The effect of deer antler from East Kalimantan to increase trabecular bone density and calcium levels in serum on osteoporotic mice

Retno Widyowati; Suciati Suciati; Dewi Melani Haryadi; Hsin-I Chang; IPG Ngurah Suryawan; Nurliana Tarigan

doi:10.1515/jbcpp-2020-0140

Article

The effect of deer antler from East Kalimantan to increase trabecular bone density and calcium levels in serum on osteoporotic mice

Retno Widyowati , Suciati Suciati , Dewi Melani Haryadi , Hsin-I Chang , IPG Ngurah Suryawan and Nurliana Tarigan

Published/Copyright: February 15, 2021

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From the journal Journal of Basic and Clinical Physiology and Pharmacology Volume 32 Issue 6

Abstract

Objectives

Glucocorticoid-induced osteoporosis (dexamethasone) is a primary cause of secondary osteoporosis by the decreasing formation and increasing resorption activities. Previously, the in vitro study showed that 70% ethanol and aqueous extract of deer antler have increased alkaline phosphatase in osteoblast cell that known as marker of bone formation. The mind of this study is to analyze the effect of deer antlers in increasing the bone trabecular density of osteoporosis-induced male mice.

Methods

This study used a post-test control group design. A total of 54 healthy male mice were randomly divided to nine groups, i.e., healthy control, osteoporotic, positive control, 70% ethanol (4, 8, and 12 mg/kg BW), and aqueous extracts (4, 8, and 12 mg/kg BW) of deer antler groups. All of the interventions were given 1 mL of test sample for 4 weeks orally. The bone densities were determined using histomorphometry by Image J and Adobe Photoshop. The statistical data were performed using SPSS 23 and statistical significance was set at p<0.05.

Results

The results showed that alendronate group, 70% ethanol, and aqueous extract groups increased bone density and calcium levels in serum (p<0.05) compared to osteoporotic group in dose dependent manner. It indicated that 70% ethanol and aqueous extract of deer antler stimulating bone turnover and aqueous extract showed the highest.

Conclusions

Dexamethasone induction for 4 weeks caused osteoporotic mice and the administration of 70% ethanol and aqueous extracts of deer antler from East Kalimantan increased trabecular bone density and calcium levels in dose dependent manner.

Keywords: bone density; bone turnover; calcium level; deer antler

Corresponding author: Retno Widyowati, Department of Pharmacognosy and Phytochemistry, Faculty of Pharmacy, Universitas Airlangga, Nanizar Zaman Joenoes Building, Campus C, Mulyorejo, Surabaya, Indonesia, Phone: +62 81615886978, E-mail: rr-retno-w@ff.unair.ac.id

Funding source: Airlangga University

Award Identifier / Grant number: 886/UN3/2018

Funding source: Faculty of Pharmacy Airlangga University

Funding source: UPTD of East Kalimantan

Funding source: National Chiayi University, Taiwan

Acknowledgments

The authors are grateful for access to Animal Laboratory of the Faculty of Pharmacy, Universitas Airlangga and would like to express their sincere thanks to Research and Innovation Institute of Universitas Airlangga and the dean of Faculty of Pharmacy, Universitas Airlangga for supporting fund.

Research funding: This research was supported by research mandatory of Airlangga University (No. 886/UN3/2018) and research collaboration between Faculty of Pharmacy Airlangga University, UPTD of East Kalimantan and National Chiayi University, Taiwan.
Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission. RW designed the research concepts, SC designed methods, DW edited the article, HC designed discussion, NS and NT provided the deer antlers.
Competing interests: The authors declared that no conflict of interest in this article.
Informed consent: Not applicable.
Ethical approval: This study was approved by ethics commission of Faculty of Veterinary Medicine, Universitas Airlangga with No. 2.KE.176.09.2019.

References

1. Agrawal, VK, Gupta, DK. Recent update on osteoporosis. Int J Med Sci Publ Health 2013;2:164–8. https://doi.org/10.5455/ijmsph.2013.2.162-166.Search in Google Scholar

2. Eiben, G, Dey, DK, Rothenberg, E, Steen, B, Björkelund, C, Bengtsson, C, et al.. Obesity in 70-year-old Swedes: secular changes over 30 years. Int J Obes 2005;29:810–7. https://doi.org/10.1038/sj.ijo.0802940.Search in Google Scholar

3. Gennari, L, Bilezikian, JP. Osteoporosis in men. Endocrinol Metab Clin N Am 2007;36:399–419. https://doi.org/10.1016/j.ecl.2007.03.008.Search in Google Scholar

4. Sözen, T, Özişik, L, Başaran, NÇ. An overview and management of osteoporosis. Eur J Rheumatol 2017;4:46–56. https://doi.org/10.5152/eurjrheum.2016.048.Search in Google Scholar

