• Title/Summary/Keyword: Osteoporosis.

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The Bone Mineral Density Impact Factors of Adult Women before the Menopause - based on the National Health and Nutrition Examination Survey - (폐경 전 성인여성의 골밀도 영향 요인 - 국민건강영양조사 자료를 이용하여 -)

  • Kim, Kyung-Hee;Lee, Jung-Hee;Yeo, Jin-Dong
    • Journal of the Korean Society of Radiology
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    • v.9 no.3
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    • pp.147-168
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    • 2015
  • In this research, we have analyzed the impact factors on the bone mineral density thru the examination of bone density difference in the entire femur, femoral neck and lumbar of adult women before the menopause in accordance with the general features, lifestyle, eating habits, health and body composition. The survey was conducted among adult women before the menopause and older than 30 years based on the data of the National Health and Nutrition Examination Survey carried out in the 4th term (2008-2009) and 5th term (2010-2011) and we would like to provide the research results for the establishment of recommendations or guidelines for the treatment of adult women before the menopause with regard to the impact factors on the bone mineral density and for the development of health education materials for the accurate measurement of bone mineral density of young women in order to prevent the postmenopausal osteoporosis. With respect to the general features of adult women before the menopause, the bone mineral density was higher in the entire femur at age 40-44, femoral neck at 35-39, in high-school education level, in the earlier menarche group, without smoking experiences, with regular walking time and exercise frequency and with the habits of eating no hamburger or pizza. With regard to the body composition, the bone mineral density was higher in obesity and lower in underweight cases, higher among people with abdominal obesity and weight control experiences. In terms of total body fat ratio, total amount of fat and muscle, the bone mineral density got gradually increased from the 1st quarter (Q1) to the 4th quarter(Q4). The obesity, disease, total amount of fat and muscle were shown to be significantly related with the bone mineral density in this research and it is required for young women to keep the adequate weight and the normal BMI in order to increase the bone mineral density. For the prevention of osteoporosis, it is advised to keep the right habits including regular exercise and no smoking discipline from the growing period and achieve the maximum bone mass thru the control of proper weight from a young age.

Anti-osteoporotic Activity of Gojineumja Aqueous Extracts on the Ovariectomized Mice (난소적출 마우스에서 고진음자(固眞飮子) 물 추출물의 골다공증 개선 효과)

  • Cho, Su-Yun;Kim, Dong-Chul
    • The Journal of Korean Obstetrics and Gynecology
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    • v.31 no.4
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    • pp.16-38
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    • 2018
  • Objectives: The objective of this in vivo study is to observe the anti-osteoporotic activities of Gojineumja aqueous extracts (GJEJ) on the ovariectomized (OVX) mice as compared to those of risedronate sodium (RES). Methods: Thirty five days after bilateral OVX, GJEJ was orally administered, for 35 days once a day and then the changes on the body weight and gain during experimental periods, femur weights, bone mineral density (BMD), bone strength (failure load), mineral contents - calcium (Ca) and inorganic phosphorus (IP), histological profiles and histomorphometrical analyses at sacrifice were conducted with serum biochemistry - osteocalcin contents and bone specific alkaline phosphatase (BALP) activities. And the results of GJEJ were compared with RES orally administered OVX mice. Results: As a result of OVX, noticeable increase of body weight and gains and serum osteocalcin levels, decrease of serum BALP activities, femur weights, femur Ca and IP contents, BMD and strength were observed as compared to those of sham control mice, respectively. Also, the decrease of all histomorphometrical indices indicating the bone mass and structure, and the increase of indices about resorption were also detected in the femur of OVX control. However, these estrogen-deficient osteoporotic signs were significantly and dose-dependently inhibited by 35 days of continuous oral treatment of GJEJ, at dose levels of 500, 250 and 125 mg/kg, respectively. Especially, GJEJ 500 mg/kg showed favorable inhibitory activities against estrogen-deficient osteoporosis symptoms induced by OVX as comparable to those of RES 2.5 mg/kg. Conclusions: The results in this study suggest that oral administrations of GJEJ have clear dose-dependent favorable anti-osteoporotic activities in OVX mice.

