The Role of Serum Expression Levels of Microrna-21 on Bone Mineral Density in Hypostrogenic Postmenopausal Women with Osteoporosis: Study on Level of RANKL, OPG, TGFβ-1, Sclerostin, RANKL/OPG Ratio, and Physical Activity

I Nyoman Suarjana, Harry Isbagio, Pradana Soewondo, Ichramsjah A Rachman, Mohammad Sadikin, Joedo Prihartono, Safarina G Malik, Joewono Soeroso


Background: MiR-21 is known to play a role in osteoclast proliferation and differentiation, but the role of serum miR-21 expression in osteoporosis remains unclear. Previous research found that serum miR-21 expression was positively correlated with bone mineral density in postmenopausal osteoporosis patients, but other factors involved in postmenopausal osteoporosis still unknown. This study aimed to determine the role of serum miR-21 expression, concentration of RANKL, OPG, TGF-β1, sclerostin and serum calcium, RANKL/OPG ratio, and physical activity on bone mineral density of spine in hypoestrogenic postmenopausal women with osteoporosis (PMOP) compared with no osteoporosis (PMNOP), with point of interest on the expression of serum miR-21. Methods: this study was conducted by comparative cross-sectional design. The subjects were divided into 2 groups of PMOP and PMNOP. We used an absolute quantification real-time PCR method to determine serum miR-21 expressions level. Results: Median of serum miR-21 expression at the PMOP group was significantly higher compared to PMNOP group (p = 0.001). Serum miR-21 expression, RANKL, RANKL/OPG ratio, and physical activity were significantly correlated with BMD values in the PMOP group. Moderate physical activity was significantly negatively correlated with serum miR-21 expression. We also obtained a linear regression equation BMD = 1.373-0.085*Ln.miR-21-0.176*Log10.RANKL (R2 = 52.5%). Conclusion: serum miR-21 expression in PMOP was higher compared with PMNOP. Serum miR-21 expression proved to have a negative effect on spinal BMD values in hypoestrogenic postmenopausal women with osteoporosis of 8.5%. Obtained equation of BMD = 1.373-0.085*Ln.miR-21-0.176*Log10.RANKL can explain the value of spinal BMD by 52.5%.


BMD; osteoporosis; serum miR-21


Kanis JA. WHO. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. Report of a WHO Study Group. World Health Organization technical report series. 1994;843:1–129.

Lane NE. Epidemiology, etiology, and diagnosis of osteoporosis. Am J Obstet Gynecol. 2006;194:S3–11.

MENKES RI. Pedoman pengendalian osteoporosis. 2008.

World Health Organization: Research on the menopause in the 1990’s. Report of a WHO Scientific Group. World Health Organ Tech Rep Ser.1996;866,12–4.

Meiyanti. Epidemiology of osteoporosis in postmenopausal women aged 47 to 60 years. Univ Med. 2010;29:169–76.

Zahoor S, Ayub U. Prevalence of osteoporosis in postmenopausal women visiting police & services hospital, Peshawar, NWFP. JPMI. 2010;24:04–8.

Lau EM, Chung HL, Ha PC, Tang H, Lam D. Bone mineral density, anthropometric indices, and the prevalence of osteoporosis in northern (Beijing) chinese and southern (Hong Kong) chinese women-the largest comparative study to date. J Clin Densitom. 2015;pii:S1094-6950(14)00240–6.

Neyro Bilbao JL, Cano Sánchez A, Palacios Gil-Antuñano S. Bone metabolism regulation through RANK-RANKL-OPG system. Rev Osteoporos Metab Miner. 2011;2.

Sapir-Koren R, Livshits G.Osteocyte control of bone remodeling: is sklerostin a key molecular coordinator of the balanced bone resorption-formation cycles?. Osteoporos Int. 2014;DOI 10.1007/s00198–014–2808–0.

Sun M, Zhou X, Chen L, et al. The Regulatory Roles of MicroRNAs in bone remodeling and perspectives as biomarkers in osteoporosis. Bio Med Res Int. 2016;2016:1-11.

Lian JB, Stein GS, van Wijnen AJ, et al. MicroRNA control of bone formation and homeostasis. Nat Rev Endocrinol. 2012;31;8:212–27.

Sugatani T, Hruska KA. Down-regulation of miR-21 biogenesis by estrogen action contributes to osteoclastic apoptosis. J Cell Biochem. 2013;114:1217–22.

Sugatani T, Vacher J, Hruska KA. A microRNA expression signature of osteoclastogenesis. Blood. 2011;117:3648–57.

Seeliger C, Karpinski K, HaugAT, et al. Five freely circulating miRNAs and bone tissue miRNAs are associated with osteoporotic fractures. J Bone Miner Res. 2014;29:1715–7.

Panach L, Mifsut D, Tarín JJ, Cano A, García-Pérez MÁ. Serum circulating MicroRNAs as biomarkers of osteoporotic fracture. Calcif Tissue Int. 2015;97:495–505.

Li H, Wang Z, Fu Q, Zhang J. Plasma miRNA levels correlate with sensitivity to bone mineral density in postmenopausal osteoporosis patients. Biomarkers. 2014;19:553–6.

Yavropoulou MP, Anastasilakis AD, Makras P, Tsalikakis DG, Grammatiki M, Yovos JG. Expression of microRNAs that regulate bone turnover in the serum of postmenopausal women with low bone mass and vertebral fractures. Eur J Endocrinol. 2017;176:169–76.

Zi-qiang W, Yan-qin LU, Jin-xiang HAN. MicroRNAs: important mediators of ossification. Chin Med J. 2012:125:4111–6.

Pitari MR, Rossi M, Amodio N, et al. Inhibition of miR-21 restores RANKL/OPG ratio in multiple myeloma-derived bone marrow stromal cells and impairs the resorbing activity of mature osteoclasts. Oncotarget. 2015;6:27343–58.

Stuss M, Sewerynek E, Król I, Stępień-Kłos W, Jędrzejczyk S. Assessment of OPG, RANKL, bone turnover markers serum levels, and BMD after treatment with strontium ranelate and ibandronate in patients with postmenopausal osteoporosis. Endokrynol Pol. 2016;67:174–84.

Coetzee M, Kruger MC. Osteoprotegerin-receptor? South activator of nuclear factor-kappa B ligand ratio: a new approach to osteoporosis treatment. South Med J. 2004;97:506–11.

Wu X-Y, Peng Y-Q, Zhang H, et al. Relationship between serum levels of OPG and TGF-β with decreasing rate of BMD in native chinese women. Int J Endocrinol. 2013;ID 727164: 2013/727164.

Estai MA, Suhaimi F, Das S, Shuid AN, Mohamed Z, Soelaiman I-N. Expression of TGF-β1 in the blood during fracture repair in an estrogen-deficient rat model. Clinics. 2011;66:2113–9.

Full Text: PDF


  • There are currently no refbacks.

Copyright (c) 2019 Acta Medica Indonesiana