Samnegård E, Cullen D M, Akhter M P, Kimmel D B
Department of Orthopaedic Surgery, Karolinska Institute, Huddinge University Hospital, Sweden.
J Orthop Res. 2001 Mar;19(2):328-36. doi: 10.1016/S0736-0266(00)90005-6.
Verapamil, a calcium channel blocker, alters the intracellular calcium concentration in bone cells in vitro, while mechanical loading stimulates calcium channels. The purpose of this study was to examine the effect of systemic verapamil treatment on the bone response to in vivo external mechanical loading. Female rats (age 5-6 months) were divided into six groups. Half were verapamil treated (0.75 mg/ml drinking water) for 12 weeks. After 8 weeks of treatment, the right tibia was loaded by a four-point bending device. In one set of verapamil and control groups, the right tibia was loaded at 31.8 +/- 0.2 N (36 cycles, 2 Hz, 3 d/wk) for four weeks. A second set was loaded at 40.1 +/- 0.3 N and the third set remained nonloaded. Tibial cortical bone formation and femur bone mineral density (BMD) were evaluated. With loading, bone formation was similarly elevated in loaded tibia of verapamil and control rats (P < 0.003). However, periosteal bone formation (P < 0.001) in the nonloaded tibia, and femoral diaphysis BMD (P < 0.04) were greater in verapamil rats than in controls. We conclude that verapamil, in the dose given, does not interfere with mechanical loading (30, 40 N) at the loaded site and that the voltage-dependent calcium channels, blocked by verapamil, are not significantly involved in the local bone response to increased strain in female rats. However, verapamil increased bone formation and BMD at nonloaded sites of loaded rats. Previously unknown systemic or regional factors associated with loading may explain the potential mechanisms for this interaction and need further investigation.
维拉帕米是一种钙通道阻滞剂，可在体外改变骨细胞内的钙浓度，而机械负荷可刺激钙通道。本研究的目的是检测全身应用维拉帕米对体内外部机械负荷引起的骨反应的影响。将雌性大鼠（5 - 6个月龄）分为六组。其中一半用维拉帕米处理（0.75毫克/毫升饮用水）12周。治疗8周后，用四点弯曲装置对右胫骨进行负荷。在一组维拉帕米组和对照组中，右胫骨以31.8±0.2牛（36次循环，2赫兹，每周3天）负荷4周。第二组以40.1±0.3牛负荷，第三组不负荷。评估胫骨皮质骨形成和股骨骨密度（BMD）。负荷后，维拉帕米组和对照组负荷的胫骨中骨形成均同样升高（P < 0.003）。然而，维拉帕米组大鼠未负荷的胫骨中的骨膜骨形成（P < 0.001）和股骨干BMD（P < 0.04）均高于对照组。我们得出结论，给予剂量的维拉帕米不会干扰负荷部位的机械负荷（30、40牛），并且被维拉帕米阻断的电压依赖性钙通道在雌性大鼠局部骨对增加应变的反应中不显著参与。然而，维拉帕米增加了负荷大鼠未负荷部位的骨形成和BMD。与负荷相关的先前未知的全身或局部因素可能解释这种相互作用潜在机制，需要进一步研究。
