title: What is the utility of biomarkers for assessing the pathophysiology of hip osteoarthritis? A systematic review.
abstract: BACKGROUND
  Innovations in biologics offer great promise in the treatment of patients with orthopaedic conditions and in advancing our ability to monitor underlying disease pathophysiology. Our understanding of the pathophysiology of hip osteoarthritis (OA) has improved significantly in the last decade. Femoroacetabular impingement (FAI) and hip dysplasia are increasingly recognized and treated as forms of prearthritic hip disease, yet the inability of radiographic and MR imaging to identify patients before the onset of irreversible articular cartilage injury limits their use for early diagnosis and treatment of patients with these conditions. Molecular biomarkers, as objectively measureable indicators of the pathophysiology of hip OA, have the potential to improve diagnosis, disease staging, and prognosis of hip OA and prearthritic hip disease. Although research into molecular biomarkers of hip OA has been conducted, investigations in prearthritic hip disease have only recently begun.
  
  
  OBJECTIVE
  The purpose of our review was to assess the use of molecular biomarkers in the pathophysiology of hip OA, including (1) diagnosis; (2) disease staging; and (3) prognosis. We additionally aimed to summarize the available literature investigating the use of biomarkers in (4) prearthritic hip disease, including FAI and hip dysplasia.
  
  
  METHODS
  We conducted a systematic review of molecular biomarkers associated with hip OA or prearthritic hip disease by searching four major electronic databases for keywords "hip", "osteoarthritis", "biomarker", and all synonyms. The search terms "femoroacetabular impingement" and "hip dysplasia" were also included. The biologic source of biomarkers was limited to serum, plasma, urine, and synovial fluid. The literature search yielded a total of 2740 results. Forty studies met all criteria and were included in our review. Studies were categorized regarding their relevance to (1) diagnosis; (2) disease staging; (3) prognosis; and/or (4) prearthritic hip disease.
  
  
  RESULTS
  Biomarker studies were characterized as relevant to diagnosis (16 studies), disease staging (15 studies), prognosis (11 studies), and prearthritic hip disease (three studies). Sixteen different biomarkers demonstrated associations relevant to the diagnosis of hip OA, 16 biomarkers demonstrated similar associations for disease staging, and six for prognosis. Six biomarkers seemed to be the most promising, demonstrating associations with hip OA in multiple studies, including: urinary level of type II collagen telopeptide (n = 5 studies), serum cartilage oligomeric protein (n = 4 studies), and serum C-reactive protein (n = 4 studies). Only three studies investigated the role of biomarkers in prearthritic hip disease, including two in FAI and one in unspecified etiology of pain. There were no studies about biomarkers in hip dysplasia.
  
  
  CONCLUSIONS
  Molecular biomarkers are increasingly investigated for their use in evaluating the pathophysiology of hip OA, but less so for prearthritic hip disease. Several biomarkers have demonstrated significant associations with hip OA across multiple studies. Further validation of these biomarkers is needed to assess their clinical use and potential application to prearthritic hip disease.
authors.affiliation: Department of Orthopaedic Surgery, Washington University School of Medicine, One Children's Place, Campus Box 8233, 4S60, St Louis, MO, 63110, USA, nepplej@wudosis.wustl.edu.
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Nepple
authors.forename: Kayla M
authors.initials: KM
authors.lastname: Thomason
authors.forename: Tonya W
authors.initials: TW
authors.lastname: An
authors.forename: Marcie
authors.initials: M
authors.lastname: Harris-Hayes
authors.forename: John C
authors.initials: JC
authors.lastname: Clohisy
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D001696:Biomechanical Phenomena; D006621:Hip Joint / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D025202:Molecular Diagnostic Techniques; D015207:Osteoarthritis, Hip / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D011237:Predictive Value of Tests; D011379:Prognosis; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers