Anti-osteoporotic effects of melatonin and misoprostol in glucocorticoid-induced osteoporosis: An experimental study

Authors

Keywords:

Glucocorticoids, Osteoporosis, Melatonin, Misoprostol

Abstract

Aim: Although there are some treatment options for glucocorticoid induced osteoporosis (GIO), new drug alternatives are still needed. In this study, we aimed to determine the protective effects of misoprostol and melatonin in an experimental GIO model.

Methods: The rats were grouped into four, with 10 rats in each group. The 1st group was chosen as the control group, which were not intervened with. Group 2 was the steroid group, group 3 the misoprostol group and group 4, the melatonin group. To the rats in groups 2, 3 and 4, 10 mg/kg subcutaneous methylprednisolone was administered for 28 days. To the rats of the 3rd group, 200 mg/day misoprostol was given per day by a cannula to the stomach. The rats in the 4th group received 5mg/kg intraperitoneal melatonin during this 28-days period. Lumbar vertebrae and femur bone mineral density (BMD) of all rats were measured by Dual-energy X-ray absorptiometry (DEXA) and assessed in pre- and post-treatment periods.

Results: In the steroid group, when the pre- and post-treatment-BMD values of the rats were compared, statistically significant decreases were found in vertebrae, whole femur, femur proximal, femur diaphysis and distal femur bone regions (P=0.011, P=0.005, P=0.007, P=0.005 and P=0.013; respectively). In the misoprostol group, a statistically significant decrease was observed only in the whole femur region (P=0.012) when the pre- and post-treatment BMD values of the rats were compared, while no significant changes were observed in vertebrae, femur proximal, femur diaphysis and distal femur bone regions (P=0.093, P=0.401, P=0.161 and P=0.123; respectively). In the melatonin group, when the pre- and post-treatment BMD values of the rats were compared, a statistically significant decrease was observed only in the vertebrae region (P=0.009), no significant changes were observed in whole femur, femur proximal, femur diaphysis and distal femur bone regions (P=0.386, P=0.445, P=1.000 and P=0.483; respectively). 

Conclusion: Positive effects of misoprostol and melatonin on bone metabolism were determined in this experimental study. Misoprostol and melatonin seem to be potential agents that can be used in the prevention of GIO.

Downloads

Download data is not yet available.

References

Weinstein RS. Glucocorticoids, osteocytes, and skeletal fragility: the role of bone vascularity. Bone. 2010;46(3):564-70.

Weinstein RS. Glucocorticoid-induced bone disease. N. Engl. J. Med. 2011;365(1):62-70.

Achiou Z, Toumi H, Touvier J, Boudenot A, Uzbekov R, Ominsky MS. Sclerostin antibody and interval treadmill training effects in a rodent model of glucocorticoid-induced osteopenia. Bone. 2015;81:691-701.

Canali E, Mazziotti G, Giustina A, Bilezikian JP. Glucocorticoid-induced osteoporosis: pathophysiology and therapy. Osteoporos Int. 2007;18(10):1319-28.

Maricic M, Deal C, Dore R, Laster A. 2017 American college of rheumatology guideline for the prevention and treatment of glucocorticoid-Induced osteoporosis: comment on the article by Buckley et al. Arthritis Care Res (Hoboken). 2018;70(6):949-50.

Raisz LG, Woodiel FN. Effects of misoprostol on bone resorption and formation in organ culture. Am J Ther. 1996;3(2):134-8.

Milcan A, Colak M, Eskandari G. Misoprostol enhances early fracture healing: a preliminary biochemical study on rats. Bone. 2007;41(4):611-3.

Yasar L, Sönmez AS, Utku N, Ozcan J, Cebi Z, Savan K, at al. Effect of misoprostol on bone mineral density in women with postmenopausal osteoporosis.cProstaglandins Other Lipid Mediat. 2006;79(3-4):199-205.

Tresguerres IF, Clemente C, Blanco L, Khraisat A, Tamimi F, Tresguerres JA. Effects of local melatonin application on implant osseointegration. Clin Implant Dent Relat Res. 2012;14(3):395-9.

Cutando A, Gómez-Moreno G, Arana C, Muñoz F, Lopez-Peña M, Stephenson J, et al. Melatonin stimulates osteointegration of dental implants. J Pineal Res. 2008;45(2):174-9.

Manolagas SC. From estrogen-centric to aging and oxidative stress: a revised perspective of the pathogenesis of osteoporosis. Endocr Rev. 2010;31(3):266-300.

Zhai M, Li B, Duan W, Jing L, Zhang B, Zhang M, et al. Melatonin ameliorates myocardial ischemia reperfusion injury through SIRT3-dependent regulation of oxidative stress and apoptosis. J Pineal Res. 2011;63(2):1-33.

Weinstein RS. Glucocorticoid-induced osteoporosis. Rev Endocr Metab Disord. 2001;2:65-73.

Mazziotti G, Angeli A, Bilezikian JP, Canalis E, Giustina A. Glucocorticoid-induced osteoporosis: an update. Trends Endocrinol Metab. 2006;17:144-49.

Compston J. Glucocorticoid-induced osteoporosis: an update. Endocrine. 2018;61(1):7-16.

Sutter S, Nishiyama KK, Kepley A, Wang J, McMahon DJ, Guo XE, at al. Abnormalities in cortical bone, trabecular plates and stiffness in postmenopausal women treated with glucocorticoids. J. Clin. Endocrinol. Metab. 2014;99(11):4231-40.

Hulley PA, Conradie MM, Langeveldt CR, Hough FS. Glucocorticoid-induced osteoporosis in the rat is prevented by the tyrosine phosphatase inhibitor, sodium orthovanadate. Bone. 2002;31:220-9.

Gruber HE, Hoelscher G, Loeffler B, Chow Y, Ingram JA, Halligan W, et al. Prostaglandin E1 and misoprostol increase epidermal growth factor production in 3D-cultured human annulus cells. Spine J. 2009;9(9):760-6.

Gardner CR, Blanqué R, Cottereaux C. Mechanisms involved in prostaglandin-induced increase in bone resorption in neonatal mouse calvaria. Prostaglandins Leukot Essent Fatty Acids. 2001;64(2):117-25.

Okman-Kilic T, Sagıroglu C. Anabolik agents as new treatment strategy in osteoporosis.In Flores MV (ed). Topics in Osteoporosis, Rijeka: In tech; 2013. P 241-57.

Sonmez AS, Birincioglu M, Ozer MK, Kutlu R, Chuong CJ. Effects of misoprostol on bone loss in ovariectomized rats. Prostaglandins Other Lipid Mediat. 1999;57(2-3):113-8.

Ahmet-Camcioglu N, Okman-Kilic T, Durmus-Altun G, Ekuklu G, M. Effects of strontium ranelate, raloxifene and misoprostol on bone mineral density in ovariectomized rats. Eur J Obstet Gynecol Reprod Biol. 2009;147(2):192-4.

Koyama H, Nakade O, Takada Y, Kaku T, Lau KH. Melatonin at pharmacologic doses increases bone mass by suppressing resorption through down-regulation of the RANKL-mediated osteoclast formation and activation. J Bone Miner Res. 2002;17(7):1219-29.

Sethi S, Radio NM, Kotlarczyk MP, Chen CT, Wei YH, Jockers R, at al. Determination of the minimal melatonin exposure required to induce osteoblast differentiation from human mesenchymal stem cells and these effects on downstream signaling pathways. J Pineal Res. 2010;49(3):222-38.

Sharan K, Lewis K, Furukawa T, Yadav VK. Regulation of bone mass through pineal-derived melatonin-MT2 receptor pathway. J Pineal Res. 2017;63(2):1-12.

Amstrup AK, Sikjaer T, Pedersen SB, Heickendorff L, Mosekilde L, Rejnmark L. Reduced fat mass and increased lean mass in response to 1 year of melatonin treatment in postmenopausal women: A randomized placebo-controlled trial. Clin Endocrinol. 2016;84(3):342-7.

Tresguerres IF, Tamimi F, Eimar H, Barralet JE, Prieto S, Torres J, et al. Melatonin dietary supplement as an anti-aging therapy for age-related bone loss. Rejuvenation Res. 2014;17(4):341-6.

Xu L, Zhang L, Wang Z, Li C, Li S, Li L, et al. Melatonin suppresses estrogen deficiency-ınduced osteoporosis and promotes osteoblastogenesis by inactivating the NLRP3 inflammasome. Calcif Tissue Int. 2018;103(4):400-10.

Lee S, Le NH, Kang D. Melatonin alleviates oxidative stress-inhibited osteogenesis of human bone marrow-derived mesenchymal stem cells through AMPK activation. Int J Med Sci. 2018;15(10):1083-91.

Adams JE. Dual-energy X-ray absorptiometry, In: Guglielmi G, editor. Osteoporosis and bone densitometry measurements. Springer (New York). 2013:101-22.

Downloads

Published

2019-08-01

Issue

Section

Research Article

How to Cite

1.
Kutlu O, Üzüm İsa, Durmuşcan M, Kekilli E, Parlakpınar H, Kutlu NO. Anti-osteoporotic effects of melatonin and misoprostol in glucocorticoid-induced osteoporosis: An experimental study. J Surg Med [Internet]. 2019 Aug. 1 [cited 2022 Dec. 7];3(8):568-73. Available from: https://jsurgmed.com/article/view/595295