{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T22:39:00Z","timestamp":1790635140979,"version":"4.1.0"},"reference-count":116,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2019,9,5]],"date-time":"2019-09-05T00:00:00Z","timestamp":1567641600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Because of its high prevalence worldwide, osteoporosis is considered a serious public health concern. Many known risk factors for developing osteoporosis have been identified and are crucial if planning health care needs. Recently, an association between uric acid (UA) and bone fractures had been explored. Extracellular UA exhibits antioxidant properties by effectively scavenging free radicals in human plasma, but this benefit might be disturbed by the hydrophobic lipid layer of the cell membrane. In contrast, intracellular free oxygen radicals are produced during UA degradation, and superoxide is further enhanced by interacting with NADPH oxidase. This intracellular oxidative stress, together with inflammatory cytokines induced by UA, stimulates osteoclast bone resorption and inhibits osteoblast bone formation. UA also inhibits vitamin D production and thereby results in hyper-parathyroidism, which causes less UA excretion in the intestines and renal proximal tubules by inhibiting the urate transporter ATP-binding cassette subfamily G member 2 (ABCG2). At normal or high levels, UA is associated with a reduction in bone mineral density and protects against bone fracture. However, in hyperuricemia or gout arthritis, UA increases bone fracture risk because oxidative stress and inflammatory cytokines can increase bone resorption and decrease bone formation. Vitamin D deficiency, and consequent secondary hyperparathyroidism, can further increase bone resorption and aggravated bone loss in UA-induced osteoporosis.<\/jats:p>","DOI":"10.3390\/nu11092111","type":"journal-article","created":{"date-parts":[[2019,9,6]],"date-time":"2019-09-06T02:59:22Z","timestamp":1567738762000},"page":"2111","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":130,"title":["The Paradoxical Role of Uric Acid in Osteoporosis"],"prefix":"10.3390","volume":"11","author":[{"given":"Kun-Mo","family":"Lin","sequence":"first","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Mackay Memorial Hospital, Taipei 10449, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9452-5179","authenticated-orcid":false,"given":"Chien-Lin","family":"Lu","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Fu Jen Catholic University Hospital, School of Medicine, Fu Jen Catholic University, New Taipei City 24352 Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9023-8925","authenticated-orcid":false,"given":"Kuo-Chin","family":"Hung","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Min-Sheng General Hospital, Taoyuan City 33044, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9662-654X","authenticated-orcid":false,"given":"Pei-Chen","family":"Wu","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Mackay Memorial Hospital, Taipei 10449, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi-Feng","family":"Pan","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Mackay Memorial Hospital, Taipei 10449, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih-Jen","family":"Wu","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Mackay Memorial Hospital, Taipei 10449, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren-Si","family":"Syu","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Min-Sheng General Hospital, Taoyuan City 33044, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin-Shuen","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung 81362, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4965-0285","authenticated-orcid":false,"given":"Po-Jen","family":"Hsiao","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Fu Jen Catholic University Hospital, School of Medicine, Fu Jen Catholic University, New Taipei City 24352 Taiwan"},{"name":"Division of Nephrology, Department of Internal Medicine, Taoyuan Armed Forces General Hospital &amp; Tri-Service General Hospital, National Defense Medical Center, Taipei 32551, Taiwan"},{"name":"Department of Life Sciences, National Central University, Taoyuan City 32001, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuo-Cheng","family":"Lu","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Fu Jen Catholic University Hospital, School of Medicine, Fu Jen Catholic University, New Taipei City 24352 Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,9,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/0026-0495(86)90152-6","article-title":"Sex differences in uric acid metabolism in adults: Evidence for a lack of influence of estradiol-17 beta (e2) on the renal handling of urate","volume":"35","author":"Anton","year":"1986","journal-title":"Metab. Clin. Exp."},{"key":"ref_2","unstructured":"Williamson, M.A., Snyder, L.M., and Wallach, J.B. (2011). Wallach\u2019s Interpretation of Diagnostic Tests, Wolters Kluwer\/Lippincott Williams & Wilkins. [9th ed.]