title: Reversible skeletal disease and high fluoride serum levels in hematologic patients receiving voriconazole.
abstract: We here investigate the occurrence of fluoride intake-associated alterations in patients with hematologic disease on triazol antifungal medication. Clinical, laboratory, and radiology data of overall 43 patients with hematologic malignancies taking voriconazole (n = 20), posaconazole (n = 8), and itraconazole (n = 4), and a hematologic patient control group (n = 11) are described. Bone pain and radiologic evidence of periostitis were exclusively observed in patients receiving long-term voriconazole. Cessation of treatment led to clinical improvement in all cases. In line with clinical evidence, fluoride serum concentration was elevated in patients receiving voriconazole (median, 156.5 μg/L; interquartile range, 96.8 μg/L; normal < 30 μg/L) but not in the other treatment groups (P < .001 for all comparisons vs voriconazole). We conclude that serum fluoride levels were elevated on average 5-fold above normal levels in hematologic patients receiving voriconazole. Clinically relevant skeletal disease was associated with renal insufficiency and above 10-fold elevated fluoride levels, and was reversible on termination of voriconazole treatment.
authors.affiliation: Division of Hematology, University Hospital Zurich, Zurich, Switzerland. bernhard.gerber@usz.ch
authors.forename: Bernhard
authors.initials: B
authors.lastname: Gerber
authors.forename: Roman
authors.initials: R
authors.lastname: Guggenberger
authors.forename: David
authors.initials: D
authors.lastname: Fasler
authors.forename: Gayathri
authors.initials: G
authors.lastname: Nair
authors.forename: Markus G
authors.initials: MG
authors.lastname: Manz
authors.forename: Georg
authors.initials: G
authors.lastname: Stussi
authors.forename: Urs
authors.initials: U
authors.lastname: Schanz
mesh_terms: D000328:Adult; D000935:Antifungal Agents / Q000627:therapeutic use*; D001847:Bone Diseases / Q000139:chemically induced* / Q000517:prevention & control*; D005260:Female; D005459:Fluorides / Q000097:blood*; D019337:Hematologic Neoplasms / Q000150:complications / Q000382:microbiology / Q000628:therapy*; D006801:Humans; D017964:Itraconazole / Q000627:therapeutic use; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000503:physiopathology*; D010522:Periostitis / Q000139:chemically induced; D011743:Pyrimidines / Q000627:therapeutic use; D012189:Retrospective Studies; D033581:Stem Cell Transplantation; D014184:Transplantation, Homologous; D014230:Triazoles / Q000627:therapeutic use; D065819:Voriconazole
chemical_list: D000935:Antifungal Agents; D011743:Pyrimidines; D014230:Triazoles; D017964:Itraconazole; C101425:posaconazole; D065819:Voriconazole; D005459:Fluorides