Increased CD14+ and decreased CD14− populations of monocytes 48 h after zolendronic acid infusion in breast cancer patients
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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.
KeywordsBisphosphonates Denosumab Osteonecrosis of the jaws Osteoclasts Macrophages Infection risk CD14
AK, MY, and RL made substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; AK, MY, RZ, CA, KA, and DK participated in drafting the manuscript or revising it critically for important intellectual content; AK, MY, RZ, CA, KA, and DK approved the final version of the submitted manuscript and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Compliance with ethical standards
The study was further approved by the Ethics Committee of the Theagenio Cancer Hospital.
Conflicts of interest
The study was supported in part by the IKY Fellowships of Excellence for Postgraduate studies in Greece–Siemens Program, State Scholarships Foundation, Grant No. SR 229146. The funding source had no role in the study design, collection, analysis, and interpretation of the data, nor in the writing of the manuscript. A.K., M.Y., and R.L. had access to the raw data. The corresponding author had full access to all of the data and the final responsibility to submit for publication.
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