Adami S, Zamberlan N
Cattedra di Reumatologia, University of Verona, Italy.
Drug Saf. 1996 Mar;14(3):158-70. doi: 10.2165/00002018-199614030-00003.
The bisphosphonates comprise a new class of drugs, and are increasingly being used to treat bone diseases characterised by increased osteoclastic bone resorption. These compounds are generally well tolerated, but toxicity may vary considerably from one compound to another. Dosages of etidronic acid above 800 mg/day impair the normal skeletal mineralisation and this may be associated with the appearance of fractures, but at the doses used for the treatment of osteoporosis, none of the bisphosphonates induce clinical or histological signs of impaired mineralisation. The skeletal half-life of bisphosphonates is of the order of several years, but this appears to be of little clinical consequence since the pharmacological effect is of relatively short duration. The mechanical properties of the skeleton of animals treated over long periods with high doses of various bisphosphonates have been shown to be perfectly preserved. However, in growing individuals, excess inhibition of bone remodelling might induce osteopetrotic-like alterations. When high doses of amino-bisphosphonates are given to patients who have never received bisphosphonate therapy, the patients may experience fevers up to 39 degrees C for 1 to 3 days, associated with transient haematological changes resembling a typical acute-phase response. Rapid intravenous injection of bisphosphonates at doses greater than 200 to 300 mg may cause severe renal failure; this can be prevented by slowing the rate of infusion (< 200 mg/h). Administration of high doses of bisphosphonates to patients with high bone turnover may induce a rapid and transient drop in serum calcium which is seldom symptomatic. The gastrointestinal absorption of bisphosphonates is low, and they must be taken without food. Oral amino derivatives may induce dose-related serious gastrointestinal lesions, with the sporadic appearance of erosive oesophagitis. Amino-bisphosphonate administration has been also associated with the sporadic occurrence of uveitis, scleritis and phlebitis and, in single cases, with irritative reactions at the skin, peritoneum and pericardium.
双膦酸盐类药物是一类新型药物，越来越多地用于治疗以破骨细胞性骨吸收增加为特征的骨疾病。这些化合物一般耐受性良好，但不同化合物的毒性可能有很大差异。依替膦酸剂量超过800mg/天会损害正常的骨骼矿化，这可能与骨折的出现有关，但在用于治疗骨质疏松症的剂量下，没有一种双膦酸盐会引起矿化受损的临床或组织学迹象。双膦酸盐的骨骼半衰期约为数年，但这似乎没有什么临床意义，因为其药理作用持续时间相对较短。长期用高剂量各种双膦酸盐治疗的动物骨骼的力学性能已被证明能得到完美保留。然而，在生长中的个体中，过度抑制骨重塑可能会诱发类骨质石化改变。当从未接受过双膦酸盐治疗的患者给予高剂量氨基双膦酸盐时，患者可能会出现高达39摄氏度的发热，持续1至3天，并伴有类似典型急性期反应的短暂血液学变化。快速静脉注射剂量大于200至300mg的双膦酸盐可能会导致严重肾衰竭；这可以通过减慢输注速度（<200mg/h）来预防。给骨转换率高的患者使用高剂量双膦酸盐可能会导致血清钙迅速短暂下降，很少出现症状。双膦酸盐的胃肠道吸收较低，必须空腹服用。口服氨基衍生物可能会引起与剂量相关的严重胃肠道病变，并偶发糜烂性食管炎。氨基双膦酸盐的使用还与葡萄膜炎、巩膜炎和静脉炎的偶发有关，在个别情况下，还与皮肤、腹膜和心包的刺激性反应有关。