5. Kling, JM, Clarke, BL, Sandhu, NP. Osteoporosis prevention, screening and treatment: a review. J Women Health (Larchmt) 2014;23:563–72. https://doi.org/10.1089/jwh.2013.4611.Search in Google Scholar

6. Licata, A. Osteoporosis in men: suspect secondary disease first. Cleve Clin J Med 2003;70:247–54. https://doi.org/10.3949/ccjm.70.3.247.Search in Google Scholar

7. Siddapur, PR, Patil, AB, Borde, VS. Comparison of bone mineral density, T-score and serum zink between diabetic and non diabetic postmenopausal women with osteoporosis. J Lab Phys 2015;7:43–8. https://doi.org/10.4103/0974-2727.151681.Search in Google Scholar

8. Kotwal, N, Upreti, V, Nachankar, A, Kumar, KVSH. A prospective, observational study of osteoporosis in men. Indian J Endocrinol Metab 2018;22:62–6.10.4103/ijem.IJEM_414_16Search in Google Scholar

9. American College of Rheumatology Ad Hoc Committee on Glucocorticoid-Induced Osteoporosis. Recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis. Arthritis Rheum 2001;44:1496–503.10.1002/1529-0131(200107)44:7<1496::AID-ART271>3.0.CO;2-5Search in Google Scholar

10. Drake, MT, Clarke, BL, Khosla, S. Bisphosphonates: mechanism of action and role in clinical practice. Mayo Clin Proc 2008;83:1032–45. https://doi.org/10.4065/83.9.1032.Search in Google Scholar

11. Epstein, S. The roles of bone mineral density, bone turnover and other properties in reducing fracture risk during antiresorptive therapy. Mayo Clin Proc 2005;80:378–88. https://doi.org/10.4065/80.3.379.Search in Google Scholar PubMed

12. Al-Anazi, AF, Qureshi, VF, Javaid, K, Qureshi, S. Prevention effects of phytoestrogens against postmenopausal osteoporosis as compared to the available therapeutic choices: an overview. J Nat Sci Biol Med 2011;2:154–63.10.4103/0976-9668.92322Search in Google Scholar PubMed PubMed Central

13. Arjmandi, BH. The role of phytoestrogens in the prevention and treatment of osteoporosis in ovarian hormone deficiency. JACN 2001;20:398S–402S. https://doi.org/10.1080/07315724.2001.10719175.Search in Google Scholar PubMed

14. Uesugi, T, Fukui, Y, Yamori, Y. Beneficial effects of soybean isoflavon supplementation on bone metabolism and serum lipids in postmenopausal Japanese women. A four weeks study. JACN 2002;21:97–102. https://doi.org/10.1080/07315724.2002.10719200.Search in Google Scholar PubMed

15. Atkinson, C, Compston, JE, Day, NE, Dowsett, M, Bingham, SA. The effects of phytoestrogen isoflavons on bone density in women: a double-blind, randomized, placebo-controlled trial. Am L Clin Nutr 2004;79:326–33. https://doi.org/10.1093/ajcn/79.2.326.Search in Google Scholar PubMed

16. Widyowati, R, Suciati, Haryadi, DM, Chang, H, Suryawan, IPGN, Utama, AW. The effect of Rusa unicolor antler extracts from East Kalimantan in bone turnover cell models. Turk J Pharm Sci 2020;17:440–5. https://doi.org/10.4274/tjps.galenos.2019.57805.Search in Google Scholar PubMed PubMed Central

17. Gong, W, Li, F. Cervi cornu pantotrichun aqueous extract promote osteoblasts differentiation and bone formation. Biomed Res 2014;25:249–52.Search in Google Scholar

18. Sui, Z, Zhang, L, Huo, Y, Zhang, Y. Bioactive components of velvet antlers and their pharmacological properties. J Pharmaceut Biomed Anal 2014;87:229–40. https://doi.org/10.1016/j.jpba.2013.07.044.Search in Google Scholar PubMed

19. Kawtikwar, PS, Bhagwat, DA, Sakarkar, DM. Deer antler-traditional use and future perspectives. Indian J Trad Knowl 2010;9:245–51.Search in Google Scholar

20. Hadiwidjojo, MGH. Aktivitas antiosteoporosis ekstrak etanol 70% dan hasil fraksinasi Spilanthes acmella dalam meningkatkan kepadatan tulang trabecular femur mencit jantan [Thesis]. Fakultas Farmasi Universitas Airlangga; 2014.Search in Google Scholar

21. Li-Xia, S, Zhang, JC, Wu, J, Hashimoto, K. Antidepressant effects of ketamine on depression-like behavior in juvenile mice after neonatal dexamethasone exposure. Clin Psychopharmacol Neurosci 2014;12:124–7. https://doi.org/10.9758/cpn.2014.12.2.124.Search in Google Scholar PubMed PubMed Central

