Effect of Folic Acid on Avascular Bone Necrosis in mice Associated with Hypercholesterolemia

Main Article Content

Hameed Abdul Hussain AL-tememy


Folic Acid, Avascular Bone Necrosis, Hypercholesterolemia


To comprehend the etiology of avascular necrosis better, many experimental models are available. Femoral head osteonecrosis, commonly known as avascular bone necrosis. is a condition with a complex origin that is defined by a significant alteration in the structure of the bones, which lowers bone resistance and causes femoral head collapse. Between February and April 2022, this study was conducted with the goals of creating a mouse model for the production of avascular necrosis (AVN) using HFD and examining the impact of folic acid on bone health. Lipid indices were found to assess how FA affected the mice's HFD-fed lipid metabolism. HE staining was used to detect morphological and structural changes in the bone. The findings of this study demonstrated that AVN had a malfunction of lipid metabolism. The mean levels of total cholesterol (TC), triglycerides (TG), and low density lipoprotein cholesterol (LDL-C) in the AVN group were significantly greater than those in the control group. Serum triglycerides were decreased in groups with FA supplementation, with the most pronounced reduction in the groups of mice that take folic acid before one week from taking HFD. The mean Low density lipoprotein cholesterol (LDL-C) values were significantly lower in the AVN + folic acid group compared with those in the HFD control group. The HFD control group's histological investigation using hematoxylin and eosin staining revealed necrotic bone, lacunae containing necrotic osteocytes, and multiple cavities that indicated lack of content, a sign that the osteocytes inside had died. Chondrocyte degradation was seen in addition to necrotic bone marrow. Additionally, it was discovered that the majority of bone trabeculae had necrotic lesions that had damaged them, and that the femur had a buildup of lipid droplets. Both folic acid-treated groups showed a decrease in osteonecrosis and an improvement in the lesion in the trabecular bone tissue.

Abstract 179 | pdf Downloads 110


1. Fondi C, Franchi A. Definition of bone necrosis by the pathologist. Clin Cases Miner Bone Metab,( 2007), 4(1):21–26. PMID:22460748 PMCID: PMC2781178
2. Yang, X., Cui, Z., Zhang, H., Wei, X., Feng, G., Liu, L., et al. (2019). Causal link between lipid profile and bone mineral density: A Mendelian randomization study. Bone 127, 37–43. doi: 10.1016/j.bone.2019.05.037
3. During, A., Penel, G., and Hardouin, P. (2015). Understanding the local actions of lipids in bone physiology. Prog. Lipid Res. 59, 126–146. doi: 10.1016/j.plipres.2015.06.002
4. Field, M. S., and Stover, P. J. (2018). Safety of Folic Acid. Ann. N.Y. Acad. Sci. 1414 (1), 59–71. doi:10.1111/nyas.13499
5. Moskal, J., Topping, R. & Franklin, L(2003).. Hypercholesterolemia: an association with osteonecrosis of the femoral head. Americanjournal of orthopedics (Belle Mead, NJ) 26, 609–612
6. Callis GM, Bancroft JD. (2008) Theory and Practice of Histological Techniques 6th ed. Edinburgh: Churchill Livingstone.;338-360.
7. Alekos, N. S., Moorer, M. C., and Riddle, R. C. (2020). Dual Effects of Lipid Metabolism on Osteoblast Function. Front. Endocrinol. 11:578194. doi: 10.3389/fendo.578194
8. Pelton, K.; Krieder, J.; Joiner, D.; Freeman, M.R.; Goldstein, S.A.; Solomon, K.R. .( 2012) Hypercholesterolemia promotes an osteoporotic phenotype. Am. J. Pathol, 181, 928–936.
9. Mandal, C.C. (2015) High Cholesterol Deteriorates Bone Health: New Insights into Molecular Mechanisms. Front. Endocrinol., 6,165.
10. Lee, J. S., Lee, L. S., Rob, H. L., Kim, C. H., Jung, J. S., and Suh, K. T. (2006). Alterations in the differentiation ability of mesenchymal stem cells in patients with nontraumatic osteonecrosis of the femoral head: Comparative analysis according to the risk factor. J. Orthopaed. Rese. 24, 604–609. doi: 10.1002/jor.20078
11. Li,N., Zhao, Y., Shen, Y., Cheng, Y., Qiao, M., Song, L., et al. (2021). Protective Effects of Folic Acid on Oxidative Damage of Rat Spleen Induced by lead Acetate.Ecotoxicology Environ. Saf. 211, 111917. doi:10.1016/j.ecoenv.2021.111917
12. Li, W., Tang, R., Ma, F., Ouyang, S., Liu, Z., and Wu, J. (2018). Folic Acid
13. Supplementation Alters the DNA Methylation Profile and Improves Insulin Resistance in High-Fat-Diet-Fed Mice. J. Nutr. Biochem. 59, 76–83.
14. McKusick VA. Heritable disorders of connective tissue.( 3rd ed. St. Louis: C.V. Mosby,:150.
15. Kang AH, Trelstad RL. A collagen defect in homocystinuria. J Clin Invest 1973;52: 2571-8.
16. Goyette P, Sumner JS, Milos R, et al. Human methylenetetrahydrofolate reduc- tase: isolation of cDNA, mapping and mutation identification. Nat Genet 1994;7:195- 200. [Erratum, Nat Genet 1994;7:551.
17. Papachristou, N.I.; Blair, H.C.; Kypreos, K.E.; Papachristou, D.J.(2017).High-density lipoprotein (HDL) metabolism and bone mass. J. Endocrinol., 233, R95–R107
18. Tintut, Y.; Demer, L.L .(2014) . Effects of bioactive lipids and lipoproteins on bone. Trends Endocrinol. Metab., 25, 53–59.
19. Zeng, X.; Zhan, K.; Zhang, L.; Zeng, D.; Yu,W.; Zhang, X.; Zhao, M.; Lai, Z.; Chen, R. (2017)The impact of high total cholesterol and high low-density lipoprotein on avascular necrosis of the femoral head in low-energy femoral neck fractures. J. Orthop. Surg. Res., 12, 30.
20. Tian, L.; Yu, X.(2015) Lipid metabolism disorders and bone dysfunction—Interrelated and mutually regulated (review). Mol. Med. Rep, 12, 783–794.