The risk of subsequent osteoporotic fractures is decreased in subjects experiencing fracture while on denosumab: results from the FREEDOM and FREEDOM Extension studies
Bibliographic record
Abstract
This post-hoc analysis queried whether women experiencing fracture on denosumab indicates inadequate treatment response or whether the risk of subsequent fracture remains low with continuing denosumab. Results showed that denosumab decreases the risk of subsequent fracture and fracture sustained while on denosumab is not necessarily indicative of inadequate treatment response. INTRODUCTION: This analysis assessed whether a fracture sustained during denosumab therapy indicates inadequate treatment response and if the risk of a subsequent fracture decreases with continuing denosumab treatment. METHODS: In FREEDOM, a clinical trial to evaluate the efficacy and safety of denosumab, postmenopausal women with osteoporosis were randomized to placebo or denosumab for 3 years. In the 7-year FREEDOM Extension, all participants were allocated to receive denosumab. Here we compare subsequent osteoporotic fracture rates between denosumab-treated subjects during FREEDOM or the Extension and placebo-treated subjects in FREEDOM. RESULTS: During FREEDOM, 438 placebo- and 272 denosumab-treated subjects had an osteoporotic fracture. Exposure-adjusted subject incidence per 100 subject-years was lower for denosumab (6.7) vs placebo (10.1). Combining all subjects on denosumab from FREEDOM and the Extension for up to 10 years (combined denosumab), 794 (13.7%) had an osteoporotic fracture while on denosumab. Of these, one or more subsequent fractures occurred in 144 (18.1%) subjects, with an exposure-adjusted incidence of 5.8 per 100 subject-years, similar to FREEDOM denosumab (6.7 per 100 subject-years) and lower than FREEDOM placebo (10.1 per 100 subject-years). Adjusting for prior fracture, the risk of having a subsequent on-study osteoporotic fracture was lower in the combined denosumab group vs placebo (hazard ratio [95% CI]: 0.59 [0.43-0.81]; P = 0.0012). CONCLUSIONS: These data demonstrate that denosumab decreases the risk of subsequent fracture and a fracture sustained while on denosumab is not necessarily indicative of inadequate treatment response.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.009 | 0.009 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.005 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".