臺灣博碩士論文加值系統

隨國民平均壽命不斷延長，骨質疏鬆(osteoporosis)的盛行率亦逐年增加。國內四次營養調查結果均顯示國人鈣質的平均攝取未達建議量，因此如何提供具有良好吸收率及生物利用率的鈣來源成為一個極重要的議題。利用奈米化處理的方法把鈣製成奈米粒子，由於表面積增加，也許可以提高其吸收率，強化有效成分的效用。惟經微細化處理後，其在食用上是否仍安全無虞，且在生物體上實際的利用率又是如何，則是須進一步加以探討的。因此本實驗之目的，首先以體外測試方式，評估微細化處理鈣複合劑之微生物安全性試驗；再進一步以體內測試方式，進行動物的口服急毒性試驗，評估對哺乳類動物急性毒性之影響，並探討人體對微細化處理鈣複合劑之鈣質生物利用率。試驗結果顯示，在微生物安全性方面，無論有無代謝酵素活性(S9)之存在下，奈米鈣和奈米複方鈣此二種測試樣品在1~5mg/plate劑量範圍下，對Salmonella typhimurium TA98, TA100, TA102及TA1535均不具微生物致突變性。在動物口服急毒性試驗結果發現，奈米化處理的鈣複合劑並不會對ICR小鼠的臟器外觀、顏色、血液及尿液生化值造成影響與變化，亦無鼠隻死亡之情形發生，顯示其LD50值大於5 g/kg body weight。而在人體試驗方面，未奈米複方鈣與奈米複方鈣在同一時間點上相互比較，各檢驗值雖然並未達到統計上之差異，但奈米複方鈣使血清中之鈣濃度及尿液中鈣與肌酸酐比值之上升速率較未奈米複方鈣快，並可有效抑制血清中副甲狀腺(PTH)之濃度。綜合上述試驗結果得知，奈米複方鈣未有致突變反應與口服急毒性，且比未奈米複方鈣有較高的鈣質生物利用效率。補充鈣質或許為防範骨質疏鬆之良好來源。

Following the extension of lifespan of Taiwanese, the prevalence of osteoporosis was also increased. According to the Nutrition and Health Survey in Taiwan, people consume considerably less than the current Dietary Reference Intakes (DRIs) of calcium, thus it is a very important issue to find and provide a good calcium source with high absorption and bioavailability. The surface area and absorption rate of calcium may increase by nanolized. However, the safety evaluation and bioavailability of nanoparticled calcium are still unknown. The aim of this study was to evaluate the safety and human bioavailability of nanoparticled calcium. The safety evaluation includes microbial mutagenesis (Ames test) and oral acute toxicity. In microbial mutagenesis assay (Ames test) the results showed either with or without rat liver enzyme mixture(S9), nanoparticled calcium and nanoparticled calcium complex has no mutagenicity effect toward all tester strains (Salmonella typhimurium TA98, TA100, TA102 and TA1535) in the concentration between 1~5mg/plate. In oral acute toxicity, after treated with nanoparticled calcium, there are no mice dead, no changes of histopathological organs, serum and urinary biochemistry in ICR mice, indicated that LD50 is more than 5 g/kg body weight. In human experiment, the testing variables were not significant different between nanoparticled calcium complex and non-nanoparticled calcium complex at the same time. But nanoparticled calcium complex had faster increasing serum calcium and urinary calcium/creatinine ratio than the non-nanoparticled calcium; furthermore, the effect of suppression PTH was more conspicuous than non-nanoparticled calcium. In summary, the nanoparticled calcium complex showed no mutagenicity and oral acute toxicity, and had higher calcium bioavailability than the non-nanolized calcium complex. It may be a good supplementation for the prevention of osteoporosis.

目 錄
中文摘要………………………………………I
英文摘要………………………………………II
目錄………………………………………IV
圖目錄………………………………………VII
表目錄………………………………………VIII


第一章 前言………………………………………1
第二章 文獻回顧………………………………………3
第一節 人體的骨骼………………………………………3
第二節 骨質疏鬆症之介紹………………………………4
第三節 骨質疏鬆的分級與診斷……………………………6
第四節 鈣對人體的重要性……………………………11
第五節 骨質疏鬆症與飲食之相關性……………………………15
第六節 奈米科技……………………………20
第七節 奈米定義……………………………21
第八節 安全性評估……………………………23
第三章 材料與方法……………………………27
第一節 材料簡介……………………………27
第二節 微生物安全性試驗……………………………28
一、 原理……………………………28
二、 菌株特性……………………………28
三、 菌株來源與取得……………………………29
四、 菌種保存與鑑定……………………………30
五、 實驗材料……………………………31
六、 實驗流程 ……………………………36
七、 統計分析……………………………37
第三節 動物急毒性試驗……………………………38
一、 實驗樣品 ……………………………38
二、 供試動物 ……………………………39
三、 實驗流程 ……………………………41
四、 統計分析 ……………………………42
第四節 人體試驗……………………………43
一、 實驗流程 ……………………………43
二、 研究對象 ……………………………44
三、 食用樣品之組成 ……………………………44
四、 實驗分組 ……………………………45
五、 實驗期間……………………………45
六、 測定項目……………………………45
七、 統計分析……………………………50
第四章 結果與討論……………………………53
第一節 微生物安全性試驗……………………………53
一、 毒性試驗……………………………53
二、 致突變性試驗……………………………60
第二節 動物及毒性試驗……………………………68
一、 體重及增重之變化……………………………68
二、 體內重要臟器之體重及肉眼病理觀察…………………68
三、 血液及尿液生化值分析……………………………72
第三節 人體試驗……………………………75
一、 基本資料分析……………………………75
二、 受試者飲食攝取紀錄分析……………………………77
三、 血液生化值分析……………………………80
四、 血液生化變化百分比值分析……………………………83
五、 尿液生化值分析……………………………88
六、 尿液生化變化百分比值分析……………………………90
第五章 結論……………………………95
第六章 參考文獻……………………………96

參考文獻
PX2健康網 (2007)：如何正確選購鈣補充品。摘自：http://px2.com.tw/ Health_ crisis/
hc41.htm。(96.08.22)
小泰生物科技報 (2002)：淺談奈米科技之應用(三)。摘自 http://www.bio.idv.tw/paper/
35.htm。 (96.07.26)
工業技術研究院 (2007)：奈米科技研發中心-奈米辭典。摘自：http://www.ntrc.itri.org.
tw/dict/content.jsp?newsid=920。(96.11.2)
尹邦躍、張勁燕 (2002)：奈米時代。五南圖書出版有限公司 1: 1-5。
尤俊傑 (2005)：奈米化紅麴菌發酵產物之安全性試驗與保健成份之血脂調節評估。
臺灣大學微生物與生化學研究所碩士論文。
王有忠 (2006)：食品衛生與安全。華香園出版社 1: 3-10.
王叔苑 (2000)：Ames test 之原理及其於產品安全性評估之應用。食品工業 32: 8-17。
王錫崗、高美媚、蔡秀純、溫小娟、廖美華、羅瑋瑜、葉濬毅 (2002)：人體生理學。
新文京開發出版有限公司 1: 334-335。
行政院國家科技委員會 (2007)：科技年鑑奈米網。摘自 http://nano.nsc.gov.tw/。
(96.07.11)
行政院國家科技委員會 (2007)：科技年鑑奈米網。摘自 http://nano.nsc.gov.tw/ main/
1/1_03.html。(96.07.26)
行政院衛生署食品資訊網 (2002)：計算理想體重值、正確體重控制方法。摘自http://
food. doh.gov.tw/children/a-02.htm。(96.10.07)
行政院衛生署食品資訊網 (2002)：國人膳食營養素參考攝取量 Dietary Reference
Intakes，DRIs。摘自：http://food.doh.gov.tw/chinese/libary/libary2_2_1.htm。
(96.09.06)
行政院衛生署食品資訊網 (2003)︰老人營養健康狀況調查結果發表會 Part Ⅲ。行
政院衛生署。
行政院衛生署食品資訊網 (2007)：健康食品查驗登記現況。摘自 http://food.doh. gov.
