Researchers determine whether discontinuing denosumab, a drug used for osteoporosis treatment, leads to an increased rate of vertebral fracture.
Denosumab is a drug typically used to treat osteoporosis and certain kinds of bone tumors. In 2009, a large clinical trial showed that denosumab was highly effective in preventing vertebral and hip fractures in postmenopausal women. As a result of this study, denosumab quickly became a treatment for women with osteoporosis.
Denosumab prevents osteoclasts from breaking down bones
Denosumab is effective because it prevents osteoclasts from developing. Osteoclasts are a specialized kind of cell that break down bones. By preventing the formation of these cells, denosumab prevents bone breakdown.
Patients discontinuing denosumab may be at an increased risk of vertebral fracture
Although researchers initially concluded that denosumab could be safely taken for 10 years, most patients quit using the drug within two years. In CMAJ, Symonds and Kline report on an alarming new discovery that patients who discontinue denosumab are at an increased risk of vertebral fracture.
Patients from the initial clinical trial rapidly lost bone density after discontinuing the medication, and a systematic review assessing 24 patients who discontinued denosumab showed an average of 4.7 vertebral fractures just a few months after discontinuing the drug. These overall rates are similar to those of patients who took a placebo during the clinical trial but, worryingly, over 60% of patients who had taken denosumab had multiple fractures, compared to only about 40% of patients who had taken a placebo.
Unwise to discontinue treatment once it has started
Symonds and Kline, as well as other researchers, suggest that once a patient starts denosumab treatment it is unwise to discontinue treatment. Patients who plan to discontinue denosumab should discuss with their doctor the possibility of immediately starting new osteoporosis treatment with other kinds of osteoporosis medications, such as a weekly oral dose of bisphosphonate, or should be prepared to continue taking denosumab indefinitely.
More research needed to understand why the effects are fast and devastating
Further research will be needed to determine why the effects of discontinuing denosumab are so quick-acting and devastating. For now, it is likely that the way in which denosumab works, by turning off osteoclasts without actually killing these specialized cells, results in an acute rebound immediately upon cessation of treatment. This means that the osteoclasts are suddenly reactivated much more quickly, and to a greater degree, than under normal circumstances. For now, denosumab is considered safe as a continuous treatment for at least 10 to 12 years.
Written by C. I. Villamil
Reference: Symonds and Kline. Warning of an increased risk of vertebral fracture after stopping denosumab. 2018. CMAJ 190:E485-486.