Clodronate is a second-generation
bisphosphonate of intermediate potency between
etidronate and aminobisphosphonates. It is an effective inhibitor of
bone resorption, but unlike
etidronate does not impair the mineralization of bone. Unlike
pamidronate, it can be given both intravenously and orally. There is wide experience in the use of
clodronate in the management of patients of
hypercalcemia. The most widely used therapeutic regimen is 300 mg intravenously repeated for 5 days or a single infusion of 1500 mg. Efficacy is nearly complete in patients with
myelomatosis, less complete in solid
tumors with
hypercalcemia but without skeletal
metastases, and intermediate in patients with solid
tumors in the presence of skeletal
metastases. Variations in effect appear to be due to differences in renal tubular reabsorption of
calcium between the three disorders. Placebo-controlled studies examining the effects of
clodronate on bone
pain in the absence of
hypercalcemia have shown significant decreases in the severity of bone
pain. These findings, coupled with the knowledge that suppression of
bone resorption persists for the
duration of treatment, has led to the long term use of oral doses of
clodronate to decrease the incidence of complications of osteolytic
bone disease. The long term control of
bone resorption with oral
clodronate has been demonstrated by double blind histologic studies. The ultimate arbiter of the value of
clodronate is whether it decreases the skeletal morbidity associated with
osteolysis. Double blind prospective controlled studies suggest that the incidence of bone
pain, fracture, and
hypercalcemia can be decreased significantly in patients with
breast carcinoma. In addition, the use of long term
clodronate in patients with
myelomatosis significantly decreases the progression of osteolytic bone lesions, the risk of fractures, and the incidence of
hypercalcemia. These studies have raised the possibility that
bone disease might be prevented in individuals at high risk. Double blind prospective studies in women with recurrent
breast carcinoma but no evidence of skeletal
metastases showed a small effect of
clodronate in decreasing the proportion of women developing metastatic disease. However, there was a large and significant decrease in the number of skeletal
metastases associated with a decrease in skeletal morbidity. These observations suggest that
clodronate may modify the natural history of the expression of skeletal disease, and thereby significantly improve the quality of life of affected patients.