4. Bai XC, Lu D, Bai J, Zheng H, Ke ZY, Li XM, Luo SQ: Oxidative stress inhibits osteoblastic differentiation of bone cells by ERK and NF-κB. Biochem Biophys Res Commun 2004, 314:197–207.10.1016/j.bbrc.2003.12.07314715266
6. Alikhani M, Alikhani Z, Boyd C, MacLellan CM, Raptis M, Liu R, Pischon N, Trackman PC, Gerstenfeld L, Graves DT: Advanced glycation end products stimulate osteoblast apoptosis via the MAP kinase and cytosolic apoptotic pathways. Bone 2007, 40:345–353.10.1016/j.bone.2006.09.011191320817064973
7. Hamada Y, Kitazawa S, Kitazawa R, Fujii H, Kasuga M, Fukagawa M: Histomorphometric analysis of diabetic osteopenia in streptozotocin-induced diabetic mice: A possible role of oxidative stress. Bone 2007, 40:1408–1414.10.1016/j.bone.2006.12.05717251074
8. Sanguineti R, Storace D, Monacelli F, Federici A, Odetti P: Pentosidine effects on human osteoblasts in vitro, in: Annals of the New York Academy of Sciences Blackwell Publishing Inc 2008, 1126(1):166–172.10.1196/annals.1433.04418448811
9. Abbassy MA, Watari I, Soma K: The effect of diabetes mellitus on rat mandibular bone formation and microarchitecture. Eur J Oral Sci 2010, 118:364–369.10.1111/j.1600-0722.2010.00739.x20662909
10. Zhen D, Chen Y, Tang X: Metformin reverses the deleterious effects of high glucose on osteoblast function. J Diabetes Complications 2010, 24:334–344.10.1016/j.jdiacomp.2009.05.00219628413
11. Okazaki K, Yamaguchi T, Tanaka KI, Notsu M, Ogawa N, Yano S, Sugimoto T: Advanced glycation end products (AGEs), but not high glucose, inhibit the osteoblastic differentiation of mouse stromal ST2 cells through the suppression of osterix expression, and inhibit cell growth and increasing cell apoptosis. Calcif Tissue Int 2012, 91:286–296.10.1007/s00223-012-9641-222903508
12. Zheng W, Wang S, Wang J, Jin F: Periodontitis promotes the proliferation and suppresses the differentiation potential of human periodontal ligament stem cells. Int J Mol Med 2015, 36:915–922.10.3892/ijmm.2015.2314456409026310866
16. Silva MJ, Brodt MD, Lynch MA, McKenzie JA, Tanouye KM, Nyman JS, Wang X: Type 1 diabetes in young rats leads to progressive trabecular bone loss, cessation of cortical bone growth, and diminished whole bone strength and fatigue life. J Bone Miner Res 2009, 24:1618–1627.10.1359/jbmr.090316273093119338453
18. Forsén L, Meyer HE, Midthjell K, Edna TH: Diabetes mellitus and the incidence of hip fracture: Results from the Nord-Trondelag health survey. Diabetologia 1999, 42:920–925.10.1007/s00125005124810491750
19. Vestergaard P, Rejnmark L, Mosekilde L: Diabetes and its complications and their relationship with risk of fractures in type 1 and 2 diabetes. Calcif Tissue Int 2009, 84:45–55.10.1007/s00223-008-9195-519067021
20. Vestergaard P: Discrepancies in bone mineral density and fracture risk in patients with type 1 and type 2 diabetes - A meta-analysis. Osteoporos Int 2007, 18:427–444.10.1007/s00198-006-0253-417068657
21. Hampson G, Evans C, Petitt RJ, Evans WD, Woodhead SJ, Peters JR, Ralston SH: Bone mineral density, collagen type 1 α 1 genotypes and bone turnover in premenopausal women with diabetes mellitus. Diabetologia 1998, 41:1314–1320.10.1007/s0012500510719833939
