Korean J Fam Pract. 2013;3:315-322 폐경전, 후여성에서대사증후군과골밀도의관련성 Original Article 이기태, 김성희 1, * 봉화해성병원응급의학과, 1 대구가톨릭대학교병원가정의학과 Association between Metabolic Syndrome and Bone Mineral Density in Pre and Post Menopausal Women Ki-Tae Lee, Sung-Hi Kim 1, * Department of Emergency Medicine, Bonghwa Haesung Hospital, Bonghwa; 1 Department of Family Medicine, Daegu Catholic University Medical Center, Catholic University of Daegu School of Medicine, Daegu, Korea Background: Metabolic syndrome (MS) is a cluster of risk factors including abdominal obesity, high fasting glucose, triglycerides, hypertension, and low high density lipoprotein cholesterol levels for type 2 diabetes and cardiovascular disease. This study examined the association of MS and bone mineral density (BMD) in 2,716 premenopausal and 760 postmenopausal women. Methods: We used multiple linear regression and multiple logistic regression analysis to examine the cross-sectional associations of MS defined by modified National Cholesterol Education Program Adult Treatment Panel III criteria with BMD. During the period of September, 2009 to December, 2010 we recruited 3,476 women who were participated in a health examination in Daegu Catholic University Hospital. Results: The prevalence of MS was 4.8% in premenopausal and 25.3% in postmenopausal women. After adjusted covariates (age, body weight, body mass index, body fat %, total cholesterol, low density lipoprotein cholesterol, glycated hemoglobin, gamma-glutamyltransferase, total-protein, smoking, drinking, and regular exercise), MS had lower BMD at lumbar-spine and femur neck in premenopausal women, but not in postmenopausal women. Conclusion: The prevalence of low BMD at lumbar-spine and femur neck were higher in premenopausal women with MS. MS maybe independent risk factor for osteoporosis. Keywords: Metabolic Syndrome; Bone Density; Premenopausal Period and Postmenopausal Period 서론 고인슐린혈증, 지질이상, 고혈압, 복부비만의집합체인대사증후군 (metabolic syndrome) 은당뇨병과심혈관질환의위험 Received: August 31, 2012, Accepted: September 9, 2013 *Corresponding Author: Sung-Hi Kim Tel: 053-650-4125, Fax: 053-654-4122 E-mail: khmksh@cu.ac.kr Korean Journal of Family Practice Copyright 2013 by The Korean Academy of Family Medicine 도를증가시킨다. 1) 우리나라에서대사증후군유병률은지속적인증가상태이며, 특히중년이후여성에서유병률은 27.8% 로매우가파른상승세이다. 2) 골다공증은골량감소, 미세구조변화로골강도가감소되어골절위험성이증가하는전신성골이상으로정의되며골절및사망위험이높아지기때문에심혈관질환과함께인구고령화시대에보건학적인의미가크다. 3) 대사증후군과골다공증은질병특성이다르지만공통점들이있는데, 연령증가에따라서질병이심해지고, 심혈관질환및골절과같이질병의결과가심각하고, 골세포 (osteocytes) 와지방세포 (adipocytes) 가모두 mesenchymal stem cell에서분화된다는점이다. 4) 가정의학 Vol. 3, No. 3 Sep 2013 315
