title: Renal tumors in male rats following long-term administration of bazedoxifene, a tissue-selective estrogen receptor modulator.
abstract: Bazedoxifene acetate (BZA) is a selective estrogen receptor modulator that is approved in a number of countries for the prevention and/or treatment of osteoporosis in postmenopausal women. To assess carcinogenic potential, BZA was administered ad libitum in the diet to male and female rats for 2 years. The achieved mean dosages of BZA were approximately 1.31 to 56.9 mg/kg/day at dietary concentrations of 0.003% to 0.1%. BZA treatment resulted in a reduction and a delayed onset in total tumor burden in both male and female rats. Survival rates were enhanced due to decreased pituitary and mammary tumors and decreased body weight gain in BZA-treated animals compared with controls. In male rats only, an increase in renal tubular tumors was observed. The greater increase in tumor incidence in male rats given BZA was associated with the increased survival and increased time for development of late onset tumors. These findings are consistent with a non-genotoxic mechanism, unique to male rats, that involves test article-induced corticomedullary mineralization, renal tubular injury, and exacerbation of naturally occurring chronic progressive nephropathy in aged male rats that led to a sequela of proliferative changes and tumor formation.
authors: 1Drug Safety Research & Development, Pfizer, Groton, Connecticut, USA.
authors: Rick
authors: R
authors: Perry
authors: Carol A
authors: CA
authors: Thompson
authors: J Nicole
authors: JN
authors: Earnhardt
authors: David J
authors: DJ
authors: Wright
authors: Steven
authors: S
authors: Bailey
authors: Barry
authors: B
authors: Komm
authors: Mark A
authors: MA
authors: Cukierski
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D015197:Carcinogenicity Tests; D004435:Eating / Q000187:drug effects; D005260:Female; D007211:Indoles / Q000008:administration & dosage / Q000633:toxicity*; D007680:Kidney Neoplasms / Q000139:chemically induced*; D008297:Male; D051381:Rats; D051436:Renal Insufficiency, Chronic / Q000139:chemically induced; D020845:Selective Estrogen Receptor Modulators / Q000008:administration & dosage / Q000633:toxicity*; D016019:Survival Analysis
chemical_list: D007211:Indoles; D020845:Selective Estrogen Receptor Modulators; C447119:bazedoxifene
keywords: Bazedoxifene; chronic progressive nephropathy; non-genotoxic carcinogenicity.; renal tumors; tissue selective estrogen