ArticleThe Journal of clinical endocrinology and metabolism2025
Fragility of Evidence for the Efficacy of Anti-Fracture Medications.
Article in The Journal of clinical endocrinology and metabolism, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
1 citing paper in PubMed.
- Fragility of Evidence for the Efficacy of Anti-Fracture Medications.The Journal of clinical endocrinology and metabolism · 2025Article
Corrections and comments
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Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
contextA P value and statistical significance, conventionally considered for assessing an intervention's effectiveness, are usually misused and misinterpreted.
objectiveTo quantify fragility of randomized controlled trial (RCT) evidence for anti-fracture efficacy.
methodsThis retrospective analysis included 27 phase 3/4 RCTs in high-impact medical journals which assessed anti-fracture efficacy, allocated participants in a 1:1 ratio to pharmacological intervention or control, and reported a statistically significant result. Fragility of the results were assessed using the Fragility Index (FI) and Fragility Quotient (FQ). FI is the minimum number of participants in a positive analysis result for whom reversing the reported status would eliminate statistical significance, while FQ is a function of FI to the sample size.
resultsThe median FI was 9 (IQR: 4, 19), indicating that adding 9 fracture patients (∼0.51% of the study size) to the intervention group would eliminate the documented evidence of anti-fracture efficacy. Notably, the number of participants lost to follow-up exceeded the corresponding FI in 60% of analyses. The most robust evidence for anti-fracture efficacy was documented for romosozumab (FI: 19.5; IQR: 7.0, 31.5); whereas the least found for denosumab (4; 3, 17) and calcium/vitamin D supplementation (7.0; 2.3, 16.8). Anti-fracture efficacy evidence improved among the results that considered fractures the primary endpoint measure (14; 11, 33) or those with P value < .001 (26; 18, 42).
conclusionThe existing RCT evidence of anti-fracture efficacy is highly fragile. The FI, its comparison with loss to follow-up and FQ should be incorporated into clinical guideline development and doctor-patient risk communication.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.