22. López-Ibarra P-J, Pastor MMC, Escobar-Jiménez F, Pardo MDS, González AG, Luna JDD, González AG, Requena MER, Diosdado MA:. Bone mineral density at time of clinical diagnosis of adult-onset type 1 diabetes mellitus. Endocr Pract 2001,. 7:346–351.10.4158/EP.7.5.34611585369
23. Mastrandrea LD, Wactawski-Wende J, Donahue RP, Hovey KM, Clark A, Quattrin T: Young women with type 1 diabetes have lower bone mineral density that persists over time. Diabetes Care 2008, 31:1729–1735.10.2337/dc07-2426251833318591404
24. Kristin K, Nicodemus BA, Aaron R, Folsom MD: Type 1 and Type 2 Diabetes and Incident Hip Fractures in Postmenopausal Women. Epidemiology 2001, 24:1192–1197.10.2337/diacare.24.7.119211423501
25. Lim DW, Kim YT: Anti-osteoporotic effects of Angelica sinensis (Oliv.) Diels extract on ovariectomized rats and its oral toxicity in rats. Nutrients 2014, 6(10): 4362–4372.10.3390/nu6104362421092225325255
27. Han X, Yang Y, Metwaly AM, Xue Y, Shi Y, Dou D: The Chinese herbal formulae (Yitangkang) exerts an antidiabetic effect through the regulation of substance metabolism and energy metabolism in type 2 diabetic rats. J Ethnopharmacol 2019, 239:111942.10.1016/j.jep.2019.11194231075380
29. Madić V, Stojanović-Radić Z, Jušković M, Jugović D, Žabar-Popović A, Vasiljević P:. Genotoxic and antigenotoxic potential of herbal mixture and five medicinal plants used in ethnopharmacology. South African J Bot 2019, 125:290–297.10.1016/j.sajb.2019.07.043
30. Madić V, Petrović A, Jušković M, Jugović D, Djordjević Lj, Stojanović G, Vasiljević P: Polyherbal mixture ameliorates hyperglycemia, hyperlipidemia and histopathological changes of pancreas, kidney and liver in a rat model of type 1 diabetes. J Ethnopharmacol 2021, 265:113210.10.1016/j.jep.2020.11321032795501
31. Liang W, Luo Z, Ge S, Li M, Du J, Yang M, Yan M, Ye Z, Luo Z: Oral administration of quercetin inhibits bone loss in rat model of diabetic osteopenia. Eur J Pharmacol 2011, 670:317–324.10.1016/j.ejphar.2011.08.01421914440
32. Abu Ayana MA, Elmasry NA, Shehata FI, Khalil NM: Efficiacy of quercetin on alveolar bone structure of rats with induced diabetes. Alexandria Dent J 2017, 42:141–146.10.21608/adjalexu.2017.57917
33. Banda M, Nyirenda J, Muzandu K, Sijumbila G, Mudenda S: Antihyperglycemic and Antihyperlipidemic Effects of Aqueous Extracts of Lannea edulis in Alloxan-Induced Diabetic Rats. Front Pharmacol 2018, 9-1099.10.3389/fphar.2018.01099617236030323764
34. Ay B, Parolia K, Liddell RS, Qiu Y, Grasselli G, Cooper DML, Davis JE: Hyperglycemia compromises Rat Cortical Bone by Increasing Osteocyte Lacunar Density and Decreasing Vascular Canal Volume. Commun Biol 2020, 3:20.10.1038/s42003-019-0747-1695240631925331
35. Mullender MG, Van Der Meer DD, Huiskes R, Lips P: Osteocyte density changes in aging and osteoporosis. Bone 1996, 18:109–113.10.1016/8756-3282(95)00444-0
36. Leite Duarte ME, da Silva RD: Histomorphometric analysis of the bone tissue in patients with non-insulin-dependent diabetes (DMNID). Rev Hosp Clin Fac Med 1996, 51:7–11.
