THE EFFECT OF CLODRONATE ON BONE IN METASTATIC PROSTATE-CANCER - HISTOMORPHOMETRIC REPORT OF A DOUBLE-BLIND RANDOMIZED PLACEBO-CONTROLLED STUDY

57 patients with advanced prostate cancer and a failure of prior hormo nal treatment were selected for a double-blind placebo-controlled tria l, in which they were randomly allocated to receive either clodronate (C) or placebo concomitantly with the basic cancer treatment, estramus tine phosphate (E) (560 mg daily). The treatment was started intraveno usly 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. Measure ments of serum calcium, phosphate, alkaline phosphatase, prostate-spec ific antigen and creatinine were made at the time of both bone biopsie s and at 1 month. Serum intact parathyroid hormone and vitamin D metab olites were measured at admission and at 3 months. Because of several discontinuations, the study groups at final analysis comprised 20 pati ents taking E+C and 19 patients taking E and placebo. Bone resorption, as judged by eroded surface and osteoclast number, was markedly incre ased especially in biopsies taken from tumour-involved bone. Treatment s 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 minera lisation of newly formed bone, i.e. osteomalacia. Since the patients w ere not vitamin D deficient, we conclude that osteomalacia resulted fr om a relative deficiency of calcium and phosphate. The transiency of p ain relief achieved with anti-resorptive agents in the treatment of bo ne metastases from prostate cancer may be due to the development of os teomalacia.