The present research determined how the anticoagulant drug Heparin caused osteoporosis in rats and how Taraxacum officinale and/or vitamins can prevent it (C, K). Fifty female Wester albino rats were used in the 30-day study. They were placed into five groups. In the heparin-treated group, bone-specific alkaline phosphatase (ALP), osteocalcin (CO), deoxypyridinoline (DPD), and tartrate-resistant acid phosphatase (TRAP) were significantly increased in contrast to the control group. Taraxacum officinale and/or Vitamins (C, K) co-treatment of rats receiving heparin significantly reversed the declines in the examined parameters and the histomorphologic bone tissue images. In conclusion, the data showed that Taraxacum officinale and /or Vitamins (C, K) could protect the bone tissues from the damaging impact of heparin, which was more pronounced in rats treated with the combination of the two agents Taraxacum officinale and Vitamins (C, K). The current study may support the utilization of this combination as a promising therapy to alleviate the adverse of the anticoagulant heparin.
1. Downey PA, Siegel MI. Bone biology and the clinical implications for osteoporosis. Phys Ther. 2006;86(1):77-91. doi:10.1093/ptj/86.1.77
2. Kini U, Nandeesh BN. Physiology of bone formation, remodeling, and metabolism. Radionucl Hybrid Bone Imaging. 2012:29-57.
3. Nanci A. Ten cate’s oral histology, development, structure and function. 8th ed. Reed Elsevier India Private Limited. 2008;92-121.
4. Crockett JC, Mellis DJ, Scott DI, Helfrich MH. New knowledge on critical osteoclast formation and activation pathways from study of rare genetic diseases of osteoclasts: focus on the RANK/RANKL axis. Osteoporos Int. 2011;22(1):1-20. doi:10.1007/s00198-010-1272-8
5. Boyce BF, Xing L. Functions of RANKL/RANK/OPG in bone modeling and remodeling. Arch Biochem Biophys. 2008;473(2):139-46. doi:10.1016/j.abb.2008.03.018
6. Oduah EI, Linhardt RJ, Sharfstein ST. Heparin: Past, Present, and Future. Pharmaceuticals (Basel). 2016;9(3):38. doi:10.3390/ph9030038
7. González-Castejón M, Visioli F, Rodriguez-Casado A. Diverse biological activities of dandelion. Nutr Rev. 2012;70(9):534-47. doi:10.1111/j.1753-4887.2012.00509.x
8. Lazrak HH, René É, Elftouh N, Leblanc M, Lafrance JP. Safety of low-molecular-weight heparin compared to unfractionated heparin in hemodialysis: a systematic review and meta-analysis. BMC Nephrol. 2017;18(1):187. doi:10.1186/s12882-017-0596-4
9. Quer PF, Davit S. Plantas medicinales: el dioscórides renovado (No. CIDAB-: RS164-F6p). Labor. 1993.
10. Ata S, Farooq F, Javed S. Elemental profile of 24 common medicinal plants of Pakistan and its direct link with traditional uses. J Med Plants Res. 2011;5(26):6164-8.
11. Abrams SA, Griffin IJ, Hawthorne KM, Liang L, Gunn SK, Darlington G, et al. A combination of prebiotic short- and long-chain inulin-type fructans enhances calcium absorption and bone mineralization in young adolescents. Am J Clin Nutr. 2005;82(2):471-6. doi:10.1093/ajcn.82.2.471
12. Brzezińska O, Łukasik Z, Makowska J, Walczak K. Role of Vitamin C in Osteoporosis Development and Treatment-A Literature Review. Nutrients. 2020;12(8):2394. doi:10.3390/nu12082394
13. Palacios C. The role of nutrients in bone health, from A to Z. Crit Rev Food Sci Nutr. 2006;46(8):621-8. doi:10.1080/10408390500466174
14. Park JK, Lee EM, Kim AY, Lee EJ, Min CW, Kang KK, et al. Vitamin C deficiency accelerates bone loss inducing an increase in PPAR-γ expression in SMP30 knockout mice. Int J Exp Pathol. 2012;93(5):332-40. doi:10.1111/j.1365-2613.2012.00820.x
15. Palermo A, Tuccinardi D, D'Onofrio L, Watanabe M, Maggi D, Maurizi AR, et al. Vitamin K and osteoporosis: Myth or reality? Metabolism. 2017;70:57-71. doi:10.1016/j.metabol.2017.01.032
16. Akbari S, Rasouli-Ghahroudi AA. Vitamin K and Bone Metabolism: A Review of the Latest Evidence in Preclinical Studies. Biomed Res Int. 2018;2018:4629383. doi:10.1155/2018/4629383
17. Fusaro M, Mereu MC, Aghi A, Iervasi G, Gallieni M. Vitamin K and bone. Clin Cases Miner Bone Metab. 2017;14(2):200-6. doi:10.11138/ccmbm/2017.14.1.200
18. Muir JM, Andrew M, Hirsh J, Weitz JI, Young E, Deschamps P, et al. Histomorphometric analysis of the effects of standard heparin on trabecular bone in vivo. Blood. 1996;88(4):1314-20.
