Bisphosphonate stimulation of osteoblasts and osteoblastic metastasis as a mechanism of hypocalcaemia

Bisphosphonates are used in the oncological setting to treat and prevent skeletal-related events and preserve bone mineral density. Bisphosphonates also possess a hypocalcaemic effect. When undesired, hypocalcaemia can result in increased morbidity and complications. The currently understood mechanism of bisphosphonate-induced hypocalcaemia is by osteoclast inhibition. The effect of bisphosphonates on osteoblasts is less well understood. Laboratory studies demonstrate that bisphosphonates increase osteoblast and osteoblastic metastases maturation, activity and bone mineralization. We hypothesize that where large populations of osteoblasts exist increased mineralization may result in hypocalcaemia. Consequently patients with bone-metastatic prostate cancer may be more susceptible to symptomatic hypocalcaemia following bisphosphonate therapy. We are currently designing a study to investigate our hypothesis and to identify the risk factors of hypocalcaemia.