."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3136","DOI":"10.1002\/art.30520","article-title":"Prevalence of gout and hyperuricemia in the us general population: The national health and nutrition examination survey 2007\u20132008","volume":"63","author":"Zhu","year":"2011","journal-title":"Arthritis Rheum."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/0002-9343(87)90441-4","article-title":"Asymptomatic hyperuricemia. Risks and consequences in the normative aging study","volume":"82","author":"Campion","year":"1987","journal-title":"Am. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/0002-9343(67)90004-6","article-title":"Epidemiology of gout and hyperuricemia. A long-term population study","volume":"42","author":"Hall","year":"1967","journal-title":"Am. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1159\/000489145","article-title":"Urate-lowering agents in asymptomatic hyperuricemia: Role of urine sediment analysis and musculoskeletal ultrasound","volume":"43","author":"Viggiano","year":"2018","journal-title":"Kidney Blood Press. Res."},{"key":"ref_7","unstructured":"(2003). Prevention and management of osteoporosis. World Health Organ. Tech. Rep. Ser., 921, 1\u2013164."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Griffith, J.F. (2013). Bone marrow changes in osteoporosis. Osteoporosis and Bone Densitometry Measurements, Springer.","DOI":"10.1007\/174_2012_614"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1002\/jmri.20367","article-title":"Osteoporosis is associated with increased marrow fat content and decreased marrow fat unsaturation: A proton mr spectroscopy study","volume":"22","author":"Yeung","year":"2005","journal-title":"J. Magn. Reson. Imaging"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.acra.2015.11.009","article-title":"Bone marrow lipid profiles from peripheral skeleton as potential biomarkers for osteoporosis: A 1h-mr spectroscopy study","volume":"23","author":"Capuani","year":"2016","journal-title":"Acad. Radiol."},{"key":"ref_11","first-page":"114","article-title":"The \u201costeoporosis disease\u201d","volume":"6","author":"Guido","year":"2009","journal-title":"Clin. Cases Miner. Bone Metab."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/j.molmed.2014.06.001","article-title":"Osteoclasts: More than \u2018bone eaters\u2019","volume":"20","author":"Charles","year":"2014","journal-title":"Trends Mol. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1038\/sj.ki.5002645","article-title":"The breast cancer resistance protein transporter abcg2 is expressed in the human kidney proximal tubule apical membrane","volume":"73","author":"Huls","year":"2008","journal-title":"Kidney Int."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.ijcard.2015.08.109","article-title":"Regulation of uric acid metabolism and excretion","volume":"213","author":"Maiuolo","year":"2016","journal-title":"Int. J. Cardiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"10338","DOI":"10.1073\/pnas.0901249106","article-title":"Identification of a urate transporter, abcg2, with a common functional polymorphism causing gout","volume":"106","author":"Woodward","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1080\/15257770.2013.866679","article-title":"Abcg2 dysfunction increases the risk of renal overload hyperuricemia","volume":"33","author":"Matsuo","year":"2014","journal-title":"Nucleosides Nucleotides Nucleic Acids"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3755","DOI":"10.1038\/srep03755","article-title":"Abcg2 dysfunction causes hyperuricemia due to both renal urate underexcretion and renal urate overload","volume":"4","author":"Matsuo","year":"2014","journal-title":"Sci. Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1038\/ncomms1756","article-title":"Decreased extra-renal urate excretion is a common cause of hyperuricemia","volume":"3","author":"Ichida","year":"2012","journal-title":"Nat. Commun."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1093\/rheumatology\/kex467","article-title":"Association between abcg2 rs2231142 and poor response to allopurinol: Replication and meta-analysis","volume":"57","author":"Wallace","year":"2018","journal-title":"Rheumatology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.jfma.2015.12.002","article-title":"Association of abcg2 rs2231142-a allele and serum uric acid levels in male and obese individuals in a han taiwanese population","volume":"116","author":"Cheng","year":"2017","journal-title":"J. Formos. Med. Assoc."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Kini, U., and Nandeesh, B.N. (2012). Physiology of bone formation, remodeling, and metabolism. Radionuclide and Hybrid Bone Imaging, Springer.","DOI":"10.1007\/978-3-642-02400-9_2"},{"key":"ref_22","first-page":"1353","article-title":"Physiology and pathophysiology of bone remodeling","volume":"45","author":"Raisz","year":"1999","journal-title":"Clin. