Efficacy of Denosumab Therapy Following Treatment with Bisphosphonates in Women with Osteoporosis: A Cohort Study

Abstract

Denosumab is a human monoclonal antibody that neutralizes RANKL, a cytokine able to interact with the RANK receptor on preosteoclasts and osteoclasts, decreasing their recruitment and differentiation, leading to a decreased bone resorption. The aim of this observational real-life study was to analyze adherence to denosumab therapy and assess its efficacy in increasing bone mineral density (BMD) and modulating biochemical skeletal markers following previous treatments with bisphosphonates in a group of post-menopausal women with osteoporosis. Women were recruited in the specialized center from March 2012 to September 2019. Biochemical markers were recorded at baseline and every six months prior to subsequent drug injection. Dual X-ray absorptiometry was requested at baseline and after 18/24 months. Comparing BMD at baseline and after denosumab therapy in naive patients and in those previously treated with bisphosphonates, a positive therapeutic effect was observed in both groups. The results of our real-life study demonstrate, as expected, that BMD values significantly increased upon denosumab treatment. Interestingly, denosumab showed an increased efficacy in patients previously treated with bisphosphonates. Moreover, biochemical markers data indicate that osteoporotic patients, without other concomitant unstable health conditions, could be evaluated once a year, decreasing the number of specialistic center access.

Mechanisms, Diagnosis and Treatment of Bone Metastases

“…They improve bone metabolism, suppress the formation, growth and spread of bone metastases and have an analgesic effect [ 241 ]. While denosumab is currently being tested in combination with bisphosphonates for the treatment of bone metastases in breast and prostate cancer patients [ 242 , 243 ], recent phase III clinical trials adding zoledronic acid to standard backbone chemotherapy of both osteosarcoma and Ewing sarcoma failed to improve patient survival [ 244 , 245 ]. Although bisphosphonates and denosumab inhibit osteoclast activity and tumor-induced osteolysis, they do not restore bone formation.…”