249
Views
21
CrossRef citations to date
0
Altmetric
Review

Relationship Between Metabolic Syndrome and Bone Health – An Evaluation of Epidemiological Studies and Mechanisms Involved

ORCID Icon, ORCID Icon, ORCID Icon & ORCID Icon
Pages 3667-3690 | Published online: 13 Oct 2020

References

  • Edwards MH, Dennison EM, Aihie Sayer A, Fielding R, Cooper C. Osteoporosis and sarcopenia in older age. Bone. 2015;80:126–130. doi:10.1016/j.bone.2015.04.016
  • Aspray TJ, Hill TR. Osteoporosis and the ageing skeleton. In: Harris JR, Korolchuk VI, editors. Biochemistry and Cell Biology of Ageing: Part II Clinical Science. Singapore: Springer Singapore; 2019:453–476.
  • Wang H, Ba Y, Xing Q, Du J-L. Diabetes mellitus and the risk of fractures at specific sites: a meta-analysis. BMJ Open. 2019;9(1):e024067. doi:10.1136/bmjopen-2018-024067
  • Johansson H, Kanis JA, Odén A, et al. A meta-analysis of the association of fracture risk and body mass index in women. J Bone Miner Res. 2014;29(1):223–233. doi:10.1002/jbmr.2017
  • Saeedi P, Petersohn I, Salpea P, et al. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: results from the International Diabetes Federation Diabetes Atlas, 9th edition. Diabetes Res Clin Pract. 2019;157:107843. doi:10.1016/j.diabres.2019.107843
  • Blüher M. Obesity: global epidemiology and pathogenesis. Nat Rev Endocrinol. 2019;15(5):288–298. doi:10.1038/s41574-019-0176-8
  • Wong SK, Chin K-Y, Suhaimi F, Ahmad F, Ima-Nirwana S. The relationship between metabolic syndrome and osteoporosis: a review. Nutrients. 2016;8(6):347. doi:10.3390/nu8060347
  • Xue P, Gao P, Li Y. The association between metabolic syndrome and bone mineral density: a meta-analysis. Endocrine. 2012;42(3):546–554. doi:10.1007/s12020-012-9684-1
  • Zhou J, Zhang Q, Yuan X, et al. Association between metabolic syndrome and osteoporosis: a meta-analysis. Bone. 2013;57(1):30–35. doi:10.1016/j.bone.2013.07.013
  • Eckstein N, Buchmann N, Demuth I, et al. Association between metabolic syndrome and bone mineral density–data from the Berlin Aging Study II (BASE-II). Gerontology. 2016;62(3):337–344. doi:10.1159/000434678
  • Kim T, Park S, Pak YS, Lee S, Lee EH. Association between metabolic syndrome and bone mineral density in Korea: the Fourth Korea National Health and Nutrition Examination Survey (KNHANES IV), 2008. J Bone Miner Metab. 2013;31(6):652–662. doi:10.1007/s00774-013-0459-4
  • Hernández JL, Olmos JM, Pariente E, et al. Metabolic syndrome and bone metabolism: the Camargo Cohort study. Menopause. 2010;17(5):955–961. doi:10.1097/gme.0b013e3181e39a15
  • World Health Organization. Assessment of Fracture Risk and Its Application to Screening for Postmenopausal Osteoporosis: Report of a World Health Organization Study Group. Geneva: World Health Organization; 1994.
  • Park KK, Kim SJ, Moon ES. Association between bone mineral density and metabolic syndrome in postmenopausal Korean women. Gynecol Obstet Invest. 2010;69(3):145–152. doi:10.1159/000264665
  • Grimston SK, Willows ND, Hanley DA. Mechanical loading regime and its relationship to bone mineral density in children. Med Sci Sports Exerc. 1993;25(11):1203–1210. doi:10.1249/00005768-199311000-00002
  • Chin K, Chan C, Subramaniam S, et al. Positive association between metabolic syndrome and bone mineral density among Malaysians. Int J Med Sci. 2020;17(16):2585–2593. doi:10.7150/ijms.49030
  • Kinjo M, Setoguchi S, Solomon DH. Bone mineral density in adults with the metabolic syndrome: analysis in a population-based U.S. sample. J Clin Endocrinol Metab. 2007;92(11):4161–4164. doi:10.1210/jc.2007-0757
  • von Muhlen D, Safii S, Jassal SK, Svartberg J, Barrett-Connor E. Associations between the metabolic syndrome and bone health in older men and women: the Rancho Bernardo Study. Osteoporos Int. 2007;18(10):1337–1344. doi:10.1007/s00198-007-0385-1
  • Wani K, Yakout SM, Ansari MGA, et al. Metabolic syndrome in Arab adults with low bone mineral density. Nutrients. 2019;11(6):1405. doi:10.3390/nu11061405
  • Kim BJ, Ahn SH, Bae SJ, et al. Association between metabolic syndrome and bone loss at various skeletal sites in postmenopausal women: a 3-year retrospective longitudinal study. Osteoporos Int. 2013;24(8):2243–2252. doi:10.1007/s00198-013-2292-y
  • Chan DC, Watts GF, Barrett PH, Burke V. Waist circumference, waist-to-hip ratio and body mass index as predictors of adipose tissue compartments in men. QJM. 2003;96(6):441–447. doi:10.1093/qjmed/hcg069
  • Pasco JA, Holloway KL, Dobbins AG, Kotowicz MA, Williams LJ, Brennan SL. Body mass index and measures of body fat for defining obesity and underweight: a cross-sectional, population-based study. BMC Obes. 2014;1(1):9. doi:10.1186/2052-9538-1-9
  • Kim HY, Kim Y. Associations of obesity with osteoporosis and metabolic syndrome in Korean postmenopausal women: a cross-sectional study using national survey data. Arch Osteoporos. 2019;14(1):64. doi:10.1007/s11657-019-0615-0
  • Chen DZ, Xu QM, Wu XX, et al. The combined effect of nonalcoholic fatty liver disease and metabolic syndrome on osteoporosis in postmenopausal females in Eastern China. Int J Endocrinol. 2018;2018:2314769. doi:10.1155/2018/2314769
  • Hwang DK, Choi HJ. The relationship between low bone mass and metabolic syndrome in Korean women. Osteoporos Int. 2010;21(3):425–431. doi:10.1007/s00198-009-0990-2
  • Kim KC, Shin DH, Lee SY, Im JA, Lee DC. Relation between obesity and bone mineral density and vertebral fractures in Korean postmenopausal women. Yonsei Med J. 2010;51(6):857–863. doi:10.3349/ymj.2010.51.6.857
  • Jeon YK, Lee JG, Kim SS, et al. Association between bone mineral density and metabolic syndrome in pre- and postmenopausal women. Endocr J. 2011;58(2):87–93. doi:10.1507/endocrj.K10E-297
  • Loke SS, Chang HW, Li WC. Association between metabolic syndrome and bone mineral density in a Taiwanese elderly population. J Bone Miner Metab. 2018;36(2):200–208.
  • Lin HH, Huang CY, Hwang LC. Association between metabolic syndrome and osteoporosis in Taiwanese middle-aged and elderly participants. Arch Osteoporos. 2018;13(1):48. doi:10.1007/s11657-018-0467-z
  • Alberti KG, Eckel RH, Grundy SM, et al. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation. 2009;120(16):1640–1645.
  • Kim H, Oh HJ, Choi H, Choi WH, Lim SK, Kim JG. The association between bone mineral density and metabolic syndrome: a Korean population-based study. J Bone Miner Metab. 2013;31(5):571–578. doi:10.1007/s00774-013-0446-9
  • National Cholesterol Education Program (NCEP) Expert Panel on Detection E, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III) final report. Circulation. 2002;106(25):3143–3421. doi:10.1161/circ.106.25.3143
  • Grundy SM, Cleeman JI, Daniels SR, et al. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation. 2005;112(17):2735–2752. doi:10.1161/CIRCULATIONAHA.105.169404
  • Kim YH, Cho KH, Choi YS, et al. Low bone mineral density is associated with metabolic syndrome in South Korean men but not in women: the 2008–2010 Korean National Health and Nutrition Examination Survey. Arch Osteoporos. 2013;8:142. doi:10.1007/s11657-013-0142-3
  • Chin KY, Ima-Nirwana S. Calcaneal quantitative ultrasound as a determinant of bone health status: what properties of bone does it reflect? Int J Med Sci. 2013;10(12):1778–1783. doi:10.7150/ijms.6765
  • Oo WM, Naganathan V, Bo MT, Hunter DJ. Clinical utilities of quantitative ultrasound in osteoporosis associated with inflammatory rheumatic diseases. Quant Imaging Med Surg. 2018;8(1):100–113. doi:10.21037/qims.2018.02.02
  • Qin Y-X, Lin W, Mittra E, et al. Prediction of trabecular bone qualitative properties using scanning quantitative ultrasound. Acta Astronaut. 2013;92(1):79–88. doi:10.1016/j.actaastro.2012.08.032
  • Langton CM, Langton DK. Comparison of bone mineral density and quantitative ultrasound of the calcaneus: site-matched correlation and discrimination of axial BMD status. Br J Radiol. 2000;73(865):31–35. doi:10.1259/bjr.73.865.10721317
  • Moayyeri A, Adams JE, Adler RA, et al. Quantitative ultrasound of the heel and fracture risk assessment: an updated meta-analysis. Osteoporos Int. 2012;23(1):143–153. doi:10.1007/s00198-011-1817-5
  • Nayak S, Olkin I, Liu H, et al. Meta-analysis: accuracy of quantitative ultrasound for identifying patients with osteoporosis. Ann Intern Med. 2006;144(11):832–841. doi:10.7326/0003-4819-144-11-200606060-00009
  • Subramaniam S, Chan CY, Soelaiman IN, et al. The performance of a calcaneal quantitative ultrasound device, CM-200, in stratifying osteoporosis risk among Malaysian population aged 40 years and above. Diagnostics. 2020;10(4):178. doi:10.3390/diagnostics10040178
  • Bulló M, Garcia-Aloy M, Basora J, Covas MI, Salas-Salvado J. Bone quantitative ultrasound measurements in relation to the metabolic syndrome and type 2 diabetes mellitus in a cohort of elderly subjects at high risk of cardiovascular disease from the PREDIMED study. J Nutr Health Aging. 2011;15(10):939–944. doi:10.1007/s12603-011-0046-0
  • Cvijetic S, Pavlovic M, Pasalic D, Dodig S. Ultrasound bone measurement in an older population with metabolic syndrome. Aging Clin Exp Res. 2011;23(1):29–34. doi:10.1007/BF03324950
  • Hernández JL, Olmos JM, de Juan J, et al. Heel quantitative ultrasound parameters in subjects with the metabolic syndrome: the Camargo Cohort Study. Maturitas. 2011;69(2):162–167. doi:10.1016/j.maturitas.2011.02.017
  • Chin KY, Ima-Nirwana S, Mohamed IN, et al. The association between bone health indicated by calcaneal quantitative ultrasound and metabolic syndrome in Malaysian men. J Diabetes Metab Disord. 2015;14:9. doi:10.1186/s40200-015-0136-3
  • Muka T, Trajanoska K, Kiefte-de Jong JC, et al. The association between metabolic syndrome, bone mineral density, hip bone geometry and fracture risk: the Rotterdam study. PLoS One. 2015;10(6):e0129116. doi:10.1371/journal.pone.0129116
  • Nelson LR, Bulun SE. Estrogen production and action. J Am Acad Dermatol. 2001;45(3):S116–124. doi:10.1067/mjd.2001.117432
  • Migliaccio S, Greco EA, Fornari R, Donini LM, Lenzi A. Is obesity in women protective against osteoporosis? Diabetes Metab Syndr Obes. 2011;4:273–282. doi:10.2147/DMSO.S11920
  • Ma L, Oei L, Jiang L, et al. Association between bone mineral density and type 2 diabetes mellitus: a meta-analysis of observational studies. Eur J Epidemiol. 2012;27(5):319–332. doi:10.1007/s10654-012-9674-x
  • Schneider AL, Williams EK, Brancati FL, Blecker S, Coresh J, Selvin E. Diabetes and risk of fracture-related hospitalization: the atherosclerosis risk in communities study. Diabetes Care. 2013;36(5):1153–1158. doi:10.2337/dc12-1168
  • Wang Y, Dai J, Zhong W, Hu C, Lu S, Chai Y. Association between serum cholesterol level and osteoporotic fractures. Front Endocrinol (Lausanne). 2018;9:30. doi:10.3389/fendo.2018.00030
  • Ahmed LA, Schirmer H, Berntsen GK, Fønnebø V, Joakimsen RM. Features of the metabolic syndrome and the risk of non-vertebral fractures: the Tromsø study. Osteoporos Int. 2006;17(3):426–432. doi:10.1007/s00198-005-0003-z
  • El Maghraoui A, Rezqi A, El Mrahi S, Sadni S, Ghozlani I, Mounach A. Osteoporosis, vertebral fractures and metabolic syndrome in postmenopausal women. BMC Endocr Disord. 2014;14:93. doi:10.1186/1472-6823-14-93
  • Lee SH, Baek S, Ahn SH, et al. Association between metabolic syndrome and incident fractures in Korean men: a 3-year follow-up observational study using national health insurance claims data. J Clin Endocrinol Metab. 2014;99(5):1615–1622. doi:10.1210/jc.2013-3608
  • Yu CY, Chen FP, Chen LW, Kuo SF, Chien RN. Association between metabolic syndrome and bone fracture risk: a community-based study using a fracture risk assessment tool. Medicine (Baltimore). 2017;96(50):e9180. doi:10.1097/MD.0000000000009180
  • Szulc P, Varennes A, Delmas PD, Goudable J, Chapurlat R. Men with metabolic syndrome have lower bone mineral density but lower fracture risk–the MINOS study. J Bone Miner Res. 2010;25(6):1446–1454. doi:10.1002/jbmr.13
  • Sun M, Cao M, Fu Q, et al. Association of calcaneal quantitative ultrasound parameters with metabolic syndrome in middle-aged and elderly Chinese: a large population-based cross-sectional study. BMC Endocr Disord. 2014;14:14. doi:10.1186/1472-6823-14-14
  • Qin L, Yang Z, Zhang W, et al. Metabolic syndrome and osteoporotic fracture: a population-based study in China. BMC Endocr Disord. 2016;16(1):27. doi:10.1186/s12902-016-0106-x
  • Wang D, Liu N, Gao Y, Li P, Tian M. Association between metabolic syndrome and osteoporotic fracture in middle-aged and elderly Chinese peoples. Cell Biochem Biophys. 2014;70(2):1297–1303. doi:10.1007/s12013-014-0054-x
  • Marcellini S, Henriquez JP, Bertin A. Control of osteogenesis by the canonical Wnt and BMP pathways in vivo: cooperation and antagonism between the canonical Wnt and BMP pathways as cells differentiate from osteochondroprogenitors to osteoblasts and osteocytes. Bioessays. 2012;34(11):953–962. doi:10.1002/bies.201200061
  • Rucci N. Molecular biology of bone remodelling. Clin Cases Miner Bone Metab. 2008;5(1):49–56.
