In a randomised trial, switching to zoledronate was associated with loss of bone density in the spine.

Denosumab improves bone-mineral density (BMD) and lowers fracture risk in people with osteoporosis. Indefinite therapy is usually recommended, because discontinuation is associated with rebound bone loss. But for patients who do stop using denosumab, does following up with a bisphosphonate lower risk for rebound bone loss?

In this randomised Taiwanese trial, 101 patients (median age, 72 years; 95% women) who had taken denosumab for two or more years were randomised to continue denosumab or to switch to intravenous zoledronate (single dose given six months after the last denosumab dose). After one year, total hip and femoral-neck BMD were similar in the two groups, but the zoledronate group’s median decline in spinal BMD was significantly greater than that of the denosumab- continuation group. Subgroup analysis showed that this difference was driven primarily by patients whose baseline denosumab duration was three or more years.

Comment: This study suggests that switching to zoledronate does not mitigate the risks of stopping denosumab, although switching might be a reasonable approach for patients whose duration of denosumab treatment was short. In my system, denosumab is prescribed mostly by specialists, but primary care physicians have an important role in deciding whom to refer. Before we make such referrals, we should emphasise to patients that indefinite therapy is generally recommended. In an accompanying editorial, the author provides some helpful context and advice for counselling and managing patients who want or need to stop the medication.

Sarah E. Post, MD, Lecturer in Medicine, Harvard Medical School; Internal Medicine Physician, Atrius Health, Boston, USA.

Lee C-C, et al. Zoledronate sequential therapy after denosumab discontinuation to prevent bone mineral density reduction: a randomized clinical trial. JAMA Netw Open 2024; 7: e2443899.
Watts NB. What to do when denosumab is stopped? JAMA Netw Open 2024; 7: e2443879.

This summary is taken from the following Journal Watch titles: General Medicine, Ambulatory Medicine.