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Fenofibrate reduces experimental osteonecrosis
Statistical analysis
The frequency of osteonecrosis/arteriopathy was compared using the χ2 test. Log-rank testing was used for survival compar- isons. For continuous variables, the two-tailed Mann-Whitney test was used (two groups); the Kruskal-Wallis test with Dunn correction was used for multiple comparisons (three or more groups). All continuous statistics are expressed as the median with 95% confidence interval. The R program (version 3.5.1)33 or GraphPad Prism34 was used for the statistical analyses and visual representation. P values <0.05 were considered statistically sig- nificant for all analyses.
Results
Fenofibrate in experimental osteonecrosis
Consistent with previous observations,21,22,28,29 mice that received dexamethasone (i.e., animals in the dexametha- sone-only and dexamethasone + fenofibrate treatment groups) gained less weight over time compared to those not treated with dexamethasone (control and fenofibrate-
A
only treatment groups) (Figure 1B). Fenofibrate supple- mentation suppressed weight gain over the course of treatment. By week 6 of treatment, control mice had gained 50% more weight than mice treated with fenofi- brate only (P=2x10-5) and mice treated with dexametha- sone only had gained 10% more weight than those treat- ed with dexamethasone + fenofibrate (P=0.01) (Figure 1B). There was no difference in survival between groups (P=0.55) (Figure 1C).
In mice treated with dexamethasone, fenofibrate signif- icantly reduced serum triglyceride levels as early as week 1, from 130.1 mg/dL (95% CI: 85.2- 201.1) to 37.4 mg/dL (95% CI: 17.1- 60.3), a 3.5-fold decrease (P=0.0004). Fenofibrate supplementation continued to suppress dexa- methasone-induced hypertriglyceridemia at week 3 (4.5- fold decrease, P<1x10-6) through to the end of treatment at week 6 (3.5-fold decrease, P=5x10-6). There was no dif- ference in triglyceride levels at weeks 1 and 3 between mice treated with fenofibrate only and those treated with
B
Figure 2. Fenofibrate reduces serum lipids and fat depots in dexamethasone-treated mice. (A) Median (with 95% confidence interval) fasting serum triglyceride lev- els at weeks 1, 3, and 6 of treatment. Week 1, n=8-12/group; week 3, n=12-27/group; week 6, n=12-31/group. (B) Perigonadal and inguinal fat pads at week 6; n=8-10/group. P-values shown between relevant groups: control versus fenofibrate only; control versus dexamethasone (DEX) only; fenofibrate only versus DEX + fenofibrate; DEX only versus DEX + fenofibrate.
haematologica | 2021; 106(8)
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