{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T12:24:38Z","timestamp":1792758278299,"version":"4.5.0"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,3,21]],"date-time":"2022-03-21T00:00:00Z","timestamp":1647820800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81273029"],"award-info":[{"award-number":["81273029"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81402647"],"award-info":[{"award-number":["81402647"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81803195"],"award-info":[{"award-number":["81803195"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005230","name":"Natural Science Foundation of Chongqing","doi-asserted-by":"publisher","award":["cstc2014jcyjA00049"],"award-info":[{"award-number":["cstc2014jcyjA00049"]}],"id":[{"id":"10.13039\/501100005230","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Nutr."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Metabolic acidosis affects bone health. It remains unclear whether drinking natural mineral water is better for maintaining bone health in the youth with metabolic acidosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>Sixty young female rats (3-weeks-old) were randomly divided into three groups and drank purified water (PW, as control), bicarbonate-rich natural mineral water (Bic-NMW), or sulfate-rich natural mineral water (Sul-NMW), which, respectively, contained calcium (0.17, 155, and 175 mg\/L), bicarbonate (0.1360, and 139 mg\/L) and sulfate (0, 35.6, and 532 mg\/L), for 16 weeks. In the last 3 weeks, metabolic acidosis was induced in 10 rats per group by adding NH<jats:sub>4<\/jats:sub>Cl (0.28 mM) to drinking water. The rats' blood, urine, and femur were collected for assessing acid-base status, calcium metabolism, bone microstructure, and strength. The difference between the three groups was determined using one-way ANOVA followed by the Student\u2013Newman\u2013Keuls test or Dunnett's T3 test.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared with the PW rats, the Bic-NMW rats and the Sul-NMW rats had less urine net acid excretion (\u22121.51, 0.20 vs. 10.77, EQ\/L), higher bone mineral density (442.50, 407.49 vs. 373.28, mg\/mm<jats:sup>3<\/jats:sup>), growth cartilage width (271.83, 283.83 vs. 233.27, \u03bcm) and cortical trabecular area (9.33, 9.55 vs. 5.05, mm<jats:sup>2<\/jats:sup>), and smaller cortical marrow cavity area (5.40, 5.49 vs. 7.27, mm<jats:sup>2<\/jats:sup>) in the femur (<jats:italic>P<\/jats:italic> &amp;lt; 0.05). Besides, the Bic-NMW rats had less serum calcium (2.53 vs. 2.68, mmol\/L) and C-terminal cross-linked telopeptide of type-I collagen (1.35 vs. 1.93, ng\/mL), and higher serum calcitonin (0.61 vs. 0.39, \u03bcg\/L), femoral trabecular thickness (0.10 vs. 0.09, \u03bcm), bone volume\/total volume (0.42 vs. 0.34, %), cortical bone area (15.91 vs. 12.80, mm<jats:sup>2<\/jats:sup>), and ultimate stress (35.12 vs. 29.32, MPa) (<jats:italic>P<\/jats:italic> &amp;lt; 0.05). The Sul-NMW rats had more osteoclasts (22.50 vs. 11.54, cells\/field) (<jats:italic>P<\/jats:italic> &amp;lt; 0.05).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Drinking natural mineral water, especially bicarbonate-rich natural mineral water, is effective in improving bone health in young rats with metabolic acidosis. These benefits include maintaining bone mineral density, and improving bone microstructure and biomechanical properties <jats:italic>via<\/jats:italic> moderating metabolic acidosis.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnut.2022.813202","type":"journal-article","created":{"date-parts":[[2022,3,25]],"date-time":"2022-03-25T07:38:05Z","timestamp":1648193885000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Drinking Natural Mineral Water Maintains Bone Health in Young Rats With Metabolic Acidosis"],"prefix":"10.3389","volume":"9","author":[{"given":"Yao","family":"Tan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anwei","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiqun","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingqiao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaohua","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huidong","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yushu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Xue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujing","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiqun","family":"Shu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,3,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"754","DOI":"10.1080\/09637486.2016.1198889","article-title":"Diet-induced