title: Elevation of serum tumor necrosis factor α in patients with periprosthetic osteolysis: a case-control study.
abstract: BACKGROUND
  Periprosthetic osteolysis is the leading reason for THA revision. The relationship of serum biomarkers with severe radiographic periprosthetic osteolysis has not been defined but may be important to direct future research and clinical therapeutics.
  
  
  OBJECTIVE
  We determined whether there was an association between measurable inflammatory markers (high-sensitivity C-reactive protein [hsCRP]) or inflammatory mediators (tumor necrosis factor α [TNF-α], IL-1β, IL-6, receptor activator of nuclear factor κB ligand [RANKL], and osteoprotegerin [OPG]) and periprosthetic osteolysis.
  
  
  METHODS
  We identified 15 patients with THAs scheduled for revision surgery because of severe periprosthetic osteolysis. For each study patient, a nonosteolytic, pain-free control patient with THAs was identified and matched for age, sex, time since initial THA, acetabular and femoral component prosthesis material, and prosthesis wear within 1.0 mm/year using a manual wear analysis technique. Overall, the study and control patients had a mean wear rate of 0.25 mm/year since index THA. There were no differences in baseline characteristics between study and control patients in age, sex, BMI, Charlson Comorbidity Index, time since initial THA, UCLA activity score, and acetabular and femoral component type. Serum hsCRP, IL-1β, IL-6, TNF-α, RANKL, and OPG were measured by ELISA in duplicate assays. Differences in values were assessed using the Wilcoxon rank-sum test.
  
  
  RESULTS
  Median TNF-α levels were higher in study patients than in controls (7.1 pg/mL [SD, 11.6 pg/mL] versus 1.5 pg/mL [SD, 1.3 pg/mL]) (p < 0.01). Median IL-6 levels tended to be higher in study patients than in controls (8.9 pg/mL [SD, 13.2 pg/mL] versus 3.5 pg/mL [SD, 0.7 pg/mL]) (p = 0.09). The other serum inflammatory proteins and mediators of bone turnover were not different between groups.
  
  
  CONCLUSIONS
  TNF-α is elevated in patients with osteolysis compared to matched controls. The role of TNF-α and its potential as a target of nonsurgical therapy to prevent osteolysis warrant further investigation in larger, prospective studies.
authors.affiliation: Division of Rheumatology, University of California, San Francisco, 400 Parnassus Avenue, Box 0326, San Francisco, CA, 94143, USA, chaganti@medicine.ucsf.edu.
authors.forename: R Krishna
authors.initials: RK
authors.lastname: Chaganti
authors.forename: Edward
authors.initials: E
authors.lastname: Purdue
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Sculco
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Mandl
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D019644:Arthroplasty, Replacement, Hip / Q000009:adverse effects* / Q000295:instrumentation; D001696:Biomechanical Phenomena; D002097:C-Reactive Protein / Q000032:analysis; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006621:Hip Joint / Q000000981:diagnostic imaging / Q000503:physiopathology / Q000601:surgery*; D006622:Hip Prosthesis; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D015207:Osteoarthritis, Hip / Q000000981:diagnostic imaging / Q000503:physiopathology / Q000601:surgery*; D010014:Osteolysis / Q000097:blood / Q000000981:diagnostic imaging / Q000276:immunology* / Q000601:surgery; D053244:Osteoprotegerin / Q000097:blood; D011474:Prosthesis Design; D011475:Prosthesis Failure; D053245:RANK Ligand / Q000097:blood; D011859:Radiography; D012086:Reoperation; D012307:Risk Factors; D013314:Stress, Mechanical; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*; D015854:Up-Regulation
chemical_list: C508600:IL6 protein, human; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D015850:Interleukin-6; D053244:Osteoprotegerin; D053245:RANK Ligand; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein