title: Association of obesity and systemic factors with bone marrow lesions at the knee: a systematic review.
abstract: OBJECTIVE
  The objective of this study was to systematically review the literature to determine whether obesity and systemic factors, including age, gender, heritability, dietary factors, smoking, serum and urine biomarkers of cartilage or bone metabolism, bone-related factors, and medication, are associated with knee bone marrow lesions (BMLs) identified on magnetic resonance imaging in asymptomatic pre-osteoarthritis and osteoarthritis populations.
  
  
  METHODS
  Electronic searches of MEDLINE and EMBASE were performed from January 1, 1996 to September 30, 2012 using the following keywords: bone marrow lesion(s), bone marrow (o)edema, osteoarthritis, and knee. Studies examining obesity and non-biomechanical factors in relation to the presence, incidence, or change in BMLs were included. Two independent reviewers extracted data and assessed methodological quality of selected studies. Due to the heterogeneity of the studies, we performed a best evidence synthesis.
  
  
  RESULTS
  Among 30 studies, 17 were considered high quality. The study populations were heterogeneous in terms of symptoms and radiographic knee osteoarthritis. There was strong evidence for an association between serum lipids and BMLs and no association between age and BMLs. There was moderate evidence for a relationship between obesity and BMLs. There was limited evidence for gender, smoking, C-telopeptide of type I collagen, anti-bone-resorptive treatments, licofelone, and chondroitin sulfate. There was a paucity of evidence for heritability and conflicting evidence for dietary fatty acids.
  
  
  CONCLUSIONS
  There is strong evidence for serum lipids and moderate evidence for obesity as risk factors for knee BMLs. Given the role of BMLs in the pathogenesis of knee osteoarthritis, identification of modifiable risk factors of BMLs and therapeutic interventions targeting BMLs has the potential to reduce the burden of knee osteoarthritis.
authors.affiliation: Department of Epidemiology & Preventive Medicine, School of Public Health & Preventive Medicine, Monash University, The Alfred Centre, Melbourne, Victoria 3004, Australia.
authors.forename: Yuan Z
authors.initials: YZ
authors.lastname: Lim
authors.affiliation: Department of Epidemiology & Preventive Medicine, School of Public Health & Preventive Medicine, Monash University, The Alfred Centre, Melbourne, Victoria 3004, Australia.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Epidemiology & Preventive Medicine, School of Public Health & Preventive Medicine, Monash University, The Alfred Centre, Melbourne, Victoria 3004, Australia.
authors.forename: Anita E
authors.initials: AE
authors.lastname: Wluka
authors.affiliation: Department of Epidemiology & Preventive Medicine, School of Public Health & Preventive Medicine, Monash University, The Alfred Centre, Melbourne, Victoria 3004, Australia.
authors.forename: Miranda L
authors.initials: ML
authors.lastname: Davies-Tuck
authors.affiliation: Department of Epidemiology & Preventive Medicine, School of Public Health & Preventive Medicine, Monash University, The Alfred Centre, Melbourne, Victoria 3004, Australia; School of Rural Health, Monash University, Victoria, Australia.
authors.forename: Fahad
authors.initials: F
authors.lastname: Hanna
authors.affiliation: Department of Epidemiology & Preventive Medicine, School of Public Health & Preventive Medicine, Monash University, The Alfred Centre, Melbourne, Victoria 3004, Australia.
authors.forename: Donna M
authors.initials: DM
authors.lastname: Urquhart
authors.affiliation: Department of Epidemiology & Preventive Medicine, School of Public Health & Preventive Medicine, Monash University, The Alfred Centre, Melbourne, Victoria 3004, Australia. Electronic address: flavia.cicuttini@monash.edu.
authors.forename: Flavia M
authors.initials: FM
authors.lastname: Cicuttini
mesh_terms: D001853:Bone Marrow / Q000473:pathology*; D001855:Bone Marrow Diseases / Q000150:complications* / Q000473:pathology; D002358:Cartilage, Articular / Q000473:pathology; D006801:Humans; D007719:Knee Joint / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D009765:Obesity / Q000150:complications* / Q000473:pathology; D020370:Osteoarthritis, Knee / Q000209:etiology* / Q000473:pathology
keywords: Age; Bone marrow lesions; Non-biomechanical; Obesity; Osteoarthritis; Serum lipids