Background

Ascorbic acid is involved in collagen biosynthesis and upregulates alkaline phosphatase, potentially alleviating cell senescence and stimulating mesenchymal stem cell proliferation and differentiation into osteoblasts. We hypothesized locally delivered ascorbic acid and β-glycerophosphate act as a bone graft extender to increase the volume of new bone formed in a murine model of posterior lumbar fusion.

Methods

Collagen sponges were used as delivery vehicles. Sponges were prepared with primary media alone or with the addition of ascorbic acid and β-glycerophosphate. Fresh morselized bone graft from 12 donor mice was used. Twenty-four healthy male C57BL/6 mice underwent an uninstrumented posterior L3-L5 lumbar fusion. One control group received morselized bone only. A second "sponge control" group received morselized bone with the control collagen sponge. The third group received morselized bone and a collagen sponge with ascorbic acid and β-glycerophosphate. Three months postoperatively, the lumbar spine underwent high-resolution micro-computed tomography for analysis of bone formation, density, and bridging fusion.

Results

Animals receiving ascorbic acid and β-glycerophosphate had a statistically significant increase in corrected bone volume compared with control and sponge groups, with a 56.3% and 25.4% increase, respectively. Mineralized bone fraction was statistically significantly decreased for animals in the ascorbic acid group compared with control and sponge groups. There was no significant difference in fusion rate between test groups.

Conclusions

Locally delivered ascorbic acid and β-glycerophosphate in a murine model of posterior spinal fusion yielded statistically significant increases in new bone formation in the lumbar spine but statistically significant decreases in mineralized bone fraction. Differences in fusion rate were not statistically significant.

Clinical relevance

This study provides early data suggesting that delivery of ascorbic acid to a spinal fusion site may be beneficial but does not yet establish an indication for clinical use. Further studies are needed to determine optimal dose and delivery of ascorbic acid.

Background

Hepatic steatosis is increasing worldwide. Whether HIV and its associated metabolic perturbations exacerbate steatosis is unclear. Sex differences in adipose tissue distribution may also affect steatosis risk. We examined the contribution of HIV and sex to steatosis.

Methods

Using MRI and spectroscopy, visceral adipose tissue (VAT) and liver fat fraction (LFF) were measured in 121 HIV-infected and 107 uninfected men and women without viral hepatitis. Differences in LFF by HIV status and sex were evaluated using multivariable linear regression, adjusting for demographic, lifestyle, VAT, homeostasis model assessment-estimated insulin resistance, and HIV-related factors.

Results

HIV-infected women had lower LFF than uninfected women (demographic-adjusted mean: 1.9 vs. 3.1%; P = 0.028); LFF was similar in HIV-infected and uninfected men (4.6 vs. 4.1%; P = 0.78). HIV-infected and uninfected women had less VAT than men (median: 139 and 161 vs. 201 cm and 188 cm, respectively). After adjustment, HIV-infected women had 34% [95% confidence interval (CI): -54%, -5.5%] lower LFF than uninfected women, whereas there was little difference in men (-5.5%; 95% CI: -26%, 21%). Among HIV-infected persons, greater VAT and homeostasis model assessment-estimated insulin resistance were associated with greater LFF. HIV-related factors (CD4 cell count, HIV RNA level, or antiretroviral therapy use) had little association with LFF. Although HIV-infected men had 81% (95% CI: 32%, 148%) greater LFF than HIV-infected women, the association was attenuated after multivariable adjustment (25%; 95% CI: -9.1%, 73%).

Conclusion

Contrary to expectation, HIV infection is not associated with greater steatosis compared with uninfected adults. It is possible that less fat is stored in the liver to maintain subcutaneous fat (which is reduced in HIV) and the effect is magnified in HIV-infected women, who also have less VAT.

Objective

Hepatic steatosis is common in HIV-infected individuals. Magnetic resonance spectroscopy (MRS) is the preferred noninvasive method for hepatic steatosis measurement but is expensive. Controlled attenuation parameter (CAP) also assesses hepatic steatosis and is conveniently performed concomitantly with transient elastography. We aimed to assess the accuracy of CAP in the setting of HIV infection.

Design

Cross-sectional study.

Methods

CAP and MRS were performed in 82 study participants (39 HIV monoinfected; seven hepatitis C virus (HCV) monoinfected; 21 HIV/HCV coinfected; 15 with neither infection). We used concordance correlation coefficients to compare log-transformed and standardized CAP and MRS values and linear regression to examine factors associated with CAP and MRS-measured hepatic steatosis (MRS-HS). The accuracy of CAP to detect at least mild hepatic steatosis, defined as MRS-liver fat fraction more than 0.05, and the factors associated with discordance between CAP and MRS were evaluated.

Results

Overall, CAP-measured hepatic steatosis and MRS-HS correlated moderately well (rc = 0.63; P < 0.001), and correlation was strongest in the HIV-monoinfected group (rc = 0.67; P < 0.001). Body composition factors (higher BMI, waist circumference, visceral and abdominal subcutaneous adipose tissue) and insulin resistance were significantly associated with both greater CAP-measured hepatic steatosis and MRS-HS. Using a validated CAP cut-off of at least 238 dB/m, sensitivity and specificity for at least mild hepatic steatosis were 84% and 75% in the entire cohort; 89% and 80% in the HIV-monoinfected group. Participants with higher body composition parameters were more likely to be misclassified as having hepatic steatosis by CAP.

Conclusion

Our findings suggest CAP is an acceptable noninvasive surrogate for hepatic steatosis in HIV-infected individuals but may overestimate hepatic steatosis prevalence, especially in individuals with high BMI. Evaluation of factors that improve CAP accuracy and determination of optimal cut-offs are warranted.