Reply to Effects of High-Dose Vitamin D Supplementation on Bone Fragility
Bibliographic record
Abstract
We thank Dr Sugiyama for his response to our article. Dr Sugiyama raises the interesting possibility that high-dose vitamin D causes an increase in serum calcium (as found in our study), which, in turn, might mediate the decrease in volumetric bone mineral density. Dr Sugiyama refers to a study suggesting a negative association between serum calcium and dual-energy X-ray absorptiometry (DXA) bone density was independent of parathyroid hormone or vitamin D status.(1) The effect of extracellular calcium on bone cells might be expected to be mediated through a calcium sensing receptor (CaSR), and CaSRs have been demonstrated in osteoblasts and osteoclasts or osteoclast precursors. However, activation of the CaSR in these cells has also been associated with reduced osteoclast production(2) and increased bone formation.(3) Although we agree that a major effect of vitamin D on bone mineral and its measurement is via its facilitation of intestinal absorption of calcium and phosphate, there is also evidence of a direct effect of vitamin D metabolites on bone cells and bone turnover, as referenced in our articles.(4, 5) Regarding our finding of a lack of significant change in estimated bone strength despite changes in bone mineral density (BMD), we agree that mechanical stimulus may play a role in tempering the negative effects of high-dose vitamin D on strength. Nevertheless, our reported lack of significant change in estimated bone strength may be a spurious finding. We are currently working on improvements in finite element precision, specifically surrounding longitudinal analyses,(6) that may in fact reveal mechanical changes in bone strength followed BMD changes. Dr Sugiyama raises an interesting point that the microarchitecture may be reconfigured as a result of the mechanical adaptation that occurs in parallel with decreased BMD. We hope to address this question in our future work involving a detailed assessment of the bone microarchitecture and physical activity in this unique cohort. Funding for the Calgary Vitamin D Study was provided by Pure North S′Energy Foundation in response to an investigator-initiated research grant proposal. Lauren Burt: Writing-original draft; writing-review and editing. Emma Billington: Writing-original draft; writing-review and editing. Marianne Rose: Writing-review and editing. Richard Kremer: Writing-review and editing. David Hanley: Writing-original draft; writing-review and editing. Steven Boyd: Writing-original draft; writing-review and editing.
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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 | 0.003 | 0.033 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.002 | 0.003 |
| Open science | 0.003 | 0.001 |
| Research integrity | 0.022 | 0.029 |
| Insufficient payload (model declined to judge) | 0.004 | 0.003 |
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".