated with neck and upper-extremity MSD? and (ii) Are there biochemical markers associated with the severity of neck and upper-extremity MSD?
  
  
  METHODS
  A literature search was conducted in PubMed and SCOPUS, and 87 studies met primary inclusion criteria. Following a quality screen, data were extracted from 44 articles of sufficient quality.
  
  
  RESULTS
  Most of the 87 studies were cross-sectional and utilized convenience samples of patients as both cases and controls. A response rate was explicitly stated in only 11 (13%) studies. Less than half of the studies controlled for potential confounding through restriction or in the analysis. Most sufficient-quality studies were conducted in older populations (mean age in one or more analysis group >50 years). In sufficient-quality articles, 82% demonstrated at least one statistically significant association between the MSD and biomarker(s) studied. Evidence suggested that: (i) the collagen-repair marker TIMP-1 is decreased in fibro proliferative disorders, (ii) 5-HT (serotonin) is increased in trapezius myalgia, and (iii) triglycerides are increased in a variety of MSD. Only 5 studies showed an association between a biochemical marker and MSD severity.
  
  
  CONCLUSIONS
  While some MSD biomarkers were identified, limitations in the articles examined included possible selection bias, confounding, spectrum effect (potentially heterogeneous biomarker associations in populations according to symptom severity or duration), and insufficient attention to comorbid conditions. A list of recommendations for future studies is provided.
authors.affiliation: Centre for Musculoskeletal Research (CBF), Department of Occupational and Public Health Sciences, University of Gävle, SE - 801 76 Gävle, Sweden. Judith.Gold@hig.se.
authors.forename: Judith E
authors.initials: JE
authors.lastname: Gold
authors.forename: David M
authors.initials: DM
authors.lastname: Hallman
authors.forename: Fredrik
authors.initials: F
authors.lastname: Hellström
authors.forename: Martin
authors.initials: M
authors.lastname: Björklund
authors.forename: Albert G
authors.initials: AG
authors.lastname: Crenshaw
authors.forename: Mats
authors.initials: M
authors.lastname: Djupsjobacka
authors.forename: Marina
authors.initials: M
authors.lastname: Heiden
authors.forename: Svend Erik
authors.initials: SE
authors.lastname: Mathiassen
authors.forename: George
authors.initials: G
authors.lastname: Piligian
authors.forename: Mary F
authors.initials: MF
authors.lastname: Barbe
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000032:analysis*; D003430:Cross-Sectional Studies; D006801:Humans; D008875:Middle Aged; D009140:Musculoskeletal Diseases / Q000175:diagnosis*; D019838:Neck Injuries / Q000175:diagnosis*; D060051:Occupational Injuries / Q000175:diagnosis; D012701:Serotonin / Q000032:analysis; D012720:Severity of Illness Index; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000032:analysis; D014280:Triglycerides / Q000032:analysis; D034941:Upper Extremity; D055815:Young Adult
chemical_list: D015415:Biomarkers; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D014280:Triglycerides; D012701:Serotonin