Exogenous PTH and Endogenous 1,25-Dihydroxyvitamin D Are Complementary in Inducing an Anabolic Effect on Bone
Bibliographic record
Abstract
PTH and 1,25(OH)(2)D each exert dual anabolic and catabolic skeletal effects. We assessed the potential interaction of PTH and 1,25(OH)(2)D in promoting skeletal anabolism by comparing the capacity of exogenous, intermittently injected PTH(1-34) to produce bone accrual in mice homozygous for the 1 alpha(OH)ase-null allele [1 alpha(OH)ase(-/-) mice] and in wildtype mice. In initial studies, 3-mo-old wildtype mice were either injected once daily (40 microg/kg) or infused continuously (120 microg/kg/d) with PTH(1-34) for up to 1 mo. Infused PTH reduced BMD, increased the bone resorption marker TRACP-5b, and raised serum calcium but did not increase serum 1,25(OH)(2)D. Injected PTH increased serum 1,25(OH)(2)D and BMD, raised the bone formation marker osteocalcin more than did infused PTH, and did not produce sustained hypercalcemia as did PTH infusion. In subsequent studies, 3-mo-old 1 alpha(OH)ase(-/-) mice, raised on a rescue diet, and wildtype littermates were injected with PTH(1-34) (40 microg/kg) either once daily or three times daily for 1 mo. In 1 alpha(OH)ase(-/-) mice, baseline bone volume (BV/TV) and bone formation (BFR/BS) were lower than in wildtype mice. PTH administered intermittently increased BV/TV and BFR/BS in a dose-dependent manner, but the increases were always less than in wildtype mice. These studies show that exogenous PTH administered continuously resorbs bone without raising endogenous 1,25(OH)(2)D. Intermittently administered PTH can increase bone accrual in the absence of 1,25(OH)(2)D, but 1,25(OH)(2)D complements this PTH action. An increase in endogenous 1,25(OH)(2)D may therefore facilitate an optimal skeletal anabolic response to PTH and may be relevant to the development of improved therapeutics for enhancing skeletal anabolism.
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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 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 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 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".