title: The effect of bisphosphonate therapy on neutrophil function: a potential biomarker.
abstract: Bisphosphonate-related osteonecrosis of the jaws (BRONJ) occurs subsequent to intravenous and oral bisphosphonate exposure in a small subset of patients. The identification of the pathophysiologic mechanisms has not been fully elucidated. Evidence of concurrent bacterial colonization at sites of bone necrosis, previous reports of neutrophil-related complications in some patients taking some bisphosphonates, along with perturbed neutrophil function in bisphosphonate-treated mice, suggest an innate immune role in the development of BRONJ. This study investigated neutrophil function in BRONJ patients to determine if neutrophil functional defects may serve as a potential biomarker for BRONJ susceptibility. Two populations were studied: patients with BRONJ and those beginning intravenous pamidronate. Healthy control patients were used for comparison. Twenty-three patients with BRONJ and five patients who were beginning pamidronate therapy provided neutrophil samples from the mouth (oral rinses) and from blood. Neutrophils from the population of patients with BRONJ and from those post-pamidronate treatment showed lower reactive-oxygen species production and impaired chemotaxis relative to controls. These data suggest that a compromise in neutrophil function may be a potential biomarker for BRONJ susceptibility.
authors.affiliation: Department of Oral and Maxillofacial Surgery and Anaesthesia, University of Toronto, Ontario, Canada.
authors.forename: C L
authors.initials: CL
authors.lastname: Favot
authors.forename: C
authors.initials: C
authors.lastname: Forster
authors.forename: M
authors.initials: M
authors.lastname: Glogauer
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000032:analysis; D059266:Bisphosphonate-Associated Osteonecrosis of the Jaw / Q000097:blood / Q000503:physiopathology; D050071:Bone Density Conservation Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002633:Chemotaxis / Q000187:drug effects; D004164:Diphosphonates / Q000009:adverse effects / Q000627:therapeutic use*; D004198:Disease Susceptibility / Q000503:physiopathology; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa / Q000166:cytology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D010025:Osteoradionecrosis / Q000503:physiopathology; D000077268:Pamidronate; D010587:Phagocytosis / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000032:analysis; D016897:Respiratory Burst / Q000187:drug effects; D012463:Saliva / Q000166:cytology; D013482:Superoxide Dismutase / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D015415:Biomarkers; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D009240:N-Formylmethionine Leucyl-Phenylalanine; D013482:Superoxide Dismutase; D013755:Tetradecanoylphorbol Acetate; D000077268:Pamidronate