Vitamin D Supplementation for 12 Months in Older Adults Alters Regulators of Bone Metabolism but Does Not Change Wnt Signaling Pathway Markers
Bibliographic record
Abstract
ABSTRACT Vitamin D status and supplementation regulates bone metabolism and may modulate Wnt signaling. We studied the response of hormonal regulators of bone metabolism, markers of Wnt signaling and bone turnover and bone mineral density (BMD) and bone mineral content (BMC) in a randomized vitamin D intervention trial (12,000 IU, 24,000 IU, 48,000 IU/mo for 1 year; men and women aged >70 years; n = 379; ISRCTN35648481). Associations with total and free 25(OH)D concentrations were analyzed by linear regression. Baseline vitamin D status was (mean ± SD) 25(OH)D: 40.0 ± 20.1 nmol/L. Supplementation dose‐dependently increased total and free 25(OH)D concentrations and decreased plasma phosphate and parathyroid hormone (PTH) (all p < 0.05). The procollagen 1 intact N‐terminal (PINP)/C‐terminal telopeptide (CTX) ratio, C‐terminal fibroblast growth factor‐23 (cFGF23), and intact FGF23 (iFGF23) significantly increased with no between‐group differences, whereas Klotho was unchanged. 1,25(OH) 2 D and PINP significantly increased in the 24 IU and 48,000 IU groups. Sclerostin (SOST), osteoprotegerin (OPG), receptor activator of NF‐κB ligand (RANKL), BMD, BMC, and CTX remained unchanged. Subgroup analyses with baseline 25(OH)D <25 nmol/L ( n = 94) provided similar results. Baseline total and free 25(OH)D concentrations were positively associated with 1,25(OH) 2 D, 24,25(OH) 2 D ( p < 0.001), vitamin D binding protein (DBP) ( p < 0.05), BMD, and BMC ( p < 0.05). Associations with PTH ( p <0.001), cFGF23 ( p < 0.01), and BAP ( p < 0.05) were negative. After supplementation, total and free 25(OH)D concentrations remained positively associated only with 24,25(OH) 2 D ( p < 0.001) and DBP ( p < 0.001) and negatively with estimated glomerular filtration rate (eGFR) ( p < 0.01). PTH and SOST were significantly associated only with free 25(OH)D. There were no significant relationships with BMD and BMC after supplementation. The decrease in PTH and increase in PINP/CTX ratio suggest a protective effect of supplementation on bone metabolism, although no significant effect on BMD or pronounced changes in regulators of Wnt signaling were found. The increase in FGF23 warrants caution because of its negative association with skeletal and cardiovascular health. Associations of total and free 25(OH)D with biomarkers were similar and known positive associations between vitamin D status and BMD were confirmed. The change in associations after supplementation might suggest a threshold effect. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
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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 | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| 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 | 0.000 |
| 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 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".