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.abb.2011.11.011","article-title":"Bone effects of vitamin d\u2014Discrepancies between in vivo and in vitro studies","volume":"523","author":"Suda","year":"2012","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"263","DOI":"10.7150\/ijms.5.263","article-title":"Eph receptors and ephrin signaling pathways: A role in bone homeostasis","volume":"5","author":"Edwards","year":"2008","journal-title":"Int. J. Med. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"148","DOI":"10.4161\/cam.20888","article-title":"Bone cell interactions through eph\/ephrin: Bone modeling, remodeling and associated diseases","volume":"6","author":"Matsuo","year":"2012","journal-title":"Cell Adh. Migr."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.cca.2018.05.035","article-title":"Role of nutritional vitamin d in osteoporosis treatment","volume":"484","author":"Hou","year":"2018","journal-title":"Clin. Chim. Acta"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1016\/j.jtbi.2009.09.021","article-title":"Theoretical investigation of the role of the rank-rankl-opg system in bone remodeling","volume":"262","author":"Pivonka","year":"2010","journal-title":"J. Theor. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1016\/S2213-8587(17)30188-2","article-title":"Osteoporosis treatment: Recent developments and ongoing challenges","volume":"5","author":"Khosla","year":"2017","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.abb.2003.10.011","article-title":"Triuret: A novel product of peroxynitrite-mediated oxidation of urate","volume":"423","author":"Robinson","year":"2004","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1080\/15257770902736400","article-title":"Reactions of peroxynitrite with uric acid: Formation of reactive intermediates, alkylated products and triuret, and in vivo production of triuret under conditions of oxidative stress","volume":"28","author":"Gersch","year":"2009","journal-title":"Nucleosides Nucleotides Nucleic Acids"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/j.bcp.2005.05.009","article-title":"Interactions of peroxynitrite with uric acid in the presence of ascorbate and thiols: Implications for uncoupling endothelial nitric oxide synthase","volume":"70","author":"Kuzkaya","year":"2005","journal-title":"Biochem. Pharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/1743-7075-1-10","article-title":"Uric acid: A new look at an old risk marker for cardiovascular disease, metabolic syndrome, and type 2 diabetes mellitus: The urate redox shuttle","volume":"1","author":"Hayden","year":"2004","journal-title":"Nutr. Metab."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1073\/pnas.95.2.675","article-title":"Uric acid, a natural scavenger of peroxynitrite, in experimental allergic encephalomyelitis and multiple sclerosis","volume":"95","author":"Hooper","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2501","DOI":"10.12659\/MSM.899852","article-title":"Hyperuricemia-related diseases and xanthine oxidoreductase (xor) inhibitors: An overview","volume":"22","author":"Chen","year":"2016","journal-title":"Med. Sci. Monit."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1186\/s13075-018-1668-y","article-title":"The relationship between ferritin and urate levels and risk of gout","volume":"20","author":"Fatima","year":"2018","journal-title":"Arthritis Res. Ther."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1080\/10715760400026088","article-title":"The association between serum ferritin and uric acid in humans","volume":"39","author":"Ghio","year":"2005","journal-title":"Free Radic. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"6858","DOI":"10.1073\/pnas.78.11.6858","article-title":"Uric acid provides an antioxidant defense in humans against oxidant- and radical-caused aging and cancer: A hypothesis","volume":"78","author":"Ames","year":"1981","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1002\/(SICI)1097-4547(19980901)53:5<613::AID-JNR11>3.0.CO;2-1","article-title":"Uric acid protects neurons against excitotoxic and metabolic insults in cell culture, and against focal ischemic brain injury in vivo","volume":"53","author":"Yu","year":"1998","journal-title":"J. Neurosci. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1067\/msy.2000.104486","article-title":"Effect of uric acid on liver injury during hemorrhagic shock","volume":"127","author":"Tsukada","year":"2000","journal-title":"Surgery"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1007\/BF00370582","article-title":"Uric acid as radical scavenger and antioxidant in the heart","volume":"415","author":"Becker","year":"1989","journal-title":"Pflugers Arch."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/j.jare.2016.11.004","article-title":"Uric acid in the pathogenesis of metabolic, renal, and cardiovascular diseases: A review","volume":"8","author":"Salem","year":"2017","journal-title":"J. Adv. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1089\/ars.2008.2378","article-title":"Redox signaling across cell membranes","volume":"11","author":"Fisher","year":"2009","journal-title":"Antioxidants Redox Signal."