The effect of sequential antiresorptive therapy after denosumab discontinuation on fracture risk: a systematic review and meta-analysis
BMC Musculoskeletal Disorders · 13 Oct 2026
† Impact is the editorial-priority score. All scores are out of 100. Clinical is a stored clinical-importance score from the earlier method; it has not been recalculated.
Why it matters
Denosumab discontinuation can trigger multiple vertebral fractures, so knowing to plan a bisphosphonate transition (often zoledronic acid) is directly relevant to fragility fracture care and exam questions on osteoporosis management.
The evidence
This systematic review and meta-analysis pooled 9 studies (4 randomised trials and 5 cohorts, 1886 patients, mostly postmenopausal women) looking at whether starting another bone drug, mainly a bisphosphonate, after stopping denosumab lowers the risk of rebound vertebral fractures. Compared with no treatment, placebo, or historical controls, sequential therapy roughly halved the risk of new vertebral fractures within about 12 months (risk ratio 0.46, 95% CI 0.23 to 0.89), with an estimated number needed to treat of about 20. Intravenous zoledronic acid gave the most consistent protection; oral alendronate and delayed starts did not reach significance, although differences between subgroups were not statistically confirmed.
Incidence of vertebral fractures within 12 months after denosumab discontinuation: Risk ratio 0.46 (95% CI 0.23 to 0.89; ratio). The interval favours the first group; the size of the benefit needs clinical interpretation.
Why this rigour score?
Meta-analysis (mixed designs)Design starting point: 42.6
Raised the score
- Prospectively registered+5.1
- Comprehensive literature search+3.4
Lowered the score
- Pools mixed study designs−3.4
Methods at a glance
Recorded assessment- Comprehensive literature searchMet
- Risk of bias assessedMet
- Bias considered in synthesisMet
- Publication bias assessedMet
- Study exclusions justifiedNot met
- Prospective registrationMet
Not reported does not mean not done. Checks have different weights; this is not a count of boxes ticked.
See the full score breakdown
- Study design starting point
- 42.6
- Prospectively registered
- +5.1
- Pools mixed study designs
- −3.4
- Comprehensive literature search
- +3.4
- Risk of bias assessed in the included studies
- +3.4
- Risk of bias carried into the synthesis
- +2.5
- Publication bias assessed
- +2.5
- Final rigour score rounded
- 56 / 100
Study design sets the starting point and a ceiling of 82. Recorded methods then adjust the score. Points are shown to one decimal place; the final score uses unrounded values.
Checklist from the stored appraisal. “Not met” describes the recorded criterion; it does not always produce a deduction. This overview supports reading the full study.
For journal club
1.For a patient with a recent fragility fracture whom you are considering starting on denosumab, how should the need for a planned exit strategy (for example zoledronic acid at the end of therapy) affect your counselling and choice of first-line agent?
2.If a patient on denosumab misses a dose or wants to stop, how would you time and choose the follow-on agent, and what follow-up (bone turnover markers, imaging) would you arrange to watch for rebound vertebral fractures?
Original publication title
The effect of sequential antiresorptive therapy after denosumab discontinuation on fracture risk: a systematic review and meta-analysis