Ki-Tae Lee, et al: Metabolic Syndrome and Bone Mineral Density 골밀도 (bone mineral density, BMD) 는유전적, 환경적요인에의해영향을받는데, 50 80% 는유전적, 30 50% 는환경적요인에의해영향받는것으로보고되고있으며 5) 비만과대사증후군도유전적요인과환경적요인이서로영향을미치는복합적인질환이다. 대사증후군, 비만그리고골다공증사이의관련성은아직명확한설명이부족한상태이며, 서로상반된연구결과들이보고되고있다. 단면연구에서체질량지수 (body mass index, BMI) 와체중이증가할수록고령자에서골소실에대한예방효과를보였고, 폐경기여성에서비만군이정상군에비하여 BMD가높고골대사속도가느리며대퇴부에축적된지방이대퇴경부의골절에완충역할을하는것으로추정되었다. 6) 반면에미국의일반인대상연구는 BMD에영향을미치는변수들을보정하기전에는대사증후군의요소들이많아질수록대퇴골경부 BMD가증가하였으나변수들을보정한후에는이전의관련성이소실되었고 7) 다른전향적연구에서는대사증후군요소가많아질수록비척추골절의발생이증가하였다. 8) 또한당뇨병, 쿠싱병, 류마티스관절염등의만성염증성질환에서는지방량증가가 BMD를낮춘다는결과들도보고되고있는데, 이는대사증후군, 비만등이 BMD 저하와관련성이있으며이러한관련성의기전으로낮은정도의염증반응이관여하는것으로추정되고있다. 9,10) 대사증후군, 비만에의해경미한염증반응이진행되면서골흡수가촉진되어 BMD를저하시키고비외상골절의위험도가높아지게된다. 11) 체지방, 대사증후군이 BMD 증가에관여하는지혹은감소에관여하는지에대한논란이있지만, 최근의연구들에따르면체중, BMI를보정한후, 체지방량과대사증후군요소들은다른연구에서도대사증후군에서정상군에비하여비척추성골절의위험이증가하였다. 12) 여성의대사증후군과골다공증연구에서폐경여부는고려해야할중요한요인인데, 폐경후혈중여성호르몬이급격하게감소함에따라서비만과복부지방침착이유의하게증가하며, 13) 골흡수증가에따른 BMD 소실이증가하기때문이다. 14) 본연구는단면연구방법으로폐경전, 후여성으로구분하여대사증후군과 BMD와의관련성을알아보고자하였다. 방법 1. 연구대상 2009년 6월부터 2011년 3월까지대구가톨릭대학교병원에서종합검진을시행한여성 3,853명을대상으로하였다. 이중에서 377명 ( 부적절한설문응답 69명, 골다공증약물치료 중인 295명, 심혈관질환합병증, 만성신장질환, 망막질환, 뇌졸중, 심근경색증등 35명 ) 을제외한 3,476명을대상으로하였다. 2. 연구방법 1) 설문조사건강검진설문지를자기기입식으로일반특성, 생활습관, 질병력등을조사하였다. 연령범위는 20 87세였고, 흡연은현재까지총흡연량 100개피 (5갑) 를기준으로현재흡연군, 과거흡연군, 비흡연군으로하고음주는국민건강영양조사에서이용한월간음주율 ( 최근 1년동안한달에 1회이상술을마신경우 ) 을기준으로현재음주군, 과거음주군, 비음주군으로구분하였고운동은일주일에 2회이상 ( 30분) 인중등도운동을기준으로규칙적운동군과그렇지않은군으로구분하였다. 생리유무에따라서지난 6개월간생리가없는경우를폐경후군으로하고나머지를폐경전군으로구분하였다. 2) 신체계측및혈액검사키와몸무게는자동신체계측기, 체지방 % 는체성분분석기 (X-scan; Jawon, Gyeongsan, Korea) 를이용하여측정하였고 BMI는체중 / 신장 (kg/m 2 ) 을이용하여구하였다. 허리둘레는직립상태에서늑골의최하단부와골반장골릉사이의중간부위둘레를수평으로유지한상태로소수점이하한자리까지 cm 단위로측정하였다. 혈압은방문후최소 5분간휴식후수은혈압계로양팔중좌측팔을이용하여측정후최소 5분이상재휴식후반복측정하여그평균을이용하였다. 공복혈당 (fasting blood sugar), 중성지방농도 (triglyceride), 고밀도지단백 (high density lipoprotein, HDL) 콜레스테롤, 총콜레스테롤 (total cholesterol, TC), 저밀도지단백 (low density lipoprotein, LDL) 콜레스테롤, 당화혈색소 (glycated hemoglobin, HbA1c), gamma-glutamyl transferase (GGT), total protein 농도는최소 8 시간공복후전주정맥에서혈액을채취하여 HITACHI 7600-210 & HITACHI 7180 chemistry analyzer (Hitachi, Tokyo, Japan) 를이용하여측정하였다. 3) 골밀도측정 Hologic DEXA scanner (QDR 4500; Hologic Inc., Bedford, MA, USA) 를이용하여요추1 4번과좌측대퇴경부의 BMD 를측정하였으며요추와좌측대퇴경부최저치를기준으로 T-score -0.9 이상을정상군으로하고 -1 이하를 BMD 감소군으로구분하였는데, 요추와대퇴경부중하나라도해당되는경우에는 BMD 감소군으로정의하였다. 316 Vol. 3, No. 3 Sep 2013 Korean J Fam Pract
