Bone Formation Following Intramedullary Femoral Reaming Is Decreased by Indomethacin and Antibodies to Insulin-like Growth Factors
Bibliographic record
Abstract
OBJECTIVE: We aimed to: 1). compare rates of in vitro bone formation following reamed and nonreamed intramedullary fixation in a murine model of femoral fracture healing; and 2). examine whether antibodies to insulin-like growth factor (IGF) I, IGF II, or indomethacin (an inhibitor of the inflammatory process) affect bone formation following intramedullary reaming. DESIGN: Experimental study. PARTICIPANTS: Twenty-four C57 black mice were randomized to two groups: reamed ( = 12), and nonreamed intramedullary nail insertion ( = 12). INTERVENTION: In the reamed group, the femoral canals were successively reamed with 30-, 27-, 25-, and 23-gauge stainless steel pins and stabilized with a 27-gauge pin. In mice randomized to the nonreamed group, a 27-gauge pin was inserted. An external three-point bending force created a midshaft transverse femoral fracture. Seven days postsurgery, each mouse was killed, and the right femur was removed. Following pin removal, the callus was minced, the bone marrow was removed, and both were ultracentrifuged at 1200 rpm for 5 minutes. The supernatent was cocultured with 3-day-old murine calvarial cells in culture media. At day 5 of culture, reamed plasma and calvarial cell cocultures were exposed to either 1.0 micro g/mL of anti-IGF I, 1.0 micro g/mL of anti-IGF II, 2 micro M indomethacin, or served as controls (calvarial cells only). The cells were cultured for a total of 21 days. MAIN OUTCOME MEASUREMENTS: The number of bone nodules was quantified by light microscopy. RESULTS: Reamed pin insertion resulted in 4.1-fold and 8.9-fold increases in the mean number of bone nodules compared to pins inserted without reaming and controls, respectively (399 +/- 40.0 vs. 97.0 +/- 21.0, < 0.001). The positive effect of intramedullary reaming on bone nodule formation was reversed with the administration of antibodies to IGF I and IGF II. The addition of anti-IGF I or anti-IGF II to calvarial, or osteoblastlike, cells treated with supernatent from the callus and bone marrow of mice with prior intramedullary reaming resulted in significant declines in the mean number of bone nodules ( < 0.001). Specifically, treatment of osteoblastlike cells with anti-IGF I or anti-IGF II resulted in 7.0-fold and 5.4-fold declines in mean bone nodule formation compared to cells without such treatment. CONCLUSIONS: Intramedullary reaming prior to pin insertion resulted in a significantly greater number of bone nodules than pin insertion only. Antibodies to IGF I, IGF II, and indomethacin reversed the stimulatory effect of reaming on bone nodule formation, suggesting their role in modulating the course of fracture healing following intramedullary reaming.
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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 | 0.000 |
| 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".