Department of Endocrinology, 424 General Military Hospital, 56429 Thessaloniki, Greece.
J Clin Endocrinol Metab. 2013 Aug;98(8):3206-12. doi: 10.1210/jc.2013-1402. Epub 2013 Jun 20.
Decreased bone formation due to a coupling effect limits bone mass increases after antiresorptive treatment.
The purpose of this study was to compare the effects of 2 potent antiresorptive agents with different mechanism of action on serum levels of Wnt antagonists, sclerostin and dickkopf-1 (Dkk-1).
This was an interventional, parallel assignment, open-label, randomized clinical trial.
The study was conducted at the outpatient clinics for metabolic bone diseases of 424 General Military Hospital, Thessaloniki, Greece.
Naive postmenopausal women with low bone mass were assigned to zoledronic acid infusion (n = 46) or denosumab injection (n = 46). One woman in the zoledronic acid group was lost to follow-up.
Serum sclerostin and Dkk-1 levels were the main outcomes. Secondary measurements were serum osteoprotegerin, receptor activator of nuclear factor κB ligand, procollagen type 1 N-terminal propeptide, and C-terminal cross-linking telopeptide of type 1 collagen.
Serum sclerostin levels significantly decreased in the zoledronic acid (P < .001) but increased in the denosumab group (P = .003). Dkk-1 levels significantly decreased in the zoledronic acid group (P = .006) but did not change in the denosumab group (P = .402). Serum osteoprotegerin remained essentially unchanged in either group, whereas receptor activator of nuclear factor κB ligand decreased in the zoledronic acid group (P = .004) but increased in the denosumab group (P = .037). Bone markers (procollagen type 1 N-terminal propeptide, C-terminal cross-linking telopeptide of type 1 collagen, and total serum alkaline phosphatase) decreased in both groups (all P < .001).
Although they both decrease bone resorption, zoledronic acid and denosumab exert opposite effects on Wnt signaling: the former decreases serum levels of both sclerostin and Dkk-1, whereas the latter increases sclerostin and does not affect Dkk-1.
由于偶联效应导致骨形成减少，限制了抗吸收治疗后骨量的增加。
本研究旨在比较两种作用机制不同的强效抗吸收剂对血清 Wnt 拮抗剂骨硬化蛋白和 Dickkopf-1（Dkk-1）水平的影响。
这是一项干预性、平行分组、开放标签、随机临床试验。
该研究在希腊塞萨洛尼基 424 总医院代谢性骨疾病的门诊进行。
未接受过治疗的绝经后低骨量女性被分配接受唑来膦酸输注（n = 46）或地舒单抗注射（n = 46）。唑来膦酸组有 1 名女性失访。
血清骨硬化蛋白和 Dkk-1 水平是主要观察指标。次要测量指标为血清护骨素、核因子κB 受体激活剂配体、I 型前胶原氨基端前肽和 I 型胶原 C 端交联肽。
唑来膦酸组血清骨硬化蛋白水平显著降低（P <.001），而地舒单抗组则升高（P =.003）。唑来膦酸组 Dkk-1 水平显著降低（P =.006），而地舒单抗组则无变化（P =.402）。两组护骨素基本不变，而核因子κB 受体激活剂配体在唑来膦酸组降低（P =.004），在地舒单抗组升高（P =.037）。两组骨标志物（I 型前胶原氨基端前肽、I 型胶原 C 端交联肽和总血清碱性磷酸酶）均降低（均 P <.001）。
虽然唑来膦酸和地舒单抗均能降低骨吸收，但对 Wnt 信号通路的作用相反：前者降低血清骨硬化蛋白和 Dkk-1 水平，而后者则升高骨硬化蛋白，不影响 Dkk-1。