acidosis and alkali supplementation","volume":"67","author":"Della Guardia","year":"2016","journal-title":"Int J Food Sci Nutr"},{"key":"B2","doi-asserted-by":"publisher","first-page":"538","DOI":"10.3390\/nu9060538","article-title":"Diet-Induced low-grade metabolic acidosis and clinical outcomes: a review","volume":"9","author":"Carnauba","year":"2017","journal-title":"Nutrients."},{"key":"B3","doi-asserted-by":"publisher","first-page":"517","DOI":"10.3390\/nu10040517","article-title":"Acid balance, dietary acid load, and bone effects - a controversial subject","volume":"10","author":"Frassetto","year":"2018","journal-title":"Nutrients."},{"key":"B4","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1053\/j.ajkd.2019.01.036","article-title":"Metabolic acidosis in CKD: core curriculum 2019","volume":"74","author":"Raphael","year":"2019","journal-title":"Am. J Kidney Dis"},{"key":"B5","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1007\/s001980170095","article-title":"Diet acids and alkalis influence calcium retention in bone","volume":"12","author":"Buclin","year":"2001","journal-title":"Osteoporos Int."},{"key":"B6","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1007\/s394-001-8351-5","article-title":"Acid-base imbalance and the skeleton","volume":"40","author":"Bushinsky","year":"2001","journal-title":"Eur J Nutr."},{"key":"B7","doi-asserted-by":"crossref","DOI":"10.1093\/jn\/138.2.415S","article-title":"Extracellular pH regulates bone cell function","volume-title":"J Nutr.","author":"Arnett","year":"2008"},{"key":"B8","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1007\/s11914-017-0408-6","article-title":"High dietary protein intake and protein-related acid load on bone health","volume":"15","author":"Cao","year":"2017","journal-title":"Curr Osteoporos Rep."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1577","DOI":"10.1007\/s00198-017-3908-4","article-title":"Dietary potassium intake is beneficial to bone health in a low calcium intake population: the Korean National Health and Nutrition Examination Survey (KNHANES) (2008-2011)","volume":"28","author":"Kong","year":"2017","journal-title":"Osteoporos Int."},{"key":"B10","doi-asserted-by":"publisher","first-page":"596","DOI":"10.3390\/nu10050596","article-title":"Kidney response to the spectrum of diet-induced acid stress","volume":"10","author":"Goraya","year":"2018","journal-title":"Nutrients."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1994","DOI":"10.1093\/jn\/nxz161","article-title":"Consumption of very low mineral water is associated with lower bone mineral content in children","volume":"149","author":"Huang","year":"2019","journal-title":"J Nutr."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1134","DOI":"10.1093\/ajcn\/85.4.1134","article-title":"More acidic dietary acid-base load is associated with reduced calcaneal broadband ultrasound attenuation in women but not in men: results from the EPIC-Norfolk cohort study","volume":"85","author":"Welch","year":"2007","journal-title":"Am J Clin Nutr."},{"key":"B13","doi-asserted-by":"publisher","first-page":"1195","DOI":"10.1017\/S0007114508061515","article-title":"The composition of mineral waters sourced from Europe and North America in respect to bone health: composition of mineral water optimal for bone","volume":"101","author":"Wynn","year":"2009","journal-title":"Br J Nutr."},{"key":"B14","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1248\/yakushi.14-00014","volume":"134","author":"Ogata","year":"2014","journal-title":"Yakugaku Zasshi."},{"key":"B15","doi-asserted-by":"publisher","first-page":"188","DOI":"10.3305\/nh.2014.30.1.7491","article-title":"The calcium concentration of public drinking waters and bottled mineral waters in Spain and its contribution to satisfying nutritional needs","volume":"30","author":"Vitoria","year":"2014","journal-title":"Nutr Hosp."