INTRAVENOUS ADMINISTRATION OF CLODRONATE IN NORMOCALCEMIC PATIENTS WITH TUMORAL BONE METASTASES - EFFECT ON SERUM PARATHORMONE AND BIOCHEMICAL MARKERS OF BONE TURNOVER

Ten normocalcemic patients with multiple osteolytic bone metastases due to various types of cancer were treated with 300 mg/day of sodium clodronate given intravenously as a three-hour infusion for 20 days. Our findings showed that clodronate administration caused a significant decrease in serum calcium levels after ten and 20 days of therapy (P < 0.002). Urinary calcium and hydroxyproline excretion were also reduced after ten and 20 days of treatment (P < 0.002). Serum parathormone midmolecule levels increased significantly after the first period of clodronate administration (P < 0.02) and more markedly ten days later (P < 0.002). Serum osteocalcin was significantly increased after 20 days of treatment (P < 0.05), but not after the first period of ten days. The rise in serum osteocalcin may be attributed to the reduction of serum calcium and to the consequent hyperparathyroidism. The increase in serum osteocalcin may be considered the result of osteoblast stimulation following an adequate period of therapy with clodronate.