이기태외 : 폐경전, 후여성에서대사증후군과골밀도의관련성 4) 대사증후군의정의수정된 National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) 의정의 15) 에따라다음중 3 가지이상에해당되는경우를대사증후군으로정의하였다 : (1) 허리둘레 : 여자 80 cm; (2) 공복혈당 : 110 mg/dl; (3) 중성지방 : 150 mg/dl; (4) HDL-콜레스테롤 : 여자 <50 mg/dl; (5) 혈압 : 수축기혈압 130 mm Hg 혹은이완기혈압 85 mm Hg. 당뇨병, 고혈압의질병력이있으면각각해당대사증후군요소 Table 1. General characteristics of study population by menopause status (n=3,476) Variable Premenopause (n=2,716) Postmenopause (n=760) P-value Age*(y) 40.4±6.8 60.3±6.1 <0.001* Body weight (kg) 56.3±11.9 57.5±7.8 0.009* Body mass index 22.1±2.8 24.1±3.1 <0.001* Body fat % 27.6±4.7 31.8±4.1 <0.001* Waist (cm) 73.1±7.2 79.8±7.5 <0.001* Fasting blood sugar 83.9±11.0 92,0±19.7 <0.001* Triglyceride 84.9±59.6 120.5±76.8 <0.001* High density lipoprotein cholesterol 61.2±14.3 57.4±14.6 <0.001* Systolic blood pressure 116.5±15.1 129±17.6 <0.001* Diastolic blood pressure 70.8±10.5 76.5±10.9 <0.001* Gamma-glutamyltransferase 16.0±15.9 24.1±52.6 <0.001* Total cholesterol 177.6±32.2 201.1±38.6 <0.001* Low density lipoprotein cholesterol 109.4±28.7 134.4±36.0 <0.001* Glycated hemoglobin 5.4±0.4 5.9±0.8 <0.001* Bone mineral density-lumbar spine -0.35±0.98-1.69±1.10 <0.001* Bone mineral density-femur neck -0.50±0.87-1.42±0.89 <0.001* Smoking status No 2,059 (75.8) 577 (75.9) 0.331 Past or current 171 (6.3) 39 (5.1) Unknown 486 (17.9) 144 (19.0) Drinking status No 1,621 (59.7) 434 (57.1) 0.605 Past or current 905 (33.3) 229 (30.2) Unknown 190 (7.0) 97 (12.7) Regular exercise No 1,059 (39.0) 319 (41.9) 0.032 Yes 1,119 (41.2) 306 (40.3) Unknown 538 (19.8) 135 (17,8) Metabolic syndrome No 2,586 (95.2) 568 (74.7) <0.001 Yes 130 (4.8) 192 (25.3) Values are presented as mean±sd or number (%). *Analyzed by t-test. Analyzed by chi-square test. Others were analyzed by t-test. 가정의학 Vol. 3, No. 3 Sep 2013 317
Ki-Tae Lee, et al: Metabolic Syndrome and Bone Mineral Density 가있는군으로구분하였으며, 허혈성심질환이나뇌경색질병력이있는경우에는대사증후군으로분류하였다. 3. 분석방법통계분석은 IBM SPSS ver. 19.0 (IBM Co., Armonk, NY, USA) 을사용하였고조사대상자전체와폐경전, 폐경후군으로구분하여분석을시행하였다. 폐경전, 후군의일반적특성비교는 t-test와 chi-square test를시행하였고요추, 대퇴경부 BMD와대사증후군위험요소와의상관관계를알아보았다. 그리고폐경전, 후군의 BMD에대한대사증후군의관련성에대해서는다중선형회귀분석을시행하였고, BMD 감소에대한대사증후군의위험도는다중로지스틱회귀분석을시행하여알아보았다. 선형회귀분석과다중로지스틱회귀분석시에는공변량 ( 연령, 체중, BMI, 체지방 %, GGT, TC, HDL, total protein, 흡연, 음주, 규칙적운동 ) 을보정하였다. 결과 1. 일반적특성조사대상자 3,476명중에서폐경전군은 2,716명 (78.1%), 폐경후군은 760명 (21.9%) 이었다. 요추 BMD 정상군은 2,093 명 (60.2%), BMD가 -1 이하인감소군은 1,383명 (39.8%) 이었 고대퇴경부 BMD 정상군은 2,141명 (61.6%), BMD 감소군은 1,335명 (38.4%) 이었다. 