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(American Journal of Pathology. 2003;163:2021-2031.)
© 2003 American Society for Investigative Pathology

Receptor Activator of Nuclear Factor {kappa}B Ligand (RANKL)/Osteoprotegerin (OPG) Ratio Is Increased in Severe Osteolysis

Eva Grimaud*, Luc Soubigou*{dagger}, Séverine Couillaud*, Patrick Coipeau*, Anne Moreau{ddagger}, Norbert Passuti*{dagger}, François Gouin*{dagger}, Françoise Redini* and Dominique Heymann*

From the Laboratoire de Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives,* Faculté de Médecine, the Clinique Chirurgicale Orthopédique{dagger} and Service d’Anatomie-Pathologique,{ddagger} Centre Hospitalier Universitaire, Nantes, France

Pathological osteolyses are considered a consequence of a disturbance in the mechanisms that govern the bone remodeling, mainly the communication between osteoclasts and osteoblasts. Osteoprotegerin (OPG) and receptor activator of NF-{kappa}B ligand (RANKL) are newly discovered molecules that play a key role in these communications. RANKL is essential for osteoclast differentiation via its receptor RANK located on the osteoclast membrane. OPG is a soluble decoy receptor that inhibits osteoclast differentiation through its binding to RANKL. The aim of this study is the analysis of the RANKL/OPG balance by complementary methods (semiquantitative reverse transcription-polymerase chain reaction, immunohistochemistry, and enzyme-linked immunosorbent assay) in human osteolysis associated to various bone etiologies (n = 60), tumoral (primitive, secondary) or not, compared to healthy tissues (n = 16). Results demonstrated that RANKL/OPG ratio was significantly increased in patients suffering from severe osteolysis compared to the control group and that this imbalance is involved in bone resorption mechanisms. In this study, OPG expression appears to reflect a protective mechanism of the skeleton to compensate increased bone resorption by inhibiting osteoclast formation and bone resorbing activity. Moreover, as revealed by immunohistochemistry, RANKL and OPG were colocalized in all of the tissues analyzed. To define the veracity of RANKL/OPG index in assessing and managing patients with severe osteolysis, an extended population of patients suffering from severe osteolysis must be now monitored.




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