Bone Abstracts

: Osteonecrosis of the jaws (ONJ) is a relatively new adverse effect associated with bisphosphonate therapy, but no causal association has been established. By definition, a patient is considered to suffer from ONJ if he has current or previous treatment with a bisphosphonate, exposed bone in the maxillofacial region that has persisted for more than 8 weeks and no history of radiation therapy to the jaws. It has been proposed that ONJ could be linked with impaired topical immune response due to the toxicity exerted by bisphosphonates on macrophages, further to their toxicity in osteoclasts. The aim of the present study was to test this theory and examine the effect of zolendronate administration in peripheral blood monocyte and NK-like cell populations.

Methods: In this pilot study, we included six breast cancer patients, on hormone therapy, who were treated with zolendronic acid for a period of at least 6 months and who did not receive chemotherapy for a period of at least 1 year. Monocytes (CD45+, CD14+CD23+, CD14+CD23−, CD14−CD23+, CD14+CD123+, CD14+CD123− and CD14−CD123+) and NK-like cells populations (CD45+CD3+, CD45+CD3-, CD45+CD16+CD56+, CD3+CD16+CD56+, CD3−CD16+CD56+, CD3+CD16+CD56− and CD19+CD45+) were examined (immune phenotype quantified sampling profile – IPQSP via flow cytometry and antibody-based fluorescence). The IPQSP was conducted prior to zolendronic acid infusion and 48 h after, on peripheral blood samples.

Results: In this preliminary clinical sample, we were able to detect a significant increase in CD14−CD123+ (Pearson’s χ², P=0.042), CD45+CD3− (P=0.004), CD3+CD16+CD56+ (P=0.036) and CD3-CD16+CD56+ (P=0.026) populations. We were also able to detect a significant decrease in the CD45+CD16+CD56+ population (P<0.0001).

Conclusions: We demonstrate changes in the monocyte and NK-like cell populations, following zolendronic acid administration in patients with breast cancer on hormone therapy. The effects of bisphosphonates in those cells may be causatively linked with the development of ONJ.