Objective: Osteoprotegerin (OPG) and its ligand 'receptor activator of NF-kB ligand' (RANKL) are important regulators of bone metabolism. RANKL, expressed in osteoblasts, activates osteoclast differentiation and osteoclast function by binding the 'receptor activator of NF-kB' (RANK), expressed in ostoclast precursors and mature osteoclasts. The effect is prevented by OPG, a soluble receptor of RANKL. In vitro studies have suggested that estrogen stimulates OPG, whereas parathyroid hormone (PTH) inhibits OPG expression and stimulates the expression of RANKL.
Design: In the present study, we examined the relationship between the menopause, serum PTH and the expression of OPG and RANKL in human bone tissue in vivo.
Methods: To address this question, we established a 5'-nuclease assay to quantify the mRNA copies of human OPG and RANKL, normalized to the number of copies of beta-actin mRNA in 169 women (mean age: 52.4+/-11.6 years), who underwent surgery for early breast cancer. Intact serum PTH was measured by chemoluminescence in 61 women.
Results: We found no significant difference in the expression of OPG and RANKL between postmenopausal women and premenopausal women. Also, the ratio of RANKL to OPG was unchanged in relation to the menopausal status. Serum PTH was negatively associated with the expression of OPG (r=-0.33, P=0.01), but also, surprisingly, with the expression of RANKL (r=-0.28, P=0.03).
Conclusion: We failed to observe the expected changes in the expression of OPG and RANKL in human bone samples at menopause. High in vivo levels of circulating PTH are accompanied by low levels of expression of the two transcripts in human bone tissue.