Changes in peripheral monocyte populations 48-72 hours after subcutaneous denosumab administration in women with osteoporosis.

Objectives: To examine the effect of denosumab administration in the peripheral blood white cell population, to further elucidate a plausible pathophysiological link between denosumab and osteonecrosis of the jaw.

Methods: Thirty women with osteoporosis, after denosumab treatment were included. Peripheral blood samples were obtained prior to and 48-72 hours following denosumab administration. Flow cytometry gated at the monocyte population for CD14/CD23/CD123/CD16 stainings were performed.

Results: We were able to record a number of changes in the monocyte populations between baseline and after denosumab administration. Most importantly, in the monocyte populations we were able to detect statistically significant increased populations of CD14+/CD23+ (p=0.044), CD14-/CD23+ (p=0.044), CD14+/CD123+ (p=0.011), CD14+/CD123- (p=0.011) and CD14-/CD16+ (p=0.028). In contrast, statistically significant decreased populations of CD14-/CD123+ (p=0.034), CD14+/CD16+ (p=0.037) and CD14+/CD16- (p=0.014) were detected.

Conclusions: Our results provide evidence supporting the hypothesis that denosumab administration modifies the monocyte mediated immune response in a manner similar to that of bisphosphonates. This may partly explain the trivial immunity changes recorded with denosumab.