Treatment withdrawal impact in post-menopausal osteoporosis

New European data released at the EULAR 2024 Congress echo findings from the US showing that long-term discontinuation of bisphosphonates is associated with increased fracture risk in post-menopausal women with osteoporosis.

Bisphosphonates are the recommended first-line treatment in post-menopausal osteoporosis, with denosumab recommended second-line. Based on the length of clinical trials for bisphosphonates, these drugs are usually prescribed for three-to-five years, or longer in patients who remain at high  risk, and recent recommendations suggest long-term discontinuation after this period. However, data from the US suggest long-term discontinuation of bisphosphonates is associated with increased fracture risk. Until now, similar data from Europe have been lacking.

These new data from a case-control cohort study of over 128,000 women included in the French national claim database charted the incidence of long-term discontinuation of bisphosphonates – either oral or intravenous formulations – and denosumab among women with post-menopausal osteoporosis. The study also compared the risk of fragility fractures in women with long-term discontinuation with the risk in women continuing treatment.

Overall, 55.1 per cent, 68.9 per cent, and 42.5 per cent of women prescribed oral bisphosphonates, intravenous bisphosphonates, or denosumab had at least one long-term discontinuation recorded. These discontinuations typically happened in a woman’s mid-to-late 70s, and after a mean treatment duration of 3.7-to-4.8 years.

Crucially, when analysed by calendar year there was an upward trend in the incidence of long-term discontinuations, increasing from 1.6-to-17.6 per cent in 2015 to 12.1-to-29.5 per cent in 2020. Compared with continuous treatment, long-term discontinuation increased the risk of fragility fracture by 12.4 per cent and 92.3 per cent for those stopping bisphosphonates or denosumab, respectively.

This increased risk was observed for almost all fracture sites, with the exception of fractures in the distal forearm in women taking oral bisphosphonates. The highest increase was seen in hip fractures, with increases of 19.0 per cent, and 108.3 per cent among women with long-term discontinuation of bisphosphonates or denosumab, respectively. No significant differences were seen between women with long-term discontinuation versus continuous treatment of intravenous bisphosphonates. The trends in occurrence of fragility fracture did not change when death was included as a competing event.

These findings are important for several reasons. Firstly, while discontinuation of denosumab is not recommended, 42.5 per cent of women in the study stopped denosumab for at least one year, with a resultant doubling of fracture risk. Furthermore, the increased fracture risk observed after treatment discontinuation differed for oral versus intravenous bisphosphonates. This may warrant further investigation and clarification in the guidelines to ensure optimal management of women with post-menopausal osteoporosis in routine clinical practice.

Reference: Laborey M, et al. Risk of fragility fracture after long-term discontinuation of osteoporosis treatment in post-menopausal osteoporosis women in France: A population-based study conducted on the nationwide claim database (SNDS). Presented at EULAR 2024; OP0035. Ann Rheum Dis 2024; doi: 10.1136/annrheumdis-2024-eular.2841.