Department of Endocrinology, 424 General Military Hospital, Thessaloniki, Greece.
Clin Endocrinol (Oxf). 2010 Jun;72(6):752-7. doi: 10.1111/j.1365-2265.2009.03728.x. Epub 2009 Oct 15.
Parathyroid hormone increases the differentiation of osteoblast precursors through canonical wingless (Wnt) signalling, resulting in an osteoanabolic effect. We aimed to evaluate serum levels of the Wnt-inhibitor Dickkopf-1 (Dkk-1) in postmenopausal women with established osteoporosis and their changes with teriparatide (TPTD - human recombinant PTH 1-34).
A total of 31 postmenopausal Caucasian women with established osteoporosis (mean age 66.3 +/- 1.4 years) received daily injections of 20 microg TPTD for 18 months. Follow-up was continued for another 6 months after treatment discontinuation (total duration of treatment 24 months).
Serum samples for total calcium (Ca), intact PTH (iPTH), bone-specific alkaline phosphatase, C-terminal cross-linking telopeptide of type 1 collagen (CTx) and Dkk-1 were obtained at baseline, and at 6, 18 and 24 months after TPTD initiation. Lumbar spine bone mineral density (BMD) was measured before and after 18 months of TPTD treatment. A total of 16 age- and gender-matched healthy controls were also analysed at baseline.
Serum Dkk-1 levels at baseline were significantly higher in osteoporotic women compared with that in controls (P < 0.002). Dkk-1 increased significantly during TPTD administration (P < 0.044) and decreased to baseline 6 months after TPTD discontinuation. Dkk-1 change was positively correlated to Ca (r = 0.530, P = 0.004) and negatively correlated to iPTH change (r = -0.398, P = 0.040). There was no correlation between Dkk-1 and BMD changes.
Our data suggest that Dkk-1 levels are increased in women with postmenopausal osteoporosis. TPTD therapy results in further increase of Dkk-1 that may be compensative to TPTD-induced enhanced Wnt signalling.
甲状旁腺激素通过经典的 Wnt 信号途径增加成骨前体细胞的分化，从而产生骨合成代谢作用。我们旨在评估绝经后骨质疏松症妇女血清中 Wnt 抑制剂 Dickkopf-1（Dkk-1）的水平及其在特立帕肽（TPTD-人重组 PTH1-34）治疗中的变化。
共有 31 名绝经后高加索白人骨质疏松症妇女（平均年龄 66.3±1.4 岁）接受每日 20μg TPTD 注射治疗 18 个月。在治疗停止后继续随访 6 个月（总治疗时间 24 个月）。
在 TPTD 治疗开始前、开始后 6、18 和 24 个月以及治疗结束后 6 个月时，采集血清样本用于测定总钙（Ca）、完整甲状旁腺激素（iPTH）、骨特异性碱性磷酸酶、I 型胶原 C 端交联肽（CTX）和 Dkk-1。在接受 18 个月 TPTD 治疗前后测量腰椎骨密度（BMD）。还在基线时分析了 16 名年龄和性别匹配的健康对照者。
骨质疏松症妇女的血清 Dkk-1 水平在基线时明显高于对照组（P<0.002）。TPTD 治疗期间 Dkk-1 显著升高（P<0.044），TPTD 治疗停止后 6 个月降至基线水平。Dkk-1 的变化与 Ca 呈正相关（r=0.530，P=0.004），与 iPTH 变化呈负相关（r=-0.398，P=0.040）。Dkk-1 与 BMD 变化之间无相关性。
我们的数据表明，绝经后骨质疏松症妇女的 Dkk-1 水平升高。TPTD 治疗导致 Dkk-1 进一步升高，这可能是对 TPTD 诱导的 Wnt 信号增强的补偿。