38. He Y, Mu C, Shen X, Yuan Z, Liu J, Chen W, Lin C, Tao B, Liu B, Cai K:Peptide LL-37 coating on micro-structured titanium implants to facilitate bone formation in vivo via mesenchymal stem cell recruitment. Acta Biomater 2018, 80:412-424.10.1016/j.actbio.2018.09.036
39. Tuukkanen J, Koivukangas A, Jämsä T, Sundquist K, MacKay CA, Marks SC: Mineral Density and Bone Strength Are Dissociated in Long Bones of Rat Osteopetrotic Mutations. J Bone Miner Res 2000, 15:1905–1911.10.1359/jbmr.2000.15.10.1905
40. Chauhan S, Sharma A, Upadhyay NK, Singh G, Lal UR, Goyal R: In-vitro osteoblast proliferation and in-vivo anti-osteoporotic activity of Bombax ceiba with quantification of Lupeol, gallic acid and β-sitosterol by HPTLC and HPLC. BMC Complement Altern Med 2018:18.10.1186/s12906-018-2299-1
41. Domazetovic V, Marcucci G, Pierucci F, Bruno G, Di Cesare Mannelli L, Ghelardini C, Brandi ML, Iantomasi T, Meacci E, Vincenzini MT: Blueberry juice protects osteocytes and bone precursor cells against oxidative stress partly through SIRT1. FEBS Open Bio 2019, 9:1082–1096.10.1002/2211-5463.12634
42. Zeiger E: Illusions of safety: antimutagens can be mutagens, and anticarcinogens can be carcinogens. Mutat Res / Reviews in Mutat Res 2003, 543:191–194.10.1016/S1383-5742(02)00111-4
43. Mody N, Parhami F, Sarafian TA, Demer LL: Oxidative stress modulates osteoblastic differentiation of vascular and bone cells. Free Radic Biol Med 2001, 31:509–519.10.1016/S0891-5849(01)00610-4
44. El-Tantawy WH, Al Haleem ENA: Therapeutic effects of stem cell on hyperglycemia, hyperlipidemia, and oxidative stress in alloxan-treated rats. Mol Cell Biochem. 2014, 391:193-200.10.1007/s11010-014-2002-x24604673
46. Tsentidis C, Gourgiotis D, Kossiva L, et al. Higher levels of s- RANKL and osteoprotegerin in children and adolescents with type 1 diabetes mellitus may indicate increased osteoclast signaling and predisposition to lower bone mass: a multivariate cross-sectional analysis. Osteoporos Int. 2016; 27:1631-1643.10.1007/s00198-015-3422-526588909
47. Shah VN, Harrall KK, Shah CS, et al. Bone mineral density at femoral neck and lumbar spine in adults with type 1 diabetes: a meta-analysis and review of the literature. Osteoporos Int. 2017, 28:2601-2610.10.1007/s00198-017-4097-x28580510
48. Yano H, Ohya K, Amagasa T: Effects of Insulin on in vitro bone formation in fetal rat parietal bone. Endocr J. 1994, 41:293-300.10.1507/endocrj.41.2937951582
49. Cortizo AM, Sedlinsky C, McCarthy D, Blanco A, Schurman L: Osteogenic actions of the anti-diabetic drug metformin on osteoblasts in culture. Eur J Pharmacol. 2006, 536:38-4610.1016/j.ejphar.2006.02.03016564524
51. Gao Y, Li Y, Xue J, Jia Y, Hu J: Effect of the anti-diabetic drug metformin on bone mass in ovariectomized rats. Eur J Pharmacol. 2010, 635:231-263.10.1016/j.ejphar.2010.02.05120307532
52. Behera HN, Patnaik BK: Recovery from alloxan diabetes as revealed by collagen characteristics of bone, skin and tendon of Swiss Mice. Gerontology 1981, 27:32-36.10.1159/0002124467215817
54. Molinuevo MS, Schurman L, McCarthy AD, Cortizo AM, Tolosa MJ, Gangoiti MV, Arnol V, Sedlinsky C: Effect of metformin on bone marrow progenitor cell differentiation: in vivo and in vitro studies. J J Bone Miner Res 2010, 25: 211-221.10.1359/jbmr.09073219594306
57. Takebayashi J, Ishii R, Chen J, Matsumoto T, Ishimi Y, Tai A: Reassessment of antioxidant activity of arbutin: Multifaceted evaluation using five antioxidant assay systems. Free Radic. Res 2010, 44:473–478.10.3109/1071576100361076020166881
58. Jeszka-Skowron M, Krawczyk M, Zgoła-Grześkowiak A: Determination of antioxidant activity, rutin, quercetin, phenolic acids and trace elements in tea infusions: Influence of citric acid addition on extraction of metals. J Food Compos Anal 2015, 40:70-77.10.1016/j.jfca.2014.12.015
61. Hasan W, Ahmad S, Thakur H, Abbas M: In vitro regulation of osteoclast generation: a cost-effective strategy to combat osteoporosis with natural antioxidants and polyphenols like EGCG. Eur J Acad Res 2014, 2:2286-4822.
