Antipsychotic Use and Risk of Low-Energy Fractures in People With Schizophrenia: A Nationwide Nested Case-Control Study in Finland
Bibliographic record
Abstract
BACKGROUND: Low-energy fractures (LEF) are more frequent in people with schizophrenia than the general population, and the role of prolactin-increasing antipsychotics is unknown. STUDY DESIGN: We conducted a nested case-control study using Finnish nationwide registers (inpatient, specialized outpatient care, prescription drug purchases). We matched each person with schizophrenia aged 16-85 years and incident LEF (cases) with 5 age/sex/illness duration-matched controls with schizophrenia, but no LEF. We investigated the association between cumulative exposure (duration, and Defined Daily Doses, DDDs) to prolactin-increasing/sparing antipsychotics and LEF. Adjusted conditional logistic regression analyses were performed. Sensitivity analyses were conducted. STUDY RESULTS: Out of 61 889 persons with schizophrenia between 1972 and 2014, we included 4960 cases. Compared with 24 451 controls, 4 years or more of exposure to prolactin-increasing antipsychotics was associated with increased risk of LEF (adjusted odds ratio (aOR) from aOR = 1.22, 95%CI = 1.09-1.37 to aOR = 1.38, 95%CI = 1.22-1.57, for 4-< 7 />13 years of exposure, respectively), without a significant association for prolactin-sparing antipsychotics. All cumulative doses higher than 1000 DDDs of prolactin-increasing antipsychotics were associated with LEF (from aOR = 1.21, 95%CI = 1.11-1.33, 1000-<3000 DDDs, to aOR = 1.64, 95%CI = 1.44-1.88, >9000 DDDs). Only higher doses of prolactin-sparing antipsychotics reached statistical significance (aOR = 1.24, 95%CI = 1.01-1.52, 6000-<9000 DDDs, aOR = 1.45, 95%CI = 1.13-1.85, >9000 DDDs). Sensitivity analyses confirmed the main analyses for prolactin-increasing antipsychotics. For prolactin-sparing antipsychotics, significant associations were limited to extreme exposure, major LEF, older age group, and males. CONCLUSIONS: Long-term exposure to prolactin-increasing antipsychotics at any dose, and high cumulative doses of prolactin-sparing antipsychotics is associated with significantly increased odds of LEF. Monitoring and addressing hyperprolactinemia is paramount in people with schizophrenia receiving prolactin-increasing antipsychotics.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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 teacher head, 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".