A Study on Bone Formation & Osteoporosis by Taeyoungion-Jahage Extracts

  • Kim, Yi-Geun;Seong, Jun-Ho;Kim, Dong-Il;Lee, Tae-Kyun;Kim, Jun-Ki;Park, Young-Duck
    • The Journal of Korean Obstetrics and Gynecology
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    • v.15 no.4
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    • pp.45-60
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    • 2002
  • Mouse calvarial osteoblast cells were isolated and cultured. To examine whether the cells produce active gelatinases in culture medium or not,the cells were analyzed using by zymograsphic analysis on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). We show that mouse calvarial osteoblasts in culture constitutively synthesize progelatinase- A. Then, mouse osteoblasts, which were stimulated by PTH, $1,25(OH)_2D_3$, mononuclear cell conditioned medium (MCM) and IL-1 as bone resorption agent's, showed increased collagenolysis by producing the active gelatinase. However, treatment of indomethacin and dexamethasone significantly decreased those effects of collagenolysis in mouse osteoblastic cells. On the other hand, IL-1 in stimulating bone resorption was examined using fetal mouse long bone organ culture. IL-1 stimulated bone resorption and produced marked resorption when present simultaneously. Furthermore, when it was examined the effects of indomethacin and dexamethasone on the dose dependent responses of $IL-1{\alpha}$, indomethacin and dexametasone produced a rightward shift in the IL-1 dose response curve. The results of in vitro cytotoxicities showed that Taeyoungjon-Jahage water extracts(T.Y.J-J.H.G extracts) have no any cytotoxicities in concentrations of $1-200\;{\mu}g/ml$ and furthermore there is no any cytotoxicity even in concentration of $300\;{\mu}g/ml$ on mouse calvarial bone cells. T.Y.J.-J.H.G. extracts had protective activity against PTH (2 units/mI), or MCM (5%, v/v), or $rhIL-1{\alpha}$ (1 ng/mI) or $1,25(OH)_2D3$ (10 ng/ml) , $IL-1{\alpha}$ and $IL-1{\beta}-induced$ collagenolysis in the mouse calvarial cells. Pretreatment of the T.Y.J.-J.H.G.extracts for 1 h, which by itself had little effect on cell survival, did not enhance the collagenolysis, nor significantly reduced the collagenolysis by pretreatment. Furthermore. the medicinal extracts were shown to have the protective effects against collagenolysis induced by $IL-1{\alpha}$ and $IL-1{\beta}$. Pretreatment of the extracts for 1 h significantly reduced the collagenolysis. Interestingly, the T.Y.J.-J.H.G. extracts were shown to have the inhibiting effects against gelatinase enzyme and processing activity induced by the bone resortion agents of PTH, $1,25(OH)_2D_3$, $IL-1{\beta}$ and $IL-1{\alpha}$, with strong protective effect in pretreatment with the extracts. T.Y.J.-J.H.G. extracts were shown to have the inhibiting effects against $IL-1{\alpha}-$ and $IL-1{\beta}-stimulated$ bone resorption and the effect of the pretreatment with a various concentrations of the medicinal extracts were significant. The inhibition extent and phenomena of IL-1 stimulated bone resorption by nonsteroidal anti-inflammatory agents of indomethacin and dexamethasone were similar to those obtained by T.Y.J.-J.H.G. extracts treatment in the mouse calvarial tissue culture system. These results indicated that the T.Y.J.-J.H.G.-water extracts are highly stable and applicable to clinical uses in osteoporosis.

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A Study on Anti-Bone Resorption & Osteoporosis by Taeyoungion-Jahage Extracts