폐경전, 후군의비교에서폐경후군에서 BMI, 체지방 %, 대사증후군요소 ( 허리둘레, 공복혈당, 중성지방농도, HDL, systolic blood pressure, diastolic blood pressure) 와 TC, LDL 수치가높았으며요추와대퇴경부의 BMD는유의하게감소되었다 (P<0.05). 흡연과음주는차이가없었으나폐경전군에서더규칙적인운동을하였다 (P<0.05). BMD의 T-score 평균은폐경전군에서요추 -0.35, 대퇴경부 -0.50이었고폐경후군은요추 -1.69, 대퇴경부 -1.42으로폐경후군에서요추와대퇴경부의 BMD가유의하게낮았다 (P<0.05). 요추 BMD 감소의유병률은폐경전군이 31.0%, 폐경후군이 70.7% 이었고대퇴경부 BMD 감소의유병률은폐경전군이 27.5%, 폐경후군이 77.1% 이었다 (P<0.05) (Table 1). 2. 대사증후군요소와요추및대퇴경부골밀도의상관관계 BMD와대사증후군요소들과의단순상관성분석을시행하였다. 폐경전여성에서요추 BMD는이완기혈압과중성지방을제외한대사증후군요소들과양의상관성을보였고 (HDL 수치와는음의상관성이있었으나이는대사증후군요소와의양의상관성을보이는것과동일함 ), 대퇴경부 BMD에 Table 2. Correlation of bone mineral density and metabolic syndrome (MS) components (n=3,476) Variable Lumber spine Femur neck No. of MS components Premenopausal 0.07 (<0.001) 0.12 (<0.001) Postmenopausal 0.07 (0.050) 0.04 (0.232) Waist (cm) Premenopausal 0.11 (<0.001) 0.19 (<0.001) Postmenopausal 0.11 (0.002) 0.11 (0.003) Systolic blood pressure (mm Hg) Premenopausal 0.05 (0.013) 0.11 (<0.001) Postmenopausal 0.02 (0.576) -0.01 (0.825) Diastolic blood pressure (mm Hg) Premenopausal 0.03 (0.081) 0.08 (<0.001) Postmenopausal 0.03 (0.148) 0.02 (0.528) High density lipoprotein cholesterol (mg/dl) Premenopausal -0.06 (0.002) -0.04 (0.033) Postmenopausal -0.01 (0.734) -0.03 (0.446) Triglyceride (mg/dl) Premenopausal 0.01 (0.711) 0.02 (0.168) Postmenopausal 0.03 (0.344) 0.04 (0.244) Fasting blood sugar (mg/dl) Premenopausal 0.05 (0.018) 0.06 (<0.001) Postmenopausal 0.07 (0.044) -0.01 (0.938) Values are presented as Pearson correlation coefficient (P-value). Analyzed by correlation analysis. 318 Vol. 3, No. 3 Sep 2013 Korean J Fam Pract
이기태외 : 폐경전, 후여성에서대사증후군과골밀도의관련성 서는중성지방을제외한대사증후군요소들과양의상관성을보였다. 폐경후여성에서는상대적으로상관관계가약화되어요추 BMD에서대사증후군요소개수, 허리둘레, 공복혈당이 BMD와양의상관성이있었고대퇴경부 BMD에서는허리둘레만이유의하였다 (P<0.05) (Table 2). 3. 폐경전군에서골밀도감소위험도분석 : 선형회귀분석요추에서는대사증후군요소개수, 연령, 체지방 % 가증 가할수록 BMD가감소되었고, 반면에체중, BMI가증가할수록 BMD는증가하였다 (P<0.05). 대퇴경부에서도대사증후군요소개수, 체지방 %, LDL이증가할수록 BMD가감소하였고 BMI가높을수록 BMD가증가하였다 (P<0.05) (Table 3). 4. 폐경전군에서골밀도감소위험도분석 : 다중로지스틱회귀분석공변량을보정하지않은상태에서폐경전군에서대사증후군에서대퇴경부 BMD 감소의위험은낮았으나 (odds ratio Table 3. Associations with metabolic syndrome (MS) components and bone mineral density (BMD) by multiple linear regression analysis Total (n=3,476) Premenopause group (n=2,716) Postmenopause group (n=760) Variable Standard coefficient P-value Standard coefficient P-value Standard coefficient P-value BMD L-spine Age -0.440 <0.001-0.044 0.032-0.245 <0.001 BW 0.077 <0.001 0.056 0.010 0.344 <0.001 BMI 0.378 <0.001 0.536 <0.001 0.019 0.786 Body fat % -0.212 <0.001-0.290 <0.001-0.079 0.172 MS-total -0.072 <0.001-0.057 0.012-0.037 0.384 GGT -0.040 0.013-0.033 0.081-0.240 0.810 HbA1C -0.079 <0.001-0.015 0.440 0.092 0.010 TC -0.018 0.584-0.014 0.718 0.081 0.218 LDL -0.103 0.003-0.043 0.267-0.080 0.226 T-protein 0.024 0.113-0.012 0.535-0.041 0.240 R 2 =0.251 R 2 =0.105 R 2 =0.178 BMD femur neck Age -0.380 <0.001-0.939 0.348-0.352 <0.001 BW 0.058 0.002 0.026 0.226 0.369 <0.001 BMI 0.489 <0.001 0.625 <0.001 0.060 0.354 Body fat % -0.207 <0.001-0.302 <0.001-0.136 0.012 MS-total -0.071 0.001-0.046 0.032-0.029 0.471 GGT -0.026 0.090-0.020 0.272-0.027 0.394 HbA1C -0.021 0.280-0.010 0.599 0.004 0.907 TC 0.068 0.022 0.055 0.136 0.032 0.603 LDL -0.081 0.013-0.093 0.014-0.013 0.833 T-protein -0.066 0.063-0.035 0.065-0.07 0.842 R 2 =0.225 R 2 =0.137 R 2 =0.176 BW: body weight, BMI: body mass index, GGT: gamma-glutamyltransferase, TC: total cholesterol, LDL: low density lipoprotein cholesterol, HbA1C: glycated hemoglobin, T-protein: total protein, BMD L-spine: bone mineral density-lumbar spine, BMD femur neck: bone mineral density-femur neck. 가정의학 Vol. 3, No. 3 Sep 2013 319
Ki-Tae Lee, et al: Metabolic Syndrome and Bone Mineral Density Table 4. Odds ratio (OR) of low bone mineral density (BMD, -1) with metabolic syndrome by multiple logistic regression analysis (n=3,476) Variable Premenopause group (n=2,716) Postmenopause group (n=760) OR (95% CI) P-value OR (95% CI) P-value BMD L-spine Adjusted 1.62 (1.01 2.60) 0.046 0.78 (0.49 1.23) 0.289 Unadjusted 0.87 (0.57 1.28) 0.441 0.69 (0.41 0.86) 0.007 BMD femur neck Adjusted 0.96 (0.57 1.67) 0.870 1.23 (0.77 1.96) 0.387 Unadjusted 0.54 (0.28 0.71) 0.002 0.91 (0.64 1.32) 0.613 Adjusted by age, body weight, body fat %, body mass index, gamma-glutamyltransferase, total cholesterol, low density lipoprotein cholesterol, glycated hemoglobin. CI: confidence interval. [OR], 0.54; 95% confidence interval [CI], 0.28 to 0.71), 공변량을보정한후에는대사증후군에서정상군에비하여요추 BMD 저하위험도는 1.62배증가하였고 (OR, 1.62; 95% CI, 1.01 to 2.60) 대퇴경부 BMD에는영향이없었다 (Table 4). 5. 폐경후군에서골밀도감소위험도분석 : 선형회귀분석요추 BMD는연령이많을수록감소하였으며체중증가, 당화혈색소증가에따라서는증가하였다 (P<0.05). 대퇴경부 BMD도연령, 체지방 % 가많아지면감소하였고체중이많아지면증가하였다 (P<0.05). 폐경후군에서대사증후군요소개수는요추와대퇴경부 BMD와관련성이없었다 (Table 3). 6. 폐경후군에서골밀도감소위험도분석 : 다중로지스틱회귀분석공변량을보정하지않은상태에서대사증후군에서요추 BMD 감소의위험이저하되었으나 (OR, 0.69; 95% CI, 0.41 to 0.86) 공변량을보정한후에는대사증후군유무에따른요추와대퇴경부 BMD는유의한관련성이없었다 (Table 4). 고찰 본연구대상자전체에서대사증후군, 체지방 % 와 BMD 사이에는음의관련성이있었다. 