Osteoporosis Canada advises individuals on denosumab therapy to discuss their treatment with their physician prior to delaying therapy, stopping therapy or missing a scheduled dose.  

Denosumab (Prolia) has been shown to reduce the risk of fractures in postmenopausal women and men aged 50 years or older with osteoporosis.  It has also been approved for steroid induced bone loss.

Individuals who were in the FREEDOM study, which evaluated denosumab in comparison to placebo, were followed, and those who stopped denosumab had a subsequent loss of bone mineral density (BMD) and an increase in the risk of fracture (Bone JCEM 2011).

Analysis of the data from the FREEDOM study as well as the Extension trial of denosumab (where treatment was continued up to a total of 10 years) confirmed that stopping denosumab was associated with an increase in the rate of bone loss, as measured by bone turnover markers, which rose 3 months after missing a scheduled dose. 12 months after missing a scheduled dose of denosumab, BMD decreased back to the baseline (pre-treatment) level (Cummings JBMR 2017).

Individuals who had received at least 2 doses of denosumab or placebo, and stopped treatment but remained in the study for at least 7 months after the last dose, were reviewed.  In the 1,001 patients who stopped denosumab, the rate of spine fractures increased from 1.2/100 patient-years (while on treatment) to 7.1/100 patient-years, a similar rate to the placebo group. Patient years is a statistical measure used to express the time at risk. 7.1 spine fractures/100 patient-years means that if you followed 100 people for 1 year, on average you would see 7.1 spine fractures. Multiple (more than 1) spine fractures appeared to be more common in the group stopping denosumab than the group stopping placebo (3.4% vs 2.2%). The risk of having multiple (more than 1) spine fractures after stopping denosumab was higher in those people who had already experienced a spine fracture, and also in those who had rapid rates of bone loss. The rates of non-spine fractures were similar in those stopping denosumab and those stopping placebo (2.8% denosumab, 3.8% placebo) (Cummings et al JBMR 2017).

Due to the risk of BMD loss and spine fractures associated with denosumab discontinuation, it is important not to miss scheduled doses of denosumab once treatment has started. Patients need to be advised of the increased risk of bone loss and vertebral fracture when therapy is stopped.  If denosumab needs to be stopped, it should be replaced by an alternative osteoporosis medication to help prevent rapid bone loss and risk of fractures (Symonds CMAJ April 2018).

Osteoporosis Canada advises individuals on denosumab therapy to discuss their treatment with their physician prior to delaying therapy, stopping therapy or missing a scheduled dose.

1. Bone HG et al JCEM 2011:96:972-980
2. Cummings et al JBMR vol 33, No2, Feb 2018 pp 190-198
3. Symonds C, Kline G CMAJ 2018 April 23:190 pp E485-486