  • Bae, Hyo-Sang;Cho, Hyung-Lae;Kim, Dong-Il;Lee, Tae-Kyun;Kim, Jun-Ki;Shin, Jung-Sik
    • The Journal of Korean Obstetrics and Gynecology
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    • v.15 no.4
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    • pp.61-75
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    • 2002
  • Recombinant human $interleukin-1{\beta}$ $(rhIL-1{\beta})$ regulates several activities of the osteoblast cells derived from mouse calvarial bone explants in vitro. $rhIL-1{\beta}$ stimulated cellular proliferation and the synthesis of prostaglandin $E_2(PGE_2)$ and plasminogen activator activity in the cultured cells in a dose-dependent manner. However, the induction of osteocalcin synthesis and alkaine phosphatase activity in response to vitamine D, two characteristics of the osteoblast phenotype, were antagonized by $rhIL-1{\beta}$ over a similar dose range. This study supports the role of $IL-1{\beta}$ in the pathological modulation of bone cell metabolism, with regard to implication in the pathogenesis of osteoporosis by $IL-1{\beta}$. When the mouse calvarial bone cells were used, the bone resorption induced by $IL-1{\beta}$ was strongly inhibited by calcitonin treatment, indicating osteoclast-mediated bone resorption. On the other hand, the medicinal extracts of Taeyoungjon-Jahage (T.Y.J-J.H.G extracts) was tested for whether they could inhibit $IL-1{\beta}-induced$ $PGE_2$ production. Cell viability was not significantly affected by treatment with the indicated concentration of the extracts. The T.Y.J.-J.H.G. extracts were shown to have the inhibitory effects against the synthesis of $PGE_2$. We also examined the effect of the pretreatment with a various concentrations of the T.Y.J.-J.H.G. extracts then treated the $PGE_2-induction$ agents. Pretreatment of the T.Y.J.-J.H.G. extracts for 1 h, which by itself had little effect on cell survival, did not enhance the synthesis of $PGE_2$. Furthermore, the T.Y.J-J.H.G. extracts were shown to have the protective effects against plasminogen dependent fibrinolysis induced by the bone resorption agents of $IL-1{\beta}$. Pretreatment of the T.Y.J.-J.H.G. extracts for 1 h did not enhance the plasminogen dependent fibrinolysis. Finally, calcitonin showed the inhibitory activity the $IL-1{\beta}-stimulated$ bone resorption in the mouse calvarial bone cells having both of the osteoblast and osteoclast cells. Seemingly, pretreatment of the T.Y.J.-J.H.G. extracts for 1 h reduced the bone resorption. These results clearly indicated that calcitonin and T.Y.J.-J.H.G. extracts play key roles in inhibition of the osteoclast-mediated bone resorption.

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The Effect of Isoflavone Supplementation on Bone Metabolism in Ovariectomized SD Rats (이소플라본 보충이 난소절제 흰쥐의 골대사에 미치는 영향)

  • Park, Young-Hee;Yoon, Sun;Chung, Soo-Youn;Yang, Seoung-Oh;Yoo, Tae-Moo;Yang, Ji-Sun;Kwon, Dae-Joong
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.30 no.4
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    • pp.657-661
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    • 2001
  • Osteoporosis that is associated with ovarian hormone deficiency following menopause (postmenopausal osteoporosis) is by far the most common cause of age-related bone loss. Isoflavone has been reported as a natural substance that possibly minimizes bone loss in postmenopausal women. This study was conducted to investigate the preventing, treating effects of isoflavone on bone loss in ovariectomized rats. 120 Sprague Dawley rats of 13 week-old were devided into 2 groups, a treatment group and prevention group. Each group was consisted of six subgroups; control (CON), sham operated (SH) or ovariectomized (OVX) and isoflavone supplemented goups: OVX+0.25mg isoflavone/kg diet (OL), OVX+0.8mg isoflavone/kg diet(OM) and OVX+2.5mg isoflavone/kg diet(OH). to study the preventing effects of isoflavone on bone loss, OL, OM and OH groups were fed with isoflavone from 4 days after ovariectomization. Treating effects of isoflavone on bone metabolism were investigated with OL, OM, OH groups supplemented with isoflavone from 8 weeks after ovariectomization. Isoflavone supplementation continued for 8 weeks. At 8 weeks after ovariectomization significant increase in alkaline phosphatase occurred comparing with CON and SH group. By isoflavone supplementation from 4 days after ovariectomy alkaline phosphatase and urinary hydroxyproline were lowered and bone mineral density, bone strength of the femur and tibia and bone dry weight were slightly enhanced with no significant difference. Isoflavone supplemented group at the level of 0.8mg/kg diet (OM group) had significantly lower serum alkaline phosphatase, urinary hydroxyproline, and higher strength of femur than OVX group. Groups with isoflavone supplementation fro 8 weeks after ovariectomy had lower level of serum alkaline phosphatase, urinary hydroxyproline than OVX group. Bone mineral density, bone dry weight and bone strength of the femur and tibia were slightly enhanced by isoflavone supplementation. However there was no significanct difference between OVS ad isoflavone supplementation groups. The results suggest that isoflavone might have potential role for preventing postmenopausal bone loss. Isoflavone supplementation at early stage of postemenopause may be beneficial to age-related bone health.

