Follow-on osteoporosis therapy after denosumab discontinuation among Medicare beneficiaries

Denosumab is an effective osteoporosis therapy, but discontinuing treatment can result in rebound-associated fractures. Guidelines recommend starting follow-on osteoporosis therapy within 6 months of the last dose, but real-world practice is under-described. We found only 6.0% of patients initiated follow-on therapy within 1 year after denosumab discontinuation, suggesting many are at increased fracture risk.

We aimed to describe the incidence and predictors of follow-on osteoporosis therapy use for US Medicare beneficiaries who discontinued denosumab.

In this cohort study, we identified patients who initiated denosumab (60 mg) between 2010 and 2021 from a 20% random sample of Medicare beneficiaries. Denosumab discontinuation was defined as 60-day gap in use. During follow-up through 2022, we identified beneficiaries with follow-on osteoporosis therapy (i.e., oral and intravenous bisphosphonates, teriparatide, and abaloparatide) within 1 year after denosumab discontinuation. Multinomial logistic regression with marginal standardization was used to estimate risk ratios with 95% confidence limits for associations between covariates and follow-on therapy use after denosumab discontinuation.

Of 120,952 denosumab initiators, we identified 82,519 individuals (mean age = 79.1 years [SD = 7.2]; 90.3% female) who discontinued denosumab. Only 4912 (6.0%) individuals initiated follow-on therapy after discontinuation; mean time from discontinuation (last claim + 243 days) to follow-on therapy initiation was 3.3 months [SD = 3.4]. Alendronate (n = 3014; 3.7%), zoledronic acid (n = 687; 0.8%), and ibandronate (n = 581; 0.7%) were most common. Most people did not initiate follow-on therapy (43.9%) or reinitiated denosumab after a gap (41.3%), with 8.8% lost to follow-up. Younger age (vs. ≥ 85 years), female sex, prior osteoporosis therapy, and Having 1-2 denosumab claims (vs. longer therapy) before discontinuation were strong predictors of follow-on therapy initiation versus no follow-on therapy.

Many patients stopping denosumab do not receive follow-on therapy. Proactive follow-up and strong clinical communication would reduce treatment gaps and prompt follow-on therapy after discontinuation.