Effects of oral contraceptives on circulating osteoprotegerin and soluble RANK ligand serum levels in healthy young women
Effects of oral contraceptives on circulating osteoprotegerin and soluble RANK ligand serum levels in healthy young women
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DOI：
10.1046/j.1365-2265.2003.01969.x
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发表时间：
2004-02-01
影响因子：
3.2
通讯作者：
Christ, M
中科院分区：
文献类型：
--
作者：
Hofbauer, LC;Schoppet, M;Christ, M
目的骨保护素（OPG）是一种分泌型细胞因子，通过阻断破骨细胞功能的主要调节因子-核因子-κ B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OPG的产生被雌激素上调，这一机制已被讨论为雌激素对骨骼的保护性旁分泌机制。为了确定雌激素对体内RANKL/OPG系统的影响，我们在有或没有口服避孕药的健康年轻女性中评估OPG和游离和总可溶性RANKL（sRANKL）的血清水平。设计和患者在有（n = 30）或没有（n = 25）组合雌激素-孕酮的健康年轻女性队列中前瞻性地评估OPG和sRANKL的血清水平。采用酶联免疫吸附试验（ELISA）测定血清OPG、总sRANKL和游离sRANKL水平。（2.71 +/- 1.42 pmol/l）与非使用者（1.35 +/- 1.02 pmol/l; P = 0.0003）相比，而游离（P = 0.55）和总（P = 0.24）sRANKL血清水平在两组之间没有差异。这导致口服避孕药的女性中OPG/游离sRANKL比率增加（P = 0.02）。在卵巢周期中，OPG（P = 0.22）和游离sRANKL（P = 0.99）未使用口服避孕药的女性（n = 19）血清水平保持不变，而卵泡期的总sRANKL水平高于黄体期（P = 0.02）。结论口服避孕药的摄入与血清OPG水平升高相关，但与sRANKL水平无关，导致更高的OPG/sRANKL比率。这可能有助于口服避孕药对骨骼的积极影响。
OBJECTIVE 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.DESIGN AND PATIENTS 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.MEASUREMENTS OPG, total and free sRANKL serum levels were determined by enzyme-linked immunosorbent assays (ELISA).RESULTS 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).CONCLUSIONS 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.