tw/files/healthfood/A00046.pdf。(96.07.22)
何鎮揚、陳雅玲、廖家榮 (2004)：奈米科技交響曲-化學篇。台大出版中心 1: 1-7。李奮生、史紅虎 (2002)：打造奈米經濟－引爆21世紀科技革命 3: 127-128。
林芸甄 (2003)︰群居老人骨質代謝指標及身體活動情形與腰椎骨密度之探討。輔仁
大學食品營養學系碩士論文。
林興中 (1993)︰骨質疏鬆症。嘉義醫訊 15: 10-15。
林興中 (1994)︰骨質疏鬆之最近進展。台灣醫界 37: 209-212。
林興中 (1995)︰骨質疏鬆症之成因。台灣醫界 38: 34-38。
姚維人、吳重慶 (1994)︰骨質疏鬆之成因。秀傳醫學雜誌 1: 179-185。
柯以勤、邱正芬、林盟喬、潘以涵 (2004)︰台灣地區老人營養健康狀況調查1999-
2000老年人骨質健康狀況。行政院衛生署。
食品工業發展研究所 (1997)︰食物與鈣。食品工業發展研究所。
食品工業發展研究所、屏東科技大學 (1998)：台灣地區食品營養成份資料庫。行政
院衛生署。
健康食品保健功效評估方法草案說明研討會 (2005)︰健康食品之改善骨質疏鬆評
估方法。行政院衛生署 p.111-114。
張天均 (1998)︰Bisphosphonate與骨質疏鬆。當代醫學 25: 447-449。
曾浩洋、林麗悅、陳淑莉、何中平、劉慧蓉、陳建元、李貽琳、黃寶雄、蔡順仁、
柯源悌 (2003)：食品衛生與安全。華格那 1: 78-81。
黃光照、李重賢、李美英、劉怡君 (2004)：奈米科技交響曲-物理篇。台大出版中心
1: 10-12。
楊榮森 (1997)︰骨質疏鬆症病因、診斷、治療。合記圖書出版社。
劉吉平、郝向陽 (2003)：奈米科學與技術。世茂出版社。
潘淑芬 (2001)：醫學生物化學。藝軒圖書出版社 1:297-302。
蔡克嵩 (1998)︰骨代謝指標之臨床應用。中華民醫學雜誌 61: S58。
蔡樹濤 (2005)：骨質疏鬆症。新潮社 1: 60-67。
論壇健康促進與疾病預防委員會第三期文獻回顧研析計劃 (2003)︰飲食與骨質疏
鬆。國家衛生研究院。
輝綠科技 (2007)：何謂奈米。摘自 http://www.feli.com.tw/nano/whatisnano.htm。
(96.07.26)
蕭寧馨 (2006)：透視營養學。藝軒圖書出版社。1: 400-401。
營養保健圖書館 (2003)：照顧骨骼健康-鈣質。摘自：http://www.whlb.com.tw/ page/
default.asp?cat_id=1&faq_id=19。(96.08.22)
謝明哲、黃士懿、邱琬淳、陳玉華、陳俊榮、楊素卿、趙振瑞、劉
珍芳、蔡雅惠、鄭心嫻、簡怡雯 (2004)：營養生化學-下冊。
華藤文化股份有限公司 3:20-24。
謝明哲、廖芳瑄、林士祥、陳金發、許重輝、鐘美玉、簡怡雯
(2003)：碳酸鈣與乳酸鈣補充劑之鈣質生物利用效性。台灣營
養學會雜誌 28: 34-40。
醫生在線 (2007)：老年醫學－骨質疏鬆症。摘自：http://big5.51daifu.com/ medical_
books/2007/0307/EB843C0238FA0AA8H127221.shtml。(96.08.22)
藤田拓男 (1994)︰神奇的鈣。國際村文庫書店。
龔建華、林唯芳 (2002)：你不可不知的奈米科技:影響世界改變未來。世茂出版社 1:
15-16。
Abbott TA, Lawrence BJ, WallachS. Osteoporosis: the need for comperehensive
treatment guidelines. Clin Ther. 1996;18:127-49.