19. Cho SY, Park JY, Park EM, Choi MS, Lee MK, Jeon SM, et al. Alternation of hepatic antioxidant enzyme activities and lipid profile in streptozotocin-induced diabetic rats by supplementation of dandelion water extract. Clin Chim Acta. 2002;317(1-2):109-17. doi:10.1016/s0009-8981(01)00762-8
20. Akiyama Y, Hara K, Kobayashi M, Tomiuga T, Nakamura T. Inhibitory effect of vitamin K2 (menatetrenone) on bone resorption in ovariectomized rats: a histomorphometric and dual energy X-ray absorptiometric study. Jpn J Pharmacol. 1999;80(1):67-74. doi:10.1254/jjp.80.67
21. Giordano V, Albuquerque RP, do Amaral NP, Chame CC, de Souza F, Apfel MÍ. Supplementary vitamin C does not accelerate bone healing in a rat tibia fracture model. Acta Ortop Bras. 2012;20(1):10-2. doi:10.1590/S1413-78522012000100001
22. Mussi Filho S, Canova RA, Cruz HAD, Vidigal L, Zaniolo FJ, Vialle LR G. The effects of low-molecular-weight heparin (Enoxaparin) on bony callus formation in rats' femurs-an experimental study. Acta Ortopédica Brasileira. 2006;14:78-82.
23. Simann M, Schneider V, Le Blanc S, Dotterweich J, Zehe V, Krug M, et al. Heparin affects human bone marrow stromal cell fate: Promoting osteogenic and reducing adipogenic differentiation and conversion. Bone. 2015;78:102-13. doi:10.1016/j.bone.2015.04.039
24. Yang S, Niu Q, Gan L, Zhang X, Tu L, Zuo L. Effect of long-term use of unfractionated or low-molecular-weight heparin on bone mineral density in maintenance hemodialysis patients. Hemodial Int. 2020;24(3):374-82. doi:10.1111/hdi.12854
25. Bick RL, Frenkel EP, Walenga J, Fareed J, Hoppensteadt DA. Unfractionated heparin, low molecular weight heparins, and pentasaccharide: basic mechanism of actions, pharmacology, and clinical use. Hematol Oncol Clin North Am. 2005;19(1):1-51. doi:10.1016/j.hoc.2004.09.003
26. Vayne C, Nguyen TH, Rollin J, Charuel N, Poupon A, Pouplard C, et al. Characterization of New Monoclonal PF4-Specific Antibodies as Useful Tools for Studies on Typical and Autoimmune Heparin-Induced Thrombocytopenia. Thromb Haemost. 2021;121(3):322-31. doi:10.1055/s-0040-1717078
27. Xue L, Jiao L, Wang Y, Nie Y, Han T, Jiang Y, et al. Effects and interaction of icariin, curculigoside, and berberine in er-xian decoction, a traditional chinese medicinal formula, on osteoclastic bone resorption. Evid Based Complement Alternat Med. 2012;2012:490843. doi:10.1155/2012/490843
28. Kwan Tat S, Padrines M, Théoleyre S, Heymann D, Fortun Y. IL-6, RANKL, TNF-alpha/IL-1: interrelations in bone resorption pathophysiology. Cytokine Growth Factor Rev. 2004;15(1):49-60. doi:10.1016/j.cytogfr.2003.10.005
29. DeLaurier A, Jackson B, Ingham K, Pfeiffer D, Horton MA, Price JS. Biochemical markers of bone turnover in the domestic cat: relationships with age and feline osteoclastic resorptive lesions. J Nutr. 2002;132(6 Suppl 2):1742S-4S. doi:10.1093/jn/132.6.1742S
30. Xia J, Zhang Z, Wang J, Zu J, Wang N, Wang D. Comparison of the effects of heparin and the direct factor Xa inhibitor, rivaroxaban, on bone microstructure and metabolism in adult rats. Connect Tissue Res. 2015;56(6):477-82. doi:10.3109/03008207.2015.1069285. Epub 2015 Aug 25. Erratum in: Connect Tissue Res. 2016;57(1):68. PMID: 26305919.
31. Sakr HF, Hussein AM, Eid EA, Boudaka A, Lashin LS. Impact of Dehydroepiandrosterone (DHEA) on Bone Mineral Density and Bone Mineral Content in a Rat Model of Male Hypogonadism. Vet Sci. 2020;7(4):185. doi:10.3390/vetsci7040185
32. Halleen JM, Tiitinen SL, Ylipahkala H, Fagerlund KM, Väänänen HK. Tartrate-resistant acid phosphatase 5b (TRACP 5b) as a marker of bone resorption. Clin Lab. 2006;52(9-10):499-509.