공변량 ( 나이, 체중, BMI, 체지방 %, GGT, HbA1C, TC, LDL, 규칙적운동, 음주, 흡연 ) 을보정하지않은상태에서는대사증후군과체지방 % 는체중, BMI처럼 BMD 증가와관련을보였으나공변량을보정한후에는체중, BMI와는달리대사증후군과체지방 % 는역으로 BMD 감 소와관련성을보였다. 조사대상자들의대사증후군유병률은 9.3%( 폐경전군 4.8%, 폐경후군 25.3%) 이었고수정된 NCEP- ATP III 기준의국내연구에서보고된여자유병률 18.4% 16) 와미국의 20-25% 8) 보다낮았다. 체지방과 BMD의관련성은복합적이어서체지방증가가 BMD 증가혹은감소에관여하는상반된결과를보이는연구결과들이보고되고있다. 전자의경우는폐경후여성에서, 후자의경우는폐경전여성에서더욱뚜렷하다. 폐경후여성에서대사증후군과 BMD 감소의관련성이약해지는이유는체중의증가가매개하는것으로추정된다. 이는폐경이후여성에서여성호르몬결핍으로인한복부비만, 체중증가가동반되며, 뼈에가해지는물리적부하량이상승하면서골흡수속도가천천히진행되어대사증후군에의한 BMD 저하를상쇄하는효과가있다. 17) 본연구에서도유사한분석결과를보였는데, 폐경전군에서공변량보정을하지않으면대사증후군, 체지방 % 는요추, 대퇴골경부모두에서 BMD 증가와관련되었으나공변량보정시에는역으로 BMD 저하효과가있었고폐경후군에서는대사증후군과체지방 % 와 BMD 사이의유의한관련성이없었다. 체지방 % 와 BMD 증가에관한단면적연구에서는대사증후군과 BMD는양의관련성을보였으나 18) 전향적연구에서체지방량이증가할수록골량은감소하였다. 19) 중국의대규모연구에서체중보정후, 체지방량은골량에역비례하였고 11) 4,489명의백인을대상으로한 BMI 구간별층화분석 (World Health Organization expert committee study) 시에체지방량과 BMD 사이에는음의관련성이있었다. 20) 폐경후여성에서 BMD와제지방량 (lean mass), 지방량사이의관련성연구에서 BMD는제지방량, 지방량모두에양의관련성이있었으며제 320 Vol. 3, No. 3 Sep 2013 Korean J Fam Pract
이기태외 : 폐경전, 후여성에서대사증후군과골밀도의관련성 지방량의영향력이더강력하였다. 21) 본연구에서도대사증후군위험요소개수, 체지방량과요추및대퇴경부 BMD 사이에는유의한음의관련성을보였고체중, BMI와는양의관련성을보였다. 다른연구들에서대사증후군, 복부비만, 인슐린저항성, 염증반응과 BMD 사이의음의관련성들이보고되고있다. 22-24) 대사증후군과 BMD 감소사이에는염증반응이매개되는데첫째, 사이토카인생산이촉진되면서지방세포와골세포의공통기원인 mesenchymal cell 분화가지방세포방향으로진행하게되고파골세포 (osteoclast) 가활성화되어골교체율증가와 BMD 감소가일어나고 23) 둘째, 대사증후군에의한경미한염증반응이진행하면서골흡수가항진되어골소실을초래하게된다. 이러한점에서대사증후군은독립적인골감소의요인이라고할수있으며혈청 high-sensitivity C-reactive protein (hs- CRP) 농도와 BMD와의관련성을본국내연구들에서 hs-crp 가증가할수록 BMD는저하되었다. 24,25) 만성염증성질환 ( 제 2형당뇨병 ) 과 BMD와의관련성에대한연구에서고혈당이 osteoblast를억제하여골생성을저하시키고파골세포활동을촉진하여골흡수를항진시킴으로서 BMD를저하시키고골절의위험을높이게된다. 26) 역학연구에서도대사증후군과대퇴경부 BMD가유의한관련성이있었고공변량을보정하지않은상태에서는대사증후군이있을수록대퇴골경부 BMD가증가하였으나나이, 성별과다른공변량을보정한이후에는대사증후군에서 BMD가감소되었다. 8,27) 본연구의제한점으로는첫째, 단면적연구이어서대사증후군과 BMD 저하사이의인과관계를규명할수없는점과둘째, 조사대상자가한기관의건강검진센터여성수검자에국한되어서전체를대표하기어려운점과셋째, 자기기입식설문지에의존하기때문에생활습관정보가부정확한점, 마지막으로 BMD에직접적인영향을주는여성호르몬과부갑상선호르몬, 비타민 D, 골교체율표지자, 소변중칼슘배설량등의변수들이측정되지않은점등이있다. 본연구에서는대사증후군, 체지방 % 는요추, 대퇴경부 BMD 감소와관련성이있었으며폐경전, 후군으로구분하여분석한결과폐경전군에서는유의하였으나폐경후군에서는유의하지않았다. 요약 연구배경 : 대사증후군은복부비만, 인슐린저항성, 이상지질 혈증, 고혈압등의제2형당뇨병및심혈관계질환위험인자들의집합체이다. 본연구에서는 2,716명의폐경전여성과 760 명의폐경후여성을대상으로대사증후군과골밀도의관련성에대해서알아보았다. 방법 : 다중선형회귀분석과다중로지스틱회귀분석을시행하여대사증후군 (modified National Cholesterol Education Program Adult Treatment Panel III 기준 ) 과골밀도의단면적관련성을분석하였다 (SPSS ver. 19.0). 2009년 9월부터 2010년 12월까지대구가톨릭대학교병원에서건강검진을받은 3,476명을대상으로하였으며, 신체계측및혈액검사를시행하였고생활습관과질병력은자기기입식설문지를이용하였다. 결과 : 대사증후군유병률은폐경전군에서 4.8% 폐경후군에서는 25.3% 이었다. 