Aloia JF, Vaswani A, Yeh JK, Ross PL, Flaster F, Dilmanian FA. Calcium
supplementation with and without hormone replacement therapy to prevent
postmenopausal bone loss. Ann Intern Med. 1994;120:97-103.
Amarshi N, Pharmd MS, Scoggin A, Pharmd MPA, Ensworth SMD. Osteoporosis:
review of guidelines and consensus statements. Am J Manag Care. 1997;3:1077-90.
Ames BN, Durston WE, Yamasaki E, Lee FD. Carcinogens are mutagens: a simple test
system combining liver homogenates for activation and bacteria for detection. Proc
Natl Acad Sci. U.S.A. 1973;70:2281-85.
Ames BN, Lee FD, Durston WE. An improved bacterial test system for the detection and
classification of mutagens and carcinogens. Proc Natl Acad Sci. U.S.A. 1973;70:
782-6.
Ames BN, McCann J, Yamasaki E. Methods for detecting carcinogens and mutagens with
Salmonella/Mammalian-microsome mutagenicity test. Mutat Res. 1975;31:347-64.
Ames BN, McCann J. Validation of the Salmonella test: a reply to rinkus and legator.
Cancer Res. 1981;41:4192-6.
Armamento VR, Villareal DT, Avioli LV, Civitelli R. Estrogen status and heredity are
major determinants of premenopausal bone mass. J Clin Invest. 1992;90:2464-71.
Barrett CE, Cheng JC, Edelstein SL. Coffee-associated osteoporosis offset by daily milk
consumption. The Rancho Bernardo Study. J Am Med Assoc. 1994;271:280-3.
Black DW. Why elderly women should be screened and treated to prevent osteoporosis.
Am J Chin Med. 1995;98:67S-75S.
Bronner F, Pansu D. Nutritional aspects of calcium absorption. J Nutr. 1999;129:9- 12.
Bronner F, Stein WD. Modulation of bone calcium-binding sites regulates plasma
calcium: an hypothesis. Calcif Tissue Int. 1992;50:483-9.
Cameron JR, Sorenson J. Measurement of bone mineral in vivo: an improved method.
Science. 1963;142:230-2.
Caricllo NF, Picgorsch WW. The Ames test: the two-fold rule revisited. Mutat Res. 1996;
369:23-31.
Castelo-Branco C, Martinez de Osaba MJ, Pons F, Gonzalez-Merlo J. The effect of
hormone replacement therapy on postmenopausal bone loss. Eur J Obstet Gynecol
Reprod Biol. 1992;44:131-6.
Castelo-Branco C, Rovira M, Pons F, Duran M, Sierra J, Vives A, Balasch J, Fortuny A,
Vanrell J. The effect of hormone replacement therapy on bone mass in patients with
ovarian failure due to bone marrow transplantation. Maturitas. 1996;23:307-12.
Chen Z, Meng H, Xing G, Chen C, Zhao Y, Jia G, Wang T, Yuan H, Ye C, Zhao F, Chai Z,
Zhu C, Fang X, Ma B, Wan L. Acute toxicological effect of copper nanoparticles in
vivo. Toxicol Lett. 2006;163:109-20.
Christiansen C. Osteoporosis: Diagnosis and management today and tomorrow. Bone.
1995;17:513S-16S.
