The Journal of Bone and Joint Surgery (American). 2006;88:1501-1509.
doi:10.2106/JBJS.E.01038
© 2006 The Journal of Bone and Joint Surgery, Inc.
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Serum Levels of Osteoprotegerin and Receptor Activator of Nuclear Factor-{kappa}B Ligand as Markers of Periprosthetic Osteolysis

Donatella Granchi, MD, PhD1, Andrea Pellacani, MD1, Mauro Spina, MD1, Elisabetta Cenni, MD1, Lucia Maria Savarino, MSc1, Nicola Baldini, MD1 and Armando Giunti, MD1

1 Laboratory for Pathophysiology of Orthopedic Implants (D.G., E.C., L.M.S., N.B., and A.G.) and VII Orthopedic and Traumatology Division (A.P., M.S., N.B., and A.G.), Istituti Ortopedici Rizzoli, via di Barbiano 1/10,40136 Bologna, Italy. E-mail address for D. Granchi: donatella.granchi{at}ior.it

Investigation performed at the Laboratory for Pathophysiology of Orthopedic Implants and the VII Orthopedic and Traumatology Division, Istituti Ortopedici Rizzoli, Bologna, Italy

In support of their research for or preparation of this manuscript, one or more of the authors received grants or outside funding from the Italian Ministry of Health for National Hospitals and Research Institutes (Ricerca Corrente). None of the authors received payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, educational institution, or other charitable or nonprofit organization with which the authors are affiliated or associated.

Background: Previous studies have suggested that the balance between receptor activator of nuclear factor-{kappa}B 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.

Level of Evidence: Diagnostic study, Level III. See Instructions to Authors for a complete description of levels of evidence.


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