Dichloromethylene diphosphonate (
clodronate), a new compound, has powerful activity against osteoclasts and has been used successfully to treat
hypercalcemia associated with
cancer. We studied its effects on
calcium balance in patients with malignant osteolytic lesions. Ten normocalcemic patients with advanced metastatic
bone disease or myeloma were evaluated in a baseline 20-day balance and
calcium kinetic study. They were then randomized to a
clodronate or placebo regimen, treated intravenously for two weeks and orally for a month, and finally reevaluated in another 20-day balance and kinetic study, conducted while they were still receiving treatment. The results show that both
calcium balance and
calcium absorption increased from base line in the
clodronate group and that these changes were significantly different from those in the placebo group (mean change [+/- S.D.] in
calcium balance [
clodronate vs. placebo], 203.8 +/- 140.1 vs. -65.2 +/- 98.8 mg [5.1 +/- 3.5 vs. -1.6 +/- 2.5 mmol] of
calcium per day, P less than 0.01; change in
calcium absorption, 158.8 +/- 158 vs. -38.2 +/- 96.0 mg [4.0 +/- 4.0 vs. -1.0 +/- 2.4 mmol] per day, P less than 0.05). There was a marginal decrease in
bone resorption in the
clodronate group and no change in bone accretion. Our results suggest that
clodronate may be a useful adjuvant in managing metastatic
bone disease.