title: Arthralgia among women taking aromatase inhibitors: is there a shared inflammatory mechanism with co-morbid fatigue and insomnia?
abstract: BACKGROUND
  Arthralgia is a common toxicity among women taking aromatase inhibitors (AIs) and can lead to premature discontinuation of therapy. We evaluated the association between arthralgia, co-morbid fatigue and/or insomnia, and inflammatory biomarkers among women taking AIs.
  
  
  METHODS
  Women taking AIs for early-stage breast cancer completed a modified version of the Brief Pain Inventory, the Brief Fatigue Inventory, and the Insomnia Severity Index and provided blood samples for simultaneous assessment of 34 inflammatory biomarkers with a Luminex kit. Two-sided t tests were used to compare inflammatory biomarker concentrations for patients with or without moderate to severe arthralgia. Multivariate linear regression analyses were performed to evaluate the relationship between comorbid arthralgia, fatigue, and insomnia with identified biomarker concentrations.
  
  
  RESULTS
  Among 203 participants, the severity of arthralgia, fatigue, and insomnia were significantly correlated with each other (p < 0.001 for all comparisons). After controlling for race, chemotherapy history, non-steroidal anti-inflammatory drug use, age, and body mass index, the coexistence of arthralgia, fatigue, and insomnia was associated with elevated C-reactive protein (CRP) (β = 93.1; 95 % confidence interval (CI): 25.1-161.1; p = 0.008), eotaxin (β = 79.9; 95 % CI: 32.5-127.2; p = 0.001), monocyte chemoattractant protein (MCP)-1 (β = 151.2; 95 % CI: 32.7-269.8; p = 0.013), and vitamin D-binding protein (VDBP) (β = 19,422; 95 % CI: 5500.5-33,344; p = 0.006).
  
  
  CONCLUSIONS
  Among women taking AIs, the coexistence of arthralgia, fatigue, and insomnia was associated with increased levels of inflammatory biomarkers (elevated CRP, eotaxin, MCP-1, and VDBP). These findings suggest a possible shared inflammatory mechanism underlying these common symptoms.
authors.affiliation: Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA. joshua.bauml@uphs.upenn.edu.|Department of Medicine, Division of Hematology/Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. joshua.bauml@uphs.upenn.edu.
authors.forename: Joshua
authors.initials: J
authors.lastname: Bauml
authors.affiliation: Center for Clinical Epidemiology and Biostatistics and Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. chenlu6@mail.med.upenn.edu.
authors.forename: Lu
authors.initials: L
authors.lastname: Chen
authors.affiliation: Center for Clinical Epidemiology and Biostatistics and Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. jinboche@upenn.edu.
authors.forename: Jinbo
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. boyerj@mail.med.upenn.edu.
authors.forename: Jean
authors.initials: J
authors.lastname: Boyer
authors.affiliation: Eli Lilly & Company, New Hyde Park, NY, USA. kalos_michael_d@lilly.com.
authors.forename: Michael
authors.initials: M
authors.lastname: Kalos
authors.affiliation: Center for Clinical Epidemiology and Biostatistics and Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. qing.li@uphs.upenn.edu.|Department of Family Medicine and Community Health, Perelman School of Medicine, University of Pennsylvania, 3400 Spruce Street, 2 Gates, Philadelphia, PA, 19104, USA. qing.li@uphs.upenn.edu.
authors.forename: Susan Q
authors.initials: SQ
authors.lastname: Li
authors.affiliation: Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA. angela.demichele@uphs.upenn.edu.|Department of Medicine, Division of Hematology/Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. angela.demichele@uphs.upenn.edu.|Center for Clinical Epidemiology and Biostatistics and Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. angela.demichele@uphs.upenn.edu.
authors.forename: Angela
authors.initials: A
authors.lastname: DeMichele
authors.affiliation: Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA. jun.mao@uphs.upenn.edu.|Center for Clinical Epidemiology and Biostatistics and Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. jun.mao@uphs.upenn.edu.|Department of Family Medicine and Community Health, Perelman School of Medicine, University of Pennsylvania, 3400 Spruce Street, 2 Gates, Philadelphia, PA, 19104, USA. jun.mao@uphs.upenn.edu.
authors.forename: Jun J
authors.initials: JJ
authors.lastname: Mao
mesh_terms: D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects* / Q000627:therapeutic use; D047072:Aromatase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D018771:Arthralgia / Q000453:epidemiology* / Q000209:etiology*; D015415:Biomarkers; D001943:Breast Neoplasms / Q000150:complications* / Q000175:diagnosis / Q000188:drug therapy; D002097:C-Reactive Protein; D015897:Comorbidity; D003430:Cross-Sectional Studies; D005221:Fatigue / Q000209:etiology; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008875:Middle Aged; D009367:Neoplasm Staging; D015995:Prevalence; D007319:Sleep Initiation and Maintenance Disorders / Q000209:etiology
chemical_list: D018931:Antineoplastic Agents, Hormonal; D047072:Aromatase Inhibitors; D015415:Biomarkers; D018836:Inflammation Mediators; D002097:C-Reactive Protein