Measurements of the Vitamin D Metabolome in the Calgary Vitamin D Study: Relationship of Vitamin D Metabolites to Bone Loss
Bibliographic record
Abstract
ABSTRACT In a 36‐month randomized controlled trial examining the effect of high‐dose vitamin D 3 on radial and tibial total bone mineral density (TtBMD), measured by high‐resolution peripheral quantitative tomography (HR‐pQCT), participants (311 healthy males and females aged 55–70 years with dual‐energy X‐ray absorptiometry T‐scores > −2.5 without vitamin D deficiency) were randomized to receive 400 IU ( N = 109), 4000 IU ( N = 100), or 10,000 IU ( N = 102) daily. Participants had HR‐pQCT radius and tibia scans and blood sampling at baseline, 6, 12, 24, and 36 months. This secondary analysis examined the effect of vitamin D dose on plasma measurements of the vitamin D metabolome by liquid chromatography–tandem mass spectrometry (LC‐MS/MS), exploring whether the observed decline in TtBMD was associated with changes in four key metabolites [25‐(OH)D 3 ; 24,25‐(OH) 2 D 3 ; 1,25‐(OH) 2 D 3 ; and 1,24,25‐(OH) 3 D 3 ]. The relationship between peak values in vitamin D metabolites and changes in TtBMD over 36 months was assessed using linear regression, controlling for sex. Increasing vitamin D dose was associated with a marked increase in 25‐(OH)D 3 , 24,25‐(OH) 2 D 3 and 1,24,25‐(OH) 3 D 3 , but no dose‐related change in plasma 1,25‐(OH) 2 D 3 was observed. There was a significant negative slope for radius TtBMD and 1,24,25‐(OH) 3 D 3 (−0.05, 95% confidence interval [CI] −0.08, −0.03, p < 0.001) after controlling for sex. A significant interaction between TtBMD and sex was seen for 25‐(OH)D 3 (female: −0.01, 95% CI −0.12, −0.07; male: −0.04, 95% CI −0.06, −0.01, p = 0.001) and 24,25‐(OH) 2 D 3 (female: −0.75, 95% CI −0.98, −0.52; male: −0.35, 95% CI −0.59, −0.11, p < 0.001). For the tibia there was a significant negative slope for 25‐(OH)D 3 (−0.03, 95% CI −0.05, −0.01, p < 0.001), 24,25‐(OH) 2 D 3 (−0.30, 95% CI −0.44, −0.16, p < 0.001), and 1,24,25‐(OH) 3 D 3 (−0.03, 95% CI −0.05, −0.01, p = 0.01) after controlling for sex. These results suggest vitamin D metabolites other than 1,25‐(OH) 2 D 3 may be responsible for the bone loss seen in the Calgary Vitamin D Study. Although plasma 1,25‐(OH) 2 D 3 did not change with vitamin D dose, it is possible rapid catabolism to 1,24,25‐(OH) 3 D 3 prevented the detection of a dose‐related rise in plasma 1,25‐(OH) 2 D 3 . © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
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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 | 0.002 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 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".