[Osteoprotegerin--a neutralizing receptor, protector of bones and a potential antiresorptive agent].

INTRODUCTION

The receptor activator of NF-B ligand (RANKL), expressed on the surface of osteoblasts and stromal cells in the bone marrow, plays an essential role in the formation and differentiation of osteoclasts and bone resorption. RANKL binds to its functional receptor, receptor activator of NF-B (RANK), expressed as a transmembrane heterotrimer on the surface of hematopoietic osteoclasts progenitors and mature osteoclasts. RANKL-RANK interaction is inhibited by soluble receptor-osteoprotegerin.

OSTEOPROTEGERIN

Osteoprotegerin (OPG), a member of the tumor necrosis factor receptor superfamily, acts as a natural decoy receptor that blocks the interaction between RANKL and RANK. The balance between RANKL and osteoprotegerin is of major importance in bone homeostasis. Osteoprotegerin inhibits differentiation and formation of osteoclasts and induces apoptosis of osteoclasts. OPG knock-out mice develop severe osteoporosis. In contrast, overexpression of OPG in transgenic mice causes osteopetrosis.

OSTEOPROTEGERIN AS A THERAPEUTIC AGENT

Antiresorptive activity of osteoprotegerin is proved in numerous experimental models. Osteoprotective effect of osteoprotegerin has recently been proved in postmenopausal women with osteoporosis as well as in patients with multiple myeloma and osteolytic metastases of breast cancer.

CONCLUSION

Osteoprotegerin is a potent antiosteoclast agent that may prove useful in the treatment of bone disorders with net bone loss, such as postmenopausal osteoporosis and cancer metastases.