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Effects of Organic Ca Supplements on Ca Bioavailability and Physiological Functions in Ovariectomized Osteoporotic Model Rats (난소절제 골다공증 흰쥐모델에서 유기태 칼슘보충제가 칼슘 이용성과 생리기능에 미치는 영향)

  • Cho, Su-Jung;Park, Mi-Na;Kim, Hee-Kyong;Kim, Jae-Hong;Kim, Min-Ho;Kim, Wan-Sik;Lee, Yeon-Sook
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.40 no.5
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    • pp.665-672
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    • 2011
  • We evaluated the effects of organic Ca supplements chelated with milk protein (CaMP) in ovariectomized osteoporotic rats. Eight week-old Sprague-Dawley female rats were ovariectomized and fed a low $CaCO_3$ diet (0.1%) for 4 weeks to create an osteoporotic model. At that point, L4-$CaCO_3$ rats were sacrificed and the rest of the rats were divided into 4 groups, each of which was fed an experimental diet for 4 weeks: low-$CaCO_3$ (0.1%; L8-$CaCO_3$) and CaMP at 3 Ca levels: low (0.1%; L8-CaMP), normal (0.5%; N8-CaMP), and high (1.5%; H8-CaMP). Daily weight gain, serum ALP, weight and breaking force of femurs, Ca content of the lumbar, and Ca absorption were measured. Daily weight gain increased in the N8-CaMP and H8-CaMP groups compared to the low Ca groups. The ALP activity in the CaMP-fed rats was significantly lower than in the $CaCO_3$-fed rats. Both breaking force and femur weight were higher in the N8-CaMP and H8-CaMP groups compared to the L8-$CaCO_3$ group. Ca content of the lumbar increased dose-dependently with Ca intake levels of CaMP. Ca absorption rates of the CaMP-fed rats increased more than that of the rats fed low Ca levels of $CaCO_3$. These results demonstrate that the CaMP supplement had positive effects on bone metabolism and Ca bioavailability in ovariectomized osteoporotic rats. Therefore, CaMP may be recommended as a useful Ca supplement to prevent bone loss in osteoporosis.

Effects of Ulmus davidiana Planch(Ulmaceae) on mineralization, bone morphogenetic protein-2, alkaline phosphatase, type I collagen and collagennase-1 in bone cells (유근피가 골세포의 mineralization, bone morphogenetic protein-2, alkaline phosphatase, type I collagen 및 collagennase-1에 미치는 영향)

  • Byun, You-seok;Yoon, Jong-hwa;Hwang, Min-seob;Kim, Kap-sung;Jo, Hyun-seog
    • Journal of Acupuncture Research
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    • v.22 no.3
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    • pp.13-22
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    • 2005
  • By extracting the sample of Ulmus davidiana Planch(Ulmaceae), which was known to have the protection of damaged organ and the anti-inflammation action, it was experimented whether it is available for the application of treatment of osteoporosis. In the previous experiment, the extracts from Ulmus davidiana Planch(Ulmaceae) were confirmed to inhibit Cathepsin K through treating the cell of long bone, which contains osteoclast. Through this, it is suggested that Ulmus davidiana Planch(Ulmaceae) can play a role of prodrug as an inhibitor of absorbing bone ash in the treatment of osteoporosis. In the present experiment, a research in vitro Ulmus davidiana Planch(Ulmaceae) on the growth and sensibilization of osteoblast in a state that induced osteosis by using the cell tissue of MC3T3-El pre-osteoblastic was conducted. As a result, it could be confirmed that Ulmus davidiana Planch(Ulmaceae) has the strengthening function by enhancing the dosage and the activity of ALP depending on the time. The dosage was observed at the minimum of $50{\mu}g/m{\ell}$ and the maximum of $150{\mu}g/m{\ell}$. The enhancement in bone morphogenetic protein-2 at $100{\mu}g/m{\ell}$ UD could be observed, and it also increased the concentration of ALP mRNA within the cell of MC3T3-El. At $60{\mu}g/m{\ell}$ UD which indicated a little increase in Type I collagen mRNA for a long time of culture. However, it was shown to sharply inhibit the expression of gene in the culture between 15-20 days. These results suggest that Ulmus davidiana Planch(Ulmaceae) has an influence upon bone metabolism through thje sensibilization of osteoblast. Therefore, it could be known that utilized Ulmus davidiana Planch(Ulmaceae) can be positively applied for the general disease of bone metabolism through future studies.

