title: Increased CD14+ and decreased CD14- populations of monocytes 48 h after zolendronic acid infusion in breast cancer patients.
abstract: It has been proposed that bisphosphonates cause osteonecrosis of the jaws through impairment of the monocyte population function and proliferation. Such changes have been confirmed in jaw tissues, ex vivo. In this clinical study, we report for the first time a similar pattern of changes in peripheral blood monocytes.
  
  
  
  The aim of this study is to examine the effect of zolendronic acid administration in the peripheral blood white cell population, seeking a plausible pathophysiological link between bisphosphonates and osteonecrosis of the jaw.
  
  
  
  Twenty-four breast cancer patients, under zolendronic acid treatment for bone metastasis, were included. Peripheral blood samples were obtained prior to and 48 h following zolendronic acid administration. Flow cytometry gated at leukocyte, monocyte, and the granulocyte populations for the CD4/CD8/CD3, CD3/CD16+56/CD45/CD19, CD14/CD123, and CD14/23 stainings were performed.
  
  
  
  We were able to record a number of changes in the white cell populations after 48 h of zolendronic acid administration. Most importantly, in the monocyte populations, we were able to detect statistically significant increased populations of CD14+/CD23+ (p = 0.038), CD14+/CD23- (p = 0.028), CD14+/CD123+ (p = 0.070, trend), and CD14+/CD123- (p = 0.043). In contrast, statistically significant decreased populations of CD14-/CD23+ (p = 0.037) and CD14-/CD123+ (p = 0.003) were detected.
  
  
  
  Our results provide evidence supporting the hypothesis that bisphosphonate administration modifies the monocyte-mediated immune response. An increase of CD14+ peripheral blood monocyte (PBMC) populations along with a decrease of CD14- PBMC populations has been recorded. The latter finding is in accordance with limited-currently existing-evidence and warrants further elucidation.
authors.affiliation: Department of Pharmacology, Clinical Pharmacology, Faculty of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece. akyrgidi@gmail.com.|Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Aristotle University of Thessaloniki, Thessaloniki, Greece. akyrgidi@gmail.com.
authors.forename: A
authors.identifier: http://orcid.org/0000-0003-3896-0309
authors.initials: A
authors.lastname: Kyrgidis
authors.affiliation: Laboratory of Clinical and Molecular Endocrinology, 1st Department of Internal Medicine, AHEPA University Hospital, Thessaloniki, Greece.
authors.forename: M P
authors.initials: MP
authors.lastname: Yavropoulou
authors.affiliation: Department of Neurology, AHEPA University Hospital, Thessaloniki, Greece.
authors.forename: R
authors.initials: R
authors.lastname: Lagoudaki
authors.affiliation: 3rd Department of Clinical Oncology, Theagenio Cancer Hospital, Thessaloniki, Greece.
authors.forename: C
authors.initials: C
authors.lastname: Andreadis
authors.affiliation: Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: K
authors.initials: K
authors.lastname: Antoniades
authors.affiliation: Department of Pharmacology, Clinical Pharmacology, Faculty of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: D
authors.initials: D
authors.lastname: Kouvelas
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D001859:Bone Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000556:secondary*; D001943:Breast Neoplasms / Q000276:immunology*; D002469:Cell Separation / Q000379:methods; D004164:Diphosphonates / Q000494:pharmacology*; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D016130:Immunophenotyping; D007962:Leukocytes / Q000187:drug effects / Q000276:immunology; D018950:Lipopolysaccharide Receptors / Q000097:blood*; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology; D011446:Prospective Studies; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D018950:Lipopolysaccharide Receptors; D000077211:Zoledronic Acid
keywords: Bisphosphonates; CD14; Denosumab; Infection risk; Macrophages; Osteoclasts; Osteonecrosis of the jaws