  • Siddiqui JA, Partridge NC. Physiological bone remodeling: systemic regulation and growth factor involvement. Physiology (Bethesda, Md). 2016;31(3):233–245.
  • Ono T, Hayashi M, Sasaki F, Nakashima T. RANKL biology: bone metabolism, the immune system, and beyond. Inflamm Regen. 2020;40:2.
  • Shetty S, Kapoor N, Bondu JD, Thomas N, Paul TV. Bone turnover markers: emerging tool in the management of osteoporosis. Indian J Endocrinol Metab. 2016;20(6):846–852. doi:10.4103/2230-8210.192914
  • Oliva-Olivera W, Leiva Gea A, Lhamyani S, et al. Differences in the osteogenic differentiation capacity of omental adipose-derived stem cells in obese patients with and without metabolic syndrome. Endocrinology. 2015;156(12):4492–4501. doi:10.1210/en.2015-1413
  • Lerchbaum E, Schwetz V, Nauck M, Völzke H, Wallaschofski H, Hannemann A. Lower bone turnover markers in metabolic syndrome and diabetes: the population-based Study of Health in Pomerania. Nutr Metab Cardiovasc Dis. 2015;25(5):458–463. doi:10.1016/j.numecd.2015.02.002
  • Gannagé-Yared MH, Fares F, Semaan M, Khalife S, Jambart S. Circulating osteoprotegerin is correlated with lipid profile, insulin sensitivity, adiponectin and sex steroids in an ageing male population. Clin Endocrinol (Oxf). 2006;64(6):652–658. doi:10.1111/j.1365-2265.2006.02522.x
  • Nabipour I, Kalantarhormozi M, Larijani B, Assadi M, Sanjdideh Z. Osteoprotegerin in relation to type 2 diabetes mellitus and the metabolic syndrome in postmenopausal women. Metabolism. 2010;59(5):742–747. doi:10.1016/j.metabol.2009.09.019
  • Pérez de Ciriza C, Moreno M, Restituto P, et al. Circulating osteoprotegerin is increased in the metabolic syndrome and associates with subclinical atherosclerosis and coronary arterial calcification. Clin Biochem. 2014;47(18):272–278. doi:10.1016/j.clinbiochem.2014.09.004
  • Bernardi S, Fabris B, Thomas M, et al. Osteoprotegerin increases in metabolic syndrome and promotes adipose tissue proinflammatory changes. Mol Cell Endocrinol. 2014;394(1–2):13–20. doi:10.1016/j.mce.2014.06.004
  • Bonewald LF. The role of the osteocyte in bone and nonbone disease. Endocrinol Metab Clin North Am. 2017;46(1):1–18. doi:10.1016/j.ecl.2016.09.003
  • Bellido T. Osteocyte-driven bone remodeling. Calcif Tissue Int. 2014;94(1):25–34. doi:10.1007/s00223-013-9774-y
  • Ali A, Ali A, Ahmad W, et al. Deciphering the role of WNT signaling in metabolic syndrome-linked Alzheimer’s disease. Mol Neurobiol. 2020;57(1):302–314.
  • Abou Ziki MD, Mani A. The interplay of canonical and noncanonical Wnt signaling in metabolic syndrome. Nutr Res. 2019;70:18–25. doi:10.1016/j.nutres.2018.06.009
  • Embi N, Rylatt DB, Cohen P. Glycogen synthase kinase-3 from rabbit skeletal muscle. Separation from cyclic-AMP-dependent protein kinase and phosphorylase kinase. Eur J Biochem. 1980;107(2):519–527. doi:10.1111/j.1432-1033.1980.tb06059.x
  • Gaur T, Lengner CJ, Hovhannisyan H, et al. Canonical WNT signaling promotes osteogenesis by directly stimulating Runx2 gene expression. J Biol Chem. 2005;280(39):33132–33140. doi:10.1074/jbc.M500608200
  • Delgado-Calle J, Sato AY, Bellido T. Role and mechanism of action of sclerostin in bone. Bone. 2017;96:29–37. doi:10.1016/j.bone.2016.10.007
  • Wong SK, Chin KY, Ima-Nirwana S. The effects of tocotrienol on bone peptides in a rat model of osteoporosis induced by metabolic syndrome: the possible communication between bone cells. Int J Environ Res Public Health. 2019;16(18):3313. doi:10.3390/ijerph16183313
  • Stoian M, Stoica V. The role of disturbances of phosphate metabolism in metabolic syndrome. Maedica. 2014;9(3):255–260.