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1595","DOI":"10.3945\/ajcn.115.112821","article-title":"Dietary acid load in early life and bone health in childhood: the Generation R Study","volume":"102","author":"Garcia","year":"2015","journal-title":"Am J Clin Nutr."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1930","DOI":"10.3390\/nu10121930","article-title":"Calcium intake in bone health: a focus on calcium-rich mineral waters","volume":"10","author":"Vannucci","year":"2018","journal-title":"Nutrients."},{"key":"B18","doi-asserted-by":"publisher","first-page":"3515","DOI":"10.29219\/fnr.v63.3515","article-title":"Effects of mineral waters on acid-base status in healthy adults: results of a randomized trial","volume":"63","author":"Wasserfurth","year":"2019","journal-title":"Food Nutr Res."},{"key":"B19","doi-asserted-by":"publisher","first-page":"e0121995","DOI":"10.1371\/journal.pone.0121995","article-title":"Multi-generational drinking of bottled low mineral water impairs bone quality in female rats","volume":"10","author":"Qiu","year":"2015","journal-title":"PLoS One."},{"key":"B20","doi-asserted-by":"publisher","first-page":"2316","DOI":"10.3390\/nu11102316","article-title":"Differential modulation of cancellous and cortical distal femur by fructose and natural mineral-rich water consumption in ovariectomized female Sprague Dawley rats","volume":"11","author":"Pereira","year":"2019","journal-title":"Nutrients."},{"key":"B21","doi-asserted-by":"crossref","DOI":"10.1093\/jn\/138.2.423S","article-title":"Drinking water constituents and disease","volume-title":"J Nutr.","author":"Rylander","year":"2008"},{"key":"B22","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1016\/j.bone.2008.09.007","article-title":"Alkaline mineral water lowers bone resorption even in calcium sufficiency: alkaline mineral water and bone metabolism","volume":"44","author":"Wynn","year":"2009","journal-title":"Bone."},{"key":"B23","doi-asserted-by":"crossref","DOI":"10.1093\/jn\/138.2.435S","article-title":"The effect of the alkali load of mineral water on bone metabolism: interventional studies","volume-title":"J Nutr.","author":"Burckhardt","year":"2008"},{"key":"B24","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1186\/1476-511X-12-92","article-title":"Increased serum triglycerides and reduced HDL cholesterol in male rats after intake of ammonium chloride for 3 weeks","volume":"12","author":"H\u00f8stmark","year":"2013","journal-title":"Lipids Health Dis."},{"key":"B25","doi-asserted-by":"publisher","first-page":"855","DOI":"10.1016\/S0041-0101(99)00202-0","article-title":"Acid-base balance following Tityus serrulatus scorpion envenoming in anaesthetized rats","volume":"38","author":"de Monico Magalhaes","year":"2000","journal-title":"Toxicon."},{"key":"B26","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1038\/nrneph.2012.186","article-title":"Treatment of acute metabolic acidosis: a pathophysiologic approach","volume":"8","author":"Kraut","year":"2012","journal-title":"Nat Rev Nephrol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1053\/j.tcam.2013.04.002","article-title":"Arterial and venous blood gas analyses","volume":"28","author":"Rieser","year":"2013","journal-title":"Top Companion Anim Med."},{"key":"B28","first-page":"174","volume":"30","author":"L\u00fcthy","year":"1977","journal-title":"Med Lab (Stuttg)."},{"key":"B29","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1038\/s41430-020-0696-2","article-title":"Renal biomarkers of acid excretion capacity: relationships with body fatness and blood pressure","volume":"74","author":"Krupp","year":"2020","journal-title":"Eur J Clin Nutr."},{"key":"B30","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1002\/jbmr.1805","article-title":"Standardized nomenclature, symbols, and units for bone histomorphometry: a 2012 update of the report of the ASBMR Histomorphometry Nomenclature Committee","volume":"28","author":"Dempster","year":"2013","journal-title":"J Bone Miner Res."},{"key":"B31","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1538\/expanim.15-0069","article-title":"Histomorphometry of the tibia and mandible of healthy female Wistar rats at different stages of growth","volume":"65","author":"Nenda","year":"2016","journal-title":"Exp Anim."