title: [Tolerability of oral bisphosponates in patients with osteoporosis and other osteopathies].
abstract: Oral nitrogen containing bisphosphonates (NCB) are effective drugs to inhibit bone metabolism turnover in osteoporosis and other bone diseases. Notwithstanding, some digestive disturbances create concern on the long term acceptance of the oral route. Side effects are mainly caused by low absorption and poor solubility in digestive content. Therefore the compound may precipitate and irritate the mucosas. Furthermore, the administered amount of a particular molecule, its intrinsic potency to irritate digestive walls and the degree of exposition to such sensitive tissue are other facts that combined, may determine the clinical tolerability. Thus, a single factor cannot predict the clinical tolerability. Pamidronate, alendronate and olpadronate are the main NCB under clinical usage. Alendronate is 10 times more potent than pamidronate but possesses a similar slight solubility (2.4 vs 3.0% W/V respectively). It also seems to be more (3 times fold) ulcerogenic in experimental assays. The current available pamidronate formulation protects from esophagus and gastric exposition. Up to now and until randomized clinical trials be performed the selection of the most tolerated aminobisphosphonate in clinical practice will depend on the interplay of many factors (table 1 shows a hypothetical view). Moreover, different patients may react dissimilarly depending on their sensitivity to a particular factor. Olpadronate is free-soluble (24% W/V), almost equipotent with alendronate (figure 1) and seems to lack relevant irritation potential, but clinical data is on its early phases and is still not available. Micronization of the bisphosphonate preparation may be of help to improve tolerability as shown with newer pamidronate oral formulations. The current clinical published data shows more or less the same safety profile for pamidronate (only when enteric coated capsules are used) 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 in those countries where the two compounds are available they may alternatively be used in the sensitive patients. Finally, extra-digestive side effects, not commented in this article, should also be weighted when selecting a bisphosphonate.
authors.affiliation: Instituto de Investigaciones Metabólicas (IDIM), Buenos Aires, Argentina.
authors.forename: R
authors.initials: R
authors.lastname: Spivacow
authors.forename: E J
authors.initials: EJ
authors.lastname: Roldán
authors.forename: D
authors.initials: D
authors.lastname: Zanetti
authors.forename: E
authors.initials: E
authors.lastname: Piccinni
authors.forename: J R
authors.initials: JR
authors.lastname: Zanchetta
mesh_terms: D000328:Adult; D001851:Bone Diseases, Metabolic / Q000188:drug therapy*; D004164:Diphosphonates / Q000009:adverse effects*; D004361:Drug Tolerance; D005753:Gastric Mucosa / Q000187:drug effects; D005767:Gastrointestinal Diseases / Q000139:chemically induced*; D006801:Humans; D010024:Osteoporosis / Q000188:drug therapy*; D012995:Solubility
chemical_list: D004164:Diphosphonates