Denosumab

What it is

Denosumab is used to treat osteoporosis and reduce fracture risk, and (at a higher, different regimen) in some cancer-related bone disease. In osteoporosis it is given as an injection twice a year.

How it works

It is an antibody that blocks a signal (RANK ligand) the body uses to make and activate the cells that break down bone. With those bone-resorbing cells suppressed, bone density rises and fracture risk falls — but because the effect depends on the drug being present, it wanes quickly once doses stop.

In practice

In practice denosumab (at osteoporosis dose) is a convenient six-monthly injection that reduces fracture risk and suits people who cannot take or tolerate bisphosphonates, including in significant renal impairment. The single most important safety message is that it must not be delayed or stopped without a plan: when denosumab is discontinued, its effect reverses rapidly and bone turnover rebounds, which has caused clusters of spontaneous vertebral fractures — so doses are kept on schedule and, if it is ever stopped, a bisphosphonate is given to "lock in" the benefit. Calcium and vitamin D must be replete before each dose because it can cause low calcium, particularly in kidney impairment. As with bisphosphonates, dental health is addressed first because of the rare risks of osteonecrosis of the jaw and atypical fractures.