Objective:  This study systematically summarizes biochemical biomarker research in non-traumatic musculoskeletal disorders (MSDs).  Two research questions guided the review:  1) Are there biochemical markers associated with neck and upper extremity MSDs? and, 2) Are there biochemical markers associated with the severity of neck and upper extremity MSDs? 

Methods:  A literature search was conducted in PubMed and SCOPUS.  Eighty-seven studies met primary inclusion criteria.  Following a quality screen, data were extracted from 44 sufficient quality articles.

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 yrs).

In sufficient quality articles, 82% demonstrated at least one statistically significant association between the MSD(s) and biomarker(s) studied.  Evidence suggested that: a) the collagen repair marker TIMP-1 is decreased in fibroproliferative disorders, b) 5-HT (serotonin) is increased in trapezius myalgia, and c) triglycerides are increased in a variety of MSDs.  Only five studies showed an association between a biochemical marker and MSD severity.

Conclusion: 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 co-morbid conditions. A list of recommendations for future studies is provided.