Clodronate (
clodronic acid, dichloromethylene
bisphosphonate) is a
bisphosphonate which has demonstrated efficacy in patients with a variety of diseases of enhanced
bone resorption including Paget's disease, hypercalcaemia of
malignancy and osteolytic bone
metastases. In addition, early reports demonstrating potential efficacy of
clodronate in the treatment of
osteoporosis suggest a possible role in this debilitating disease. Short term
intravenous administration (usually 300 mg/day for 5 days) or longer courses of oral
clodronate (usually 1600 mg/day for 6 months) effectively reduced bone
pain and/or improved mobility in most patients with Paget's disease, and these effects persisted for up to 12 months after discontinuing
clodronate. When administered intravenously (300 mg/day for up to 12 days) to patients with malignant hypercalcaemia, serum
calcium levels declined significantly within 2 days of starting treatment and approximately 70 to 95% of patients became normocalcaemic. While there is less experience with
oral administration,
clodronate (800 to 3200 mg/day) achieved normocalcaemia in the majority of patients, usually within 1 week, and serum
calcium levels remained significantly reduced from baseline for up to 6 months with continued treatment.
Clodronate is clearly superior to placebo and, based on a retrospective analysis, appears to produce greater and more sustained reductions in serum
calcium levels than
calcitonin in patients with malignant hypercalcaemia. The few available prospective comparative trials showed that
clodronate is at least as effective as
etidronate, but comparisons with
alendronate and
pamidronate produced results of questionable clinical relevance because of low
bisphosphonate dosages used in these trials. Nevertheless, single intravenous doses of
clodronate 600 mg or
alendronate 7.5 mg (both agents repeated on day 3 if necessary) were comparable in efficacy, whereas a single intravenous dose of
pamidronate 30 mg was more effective than a single intravenous dose of
clodronate 600 mg. Normocalcaemic patients with osteolytic bone
metastases due to advanced
breast cancer experienced significant reductions in the number of episodes of hypercalcaemia and terminal hypercalcaemia, incidence of vertebral fractures and overall rate of morbid events, including the need for
radiotherapy to treat bone-related
pain, following treatment with
clodronate 1600 mg/day for 3 years in a large placebo-controlled study. A similar large placebo-controlled trial in patients with
multiple myeloma demonstrated that
clodronate 2400 mg/day orally for 2 years significantly reduced progression of osteolytic bone lesions. Follow-up data from clinical trials revealed that the effects on development of fractures and hypercalcaemia persisted for at least 12 months after the
drug was discontinued.(ABSTRACT TRUNCATED AT 400 WORDS)