Preclinical perspectives on bisphosphonate renal safety.
Renal insufficiency is not rare in cancer patients who may receive nephrotoxic medications as antineo-plastic agents or for comorbid conditions. Thus, the choice of a particular bisphosphonate for patients with metastatic bone disease should be based not only on efficacy but also on the risk for renal deterioration. Some i.v. bisphosphonates have been associated with occasional renal toxicity in the clinical setting. Preclinical studies have also shown that there may be considerable differences among bisphosphonate renal safety profiles. Comparative studies show variations in the risk for histopathologic damage and the ability to cause cumulative toxicity during intermittent dosing. Reasons for the differences among bisphosphonates are not fully understood; however, research shows that they may be influenced by pharmacokinetic properties such as renal tissue half-life or protein binding and intracellular potency. Further preclinical analyses are needed to confirm and evaluate differences among bisphosphonates.
Body
Jean-Jacques
JJ
Institut Jules Bordet, Université Libre de Bruxelles, 1 Rue Héger-Bordet, 1000 Brussels, Belgium. jj.body@bordet.be
Pfister
Thomas
T
Bauss
Frieder
F
D000818:Animals; D001706:Biopsy; D050071:Bone Density Conservation Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy / Q000556:secondary; D004164:Diphosphonates / Q000009:adverse effects / Q000627:therapeutic use*; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000473:pathology
D050071:Bone Density Conservation Agents; D004164:Diphosphonates