Osteoprotegerin OPG/RANK/RANK-L

Cytokines are involved, beside calcitonin, parathyroid hormone and vitamin D, in the modulation of the osteogenic/osteoclastic balance.

RANK (receptor activator of nuclear Factor kappa B) is present in osteoclasts and belongs to the family of TNF receptors. The agonist of RANK receptor is RANK-L (RANK-ligand), protein expressed and released by osteoblasts and T lymphocytes.

The activation of RANK receptors induces maturation and activation of osteoclasts and bone resorption contributing to osteoporosis development.

Osteoprotegerin, called OPG, secreted by osteoblasts, is a soluble protein which is a trap-receptor for RANK-L (i.e. RANK-L binds to OPG and thus is neutralized).

In experiments OPG, administered in injection, reduced bone resorption and is thus likely to reduce the loss of bone and osteoporosis. Clinical trials of OPG are ongoing but one does not know yet which place it will be able to occupy in the treatment of osteoporosis.

Plasma concentration of osteoprotegerin rises during ageing, in healthy people and much more in patients with osteoporosis. It rises also after myocardial infarction. Is this increase a defence reaction with some beneficial consequence?

Note: Estradiol protects undoubtedly from the development of postmenopausal osteoporosis. Molecules like raloxifene, classified among SERM or selective estrogen receptor modulators, also have a beneficial effect on bone. See: Estrogens .