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1709","DOI":"10.1016\/S0021-9258(19)77933-2","article-title":"Free radical metabolite of uric acid","volume":"263","author":"Maples","year":"1988","journal-title":"J. Biol. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1006\/abbi.1999.1491","article-title":"Uric acid oxidation by peroxynitrite: Multiple reactions, free radical formation, and amplification of lipid oxidation","volume":"372","author":"Santos","year":"1999","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1080\/15257770802138558","article-title":"Uric acid: The oxidant-antioxidant paradox","volume":"27","author":"Sautin","year":"2008","journal-title":"Nucleosides Nucleotides Nucleic Acids"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1042\/bj3400143","article-title":"When and why a water-soluble antioxidant becomes pro-oxidant during copper-induced low-density lipoprotein oxidation: A study using uric acid","volume":"340","author":"Bagnati","year":"1999","journal-title":"Biochem. J."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1089\/scd.2014.0484","article-title":"The role of reactive oxygen species in mesenchymal stem cell adipogenic and osteogenic differentiation: A review","volume":"24","author":"Atashi","year":"2015","journal-title":"Stem Cells Dev"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1006\/bbrc.1998.8175","article-title":"Nitric oxide superoxide and peroxynitrite modulate osteoclast activity","volume":"243","author":"Mancini","year":"1998","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1359\/jbmr.2002.17.3.434","article-title":"Evidence that peroxynitrite affects human osteoblast proliferation and differentiation","volume":"17","author":"Fernandes","year":"2002","journal-title":"J. Bone Miner. Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"209","DOI":"10.11138\/ccmbm\/2017.14.1.209","article-title":"Oxidative stress in bone remodeling: Role of antioxidants","volume":"14","author":"Domazetovic","year":"2017","journal-title":"Clin. Cases Miner. Bone Metab."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.bbrc.2003.12.073","article-title":"Oxidative stress inhibits osteoblastic differentiation of bone cells by erk and nf-kappab","volume":"314","author":"Bai","year":"2004","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/S0891-5849(01)00610-4","article-title":"Oxidative stress modulates osteoblastic differentiation of vascular and bone cells","volume":"31","author":"Mody","year":"2001","journal-title":"Free Radic. Biol. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1083\/jcb.126.3.765","article-title":"Nadph-oxidase expression and in situ production of superoxide by osteoclasts actively resorbing bone","volume":"126","author":"Steinbeck","year":"1994","journal-title":"J. Cell Biol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/8756-3282(94)90821-4","article-title":"Superoxide and bone resorption","volume":"15","author":"Key","year":"1994","journal-title":"Bone"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1172\/JCI114485","article-title":"Oxygen-derived free radicals stimulate osteoclastic bone resorption in rodent bone in vitro and in vivo","volume":"85","author":"Garrett","year":"1990","journal-title":"J. Clin. Investig."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/8756-3282(96)00177-9","article-title":"Hydrogen peroxide, but not superoxide, stimulates bone resorption in mouse calvariae","volume":"19","author":"Fraser","year":"1996","journal-title":"Bone"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/S0006-291X(05)80311-0","article-title":"Stimulation of osteoclastic bone resorption by hydrogen peroxide","volume":"183","author":"Bax","year":"1992","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1080\/14397595.2017.1369924","article-title":"Tnf-alpha potentiates uric acid-induced interleukin-1beta (il-1beta) secretion in human neutrophils","volume":"28","author":"Yokose","year":"2018","journal-title":"Mod. Rheumatol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1172\/JCI115142","article-title":"Urate crystals stimulate production of tumor necrosis factor alpha from human blood monocytes and synovial cells. Cytokine mrna and protein kinetics, and cellular distribution","volume":"87","author":"Malawista","year":"1991","journal-title":"J. Clin. Investig."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1186\/s13075-018-1704-y","article-title":"Monosodium urate crystals reduce osteocyte viability and indirectly promote a shift in osteocyte function towards a proinflammatory and proresorptive state","volume":"20","author":"Chhana","year":"2018","journal-title":"Arthritis Res. Ther."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1883","DOI":"10.1084\/jem.167.6.1883","article-title":"Molecular cloning of a human monocyte-derived neutrophil chemotactic factor (mdncf) and the induction of mdncf mrna by interleukin 1 and tumor necrosis factor","volume":"167","author":"Matsushima","year":"1988","journal-title":"J. Exp. