Effects of oral contraceptives on circulating osteoprotegerin and soluble RANK ligand serum levels in healthy young women.

Abstract

Osteoprotegerin (OPG) represents a secreted cytokine which regulates bone mass by blocking receptor activator of nuclear factor-kappaB ligand (RANKL), the principal regulator of osteoclast function. In vitro, OPG production is upregulated by oestrogens in osteoblastic lineage cells, a mechanism that has been discussed as a protective paracrine mechanism of oestrogens on the skeleton. To define the effects of oestrogens on the RANKL/OPG system in vivo, we evaluated OPG and both free and total soluble RANKL (sRANKL) serum levels in healthy young women with or without oral contraceptives. Serum levels of OPG and sRANKL were prospectively assessed in a cohort of healthy young women with (n = 30) or without (n = 25) combined oestrogen-progestin-based oral contraceptives. OPG, total and free sRANKL serum levels were determined by enzyme-linked immunosorbent assays (ELISA). In women using oral contraceptives, OPG serum levels were significantly higher (2.71 +/- 1.42 pmol/l) compared to nonusers (1.35 +/- 1.02 pmol/l; P = 0.0003), whereas free (P = 0.55) and total (P = 0.24) sRANKL serum levels did not differ between both groups. This resulted in an increased OPG/free sRANKL ratio (P = 0.02) in women on oral contraceptives. During the ovarian cycle, OPG (P = 0.22) and free sRANKL (P = 0.99) serum levels remained unchanged in women without oral contraceptives (n = 19), while total sRANKL levels were higher in the follicular than in the luteal phase (P = 0.02). Intake of oral contraceptives is associated with increased OPG serum levels, but not sRANKL levels, resulting in a higher OPG/sRANKL ratio. This may contribute to the positive effects of oral contraceptives on the skeleton.