Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel.
Department of Medicine A, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6423906, Israel.
Int J Mol Sci. 2020 May 27;21(11):3817. doi: 10.3390/ijms21113817.
Recent studies have demonstrated that erythropoietin (EPO) treatment in mice results in trabecular bone loss. Here, we investigated the dose-response relationship between EPO, hemoglobin (Hgb) and bone loss and examined the reversibility of EPO-induced damage. Increasing doses of EPO over two weeks led to a dose-dependent increase in Hgb in young female mice, accompanied by a disproportionate decrease in trabecular bone mass measured by micro-CT (µCT). Namely, increasing EPO from 24 to 540 IU/week produced a modest 12% rise in Hgb (20.2 ± 1.3 mg/dL vs 22.7 ± 1.3 mg/dL), while trabecular bone volume fraction (BV/TV) in the distal femur decreased dramatically (27 ± 8.5% vs 53 ± 10.2% bone loss). To explore the long-term skeletal effects of EPO, we treated mice for two weeks (540 IU/week) and monitored bone mass changes after treatment cessation. Six weeks post-treatment, there was only a partial recovery of the trabecular microarchitecture in the femur and vertebra. EPO-induced bone loss is therefore dose-dependent and mostly irreversible at doses that offer only a minor advantage in the treatment of anemia. Because patients requiring EPO therapy are often prone to osteoporosis, our data advocate for using the lowest effective EPO dose for the shortest period of time to decrease thromboembolic complications and minimize the adverse skeletal outcome.
最近的研究表明，促红细胞生成素（EPO）治疗小鼠会导致小梁骨丢失。在这里，我们研究了 EPO、血红蛋白（Hgb）和骨丢失之间的剂量反应关系，并检查了 EPO 诱导损伤的可逆性。在两周内增加 EPO 的剂量会导致年轻雌性小鼠的 Hgb 呈剂量依赖性增加，同时通过 micro-CT（µCT）测量的小梁骨量不成比例地减少。也就是说，将 EPO 从 24 增加到 540 IU/周会使 Hgb 适度升高 12%（20.2 ± 1.3 mg/dL 与 22.7 ± 1.3 mg/dL），而远端股骨的小梁骨体积分数（BV/TV）则急剧下降（27 ± 8.5% 与 53 ± 10.2% 的骨丢失）。为了探索 EPO 对骨骼的长期影响，我们治疗小鼠两周（540 IU/周），并在治疗停止后监测骨量变化。治疗后 6 周，股骨和椎体的小梁微观结构仅部分恢复。因此，EPO 诱导的骨丢失是剂量依赖性的，并且在仅对贫血治疗有较小优势的剂量下，大部分是不可逆转的。由于需要 EPO 治疗的患者通常容易发生骨质疏松症，我们的数据主张使用最低有效 EPO 剂量治疗最短时间，以减少血栓栓塞并发症并最小化不良骨骼结局。
