Denosumab Treatment Delays

The product information documents have been updated for denosumab medicines used in the treatment of osteoporosis. These revisions strengthen existing warnings regarding the risk of multiple vertebral fractures following treatment delay or discontinuation.

Bone metabolism is a dynamic process balancing activity between bone-forming osteoblasts and bone-resorbing osteoclasts. A key regulator of this process is the RANK/RANKL/OPG pathway. Denosumab binds to RANKL, preventing it from activating the RANK receptor. This inhibits osteoclast formation and activation, effectively reducing bone resorption.

However, accelerated bone turnover and rapid loss of bone mineral density can occur following discontinuation of denosumab. While the mechanism is not completely understood, denosumab may cause osteoclasts to fission into daughter cells, called osteomorphs. These cells accumulate during denosumab treatment and can quickly fuse to form functional osteoclasts once the inhibitory effect of denosumab is removed. This may explain the increased risk of multiple vertebral fractures, particularly in patients with a history of vertebral fracture.

Denosumab is administered subcutaneously every six months. Patients should be advised of the importance of adhering to the dosing schedule as dosing delays of just 30 days have been associated with a significant increase in fracture risk. If treatment must be stopped, Healthy Bones Australia recommends patients be started on a bisphosphonate within four weeks of the next scheduled denosumab dose.