Use of Gastrointestinal Proton Pump Inhibitors to Regulate Osteoclast- Mediated Resorption of Calcium Phosphate Cements In Vivo
Bibliographic record
Abstract
Osteoclasts degrade bone through the creation of an enclosed, acidic extracellular microenvironment adjacent to the bone surface. Membrane bound proton pumps in the osteoclast cell membrane function to create this acidified environment. Accordingly, this H(+) ion transport mechanism provides a potential target for a specific class of drugs, proton pump inhibitors (PPI), with a view to controlling osteoclast mediated bone resorption. Self setting calcium phosphate cements are common bone graft materials that are degraded by osteoclastic activity. We have already shown that incorporation of bafilomycin, a non-regulated PPI, within these cements prevents or delays osteoclast mediated resorption of the cement. We demonstrate here that two regulated proton pump inhibitors, Pantaprazole and Omeprazole, currently used clinically to treat gastroesophageal reflux disorders, are effective in inhibiting osteoclast mediated resorption in-vivo when delivered to a bony defect in self setting calcium phosphate cements. As determined by qualitative histology, Pantaprazole at a dose of 0.5mg/ml produced a delay in osteoclast resorption whilst this effect was not as evident using Omeprazole at an equivalent dose, but higher doses of Omeprazole (40mg/ml) did delay cement resorption. These data demonstrate, for the first time, the functional effect of blocking the H(+)/K(+) ATPase pump in-vivo on the capacity of osteoclasts to resorb bone and the potential of this strategy to modulate osteoclast mediated resorption of calcium phosphate biomaterials.
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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 | 0.000 |
| 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 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".