Denosumab for prevention of fractures in men receiving androgen deprivation therapy (ADT) for prostate cancer (PC)
Bibliographic record
Abstract
5056 Background: ADT increases bone resorption, reduces bone mineral density (BMD), and increases fracture risk. Previously, we reported that denosumab, a fully human monoclonal antibody against RANKL, increased BMD and reduced the incidence of vertebral fractures in men with PC on ADT. We now describe in further detail the effects of denosumab on fractures at other skeletal sites. Methods: Men receiving ADT for nonmetastatic PC were randomized to receive subcutaneous denosumab 60 mg every 6 months (n = 734) or placebo (n = 734), with daily calcium and vitamin D supplements for 3 years. Men < 70 years old were required to have low BMD or a history of osteoporotic fracture. The primary endpoint was percentage change in lumbar spine BMD at 24 months. Key secondary endpoints were subject incidence of new vertebral fractures and fractures at any site (excluding fractures from severe trauma or pathologic fractures) over 3 years. Here, we evaluate the frequency of all fractures and fractures at key osteoporotic sites. The planned sample size (N = 1226) provided power to differentiate effects of denosumab from placebo for the primary and key secondary endpoints. Results: As previously reported, denosumab reduced the incidence of new vertebral fractures by 62% (p = 0.006), fractures at any site by 28% (p = 0.10), and multiple fractures at any site by 72% (p = 0.006) over 3 years. In a post-hoc analysis, we found a consistent trend showing a positive effect of denosumab on nonvertebral fractures. The occurrence of any fractures (counting all fractures within a subject) over 3 years was lower with denosumab than placebo (43 vs 77, p < 0.01). The subject incidence of fractures at 6 high-risk sites (wrist, humerus, hip, pelvis, leg [excluding patella], and clavicle) was numerically lower with denosumab (15 vs 24 placebo; p = 0.12). Also, fewer subjects in the denosumab arm than in the placebo arm reported fractures at key osteoporotic sites (e.g., 2 for denosumab vs 10 for placebo at the radius). Overall rates of adverse events were balanced between treatment arms. Conclusions: Denosumab significantly reduced the incidence of new vertebral fractures and in a post-hoc analysis, showed a trend toward a positive effect on nonvertebral fractures in men receiving ADT for nonmetastatic PC. [Table: see text]
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".