  • Jüppner H. Phosphate and FGF-23. Kidney Int Suppl. 2011;79(121):S24–S27. doi:10.1038/ki.2011.27
  • Perwad F, Zhang MY, Tenenhouse HS, Portale AA. Fibroblast growth factor 23 impairs phosphorus and vitamin D metabolism in vivo and suppresses 25-hydroxyvitamin D-1alpha-hydroxylase expression in vitro. Am J Physiol Renal Physiol. 2007;293(5):F1577–1583. doi:10.1152/ajprenal.00463.2006
  • Mirza MAI, Alsiö J, Hammarstedt A, et al. Circulating fibroblast growth factor-23 is associated with fat mass and dyslipidemia in two independent cohorts of elderly individuals. Arterioscler Thromb Vasc Biol. 2011;31(1):219–227. doi:10.1161/ATVBAHA.110.214619
  • Gateva A, Assyov Y, Tsakova A, Kamenov ZJH. metabolisme mrH-uSHe. Prediabetes is characterized by higher FGF23 levels and higher prevalence of vitamin D deficiency compared to normal glucose tolerance subjects. Horm Metab Res. 2019;51(2):106–111. doi:10.1055/a-0813-3164
  • Cao JJ. Effects of obesity on bone metabolism. J Orthop Surg Res. 2011;6:30. doi:10.1186/1749-799X-6-30
  • Purohit A, Reed MJ. Regulation of estrogen synthesis in postmenopausal women. Steroids. 2002;67(12):979–983. doi:10.1016/S0039-128X(02)00046-6
  • Hetemäki N, Savolainen-Peltonen H, Tikkanen MJ, et al. Estrogen metabolism in abdominal subcutaneous and visceral adipose tissue in postmenopausal women. J Clin Endocrinol Metab. 2017;102(12):4588–4595. doi:10.1210/jc.2017-01474
  • Nishimura S, Manabe I, Nagai R. Adipose tissue inflammation in obesity and metabolic syndrome. Discov Med. 2009;8(41):55–60.
  • Jonas MI, Kurylowicz A, Bartoszewicz Z, et al. Interleukins 6 and 15 levels are higher in subcutaneous adipose tissue, but obesity is associated with their increased content in visceral fat depots. Int J Mol Sci. 2015;16(10):25817–25830. doi:10.3390/ijms161025817
  • Agidigbi TS, Kim C. Reactive oxygen species in osteoclast differentiation and possible pharmaceutical targets of ROS-mediated osteoclast diseases. Int J Mol Sci. 2019;20(14):3576. doi:10.3390/ijms20143576
  • Migliaccio S, Di Nisio A, Mele C, et al. Obesity and hypovitaminosis D: causality or casualty? Int J Obes Suppl. 2019;9(1):20–31. doi:10.1038/s41367-019-0010-8
  • Di Nisio A, Sabovic I, De Toni L, et al. Testosterone is sequestered in dysfunctional adipose tissue, modifying androgen-responsive genes. Int J Obes (Lond). 2020;44(7):1617–1625. doi:10.1038/s41366-020-0568-9
  • Zhang M, Li P, Zhu Y, et al. Higher visceral fat area increases the risk of vitamin D insufficiency and deficiency in Chinese adults. Nutr Metab (Lond). 2015;12:50. doi:10.1186/s12986-015-0046-x
  • Khan M, Joseph F. Adipose tissue and adipokines: the association with and application of adipokines in obesity. Scientifica. 2014;2014:328592. doi:10.1155/2014/328592
  • Reid IR, Baldock PA, Cornish J. Effects of leptin on the skeleton. Endocr Rev. 2018;39(6):938–959. doi:10.1210/er.2017-00226
  • Liu K, Liu P, Liu R, Wu X, Cai M. Relationship between serum leptin levels and bone mineral density: a systematic review and meta-analysis. Clin Chim Acta. 2015;444:260–263. doi:10.1016/j.cca.2015.02.040
  • Biver E, Salliot C, Combescure C, et al. Influence of adipokines and ghrelin on bone mineral density and fracture risk: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2011;96(9):2703–2713. doi:10.1210/jc.2011-0047
  • Pal China S, Sanyal S, Chattopadhyay N. Adiponectin signaling and its role in bone metabolism. Cytokine. 2018;112:116–131. doi:10.1016/j.cyto.2018.06.012
  • Jia P, Bao L, Chen H, et al. Risk of low-energy fracture in type 2 diabetes patients: a meta-analysis of observational studies. Osteoporos Int. 2017;28(11):3113–3121.