},{"key":"B32","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1016\/j.bone.2011.11.007","article-title":"GSK-3 inhibition by an orally active small molecule increases bone mass in rats","volume":"50","author":"Marsell","year":"2012","journal-title":"Bone."},{"key":"B33","doi-asserted-by":"publisher","first-page":"1075","DOI":"10.16016\/j.1000-5404.201612086","article-title":"Comparison of 5 types of drinking water on bone metabolism, microarchitecture and stiffness in developmental rats","volume":"11","author":"Xu","year":"2017","journal-title":"J Third Military Med Univ"},{"key":"B34","doi-asserted-by":"publisher","first-page":"692","DOI":"10.1681\/ASN.2007121329","article-title":"Bicarbonate therapy in severe metabolic acidosis","volume":"20","author":"Sabatini","year":"2009","journal-title":"J Am Soc Nephrol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1038\/nrneph.2010.33","article-title":"Metabolic acidosis: pathophysiology, diagnosis and management","volume":"6","author":"Kraut","year":"2010","journal-title":"Nat Rev Nephrol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1186\/1550-2783-7-29","article-title":"Acid-base balance and hydration status following consumption of mineral-based alkaline bottled water","volume":"7","author":"Heil","year":"2010","journal-title":"J Int Soc Sports Nutr."},{"key":"B37","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/S8756-3282(99)00098-8","article-title":"The ability of three-dimensional structural indices to reflect mechanical aspects of trabecular bone","volume":"25","author":"Ulrich","year":"1999","journal-title":"Bone."},{"key":"B38","doi-asserted-by":"publisher","first-page":"38441","DOI":"10.1038\/srep38441","article-title":"Effects of dose reduction on bone strength prediction using finite element analysis","volume":"6","author":"Anitha","year":"2016","journal-title":"Sci Rep."},{"key":"B39","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/S2213-8587(18)30308-5","article-title":"Cortical and trabecular bone microarchitecture as an independent predictor of incident fracture risk in older women and men in the Bone Microarchitecture International Consortium (BoMIC): a prospective study","volume":"7","author":"Samelson","year":"2019","journal-title":"Lancet Diabetes Endocrinol."},{"key":"B40","doi-asserted-by":"publisher","first-page":"1239","DOI":"10.1093\/ajcn\/62.6.1239","article-title":"Calcium bioavailability from a calcium- and sulfate-rich mineral water, compared with milk, in young adult women","volume":"62","author":"Couzy","year":"1995","journal-title":"Am J Clin Nutr."},{"key":"B41","doi-asserted-by":"publisher","first-page":"999","DOI":"10.1093\/ajcn\/71.4.999","article-title":"Mineral water as a source of dietary calcium: acute effects on parathyroid function and bone resorption in young men","volume":"71","author":"Guillemant","year":"2000","journal-title":"Am J Clin Nutr."},{"key":"B42","first-page":"380","article-title":"Biological effects of drinking-water mineral composition on calcium balance and bone remodeling markers","volume":"8","author":"Roux","year":"2004","journal-title":"J Nutr Health Aging."},{"key":"B43","first-page":"347","volume":"63","author":"Drywien","year":"2012","journal-title":"Rocz Panstw Zakl Hig."},{"key":"B44","doi-asserted-by":"publisher","first-page":"144855","DOI":"10.1016\/j.gene.2020.144855","article-title":"Alkaline phosphatase: structure, expression and its function in bone mineralization","volume":"754","author":"Vimalraj","year":"2020","journal-title":"Gene."}],"container-title":["Frontiers in Nutrition"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2022.813202\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,25]],"date-time":"2022-03-25T07:38:16Z","timestamp":1648193896000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2022.813202\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,21]]},"references-count":44,"alternative-id":["10.3389\/fnut.2022.813202"],"URL":"https:\/\/doi.org\/10.3389\/fnut.2022.813202","relation":{},"ISSN":["2296-861X"],"issn-type":[{"value":"2296-861X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,21]]},"article-number":"813202"}}