Taube T, Kylmälä T, Lamberg-Allardt C, Tammela T L, Elomaa I
Department of Radiotherapy and Oncology, University of Helsinki, Finland.
Eur J Cancer. 1994;30A(6):751-8. doi: 10.1016/0959-8049(94)90287-9.
57 patients with advanced prostate cancer and a failure of prior hormonal treatment were selected for a double-blind placebo-controlled trial, in which they were randomly allocated to receive either clodronate (C) or placebo concomitantly with the basic cancer treatment, estramustine phosphate (E) (560 mg daily). The treatment was started intravenously with 300 mg of C or placebo in 5 consecutive days, and thereafter maintained orally with 1600 mg of C or identical placebo daily for 3 months. Bone biopsies were taken at admission and at 3 months. Measurements of serum calcium, phosphate, alkaline phosphatase, prostate-specific antigen and creatinine were made at the time of both bone biopsies and at 1 month. Serum intact parathyroid hormone and vitamin D metabolites were measured at admission and at 3 months. Because of several discontinuations, the study groups at final analysis comprised 20 patients taking E + C and 19 patients taking E and placebo. Bone resorption, as judged by eroded surface and osteoclast number, was markedly increased especially in biopsies taken from tumour-involved bone. Treatments with E + C or E both induced a significant decrease in bone resorption, but were associated with the development of hypocalcaemia, secondary hypoparathyroidism, hypophosphataemia and severe impairment of mineralisation of newly formed bone, i.e. osteomalacia. Since the patients were not vitamin D deficient, we conclude that osteomalacia resulted from a relative deficiency of calcium and phosphate. The transiency of pain relief achieved with anti-resorptive agents in the treatment of bone metastases from prostate cancer may be due to the development of osteomalacia.
57例晚期前列腺癌且先前激素治疗失败的患者被选入一项双盲安慰剂对照试验，在该试验中，他们被随机分配接受氯膦酸盐（C）或安慰剂，同时接受基础癌症治疗磷酸雌莫司汀（E）（每日560毫克）。治疗开始时静脉注射300毫克C或安慰剂，连续5天，此后口服维持，每日1600毫克C或相同安慰剂，持续3个月。在入院时和3个月时进行骨活检。在两次骨活检时和1个月时测量血清钙、磷、碱性磷酸酶、前列腺特异性抗原和肌酐。在入院时和3个月时测量血清完整甲状旁腺激素和维生素D代谢产物。由于几例患者退出，最终分析时研究组包括20例服用E + C的患者和19例服用E和安慰剂的患者。根据侵蚀表面和破骨细胞数量判断，骨吸收明显增加，尤其是在取自肿瘤累及骨的活检标本中。E + C或E治疗均导致骨吸收显著降低，但与低钙血症、继发性甲状旁腺功能减退、低磷血症以及新形成骨矿化严重受损（即骨软化症）的发生有关。由于患者不存在维生素D缺乏，我们得出结论，骨软化症是由钙和磷相对缺乏所致。抗吸收剂在治疗前列腺癌骨转移时实现的疼痛缓解短暂性可能归因于骨软化症的发生。
