title: Serum levels of osteoprotegerin and receptor activator of nuclear factor-kappaB ligand as markers of periprosthetic osteolysis.
abstract: BACKGROUND
  Previous studies have suggested that the balance between receptor activator of nuclear factor-kappaB ligand (RANKL) and its decoy-receptor osteoprotegerin (OPG) in local tissue seems to play a crucial role in the loosening of the total hip replacement. The aim of this study was to evaluate whether the circulating levels of OPG and RANKL, as well as their ratio, could be different in patients with aseptic loosening compared with patients with stable implants.
  
  
  METHODS
  One hundred and twenty-eight subjects were recruited. They included thirty-nine patients with osteoarthritis who had not yet undergone total hip arthroplasty, thirty-three patients who had undergone total hip arthroplasty and had clinically and radiographically stable implants, thirty-six patients with aseptic loosening of total hip arthroplasty components, and twenty healthy volunteers. Serum levels of OPG and RANKL were measured with use of an immunoenzymatic method, and in each individual the OPG-to-RANKL ratio was calculated.
  
  
  RESULTS
  In every group, a significant correlation was detected between OPG concentration and age (r = 0.58, p < 0.0001), especially in individuals older than fifty years, while gender and underlying disease were not found to influence serum levels of the tested parameters. In comparison with the levels in healthy donors and patients with a stable total hip replacement, the serum levels of OPG were increased in the patients who had not yet had an arthroplasty, those with aseptic loosening of a total hip replacement, and those with a cemented total hip replacement. Moreover, the OPG serum level provided good diagnostic accuracy in detecting the implant failure. A correlation was found between the sum of the osteolytic areas seen radiographically around the femoral stem and the RANKL level (r = 0.38, p = 0.02) and the OPG-to-RANKL ratio (r = -0.29, p = 0.04).
  
  
  CONCLUSIONS
  An increase in OPG levels may reflect a protective mechanism of the skeleton to compensate for the osteolytic activity that occurs in severe osteoarthritis and in aseptic loosening. Prospective studies are needed to determine whether serum OPG levels could be used as markers for monitoring the stability of the implant, as well as for predicting aseptic loosening.
  
  
  METHODS
  Diagnostic study, Level III. See Instructions to Authors for a complete description of levels of evidence.
authors.affiliation: Laboratory for Pathophysiology of Orthopedic Implants, Istituti Ortopedici Rizzoli, via di Barbiano 1/10,40136 Bologna, Italy. donatella.granchi@ior.it
authors.forename: Donatella
authors.initials: D
authors.lastname: Granchi
authors.forename: Andrea
authors.initials: A
authors.lastname: Pellacani
authors.forename: Mauro
authors.initials: M
authors.lastname: Spina
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Cenni
authors.forename: Lucia Maria
authors.initials: LM
authors.lastname: Savarino
authors.forename: Nicola
authors.initials: N
authors.lastname: Baldini
authors.forename: Armando
authors.initials: A
authors.lastname: Giunti
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019644:Arthroplasty, Replacement, Hip; D015415:Biomarkers / Q000097:blood; D002352:Carrier Proteins / Q000097:blood*; D016022:Case-Control Studies; D005260:Female; D006023:Glycoproteins / Q000097:blood*; D006622:Hip Prosthesis; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood*; D008875:Middle Aged; D015207:Osteoarthritis, Hip / Q000097:blood* / Q000601:surgery; D010014:Osteolysis / Q000097:blood*; D053244:Osteoprotegerin; D011475:Prosthesis Failure; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000097:blood*; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood*
chemical_list: D015415:Biomarkers; D002352:Carrier Proteins; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C505686:TNFRSF11A protein, human; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human