Cosman Felicia, Nieves Jeri, Zion Marsha, Woelfert Lillian, Luckey Marjorie, Lindsay Robert
Clinical Research Center, Helen Hayes Hospital, West Haverstraw, NY 10993, USA.
N Engl J Med. 2005 Aug 11;353(6):566-75. doi: 10.1056/NEJMoa050157.
We evaluated whether patients with osteoporosis treated with long-term alendronate have a response to parathyroid hormone treatment and whether short, three-month cycles of parathyroid hormone therapy could be as effective as daily administration.
We randomly assigned 126 women with osteoporosis who had been taking alendronate for at least 1 year to continued alendronate plus parathyroid hormone (1-34) subcutaneously daily, continued alendronate plus parathyroid hormone (1-34) subcutaneously daily for three 3-month cycles alternating with 3-month periods without parathyroid hormone, or alendronate alone for 15 months.
In both parathyroid hormone groups, bone formation indexes rose swiftly. Among the women who were receiving cyclic parathyroid hormone, bone formation declined during cycles without parathyroid hormone and increased again during cycles with parathyroid hormone. Bone resorption increased in both parathyroid hormone groups but increased progressively more in the daily-treatment group than in the cyclic-therapy group. Spinal bone mineral density rose 6.1 percent in the daily-treatment group and 5.4 percent in the cyclic-therapy group (P<0.001 for each parathyroid hormone group as compared with the alendronate group and no significant difference between parathyroid hormone groups). One woman in the daily-treatment group, two in the cyclic-therapy group, and four in the alendronate group had new or worsening vertebral deformities.
This study suggests that a regimen of three-month cycles of parathyroid hormone alternating with three-month cycles without parathyroid hormone causes the early phase of action of parathyroid hormone (characterized by pure stimulation of bone formation) to be dissociated from the later phase (activation of bone remodeling). The early phase may be more important to the increase in spinal bone mineral density. In patients with persistent osteoporosis after prior alendronate treatment, both daily treatment and cyclic treatment with parathyroid hormone increase spinal bone mineral density.
我们评估了长期接受阿仑膦酸盐治疗的骨质疏松症患者对甲状旁腺激素治疗是否有反应，以及为期三个月的短期甲状旁腺激素治疗周期是否与每日给药一样有效。
我们将126名服用阿仑膦酸盐至少1年的骨质疏松症女性随机分为三组，分别为继续每日皮下注射阿仑膦酸盐加甲状旁腺激素（1-34）；继续每日皮下注射阿仑膦酸盐加甲状旁腺激素（1-34），为期三个月，之后三个月不使用甲状旁腺激素，如此交替进行；单独使用阿仑膦酸盐治疗15个月。
在两个甲状旁腺激素治疗组中，骨形成指标迅速上升。在接受周期性甲状旁腺激素治疗的女性中，在无甲状旁腺激素的周期中骨形成下降，而在有甲状旁腺激素的周期中再次上升。两个甲状旁腺激素治疗组的骨吸收均增加，但每日治疗组的增加幅度逐渐大于周期治疗组。每日治疗组的脊柱骨矿物质密度上升了6.1%，周期治疗组上升了5.4%（每个甲状旁腺激素治疗组与阿仑膦酸盐组相比，P<0.001，且甲状旁腺激素治疗组之间无显著差异）。每日治疗组有1名女性、周期治疗组有2名女性、阿仑膦酸盐组有4名女性出现了新的或恶化的椎体畸形。
本研究表明，为期三个月的甲状旁腺激素周期与为期三个月的无甲状旁腺激素周期交替，会使甲状旁腺激素的早期作用阶段（以单纯刺激骨形成为特征）与后期阶段（激活骨重塑）分离。早期阶段可能对脊柱骨矿物质密度的增加更为重要。在先前接受阿仑膦酸盐治疗后仍持续存在骨质疏松症的患者中，每日治疗和甲状旁腺激素周期治疗均可增加脊柱骨矿物质密度。