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Effects of antler, red ginseng, safflower, ipriflavone and estrogen on body weight, bone mineral density, organ weight and histological change in ovariectomized rats (녹용, 홍삼, 홍화, ipriflavone 및 estrogen이 난소적출 rat의 체중, 골밀도, 장기중량 및 조직학적 변화에 관한 연구)

  • 유상식;김상근;이명헌;송운재;문병천;김무강
    • Korean Journal of Veterinary Service
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    • v.23 no.3
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    • pp.235-245
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    • 2000
  • This study was peformed to elucidate the effects of antler, red ginseng, safflower seed, ipriflavone and estrogen on ovariectomized rats. The rats were fed with Ca and P deficient diet for five weeks to induce osteoporosis. After this period, these animals were fed with normal for and treated every other day with antler(600mg/kg, PO), red ginseng(200mg/kg, PO), safflower(200mg/kg, PO), ipriflavone(80mg/kg, PO) and estrogene(400$\mu\textrm{g}$/kg, IM) for S weeks. During the treatment, the rats were examined for body, organ, femur and femur ash weights. And electron-microscopical examinations were also performed on femora. The results are summarized as follows : 1. The body weights of the antler, red ginseng, safflower, ipriflavone and estrogen-treated groups after five weeks of treatment, were 303.0$\pm$3.0g, 273.3$\pm$4.4g, 288.3$\pm$5.1g, 300.5$\pm$5.2g, 320.5$\pm$4.2g, respectively. They, except the red ginseng-treated group, were significantly higher than 278.4$\pm$2.7g of normal control group(P<0.05). And the body weight of non-treatment group was 29it.2$\pm$5.5g which was higher than that of control group, too. 2. The weights of left femur after five weeks of treatment were showed 0.83$\pm$0.2g by antler, 0.89$\pm$0.2g by red ginseng, 0.87$\pm$0.2g by safflower 0.83$\pm$0.1g by ipriflavone and 0.78$\pm$0.1g by estrogen-treated group. They were a little lower than 0.97$\pm$0.1g of normal control group. Non-treatment group showed 0.83$\pm$0.1g which was lower than that of control group but not significant. 3. The weights of ashed left femora after five weeks of treatment were showed 0.36$\pm$0.01g by antler, 0.40$\pm$0.01g by red ginseng, 0.41$\pm$0.01g by safflower, 0.36$\pm$0.01g by ipriflavone and 0.35$\pm$0.01g by estrogen-treated group. Those results were significantly lower than 0.43$\pm$0.01g of normal control group. And non-treatment group showed 0.29$\pm$0.01g of femoral ash which was significantly lower than that showed by control group(p<0.05). 4. The femoral Ca contents of the antler, red ginseng, safflower, ipriflavone and estrogen-treated rats were 19.6$\pm$0.7%, 17.8$\pm$1.1%, 18.8$\pm$0.9%, 18.0$\pm$1.1%, 15.3$\pm$1.1%, respectively, after five weeks of treatment. The femoral Ca contents of antler and safflower-treated groups were higher than that of control group which showed 18.2$\pm$0.9% of Ca The non-treatment group, showing 15.3$\pm$0.7%, had significantly lower content of Ca than normal group(p<0.05). 5. The weights of liver, spleen, and kidney in the osteoporosis-induced rats during the treatment with antler, red ginseng, safflower, jpriflavone and estrogen showed not significant changes. 6. The connections among the trabeculae of control group were maintained well, showing no bone loss. However, the connections among the trabeculae of non-treatment group were thinner than those of control group and were almost disconnected and the lacunae were found to be broadened. Antler and safflower-treated group showed only slight changes. The recovery rates were prominent in antler, safflower, estrogen-treated groups but they were insignificant in red ginseng and ipriflavone-treated groups.