Chugai Pharmaceutical Co., Ltd. Launch "EVISTA Tablets 60 mg" (raloxifene
hydrochloride) For the treatment of postmenopausal osteoporosis. Eli Lilly Japan K.K. 2004. Available from: http://www.chugai-pharm.co.jp/html/press/english/ 2004/040511e Evista.html. (96.07.21)
Cohen AJ, Roe FJC. Review of risk factors for osteoporosis with particular reference to a
possible aetiological role of dietary salt. Food Chem Toxicol. 2000;38:237-53.
Farley JR, Fitzsimmons R, Taylor AK, Jorch UM, Lau KH. Direct effect of ethanol on
bone resorption and formation in vitro. Arch Biochem Biophys. 1985;238:305-14.
Friday KE, Howard GA. Ethanol inhibits human bone cell proliferation and function in
vitro. Metab Clin Exp. 1991;40:562-5.
Gonneli S, Cepollaro C, Camporeale A, Nardi P, Rossi S, Gennari C. Acute biochemical
variations induced by two different calcium salts in healthy perimenopausal women.
Calcif Tissue Int. 1995;57:175-7.
Harris SS, Dawson HB. Caffeine and bone loss in healthy postmenopausal women. Am J
Clin Nutr. 1994;60:573-8.

Heaney RP, Weaver CM. Oxalate in vegetables: effect on calcium absorbability. J Bone
Miner Res. 1993;8:S333.
Hillyer JF, Albrecht RM. Gastrointestinal persorption and tissue distribution of differently
sized colloidal gold nanoparticles. J Pharm Sci. 2001;90:1927-36.
Holick MF, Uskokovic M, Henley JW, Maclaughlin J, Holick SA, Potts JT. The
photoproduction of 1 alpha,25-dihydroxyvitamin D3 in skin: an approach to the
therapy of vitamin-D-resistant syndromes. N Engl J Med. 1980;303:349-54.
Hollis BW, Waqner CL, Drezner MK, Binklev NC. Circulating vitamin D3 and 25-
hydroxyvitamin D in humans: an important to define adequate nutritional vitamin D
status. J Steroid Biochem Mol Biol. 2007;103:631-4.
Horowitz M, Morris HA, Hartley TF, Need AG, Wishart J, Ryan P, Nordin BEC. The
effect of an oral calcium load on plasma ionized calcium and parathyroid hormone
concentrations in osteoporotic postmenopausal women. Calcif Tissue Int. 1987;40:
133-6.
Huanq B, Zhang J, Hou J, Chen C. Free radical scavenging efficiency of Nano-Se in vitro. Free Radic Biol Med. 2003;35:805-13.
Hung YH, Hung HY, Chou CC. Mutagenic and antimutagenic effects of methanol
extracts of unfermented and fermented black soybeans. Int J Food Microbiol. 2007;
118:62-8.
Ireland P, Fordtran JS. Effect of dietary calcium and age on jejunal calcium absorption in
humans studied by intestinal perfusion. J Clin Invest. 1973;52:2672-81.
Jani P, Halbert GW, Langridge J, Florence AT. Nanoparticle uptake by the rat
gastrointestinal mucosa: quantitation and particle size dependency. J Pharm
Pharmacol. 1990;42:821-6.

Jesse B, Mary RL. Maintaining copper homeostasis: regulation of copper-trafficking
proteins in response to copper deficiency or overload. J Nutr Biochem. 2004;15:
316-22.
Kemi VE, Karkkainen MU, Lamberg-Allardt CJ. High phosphorus intakes acutely and
negatively affect Ca and bone metabolism in a dose-dependent manner in healthy
young females. Br J Nutr. 2006;96:545-52.
Koshihara M, Katsumata S, Uehara M, Suzuki K. Effects of dietary phosphorus intake on
bone mineralization and calcium absorption in adult female rats. Biosci Biotechnol
Biochem. 2005;69:1025-8.