  • Dragsbæk K, Neergaard JS, Laursen JM, et al. Metabolic syndrome and subsequent risk of type 2 diabetes and cardiovascular disease in elderly women: challenging the current definition. Medicine. 2016;95(36):e4806–e4806. doi:10.1097/MD.0000000000004806
  • Nowotny K, Jung T, Höhn A, Weber D, Grune T. Advanced glycation end products and oxidative stress in type 2 diabetes mellitus. Biomolecules. 2015;5(1):194–222. doi:10.3390/biom5010194
  • Suzuki R, Fujiwara Y, Saito M, et al. Intracellular accumulation of advanced glycation end products induces osteoblast apoptosis via endoplasmic reticulum stress. J Bone Miner Res. 2020. doi:10.1002/jbmr.4053
  • Li Z, Li C, Zhou Y, et al. Advanced glycation end products biphasically modulate bone resorption in osteoclast-like cells. Am J Physiol Endocrinol Metab. 2016;310(5):E355–366. doi:10.1152/ajpendo.00309.2015
  • Tanaka K, Yamaguchi T, Kanazawa I, Sugimoto T. Effects of high glucose and advanced glycation end products on the expressions of sclerostin and RANKL as well as apoptosis in osteocyte-like MLO-Y4-A2 cells. Biochem Biophys Res Commun. 2015;461(2):193–199. doi:10.1016/j.bbrc.2015.02.091
  • Samakkarnthai P, Sfeir JG, Atkinson EJ, et al. SUN-LB68 advanced glycation endproducts are associated with worse bone material strength in older adults with and without type 2 diabetes. J Endocrine Soc. 2020;4(Supplement_1). doi:10.1210/jendso/bvaa046.2045.
  • Samakkarnthai P, Sfeir JG, Atkinson EJ, et al. Determinants of bone material strength and cortical porosity in patients with type 2 diabetes mellitus. J Clin Endocrinol Metab. 2020;105(10). doi:10.1210/clinem/dgaa388.
  • Moseley KF, Chia CW, Simonsick EM, Egan JM, Ferrucci L, Sellmeyer DE. Sex-specific differences in progressive glucose intolerance and hip geometry: the Baltimore longitudinal study of aging. Osteoporos Int. 2015;26(5):1555–1562. doi:10.1007/s00198-015-3027-z
  • Kim TY, Schafer AL. Diabetes and Bone Marrow Adiposity. Curr Osteoporos Rep. 2016;14(6):337–344.
  • Zhang N, Jiang H, Bai Y, et al. The molecular mechanism study of insulin on proliferation and differentiation of osteoblasts under high glucose conditions. Cell Biochem Funct. 2019;37(5):385–394. doi:10.1002/cbf.3415
  • Burghardt AJ, Issever AS, Schwartz AV, et al. High-resolution peripheral quantitative computed tomographic imaging of cortical and trabecular bone microarchitecture in patients with type 2 diabetes mellitus. J Clin Endocrinol Metab. 2010;95(11):5045–5055. doi:10.1210/jc.2010-0226
  • Trierweiler H, Kisielewicz G, Hoffmann Jonasson T, Rasmussen Petterle R, Aguiar Moreira C, Zeghbi Cochenski Borba V. Sarcopenia: a chronic complication of type 2 diabetes mellitus. Diabetol Metab Syndr. 2018;10(1):25. doi:10.1186/s13098-018-0326-5
  • Yeung SSY, Reijnierse EM, Pham VK, et al. Sarcopenia and its association with falls and fractures in older adults: a systematic review and meta-analysis. J Cachexia Sarcopenia Muscle. 2019;10(3):485–500.
  • Caudarella R, Vescini F, Rizzoli E, Francucci CM. Salt intake, hypertension, and osteoporosis. J Endocrinol Invest. 2009;32(4Suppl):15–20.