공변량 ( 연령, 체중, 체지방 %, body mass index, gamma-glutamyl transferase, total cholesterol, low density lipoprotein, glycated hemoglobin, t-protein, smoking status, drinking status, regular exercise) 을보정한후, 폐경전여성의경우에는대사증후군에서요추와대퇴경부골밀도가유의하게감소하였으나폐경후여성에서는유의한관련성이없었다. 결론 : 폐경전여성에서대사증후군이있는경우요추와대퇴경부의낮은골밀도유병률이증가하였으며, 폐경전여성에서는대사증후군이골다공증에대한독립적인위험인자임을추정할수있었다. 중심단어 : 대사증후군 ; 골밀도 ; 폐경전시기및폐경후시기 REFERENCES 1. Kim MH, Kim MK, Choi BY, Shin YJ. Prevalence of the metabolic syndrome and its association with cardiovascular diseases in Korea. J Korean Med Sci 2004;19:195-201. 2. Korea Centers for Disease Control and Prevention. In-depth analysis of the third National Health and Nutrition Survey: the health interview and health behavior survey part. Cheongwon: Korea Centers for Disease Control and Prevention; 2007. 3. World Health Organization Study Group. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis: report of a WHO Study Group. Geneva: World Health Organization; 1994. 4. Rosen CJ, Bouxsein ML. Mechanisms of disease: is osteoporosis the obesity of bone? Nat Clin Pract Rheumatol 2006;2:35-43. 5. Lau HH, Ng MY, Ho AY, Luk KD, Kung AW. Genetic and environmental determinants of bone mineral density in Chinese 가정의학 Vol. 3, No. 3 Sep 2013 321
Ki-Tae Lee, et al: Metabolic Syndrome and Bone Mineral Density women. Bone 2005;36:700-9. 6. Holecki M, Zahorska-Markiewicz B, Nieszporek T. Selected parameters of bone turnover in obese perimenopausal women. Ann Acad Med Siles 2006;60:186-91. 7. Ahmed LA, Schirmer H, Berntsen GK, Fonnebo V, Joakimsen RM. Features of the metabolic syndrome and the risk of non-vertebral fractures: the Tromso study. Osteoporos Int 2006;17:426-32. 8. Kinjo M, Setoguchi S, Solomon DH. Bone mineral density in adults with the metabolic syndrome: analysis in a populationbased U.S. sample. J Clin Endocrinol Metab 2007;92:4161-4. 9. Inaba M. Secondary osteoporosis: thyrotoxicosis, rheumatoid arthritis, and diabetes mellitus. J Bone Miner Metab 2004;22:287-92. 10. Yamaguchi T, Kanazawa I, Yamamoto M, Kurioka S, Yamauchi M, Yano S, et al. Associations between components of the metabolic syndrome versus bone mineral density and vertebral fractures in patients with type 2 diabetes. Bone 2009;45:174-9. 11. Zhao LJ, Liu YJ, Liu PY, Hamilton J, Recker RR, Deng HW. Relationship of obesity with osteoporosis. J Clin Endocrinol Metab 2007;92:1640-6. 12. Finkelstein JS, Brockwell SE, Mehta V, Greendale GA, Sowers MR, Ettinger B, et al. Bone mineral density changes during the menopause transition in a multiethnic cohort of women. J Clin Endocrinol Metab 2008;93:861-8. 