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1038\/ni.1831","article-title":"Thioredoxin-interacting protein links oxidative stress to inflammasome activation","volume":"11","author":"Zhou","year":"2010","journal-title":"Nat. Immunol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1007\/s11926-010-0092-3","article-title":"Update on biology: Uric acid and the activation of immune and inflammatory cells","volume":"12","author":"Martinon","year":"2010","journal-title":"Curr. Rheumatol. Rep."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1093\/intimm\/dxq431","article-title":"Il-1 plays an important role in the bone metabolism under physiological conditions","volume":"22","author":"Manaka","year":"2010","journal-title":"Int. Immunol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.1084\/jem.182.5.1461","article-title":"Interleukin (il)-6 induction of osteoclast differentiation depends on il-6 receptors expressed on osteoblastic cells but not on osteoclast progenitors","volume":"182","author":"Udagawa","year":"1995","journal-title":"J. Exp. Med."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1172\/JCI200316069","article-title":"Mechanisms of tnf-alpha- and rankl-mediated osteoclastogenesis and bone resorption in psoriatic arthritis","volume":"111","author":"Ritchlin","year":"2003","journal-title":"J. Clin. Investig."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1084\/jem.191.2.275","article-title":"Tumor necrosis factor alpha stimulates osteoclast differentiation by a mechanism independent of the odf\/rankl-rank interaction","volume":"191","author":"Kobayashi","year":"2000","journal-title":"J. Exp. Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.yexcr.2016.03.004","article-title":"Allopurinol and oxypurinol promote osteoblast differentiation and increase bone formation","volume":"342","author":"Orriss","year":"2016","journal-title":"Exp. Cell Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.metabol.2013.09.018","article-title":"Uric acid suppresses 1 alpha hydroxylase in vitro and in vivo","volume":"63","author":"Chen","year":"2014","journal-title":"Metab. Clin. Exp."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1681\/ASN.V441035","article-title":"Effect of uric acid on plasma levels of 1,25(oh)2d in renal failure","volume":"4","author":"Vanholder","year":"1993","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"e61159","DOI":"10.1371\/journal.pone.0061159","article-title":"Association between vitamin d insufficiency and elevated serum uric acid among middle-aged and elderly Chinese Han women","volume":"8","author":"Peng","year":"2013","journal-title":"PLoS ONE"},{"key":"ref_72","first-page":"87","article-title":"Negative association between serum 25 hydroxy vitamin d and serum uric acid among stage 35 chronic kidneydisease patient","volume":"8","author":"Elnokeety","year":"2018","journal-title":"Ann. Med. Health Sci. Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"R56","DOI":"10.1186\/ar3769","article-title":"The independent association between parathyroid hormone levels and hyperuricemia: A national population study","volume":"14","author":"Hui","year":"2012","journal-title":"Arthritis Res. Ther."},{"key":"ref_74","first-page":"1738","article-title":"Parathyroid function and uric acid metabolism","volume":"59","author":"Yoneda","year":"1983","journal-title":"Nihon Naibunpi Gakkai Zasshi"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.2147\/CIA.S90233","article-title":"Significant association between parathyroid hormone and uric acid level in men","volume":"10","author":"Chin","year":"2015","journal-title":"Clin. Interv. Aging"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1007\/s00268-007-9091-6","article-title":"Serum levels of uric acid and diabetes mellitus influence survival after surgery for primary hyperparathyroidism: A prospective cohort study","volume":"31","author":"Bergenfelz","year":"2007","journal-title":"World J. Surg."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1007\/BF01655570","article-title":"Decrease in serum uric acid level following parathyroidectomy in patients with primary hyperparathyroidism","volume":"10","author":"Duh","year":"1986","journal-title":"World J. Surg."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1007\/s00198-006-0189-8","article-title":"Teriparatide in postmenopausal women with osteoporosis and mild or moderate renal impairment","volume":"18","author":"Miller","year":"2007","journal-title":"Osteoporos. Int."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"807","DOI":"10.2169\/internalmedicine.31.807","article-title":"Renal handling of urate in two patients with hyperuricemia and primary hyperparathyroidism","volume":"31","author":"Hisatome","year":"1992","journal-title":"Intern. Med."