  • Cruz DN. The renal tubular Na-Cl co-transporter (NCCT): a potential genetic link between blood pressure and bone density? Nephrol Dial Transplant. 2001;16(4):691–694. doi:10.1093/ndt/16.4.691-a
  • Itoh T, Fairall L, Amin K, et al. Structural basis for the activation of PPARgamma by oxidized fatty acids. Nat Struct Mol Biol. 2008;15(9):924–931. doi:10.1038/nsmb.1474
  • Zhuang H, Zhang X, Zhu C, et al. Molecular mechanisms of PPAR-γ governing MSC osteogenic and adipogenic differentiation. Curr Stem Cell Res Ther. 2016;11(3):255–264. doi:10.2174/1574888X10666150531173309
  • Mazière C, Savitsky V, Galmiche A, Gomila C, Massy Z, Mazière JC. Oxidized low density lipoprotein inhibits phosphate signaling and phosphate-induced mineralization in osteoblasts. Involvement of oxidative stress. Biochim Biophys Acta. 2010;1802(11):1013–1019. doi:10.1016/j.bbadis.2010.07.010
  • Brodeur MR, Brissette L, Falstrault L, Ouellet P, Moreau R. Influence of oxidized low-density lipoproteins (LDL) on the viability of osteoblastic cells. Free Radic Biol Med. 2008;44(4):506–517. doi:10.1016/j.freeradbiomed.2007.08.030
  • Mazière C, Salle V, Gomila C, Mazière JC. Oxidized low density lipoprotein enhanced RANKL expression in human osteoblast-like cells. Involvement of ERK, NFkappaB and NFAT. Biochim Biophys Acta. 2013;1832(10):1756–1764. doi:10.1016/j.bbadis.2013.05.033
  • Dawodu D, Patecki M, Dumler I, Haller H, Kiyan Y. oxLDL inhibits differentiation of mesenchymal stem cells into osteoblasts via the CD36 mediated suppression of Wnt signaling pathway. Mol Biol Rep. 2019;46(3):3487–3496. doi:10.1007/s11033-019-04735-5
  • Dawodu D, Patecki M, Hegermann J, Dumler I, Haller H, Kiyan Y. oxLDL inhibits differentiation and functional activity of osteoclasts via scavenger receptor-A mediated autophagy and cathepsin K secretion. Sci Rep. 2018;8(1):11604. doi:10.1038/s41598-018-29963-w
  • Weivoda MM, Oursler MJ. The roles of small GTPases in osteoclast biology. Curr Res. 2014;3:1000161.
  • Wan Hasan WN, Chin KY, Jolly JJ, Abd Ghafar N, Soelaiman IN. Identifying potential therapeutics for osteoporosis by exploiting the relationship between mevalonate pathway and bone metabolism. Endocr Metab Immune Disord Drug Targets. 2018;18(5):450–457. doi:10.2174/1871530318666180423122409
  • Brodeur MR, Brissette L, Falstrault L, Moreau R. HDL3 reduces the association and modulates the metabolism of oxidized LDL by osteoblastic cells: a protection against cell death. J Cell Biochem. 2008;105(6):1374–1385. doi:10.1002/jcb.21938
  • Eren E, Ellidag HY, Aydin O, Yılmaz N. HDL-associated paraoxonase 1 as a bridge between postmenopausal osteoporosis and cardiovascular disease. Chonnam Med J. 2014;50(3):75–81. doi:10.4068/cmj.2014.50.3.75
  • Inoue M, Niki M, Ozeki Y, et al. High-density lipoprotein suppresses tumor necrosis factor alpha production by mycobacteria-infected human macrophages. Sci Rep. 2018;8(1):6736. doi:10.1038/s41598-018-24233-1
  • Singh A, Mehdi AA, Srivastava RN, Verma NS. Immunoregulation of bone remodelling. Int J Crit Illn Inj Sci. 2012;2(2):75–81. doi:10.4103/2229-5151.97271
  • Wang X, Chen B, Sun J, et al. Iron-induced oxidative stress stimulates osteoclast differentiation via NF-κB signaling pathway in mouse model. Metabolism. 2018;83:167–176. doi:10.1016/j.metabol.2018.01.005
  • Zhao B. TNF and bone remodeling. Curr Osteoporos Rep. 2017;15(3):126–134. doi:10.1007/s11914-017-0358-z
  • Redlich K, Smolen JS. Inflammatory bone loss: pathogenesis and therapeutic intervention. Nat Rev Drug Discov. 2012;11(3):234–250.
  • Boyce BF, Xiu Y, Li J, Xing L, Yao Z. NF-κB-mediated regulation of osteoclastogenesis. Endocrinol Metab. 2015;30(1):35–44. doi:10.3803/EnM.2015.30.1.35
  • Krum SA, Chang J, Miranda-Carboni G, Wang C-Y. Novel functions for NFκB: inhibition of bone formation. Nat Rev Rheumatol. 2010;6(10):607–611. doi:10.1038/nrrheum.2010.133
  • Volpe CMO, Villar-Delfino PH, Dos Anjos PMF, Nogueira-Machado JA. Cellular death, reactive oxygen species (ROS) and diabetic complications. Cell Death Dis. 2018;9(2):119. doi:10.1038/s41419-017-0135-z
  • Vona R, Gambardella L, Cittadini C, Straface E, Pietraforte D. Biomarkers of oxidative stress in metabolic syndrome and associated diseases. Oxid Med Cell Longev. 2019;2019:8267234. doi:10.1155/2019/8267234
  • Biswas SK. Does the Interdependence between oxidative stress and inflammation explain the antioxidant paradox? Oxid Med Cell Longev. 2016;2016:5698931. doi:10.1155/2016/5698931
