The effect of clodronate on bone in metastatic prostate cancer. Histomorphometric report of a double-blind randomised placebo-controlled study.
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.
Taube
T
T
Department of Radiotherapy and Oncology, University of Helsinki, Finland.
Kylmälä
T
T
Lamberg-Allardt
C
C
Tammela
T L
TL
Elomaa
I
I
D000368:Aged; D000369:Aged, 80 and over; D001859:Bone Neoplasms / Q000556:secondary*; D001862:Bone Resorption / Q000517:prevention & control*; D001842:Bone and Bones / Q000187:drug effects*; D004002:Clodronic Acid / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D006801:Humans; D008297:Male; D008875:Middle Aged; D010012:Osteogenesis / Q000187:drug effects; D010018:Osteomalacia / Q000139:chemically induced; D011471:Prostatic Neoplasms / Q000473:pathology*
D004002:Clodronic Acid