Chapuy M C, Meunier P J, Alexandre C M, Vignon E P
J Clin Invest. 1980 May;65(5):1243-7. doi: 10.1172/JCI109780.
The aim of this study was to determine the ability of disodium dichloromethylene diphosphonate (Cl2MDP) to reduce the hypercalcemia secondary to skeletal metastases and induced by stimulation of bone resorption by malignant cells. Five patients with hypercalcemia due to bone metastases of breast or renal cancer were treated orally for 4 wk with 3,200 mg of Cl2MDP and 4 wk with a placebo in a double blind, crossover study. During the Cl2MDP period of administration four patients experienced a rapid and significant decrease in serum calcium and urinary calcium excretion together with an increase in alkaline phosphatase. In the remaining patient who developed a sudden paraplegia at the onset of the therapy followed by a marked increase in serum calcium levels and urinary calcium excretion, Cl2MDP was able to reverse this worsening of hypercalcemia or to reduce serum and urinary calcium to normal values. For all patients, urinary hydroxyproline excretion was unchanged during the Cl2MDP period when compared with the prestudy or placebo periods. From these results, and because of the rapid relapse of hypercalcemia during the placebo period or after withdrawal of the treatment, we can conclude that Cl2MDP is capable of reducing excessive mobilization of calcium resulting from bone metastases.
本研究的目的是确定二氯亚甲基二膦酸二钠(Cl2MDP)降低继发于骨转移且由恶性细胞刺激骨吸收所诱导的高钙血症的能力。在一项双盲、交叉研究中,5例因乳腺癌或肾癌骨转移导致高钙血症的患者口服3200 mg Cl2MDP治疗4周,然后口服安慰剂治疗4周。在Cl2MDP给药期间,4例患者血清钙和尿钙排泄迅速且显著下降,同时碱性磷酸酶升高。在治疗开始时突然发生截瘫且血清钙水平和尿钙排泄显著增加的其余1例患者中,Cl2MDP能够逆转高钙血症的恶化或使血清和尿钙降至正常水平。对于所有患者,与研究前或安慰剂治疗期相比,Cl2MDP治疗期间尿羟脯氨酸排泄未发生变化。基于这些结果,并且由于在安慰剂治疗期或停药后高钙血症迅速复发,我们可以得出结论,Cl2MDP能够减少骨转移导致的钙过度动员。