62. Nicolin, V., De Tommasi, N., Nori, S.L., Costantinides, F., Berton, F., Di Lenarda, R., 2019. Modulatory Effects of Plant Polyphenols on Bone Remodeling: A Prospective View From the Bench to Bedside. Front Endocrinol (Lausanne). 10, 494.10.3389/fendo.2019.00494666399531396157
64. Kyung TW, Lee JE, Shin HH, Choi HS: Rutin inhibits osteoclast formation by decreasing reactive oxygen species and TNF-α by inhibiting activation of NF-κB. Exp Mol Med 2008, 40:52–58.10.3858/emm.2008.40.1.52267932118305398
67. Yokoyama A, Sakakibara H, Crozier A, Kawai Y, Matsui A, Terao J, Kumazawa S, Shimoi K: Quercetin metabolites and protection against peroxynitrite-induced oxidative hepatic injury in rats. Free Radic Res 2009, 43:913-21.10.1080/1071576090313701019669999
68. Man X, Yang L, Liu S, Yang L, Li M, Fu Q: Arbutin promotes MC3T3-E1 mouse osteoblast precursor cell proliferation and differentiation via the Wnt/ß-catenin signaling pathway. Mol Med Rep 2019, 19:4637–4644.10.3892/mmr.2019.10125652280130957189
69. Prouillet C, Mazière J-C, Mazière C, Wattel A, Brazier M, Kamel S: Stimulatory effect of naturally occurring flavonols quercetin and kaempferol on alkaline phosphatase activity in MG-63 human osteoblasts through ERK and estrogen receptor pathway. Biochem Pharmacol 2004, 67:1307–1313.10.1016/j.bcp.2003.11.00915013846
70. Kanter M, Altan MF, Donmez S, Ocakci A, Kartal ME: The effects of quercetin on bone minerals, biomechanical behavior, and structure in streptozotocin-induced diabetic rats. Cell Biochem Funct 2007, 25:747–752.10.1002/cbf.139717265531
71. Derakhshanian H, Ghadbeigi S, Rezaian M, Bahremand A, Javanbakht MH, Golpaie A, Hosseinzadeh P, Tajik N, Dehpour AR: Quercetin improves bone strength in experimental biliary cirrhosis. Hepatol Res 2013, 43:394–400.10.1111/j.1872-034X.2012.01075.x22882531
72. Omori A, Yoshimura Y, Deyama Y, Suzuki K: Rosmarinic acid and arbutin suppress osteoclast differentiation by inhibiting superoxide and NFATc1 downregulation in RAW 264.7 cells. Biomed Reports 2015, 3:483–490.10.3892/br.2015.452448701826171153
73. Barhoma RA, Hegab II, Atef MM, El-Shamy AM: Unraveling the Role of Melatonin/ Quercetin in Attenuating the Metabolic and Bone Turnover Alternations in Iron Treated-Ovariectomized Female Rats. Med J Cairo Univ 2019, 87:2857-2870.10.21608/mjcu.2019.59320
74. Chen Y, Dai F, He Y, Chen Q, Xia Q, Cheng G, Lu Y, Zhang Q: Beneficial effects of hyperoside on bone metabolism in ovariectomized mice. Biomed Pharmacother 2018, 107:1175–1182.10.1016/j.biopha.2018.08.06930257331
76. Liu L, Wang D, Qin Y, Xu M, Zhou L, Xu W, Liu X, Ye L, Yue S, Zheng Q, Li D: Astragalin Promotes Osteoblastic Differentiation in MC3T3-E1 Cells and Bone Formation in vivo. Front Endocrinol (Lausanne) 2019, 10:228.10.3389/fendo.2019.00228647698431040823
77. Karadeniz F, Oh JH, Lee JI, Seo Y, Kong CS: 3,5-dicaffeoyl-epi-quinic acid from Atriplex gmelinii enhances the osteoblast differentiation of bone marrow-derived human mesenchymal stromal cells via WnT/BMP signaling and suppresses adipocyte differentiation via AMPK activation. Phytomedicine 2020, 71:153225.10.1016/j.phymed.2020.15322532464299