Department of Obstetrics and Gynecology, International University of Health and Welfare Atami Hospital, Atami, Shizuoka, 413-0012, Japan.
J Bone Miner Metab. 2012 May;30(3):349-58. doi: 10.1007/s00774-011-0325-1. Epub 2011 Dec 2.
Vitamin D insufficiency is prevalent in osteopenic and osteoporotic postmenopausal women. The persistent increase in circulating parathyroid hormone (PTH) caused by vitamin D insufficiency reduces bone density response to antiresorptive agents in these postmenopausal women. It is not well known whether administration of raloxifene might increase serum PTH secondary to the suppression of serum calcium in postmenopausal women with osteopenia or osteoporosis. We tried to assess whether raloxifene might affect serum PTH and whether the addition of alfacalcidol to raloxifene therapy could have favorable effects on bone mineral density (BMD) and bone turnover as compared to raloxifene-alone therapy in postmenopausal Japanese women with osteoporosis or osteopenia (≤2.0 SD based on young Japanese women). A total of 169 subjects were randomly assigned to groups receiving 60 mg raloxifene (R), or 1 μg alfacalcidol (D), or a combination of both (R + D) for 2 years. Serum levels of 25-hydroxyvitamin D [25(OH)D] were measured at randomization. The modified 'intention to treat' method was used. We compared the groups using a Tukey-Kramer test for changes in L- and TH-BMD and calcium metabolism when significant differences were found using one-way ANOVA. The parameters in each group during the experimental period were analyzed by means of paired t tests. Baseline 25(OH)D and i-PTH were 23.7 ng/ml and 38.4 pg/ml, respectively. At 6 months, i-PTH demonstrated a significant increase (+21.0%) in the R-group whereas significant decreases in i-PTH were observed in the D-group and combination-group (-15.9 and -8.9%, respectively). There were significant increases in L-BMD in the R + D-group (+4.1% at 1 year and +4.7% at 2 years, P < 0.0001) and in the R-group (+2.9% at 1 year and +2.8% at 2 years, P < 0.001), but the difference between the groups did not reach a significant level. Vitamin D status at randomization did not affect the subsequent BMD response in coadministration of alfacalcidol with raloxifene. Supplementation with alfacalcidol to raloxifene therapy demonstrates a greater bone-sparing effect by suppressing the secondary increment of serum PTH than when raloxifene is used alone.
维生素 D 不足在骨质疏松和骨质疏松的绝经后妇女中很常见。维生素 D 不足引起的循环甲状旁腺激素（PTH）持续增加，降低了这些绝经后妇女对抗吸收剂的骨密度反应。目前尚不清楚在患有骨质减少或骨质疏松的绝经后妇女中，使用雷洛昔芬是否会因抑制血清钙而导致血清 PTH 升高。我们试图评估雷洛昔芬是否会影响血清 PTH，以及与单独使用雷洛昔芬相比，在日本绝经后妇女中添加阿尔法骨化醇（一种维生素 D 类似物）是否对骨矿物质密度（BMD）和骨转换有更好的影响（≤2.0 基于年轻日本女性的 SD）。共有 169 名受试者被随机分为接受 60 毫克雷洛昔芬（R）、1 微克阿尔法骨化醇（D）或两者联合治疗（R+D）2 年的组。在随机分组时测量血清 25-羟维生素 D [25（OH）D]水平。采用修改后的“意向治疗”方法进行比较。当使用单因素方差分析发现显著差异时，使用 Tukey-Kramer 检验比较组间 L-和 TH-BMD 和钙代谢的变化。在实验期间，使用配对 t 检验分析每组的参数。基线时 25（OH）D 和 i-PTH 分别为 23.7ng/ml 和 38.4pg/ml。在 6 个月时，R 组的 i-PTH 显著增加（+21.0%），而 D 组和联合组的 i-PTH 显著下降（-15.9%和-8.9%）。R+D 组的 L-BMD 显著增加（1 年时增加 4.1%，2 年时增加 4.7%，P<0.0001），R 组也显著增加（1 年时增加 2.9%，2 年时增加 2.8%，P<0.001），但组间差异未达到显著水平。随机分组时的维生素 D 状态不影响与雷洛昔芬联合使用时的后续 BMD 反应。与单独使用雷洛昔芬相比，补充阿尔法骨化醇可通过抑制血清 PTH 的二次增加来发挥更大的保骨作用。
