- Design
- Systematic review and meta-analysis, GRADE, mainly observational studies
- Population
- 683 adults who discontinued denosumab (6 studies)
- Primary outcome
- Incident vertebral fractures
- Effect
- RR 0.29 (0.14-0.59); multiple vertebral RR 0.08 (0.01-0.43)
A GRADE-assessed systematic review and meta-analysis pooled six studies of adults who stopped denosumab and then received alendronate or zoledronic acid, compared with no follow-on therapy or a SERM; 683 contributed to the primary analysis.
Bisphosphonate follow-on was associated with fewer vertebral fractures (RR 0.29, 95% CI 0.14-0.59), multiple vertebral fractures (RR 0.08, 0.01-0.43) and clinical vertebral fractures (RR 0.18, 0.07-0.49). The effect came mainly from comparisons with no treatment; comparisons with SERMs were few and not significant. Any fracture (RR 0.35, 0.10-1.24) and non-vertebral fracture were not significantly reduced. Certainty was low to very low.
Guidelines already recommend a bisphosphonate after denosumab, but in practice treatment often simply lapses when a patient moves, runs out of supply or is deprescribed. These pooled data put a size on what is lost.
Whenever denosumab ends, for whatever reason, a potent bisphosphonate should start, typically zoledronic acid around the time the next denosumab dose would have been due.
- Never stop denosumab without starting alendronate or zoledronic acid.
- Time zoledronic acid for about when the next denosumab dose would have been due.
- Check bone turnover markers or bone density after the switch where available.
- Longer denosumab courses may need more than one bisphosphonate dose.
Why it matters
It quantifies the fracture cost of letting denosumab lapse without follow-on therapy.
Don't overread it
Most studies were observational with low to very low certainty, and there was no significant reduction in non-vertebral fractures.
The statistics, in plain English
A relative risk of 0.29 means about 71% fewer vertebral fractures, but with only 683 patients and mostly observational data the true effect could be smaller. The wide interval for any fracture, 0.10 to 1.24, means that outcome is inconclusive.
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