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1016\/j.kint.2016.09.041","article-title":"Down-regulation of abcg2, a urate exporter, by parathyroid hormone enhances urate accumulation in secondary hyperparathyroidism","volume":"91","author":"Sugimoto","year":"2017","journal-title":"Kidney Int."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"976","DOI":"10.2337\/db13-1396","article-title":"Effect of plasma uric acid on antioxidant capacity, oxidative stress, and insulin sensitivity in obese subjects","volume":"63","author":"Fabbrini","year":"2014","journal-title":"Diabetes"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1002\/jbmr.286","article-title":"Serum uric acid is associated with bone health in older men: A cross-sectional population-based study","volume":"26","author":"Nabipour","year":"2011","journal-title":"J. Bone Miner. Res."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1007\/s00198-013-2571-7","article-title":"Association between serum uric acid and lumbar spine bone mineral density in peri- and postmenopausal Japanese women","volume":"25","author":"Ishii","year":"2014","journal-title":"Osteoporos. Int."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1016\/j.bone.2012.10.025","article-title":"Serum uric acid plays a protective role for bone loss in peri- and postmenopausal women: A longitudinal study","volume":"52","author":"Makovey","year":"2013","journal-title":"Bone"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.1002\/jbmr.2164","article-title":"Association of serum uric acid and incident nonspine fractures in elderly men: The osteoporotic fractures in men (mros) study","volume":"29","author":"Lane","year":"2014","journal-title":"J. Bone Miner. Res."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1017\/S0954422414000195","article-title":"Is there a role for vitamin c in preventing osteoporosis and fractures? A review of the potential underlying mechanisms and current epidemiological evidence","volume":"27","author":"Finck","year":"2014","journal-title":"Nutr. Res. Rev."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1589\/jpts.28.725","article-title":"Osteoporosis, vitamin c intake, and physical activity in Korean adults aged 50 years and over","volume":"28","author":"Kim","year":"2016","journal-title":"J. Phys. Ther. Sci."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1007\/BF03324879","article-title":"The role of vitamin e in reversing bone loss","volume":"20","author":"Chai","year":"2008","journal-title":"Aging Clin. Exp. Res."},{"key":"ref_89","first-page":"250584","article-title":"Vitamin e and bone structural changes: An evidence-based review","volume":"2012","author":"Borhanuddin","year":"2012","journal-title":"Evid.-Based Complementary Altern. Med."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1017\/S0007114515004134","article-title":"Association of dietary and serum vitamin e with bone mineral density in middle-aged and elderly Chinese adults: A cross-sectional study","volume":"115","author":"Shi","year":"2016","journal-title":"Br. J. Nutr."},{"key":"ref_91","first-page":"441","article-title":"The plasma antioxidant activity of superoxide dismutase enzyme in osteoporosis","volume":"46","author":"Behfar","year":"2008","journal-title":"Acta Med. Iran."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1210\/jc.2002-021496","article-title":"Marked decrease in plasma antioxidants in aged osteoporotic women: Results of a cross-sectional study","volume":"88","author":"Cherubini","year":"2003","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_93","first-page":"931","article-title":"Correlation between serum glutathione reductases and bone densitometry values","volume":"67","author":"Avitabile","year":"1991","journal-title":"Bollettino della Societa Italiana di Biologia Sperimentale"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"4145","DOI":"10.2174\/138161205774913255","article-title":"Uric acid and oxidative stress","volume":"11","author":"Glantzounis","year":"2005","journal-title":"Curr. Pharm. Des."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.1152\/physrev.00047.2003","article-title":"Role of oxidative modifications in atherosclerosis","volume":"84","author":"Stocker","year":"2004","journal-title":"Physiol. Rev."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1016\/j.metabol.2014.11.006","article-title":"Serum urate levels and the risk of hip fractures: Data from the cardiovascular health study","volume":"64","author":"Mehta","year":"2015","journal-title":"Metab. Clin. Exp."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1002\/art.39852","article-title":"Gout and risk of fracture in women: A prospective cohort study","volume":"69","author":"Paik","year":"2017","journal-title":"Arthritis Rheumatol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1097\/00001433-199910000-00003","article-title":"The effect of vitamin d on osteoblasts and osteoclasts","volume":"10","author":"Ikeda","year":"1999","journal-title":"Curr. Opin. Orthop."},{"key":"ref_99","first-page":"493","article-title":"Vitamin d endocrine system and osteoblasts","volume":"3","year":"2014","journal-title":"BoneKEy Rep."