13. Lovejoy JC. The menopause and obesity. Prim Care 2003;30: 317-25. 14. Svejme O, Ahlborg HG, Nilsson JA, Karlsson MK. Early menopause and risk of osteoporosis, fracture and mortality: a 34-year prospective observational study in 390 women. BJOG 2012;119:810-6. 15. Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, et al. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation 2005;112:2735-52. 16. Lym YL, Hwang SW, Shim HJ, Oh EH, Chang YS, Cho BL. Prevalence and risk factors of the metabolic syndrome as defined by NCEP-ATP III. J Korean Acad Fam Med 2003;24:135-43. 17. Kim BJ, Ahn SH, Bae SJ, Kim EH, Kim TH, Lee SH, et al. Association between metabolic syndrome and bone loss at various skeletal sites in postmenopausal women: a 3-year retrospective longitudinal study. Osteoporos Int 2013;24:2243-52. 18. Jeon YK, Lee JG, Kim SS, Kim BH, Kim SJ, Kim YK, et al. Association between bone mineral density and metabolic syndrome in pre- and postmenopausal women. Endocr J 2011;58:87-93. 19. Blum M, Harris SS, Must A, Naumova EN, Phillips SM, Rand WM, et al. Leptin, body composition and bone mineral density in premenopausal women. Calcif Tissue Int 2003;73:27-32. 20. World Health Organization. Obesity: preventing and managing the global epidemics. Geneva: World Health Organization; 1997. 21. Ho-Pham LT, Nguyen ND, Lai TQ, Nguyen TV. Contributions of lean mass and fat mass to bone mineral density: a study in postmenopausal women. BMC Musculoskelet Disord 2010;11:59. 22. Muller B. Cytokine imbalance in non-immunological chronic disease. Cytokine 2002;18:334-9. 23. Reid IR. Relationships among body mass, its components, and bone. Bone 2002;31:547-55. 24. Bae SJ, Son HY, Pyun DK, Nah SS. Higher circulating hscrp levels are associated with lower bone mineral density in healthy premenopausal and postmenopausal women: evidence for link between systemic inflammation and osteoporosis. Korean Soc Bone Miner Res 2004;11:147-58. 25. Manolagas SC, Jilka RL. Bone marrow, cytokines, and bone remodeling. Emerging insights into the pathophysiology of osteoporosis. N Engl J Med 1995;332:305-11. 26. Wongdee K, Charoenphandhu N. Osteoporosis in diabetes mellitus: Possible cellular and molecular mechanisms. World J Diabetes 2011;2:41-8. 27. Kim HY, Choe JW, Kim HK, Bae SJ, Kim BJ, Lee SH, et al. Negative association between metabolic syndrome and bone mineral density in Koreans, especially in men. Calcif Tissue Int 2010;86:350-8. 322 Vol. 3, No. 3 Sep 2013 Korean J Fam Pract