Hofbauer Lorenz C, Schoppet Michael, Schüller Per, Viereck Volker, Christ Michael
Department of Internal Medicine and Cardiology, Philipps-University, Marburg, Germany.
Clin Endocrinol (Oxf). 2004 Feb;60(2):214-9. doi: 10.1046/j.1365-2265.2003.01969.x.
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.
骨保护素(OPG)是一种分泌性细胞因子,通过阻断破骨细胞功能的主要调节因子——核因子κB受体活化因子配体(RANKL)来调节骨量。在体外,成骨细胞系细胞中的雌激素可上调OPG的产生,这一机制被认为是雌激素对骨骼的一种保护性旁分泌机制。为了确定雌激素在体内对RANKL/OPG系统的影响,我们评估了服用或未服用口服避孕药的健康年轻女性的OPG以及游离和总可溶性RANKL(sRANKL)的血清水平。
前瞻性评估了一组服用(n = 30)或未服用(n = 25)基于雌激素-孕激素的复方口服避孕药的健康年轻女性的OPG和sRANKL血清水平。
采用酶联免疫吸附测定(ELISA)法测定OPG、总sRANKL和游离sRANKL的血清水平。
服用口服避孕药的女性OPG血清水平(2.71±1.42 pmol/l)显著高于未服用者(1.35±1.02 pmol/l;P = 0.0003),而两组间游离sRANKL(P = 0.55)和总sRANKL(P = 0.24)血清水平无差异。这导致服用口服避孕药的女性OPG/游离sRANKL比值升高(P = 0.02)。在卵巢周期中,未服用口服避孕药的女性(n = 19)的OPG(P = 0.22)和游离sRANKL(P = 0.99)血清水平保持不变,而总sRANKL水平在卵泡期高于黄体期(P = 0.02)。
口服避孕药的摄入与OPG血清水平升高有关,但与sRANKL水平无关,导致OPG/sRANKL比值升高。这可能有助于解释口服避孕药对骨骼的积极作用。