Koshihara M, Masuvama R, Uehara M, Suzuki K. Effect of dietary clacium: phosphorus
ratio on bone mineralization and intestinal calcium absorption in ovariectomized rats. Biofactors. 2004;22:39-42.
Koshihara M, Masuvama R, Uehara M, Suzuki K. Reduction in dietary calcium/
phosphorus ratio reduces bone mass and strength in ovariectomized rats enhancing
bone turnover. Biosci Biotechnol Biochem. 2005;69:1970-3.
Li H, Li J, Prasain JK, Tezuka Y, Namba T, Miyahara T, Tonami S, Seto H, Tada T,
Kadota S. Antiosteoporotic activity of the stems of Sambucus sieboldiana. Biol
Pharm Bull. 1998;21:594-8.
Lloyd T, Andon MB, Rollings N, Martel JK, Landis JR, Demers LM, Eggli DF,
Kieselhorst K, Kulin HE. Calcium supplementation and bone mineral density in
adolescent girls. JAMA. 1993;18:841-4.
Lufkin EG, Wahner HW, O’Fallon WM, Hodgson SF, Kotowicz MA, Lane AW, Judd HL,
Caplan RH, Riggs BL. Treatment of postmenopausal osteoporosis with transdermal
estrogen. Ann Intern Med. 1992;117:1-9.

Maron DM, Ames BN. Revised methods for the salmonella mutagenicity test. Mutat Res.
1983;113:173-215.
Meier DE, Luckey MM, Wallenstein S, Lapinski RH, Catherwood B. Racial differences
in pre- and postmenopausal bone homeostasis: association with bone density. J Bone
Miner Res. 1992;7:1181-9.
Mortelmans K, Zwiger E. The Ames Sslmonella/microsome mutagenicity assay. Mutat
Res. 2000;455:29-60.
Nelson BW. Clinical utility of biochemical markers of bone remodeling. Clin Chem.
1999;45:1359-68.
Newman MC, Kashzniak AW. Spatial memory and aging:performance on a human analog
of Morris water maze. Aging Neuropsychol Cong. 2000;7:86-93.
Oberdorster G, Ferin J, Lehnert BE. Correlation between particle size, in vivo particle
persistence and lung injury. Environ Health Perspect. 1994;102:173-9.
Ostlere SJ, Gold RH. Osteoporosis and bone density measurement methods. Clin Orthop
Relat Res. 1991;271:149-63.
Peterlik M. Aging, neuroendocrine function, and osteoporosis. Exp Gerontol. 1997;32:557-86.
Pongchaiyakul C, Nguyen TV, Kosulwat V, Rojroongwasinkul N, Charoenkiatkul S, Eisman JA, Rajatanavin R. Effects of physical activity and dietary calcium intake on bone mineral density and osteoporosis risk in a rural Thai population. Osteoporos Int. 2004;15:807-13.
Price PA, Parthemore JG, Deftos LJ. New biochemical marker for bone metabolism: measurement by radioimmunoassay of bone GLA protein in the plasma of normal subjects and patients with bone disease. J Clin Invest. 1980;66:878-83.
Raisz LG. The osteoporosis revolution. Ann Intern Med. 1997;126:458-62.
Recker RR. Continuous treatment of osteoporosis: current status. Orthop Clin North Am. 1981;12:611-27.
Reginster JY, Denis D, Bartsch V, Deroisy R, Zegels B, Franchimont P. Acute biochemical variations induced by four different calcium salts in healthy male volunteers. Osteoprorsis Int. 1993;3:271-5.
Riis B, Thomsen K, Christiansen C. Does calcium supplementation prevent postmenopausal bone loss? N Engl J Med. 1987;316:173-7.
Rolfes SR, DeBruyne LK, Whitney EN. Life Span Nutrition, Conception through Life. West/Wadsworth Publishing Co Calif. USA. 1998;2:385-413.