33. Li B, Lu D, Chen Y, Zhao M, Zuo L. Unfractionated Heparin Promotes Osteoclast Formation in Vitro by Inhibiting Osteoprotegerin Activity. Int J Mol Sci. 2016;17(4):613. doi:10.3390/ijms17040613
34. Xiong J, Onal M, Jilka RL, Weinstein RS, Manolagas SC, O'Brien CA. Matrix-embedded cells control osteoclast formation. Nat Med. 2011;17(10):1235-41. doi:10.1038/nm.2448
35. Kuo TR, Chen CH. Bone biomarker for the clinical assessment of osteoporosis: recent developments and future perspectives. Biomarker Res. 2017;5(1):1-9.
36. Dai QG, Zhang P, Wu YQ, Ma XH, Pang J, Jiang LY, et al. Ovariectomy induces osteoporosis in the maxillary alveolar bone: an in vivo micro-CT and histomorphometric analysis in rats. Oral Dis. 2014;20(5):514-20. doi:10.1111/odi.12166
37. Wawrzyńska L, Tomkowski WZ, Przedlacki J, Hajduk B, Torbicki A. Changes in bone density during long-term administration of low-molecular-weight heparins or acenocoumarol for secondary prophylaxis of venous thromboembolism. Pathophysiol Haemost Thromb. 2003;33(2):64-7. doi:10.1159/000073848
38. Lee NK, Sowa H, Hinoi E, Ferron M, Ahn JD, Confavreux C, et al. Endocrine regulation of energy metabolism by the skeleton. Cell. 2007;130(3):456-69. doi:10.1016/j.cell.2007.05.047
39. Nishiyama M, Itoh F, Ujiie A. Low-molecular-weight heparin (dalteparin) demonstrated a weaker effect on rat bone metabolism compared with heparin. Jpn J Pharmacol. 1997;74(1):59-68. doi:10.1254/jjp.74.59
40. Shaughnessy SG, Hirsh J, Bhandari M, Muir JM, Young E, Weitz JI. A histomorphometric evaluation of heparin-induced bone loss after discontinuation of heparin treatment in rats. Blood. 1999;93(4):1231-6.
41. Aghajanian P, Hall S, Wongworawat MD, Mohan S. The Roles and Mechanisms of Actions of Vitamin C in Bone: New Developments. J Bone Miner Res. 2015;30(11):1945-55. doi:10.1002/jbmr.2709
42. Franceschi RT, Iyer BS. Relationship between collagen synthesis and expression of the osteoblast phenotype in MC3T3-E1 cells. J Bone Miner Res. 1992;7(2):235-46. doi:10.1002/jbmr.5650070216
43. Akman S, Canakci V, Kara A, Tozoglu U, Arabaci T, Dagsuyu IM. Therapeutic effects of alpha lipoic acid and vitamin C on alveolar bone resorption after experimental periodontitis in rats: a biochemical, histochemical, and stereologic study. J Periodontol. 2013;84(5):666-74. doi:10.1902/jop.2012.120252
44. Villa JKD, Diaz MAN, Pizziolo VR, Martino HSD. Effect of vitamin K in bone metabolism and vascular calcification: A review of mechanisms of action and evidences. Crit Rev Food Sci Nutr. 2017;57(18):3959-70. doi:10.1080/10408398.2016.1211616
45. Kim M, Na W, Sohn C. Vitamin K1 (phylloquinone) and K2 (menaquinone-4) supplementation improves bone formation in a high-fat diet-induced obese mice. J Clin Biochem Nutr. 2013;53(2):108-13. doi:10.3164/jcbn.13-25
46. Poon CC, Li RW, Seto SW, Kong SK, Ho HP, Hoi MP, et al. In vitro vitamin K2 and 1α, 25-dihydroxyvitamin D3 combination enhances osteoblasts anabolism of diabetic mice. Eur J Pharmacol. 2015;767:30-40.
47. van Summeren M, Braam L, Noirt F, Kuis W, Vermeer C. Pronounced elevation of undercarboxylated osteocalcin in healthy children. Pediatr Res. 2007; 61(3):366-70. doi:10.1203/pdr.0b013e318030d0b1
48. Rangel LBA, de Siqueira D, do Rosário Soares O, Santana HS, de Castro Miguel E, da Cunha M, et al. Vitamin K supplementation modulates bone metabolism and ultra-structure of ovariectomized mice. Cell Physiol Biochem. 2018;51(1):356-74.
Copyright © 2024 Archives of Pharmacy Practice. Authors retain copyright of their article if they are accepted for publication.
Developed by Archives of Pharmacy Practice