  • Domazetovic V, Marcucci G, Iantomasi T, Brandi ML, Vincenzini MT. Oxidative stress in bone remodeling: role of antioxidants. Clin Cases Miner Bone Metab. 2017;14(2):209–216. doi:10.11138/ccmbm/2017.14.1.209
  • Zhang B, Xie Q-Y, Quan Y, Pan X-M, Liao D-F. Reactive oxygen species induce cell death via Akt signaling in rat osteoblast-like cell line ROS 17/2.8. Toxicol Ind Health. 2015;31(12):1236–1242. doi:10.1177/0748233713491801
  • Srikanthan K, Feyh A, Visweshwar H, Shapiro JI, Sodhi K. Systematic review of metabolic syndrome biomarkers: a panel for early detection, management, and risk stratification in the West Virginian population. Int J Med Sci. 2016;13(1):25–38. doi:10.7150/ijms.13800
  • de Pablo P, Cooper MS, Buckley CD. Association between bone mineral density and C-reactive protein in a large population-based sample. Arthritis Rheum. 2012;64(8):2624–2631. doi:10.1002/art.34474
  • Ilesanmi-Oyelere BL, Schollum L, Kuhn-Sherlock B, et al. Inflammatory markers and bone health in postmenopausal women: a cross-sectional overview. Immun Ageing. 2019;16:15. doi:10.1186/s12979-019-0155-x
  • Gulyás K, Horváth Á, Végh E, et al. Effects of 1-year anti-TNF-α therapies on bone mineral density and bone biomarkers in rheumatoid arthritis and ankylosing spondylitis. Clin Rheumatol. 2020;39(1):167–175. doi:10.1007/s10067-019-04771-3
  • Adil M, Khan RA, Kalam A, et al. Effect of anti-diabetic drugs on bone metabolism: evidence from preclinical and clinical studies. Pharmacol Rep. 2017;69(6):1328–1340. doi:10.1016/j.pharep.2017.05.008
  • Hung YC, Lin CC, Chen HJ, et al. Severe hypoglycemia and hip fracture in patients with type 2 diabetes: a nationwide population-based cohort study. Osteoporos Int. 2017;28(7):2053–2060. doi:10.1007/s00198-017-4021-4
  • Zhang Z, Cao Y, Tao Y, et al. Sulfonylurea and fracture risk in patients with type 2 diabetes mellitus: a meta-analysis. Diabetes Res Clin Pract. 2020;159:107990. doi:10.1016/j.diabres.2019.107990
  • Wiens M, Etminan M, Gill SS, Takkouche B. Effects of antihypertensive drug treatments on fracture outcomes: a meta-analysis of observational studies. J Intern Med. 2006;260(4):350–362. doi:10.1111/j.1365-2796.2006.01695.x
  • Soltani S, Hunter GR, Kazemi A, Shab-Bidar S. The effects of weight loss approaches on bone mineral density in adults: a systematic review and meta-analysis of randomized controlled trials. Osteoporos Int. 2016;27(9):2655–2671.
  • Seimon RV, Wild-Taylor AL, Keating SE, et al. Effect of weight loss via severe vs moderate energy restriction on lean mass and body composition among postmenopausal women with obesity: the TEMPO diet randomized clinical trial. JAMA Netw Open. 2019;2(10):e1913733–e1913733. doi:10.1001/jamanetworkopen.2019.13733
  • Hunter GR, Plaisance EP, Fisher G. Weight loss and bone mineral density. Curr Opin Endocrinol Diabetes Obes. 2014;21(5):358–362. doi:10.1097/MED.0000000000000087
  • Liu C, Wu D, Zhang JF, et al. Changes in bone metabolism in morbidly obese patients after bariatric surgery: a meta-analysis. Obes Surg. 2016;26(1):91–97. doi:10.1007/s11695-015-1724-5
  • Zhang Q, Chen Y, Li J, et al. A meta-analysis of the effects of bariatric surgery on fracture risk. Obes Rev. 2018;19(5):728–736. doi:10.1111/obr.12665
  • Tian Z, Fan XT, Li SZ, Zhai T, Dong J. Changes in bone metabolism after sleeve gastrectomy versus gastric bypass: a meta-analysis. Obes Surg. 2020;30(1):77–86. doi:10.1007/s11695-019-04119-5
  • Ben-Porat T, Elazary R, Sherf-Dagan S, et al. Bone health following bariatric surgery: implications for management strategies to attenuate bone loss. Adv Nutr. 2018;9(2):114–127.
  • Alberti KGMM, Zimmet PZ. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus. Provisional report of a WHO consultation. Diabetic Med. 1998;15(7):539–553. doi:10.1002/(SICI)1096-9136(199807)15:7<539::AID-DIA668>3.0.CO;2-S
  • Expert Panel on Detection E, and Treatment of High Blood Cholesterol in Adults. Executive summary of the third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA. 2001;285(19):2486–2497. doi:10.1001/jama.285.19.2486
  • Alberti KG, Zimmet P, Shaw J. The metabolic syndrome–a new worldwide definition. Lancet. 2005;366(9491):1059–1062. doi:10.1016/S0140-6736(05)67402-8
  • Kim HY, Choe JW, Kim HK, et al. Negative association between metabolic syndrome and bone mineral density in Koreans, especially in men. Calcif Tissue Int. 2010;86(5):350–358. doi:10.1007/s00223-010-9347-2