Weisbrode S E, Capen C C, Pendley C B
Am J Pathol. 1977 Oct;89(1):137-52.
Dichloromethylene diphosphonate (Cl2MDP) antagonized the action of vitamin D on bone in thyroparathyroidectomized rats by reducing the metabolic activity of osteoblasts and osteocytes and decreasing the number of osteoclasts. Ultrastructurally, osteoblasts in Cl2MDP-treated rats were interpreted to be less active in bone matrix synthesis. Osteocytes in Cl2MDP-treated rats were interpreted ultrastructurally to be inactive; there was no evidence of bone resorption when compared to osteocytes in rats given vitamin D alone. Abnormal osmiophilic densities in the pericellular bone matrix of rats given vitamin D alone were not present in rats given vitamin D and Cl2MDP. The ultrastructure of osteoclasts was unaltered by Cl2MDT. These cellular changes were associated with a decrease in serum calcium and increase in bone ash and magnesium concentration in rats given high levels (10 mg/kg) of Cl2MDP. Bone adenosine triphosphatase and alkaline phosphatase activities were not affected by Cl2MDP. These results suggest that Cl2MDP may limit the hypercalcemia of hypervitaminosis D by directly inhibiting bone cells in addition to its physicochemical action.
二氯亚甲基二膦酸盐（Cl2MDP）通过降低成骨细胞和骨细胞的代谢活性以及减少破骨细胞数量，拮抗了维生素D对甲状旁腺切除大鼠骨骼的作用。在超微结构上，经Cl2MDP处理的大鼠成骨细胞被认为在骨基质合成中活性较低。经Cl2MDP处理的大鼠骨细胞在超微结构上被认为是无活性的；与单独给予维生素D的大鼠的骨细胞相比，没有骨吸收的证据。单独给予维生素D的大鼠细胞周围骨基质中异常的嗜锇密度在给予维生素D和Cl2MDP的大鼠中不存在。Cl2MDT未改变破骨细胞的超微结构。这些细胞变化与给予高剂量（10 mg/kg）Cl2MDP的大鼠血清钙降低、骨灰和镁浓度增加有关。骨腺苷三磷酸酶和碱性磷酸酶活性不受Cl2MDP影响。这些结果表明，Cl2MDP除了其物理化学作用外，还可能通过直接抑制骨细胞来限制维生素D过多症的高钙血症。
