TOLERABILITY OF ORAL BISPHOSPHONATES IN PATIENTS WITH OSTEOPOROSIS AND OTHER OSTEOPATHIES

Oral nitrogen containing bisphosphonates (NCB) are effective drugs to inhibit bone metabolism turnover in osteoporosis and other bone diseas es. Notwithstanding, some digestive disturbances create concern on the long term acceptance of the oral route. Side effects are mainly cause d by low absorption and poor solubility in digestive content. Therefor e the compound may precipitate and irritate the mucosas. Furthermore, the administered amount of a particular molecule, its intrinsic potenc y to irritate digestive walls and the degree of exposition to such sen sitive tissue are other facts that combined, may determine the clinica l tolerability. Thus, a single factor cannot predict the clinical tole rability. Pamidronate, alendronate and olpadronate are the main NCB un der clinical usage. Alendronate is 10 times more potent than pamidrona te but possesses a similar slight solubility (2.4 vs 3.0% W/V respecti vely). It also seems to be more (3 times fold) ulcerogenic in experime ntal assays. The current available pamidronate formulation protects fr om esophagus and gastric exposition. Up to now and until randomized cl inical trials be performed the selection of the most tolerated aminobi sphosphonate in clinical practice will depend on the interplay of many factors (table 1 shows a hypothetical view). Moreover, different pati ents may react dissimilarly depending on their sensitivity to a partic ular factor.Olpadronate is free-soluble (24% W/V), almost equipotent w ith alendronate (figure 1) and seems to lack relevant irritation poten tial, but clinical data is on its early phases and is still not availa ble. Micronization of the bisphosphonate preparation may be of help to improve tolerability as shown with newer pamidronate oral formulation s. The current clinical published data shows more or less the same saf ety profile for pamidronate (only when enteric coated capsules are use d) as alendronate, with more than 90% of patients complying with long term treatments. Anyway the trials are not entirely comparable as said before. Some other pamidronate formulations proved to be intolerable and have not been accepted. Identifying the many factors of oral NCB's digestive tolerability may help with their clinical management. And i n those countries where two compounds are available they may alternati vely be used in the sensitive patients. Finally, extra-digestive side effects, not commented in this article, should also be weighted when s electing a bisphosphonate.