Olpadronate: a new amino-bisphosphonate for the treatment of medical osteopathies

Olpadronate is a nitrogenated bisphosphonate. Although it shares the therapeutic and pharmacological properties of pamidronate and alendronate, it has a greater dosage amplitude, more predictable effects and a greater digestive tolerability than other bisphosphates. Therefore, it may be more appropriate in the treatment of medical osteopathies, by both oral and parenteral routes of administration. According to various experimental and human models, the pharmacological potency of olpadronate is 5- to 10-times higher than that of pamidronate and close to that of alendronate. The two methyl groups bound to the nitrogen atom give the compound a high water solubility, which is about 8-times higher than that of the two other bisphosphonates. The lack of a terminal amino group in the side-chain of the molecule and the absence of crystallised forms of the compound in the digestive tract (due to its high water solubility) may avoid the potential for inducing oesophageal and gastrointestinal side-effects. These features may explain the high tolerability reported after the administration of doses of olpadronate (by the oral route) up to 5- to 10-times higher than the maximum tolerated dose of alendronate in Paget's bone disease and bone metastases, thus widening the possibilities for its clinical usage. In addition, initial pharmacokinetic studies suggest that olpadronate's oral bioavailability would fit into a confidence range of 2-4%, which contrasts with the erratic absorption shown by other highly potent bisphosphonates. The clinical efficacy demonstrated in preliminary studies in Paget's bone disease (including ultra-short treatments), and also in single-dose iv. therapy of hypercalcaemia of malignancies, renders olpadronate among the most promising bisphosphonate compounds, with potential use in the treatment of a variety of bone-involving diseases, such as osteoporosis, malignancies and rheumatoid arthritis.