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The Effects of Estrogen on Experimental Tooth Movement in Ovariectomized Rats (난소적출 백서에서 estrogen투여가 실험적 치아이동에 미치는 영향)

  • Jin, Keun-Ho;Kim, Jong-Ghee;Park, Byung-Keon;Kim, Oh-Hwan
    • The korean journal of orthodontics
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    • v.27 no.4 s.63
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    • pp.585-597
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    • 1997
  • The purpose of this study was to evaluate the effect of estrogen on the periodontium and alveolar bone tissue response during experimental tooth movement in ovariectomized rats. Eighty female rats, 250gm in body weight, were classified into four groups ; sham operated group(NN), ovariectomized group(ON), ovariectomized & estrogen injected group(OE), sham operated & estrogen injected group(NE). flats were ovariectomized before 3 weeks to begin the experiment, which resulted in estrogen-deficient osteoporosis. In OE group & NE group, estrogen was injected $50{\mu}g/kg\;B.W.$ every other days. The left maxillary 1st molar was moved mesially with 60g force. Each foot rats were sacrificed after 1, 3, 7, 15 days from application of orthodontic appliance and alter additional 7 days from removal of orthodontic appliance. Histological findings on mesial roots of upper 1st molar in pressure and tension side are observed. The results were summarized as follows ; 1. In pressure side of alveolar bone, the number of osteoclasts and Howship's lacuna of ON group was significantly more than that of NN group from 1 day to 15 days(P<0.05). Especially the number of Howship's lacuna of ON group was significantly more than that of OE group during all experimental period(P<0.05). 2. In tension side of alveolar tune, the number of osteoclasts of ON group was significantly increased from 1 day to 3 days and decreased after 7 days. But the number of osteoclast of ON group was significantly mote than that of NN group during all experimental period(P<0.05). Also the number of Howship's lacuna of all groups was abruptly increased at 1 day, but slowly decreased till experimental 15 days. And the number of Howship's lacuna of of group was significantly more than that of NN group from 0 hr to 7 days(P<0.05). 3. The speed of tooth movement of OE group & NE group was similar to that of NN group(P>0.05). The amount of tooth movement of ON group between 7 days and 15 days was significantly greater than those of other groups(P<0.05). 4. The degree of relapse of ON group after 7 days from removal of orthodontic appliance was similar to those of other groups(P>0.05).

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Relationship between Intake of Milk and Milk Products and Bone Health by Sex and Age-Group in Koreans - Using Data from the Korea National Health and Nutrition Examination Survey 2008~2011 (성별, 연령별에 따른 우유·유제품 섭취와 골 건강과의 관련성 - 2008~2011 국민건강영양조사 자료를 이용하여)

  • Baek, Sang Woo;Lee, Heon Ok;Kim, Hyun Ja;Won, Eun Sook;Ha, Young Sik;Shin, Yong Kook;Om, Ae Son
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.46 no.4
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    • pp.513-522
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    • 2017
  • This study was conducted to examine the relationships between milk and milk product intake and bone health. The data from the 2008~2011 Korean National Health and Nutrition Examination Survey (KNHANES) were used for data analysis. Subjects included 4,626 men and 6,144 women aged 19 to 64 years. Daily intake frequency of milk and milk products was obtained using a food frequency questionnaire and divided into two categories: less than one serving per day and more than one serving per day. Bone mineral density (BMD) values of total femur, femoral neck, and lumbar spine were compared based on daily intake frequency, and relationships between milk and milk product daily intake frequency and osteoporosis risk were evaluated based on logistic regression. In men aged 30~39, BMDs of total femur and femoral neck were significantly higher in the group that consumed milk more than one serving per day (P<0.05). Intake frequency of milk and milk products was also significantly related to both BMDs of total femur and femoral neck. The odds ratio (OR) for milk intake frequency (more than one serving per day) compared to intake frequency less than one serving per day was 0.36 [95% confidence interval (CI) 0.21~0.62], and the OR for milk and milk products intake frequency (more than one serving per day) was 0.49 (95% CI 0.28~0.86) in women aged 50~64. These results indicate that increased consumption of milk and its products is associated with reduced risk of bone health disease, and adequate intakes of milk and milk products might play an important role in maintaining optimum bone health. Further research on the causal relationship and dose-response association between milk intake and bone heath using prospective cohort data is required prior to applying the observed results to programs that prevent bone health problems.