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Lu, C.L., Shyu, J.F., Wu, C.C., Hung, C.F., Liao, M.T., Liu, W.C., Zheng, C.M., Hou, Y.C., Lin, Y.F., and Lu, K.C. (2018). Association of anabolic effect of calcitriol with osteoclast-derived wnt 10b secretion. Nutrients, 10.","DOI":"10.3390\/nu10091164"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1186\/s40200-016-0266-2","article-title":"Vitamin d deficiency, bone turnover markers and causative factors among adolescents: A cross-sectional study","volume":"15","author":"Larijani","year":"2016","journal-title":"J. Diabetes Metab. Disord."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"18138","DOI":"10.1038\/srep18138","article-title":"Associations between serum 25-hydroxyvitamin d and bone turnover markers in a population based sample of german children","volume":"5","author":"Thiering","year":"2015","journal-title":"Scie. Rep."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1007\/s00198-018-4395-y","article-title":"Effect of isolated vitamin d supplementation on bone turnover markers in younger postmenopausal women: A randomized, double-blind, placebo-controlled trial","volume":"29","author":"Cangussu","year":"2018","journal-title":"Osteoporos. Int."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1210\/edrv.22.4.0437","article-title":"Vitamin d deficiency and secondary hyperparathyroidism in the elderly: Consequences for bone loss and fractures and therapeutic implications","volume":"22","author":"Lips","year":"2001","journal-title":"Endocr. Rev."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1136\/ard.61.5.456","article-title":"Relationship of hypovitaminosis d and secondary hyperparathyroidism with bone mineral density among uk resident indo-asians","volume":"61","author":"Serhan","year":"2002","journal-title":"Ann. Rheum. Dis."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1002\/jbmr.5650100806","article-title":"Vitamin d status and sex hormone binding globulin: Determinants of bone turnover and bone mineral density in elderly women","volume":"10","author":"Ooms","year":"1995","journal-title":"J. Bone Miner. Res."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1136\/bmj.305.6848.273","article-title":"Bone density parathyroid hormone and 25-hydroxyvitamin d concentrations in middle aged women","volume":"305","author":"Khaw","year":"1992","journal-title":"BMJ"},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Steingrimsdottir, L., Halldorsson, T.I., Siggeirsdottir, K., Cotch, M.F., Einarsdottir, B.O., Eiriksdottir, G., Sigurdsson, S., Launer, L.J., Harris, T.B., and Gudnason, V. (2014). Hip fractures and bone mineral density in the elderly\u2013importance of serum 25-hydroxyvitamin d. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0091122"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1002\/jbmr.1545","article-title":"Calciotropic hormones and the risk of hip and nonspine fractures in older adults: The health abc study","volume":"27","author":"Barbour","year":"2012","journal-title":"J. Bone Miner. Res."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"39849","DOI":"10.18632\/oncotarget.16337","article-title":"The serum 25-hydroxyvitamin d levels and hip fracture risk: A meta-analysis of prospective cohort studies","volume":"8","author":"Lv","year":"2017","journal-title":"Oncotarget"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"e4669","DOI":"10.1097\/MD.0000000000004669","article-title":"Gout increases risk of fracture: A nationwide population-based cohort study","volume":"95","author":"Tzeng","year":"2016","journal-title":"Medicine"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1007\/s00198-018-4375-2","article-title":"Gout as a risk factor for osteoporosis: Epidemiologic evidence from a population-based longitudinal study involving 108,060 individuals","volume":"29","author":"Kok","year":"2018","journal-title":"Osteoporos. Int."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"E581","DOI":"10.1503\/cmaj.170806","article-title":"Risk of fragility fracture among patients with gout and the effect of urate-lowering therapy","volume":"190","author":"Sultan","year":"2018","journal-title":"CMAJ"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.bone.2016.01.003","article-title":"Association between allopurinol use and hip fracture in older patients","volume":"84","author":"Basu","year":"2016","journal-title":"Bone"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"40","DOI":"10.3389\/fendo.2015.00040","article-title":"Marrow fat and bone: Review of clinical findings","volume":"6","author":"Schwartz","year":"2015","journal-title":"Front. Endocrinol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.chemphyslip.2007.10.006","article-title":"Analysis of bone marrow fatty acid composition using high-resolution proton nmr spectroscopy","volume":"151","author":"Yeung","year":"2008","journal-title":"Chem. Phys. 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