Clodronic acid formulations available in Europe and their use in osteoporosis: a review

Clodronic acid (Cl(2)-MBP [dichloromethylene bisphosphonic acid], clodronate) is a halogenated non-nitrogen-containing bisphosphonate with antiresorptive efficacy in a variety of diseases associated with excessive bone resorption. The drug is believed to inhibit bone resorption through induction of osteoclast Apoptosis, but appears also to possess anti-inflammatory and analgesic properties that contrast with the acute-phase and inflammatory effects seen with nitrogen-containing bisphosphonates. Clodronic acid has been shown to be effective in the maintenance or improvement of bone mineral density when given orally, intramuscularly or intravenously in patients with osteoporosis. Use of the drug is also associated with reductions in fracture risk. The intramuscular formulation, which is given at a dose of 100 mg weekly or biweekly, is at least as effective as daily oral therapy and appears more effective than intermittent intravenous treatment. Intramuscular clodronic acid in particular has also been associated with improvements in back pain. The drug is well tolerated, with no deleterious effects on bone mineralization, and use of parenteral therapy eliminates the risk of gastrointestinal adverse effects that may be seen in patients receiving bisphosphonate therapy.