Division of Rheumatology, Department of Internal Medicine, School of Medicine, Faculty of Medicine, Toho University, 6-11-1 Omori-Nishi, Ota-ku, Tokyo 143-8541, Japan.
J Clin Endocrinol Metab. 2012 Oct;97(10):E1909-17. doi: 10.1210/jc.2012-1971. Epub 2012 Jul 12.
Osteoporosis is a serious complication of systemic glucocorticoid therapy. The role of serum soluble receptor activator for nuclear factor-κB ligand (RANKL) in glucocorticoid-induced osteoporosis remains unclear.
The objective of the study was to clarify the influence of serum soluble RANKL on the osteoprotegerin (OPG)/RANKL/receptor activator for nuclear factor-κB system in patients with systemic autoimmune diseases receiving glucocorticoid therapy.
Sixty patients (40 women) with systemic autoimmune diseases who received initial glucocorticoid therapy with prednisolone (30-60 mg/d) plus bisphosphonate therapy were prospectively enrolled. Serum soluble RANKL and OPG levels were measured at 0, 1, 2, 3, and 4 wk after starting glucocorticoid therapy. The effects of dexamethasone on production of RANKL and OPG mRNA and protein by cultured normal human osteoblasts were evaluated by RT-PCR and ELISA, respectively.
The mean serum soluble RANKL level of the patients was unchanged by glucocorticoid therapy. Because the distribution of serum soluble RANKL was bimodal, the patients were stratified into two groups. Serum soluble RANKL decreased significantly in the higher soluble RANKL group (≥0.16 pmol/liter), whereas it increased significantly in the lower soluble RANKL group. The mean serum OPG level of the patients decreased significantly. Bone mineral density increased in the higher soluble RANKL group after starting glucocorticoid therapy, whereas it decreased in the lower soluble RANKL group. In cultures of unstimulated human osteoblasts, RANKL mRNA expression was increased and OPG mRNA was decreased by dexamethasone. Up-regulation of RANKL and OPG mRNA by IL-6 was suppressed by dexamethasone.
Serum soluble RANKL might be a useful marker of bone remodeling in patients with systemic autoimmune diseases receiving glucocorticoid therapy.
骨质疏松症是全身性糖皮质激素治疗的严重并发症。血清可溶性核因子-κB 配体受体激活剂(RANKL)在糖皮质激素诱导的骨质疏松症中的作用尚不清楚。
本研究旨在阐明血清可溶性 RANKL 对接受糖皮质激素治疗的系统性自身免疫性疾病患者的护骨素(OPG)/RANKL/受体激活剂核因子-κB 系统的影响。
前瞻性纳入 60 例(40 名女性)接受初始糖皮质激素治疗(泼尼松龙 30-60mg/d)加双膦酸盐治疗的系统性自身免疫性疾病患者。在开始糖皮质激素治疗后 0、1、2、3 和 4 周时测量血清可溶性 RANKL 和 OPG 水平。通过 RT-PCR 和 ELISA 分别评估地塞米松对培养的正常人成骨细胞中 RANKL 和 OPG mRNA 和蛋白产生的影响。
患者的血清可溶性 RANKL 水平在糖皮质激素治疗中无变化。由于血清可溶性 RANKL 的分布呈双峰型,将患者分为两组。较高可溶性 RANKL 组(≥0.16pmol/L)的血清可溶性 RANKL 显著下降,而较低可溶性 RANKL 组的血清可溶性 RANKL 显著升高。患者的血清 OPG 水平显著降低。开始糖皮质激素治疗后,较高可溶性 RANKL 组的骨密度增加,而较低可溶性 RANKL 组的骨密度降低。在未受刺激的人成骨细胞培养物中,地塞米松增加了 RANKL mRNA 的表达并降低了 OPG mRNA 的表达。地塞米松抑制了 IL-6 对 RANKL 和 OPG mRNA 的上调。
血清可溶性 RANKL 可能是接受糖皮质激素治疗的系统性自身免疫性疾病患者骨重建的有用标志物。