22. Egan, KP, Brennan, TA, Pignolo, RJ. Bone histomorphometry using free and commonly available software. Histopathology 2012;61:1168–73. https://doi.org/10.1111/j.1365-2559.2012.04333.x.Search in Google Scholar PubMed PubMed Central

23. Duque, G, Watanabe, K. Osteoporosis research animal models. London Dordrecht Heidelberg, New York: Spinger; 2011.10.1007/978-0-85729-293-3Search in Google Scholar

24. Sim, JS, Sunwoo, HH. Antler nutraceuticals for the newly emerging functional food market in North America: ASPT research update. In: Sim, JS, Sunwoo, HH, Hudson, RJ, Jeon, BT, editors Antler science and product technology. Edmonton Canada: ASPTRC; 2001.Search in Google Scholar

25. Shozu, M, Simpson, ER. Aromatase expression of human osteoblast-like cell. Mol Cell Endocrinol 1998;139:117–29. https://doi.org/10.1016/s0303-7207(98)00069-0.Search in Google Scholar

26. Chiechi, LM, Micheli, L. Utility of dietary phytoestrogens in preventing postmenopausal osteoporosis. Curr Top Nutraceutical Res 2005;3:15–28.Search in Google Scholar

27. Ma, Y, Nyman, JS, Tao, H, Moss, HH, Yang, X, Elefteriou, F. Β2-Adrenergic receptor signaling in osteoblasts contributes to the catabolic effect of glucocorticoids on bone. Endocrinology 2011;152:1412–22. https://doi.org/10.1210/en.2010-0881.Search in Google Scholar PubMed PubMed Central

28. Elkomy, MM, Elsaid, FG. Anti-osteoporotic effect of medical herbs and calcium supplementation on ovariectomized rats. JOBAZ 2015;72:81–8. https://doi.org/10.1016/j.jobaz.2015.04.007.Search in Google Scholar

29. Zaqqa, D, Jackson, RD. Diagnosis and treatment of glucocorticoid-induced osteoporosis. CCJM 1999;66:221–30.10.3949/ccjm.66.4.221Search in Google Scholar PubMed

30. Shimon, I, Eshed, V, Doolman, R, Sela, B-A, Karasik, A, Vered, I. Alendronate for osteoporosis in men with androgen-releted hypogonadism. Osteoporos Int 2005;16:1591–6. https://doi.org/10.1007/s00198-005-1879-3.Search in Google Scholar PubMed

31. Karsenty, G, Oury, F. Regulation of male fertility by the bone derived hormone osteocalcin. Mol Cell Endocrinol 2014;382:1–13. https://doi.org/10.1016/j.mce.2013.10.008.Search in Google Scholar PubMed PubMed Central

32. Orwoll, E, Ettinger, M, Weiss, S, Miller, P, Kendler, D, Graham, J, et al.. Alendronate for the treatment of osteoporosis in men. N Engl J Med 2000;343:604–10. https://doi.org/10.1056/nejm200008313430902.Search in Google Scholar

33. Melsen, F, Melsen, B, Moseklide, L, Bergmann, S. Histomorphometric analysis of normal bone from the iliac crest. Acta Pathol Microbiol Scand 1978;86:70–81.10.1111/j.1699-0463.1978.tb02014.xSearch in Google Scholar PubMed

34. Revell, P. Histomorphometry of bone. J Clin Pathol 1983;36:1323–31. https://doi.org/10.1136/jcp.36.12.1323.Search in Google Scholar PubMed PubMed Central

35. Hemmings, SJ, Song, X. The effects of elk velvet antler consumption on the rat: development, behavior, toxicity and the activity of liver γ-glutamyltranspeptidase. CBP Part C 2004;138:105–12. https://doi.org/10.1016/j.cca.2004.06.001.Search in Google Scholar PubMed

36. Sunwoo, HH, Sim, LYM, Nakano, T, Hudson, RJ, Sim, JS. Glycosaminoglycans from growing antlers of wapiti (Cervus elaphus). Can J Anim Sci 1997;77:715–21. https://doi.org/10.4141/a97-033.Search in Google Scholar

37. Sunwoo, HH, Nakano, T, Hudson, RJ, Sim, JS. Isolation, characterization and localization of glycosaminoglycans in growing antlers of wapiti (Cervus elaphus). CBP Part B 1998;120:273–83. https://doi.org/10.1016/s0305-0491(98)10017-2.Search in Google Scholar

38. Sunwoo, HH, Nakano, T, Sim, JS. Effect of water-soluble extract from antler of wapiti (Cervus elaphus) on the growth of fibroblasts. Can J Anim Sci 1997;77:343–5. https://doi.org/10.4141/a96-121.Search in Google Scholar

Received: 2020-05-07

Accepted: 2020-09-23

Published Online: 2021-02-15

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Articles in the same Issue

https://doi.org/10.1515/jbcpp-2020-0140

Keywords for this article

bone density; bone turnover; calcium level; deer antler