Tao TY, Liu FL, Klomp L, Wijmenga C, Gitlin JD. The copper toxicosis gene product Murr1 directly interacts with the Wilson disease protein. J Biol Chem. 2004; 278:41593-6.
Scheiber MD, Rebar RW. Isoflavones and postmenopausal bone health: a viable altermative to estrogen therapy? Menopause. 1999;6:233-41.
Schneider EL, Guralnik JM. The aging in America: impact on health care costs. JAMA. 1990;263:2335-40.
Sugimoto T, Tsutsumi M, Fujii Y, Kawakatsu M, Negishi H, Lee MC, Tsai KS, Fukase M, Fujita T. Comparison of bone mineral content among Japanese, Koreans, and Taiwanese assessed by dual-photon absorptiometry. J Bone Miner Res. 1992;7:153-9.
Teegarden D, Legowski P, Gunther CW, McCabe GP, Peacock M, Lyle RM. Dietary Calcium Intake Protects Women Consuming Oral Contraceptives from Spine and Hip Bone Loss. J Clin Endocrinol Metab. 2007;90:5127-33.
Tsai KS, Hsu SH, Cheng JP, Yang RS. Vitamn D stores of urban women in Taipei: Effect on bone density and bone turnover, and seasonal variation. Bone. 1997;20:371-4.
Tsai KS, Pan WH, Hsu SH, Cheng WC, Chen CK, Chieng PU, Yang RS, Twu ST. Sexual differences in bone markers and bone meneral density of normal Chinese. Calcif Tissue Int. 1996;59:454-60.
Tucker KL, Morita K, Qiao N, Hannan MT, Cupples LA, Kiel DP. Colas, but not other carbonated beverages, are associated with low bone mineral density in older women: The Framingham Osteoporosis Study. Am J Clin Nutr. 2006;84:936-42.
Turnlund JR, Scott KC, Peiffer GL, Jang AM, Keyes WR, Sakanashi TM. Copper status of young men consuming a low-copper diet. Am J Clin Nutr. 1997;65:72-8.
Wang B, Feng WY, Wang TC, Jia G, Wang M, Shi JW, Zhang F, Zhao YL, Chai ZF. Acute toxicity of nano- and micro-scale zinc powder in healthy adult mice. Toxicol Lett. 2006;161:115-23.
Wang J, Zhou G, Chen C, Yu H, Wang T, Ma Y, Jia G, Gao Y, Li B, Sun J, Li Y, Jiao F, Zhao Y, Chai Z. Acute toxicity and biodistribution of different sized titanium dioxide particles in mice after oral administration. Toxicol Lett. 2007;168:176-85.
Watts NB, Harris ST, Genant HK, Wasnich RD, Miller PD, Jackson RD, Licata AA, Ross P, Woodson GC, Yanover MJ. Intermittent cyclical etidronate treatment of postmenopausal osteoporosis. N Engl J Med. 1990;323:73-9.
Weaver CM, Heaney RP, Martin BR, Fitzsimmons M L. Human calcium absorption from whole wheat products. J Nutr. 1991;121:1769-75.
Wilkinson G, Cundy T, Parsons V, Lawson MP. Metabolic bone disease and fractures in male alcoholics: a pilot study. Br J Addict. 1985;80:65-8.
Wu C, Kenny MA. Circulating total and ionized magnesium after ethanol ingestion. Clin Chim Acta. 1996;42:625-9.
Yamamoto A, Honma R, Sumita M, Hanawa T. Cytotoxicity evaluation of ceramic particles of different sizes and shapes. J Biomed Mater Res. 2004;68:244-56.
Yang RS, Liu TK, Tsai KS. The acute metabolic effects of oral tricalcium phosphate and calcium carbonate. Calcif Tissue Int. 1994;55:335-41.
Yeh LR, Chen CK, Lai PH. Normal bone mineral density in anteroposterior, lateral spine and hip of Chinese men in Taiwan: effect of age change, body weight and height. J Chin Med Assoc. 2004;67:287-95.