Exercise Science Vol.25, No.1, February 2016: ISSN(Print) ISSN(Online) ORIGINAL AR

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Exercise Science ISSN(Print) 1226-1726 ISSN(Online) 2384-0544 ORIGINAL ARTICLE 골다공증노인의운동수행효과분석을위한골대사지표와혈청및타액코티졸농도의유용성 안나영, 김기진 계명대학교체육대학 Utility of Bone Metabolic Markers, Serum and Salivary Cortisol

1 Exercise Science ISSN(Print) ISSN(Online) ORIGINAL ARTICLE 골다공증노인의운동수행효과분석을위한골대사지표와혈청및타액코티졸농도의유용성 안나영, 김기진 계명대학교체육대학 Utility of Bone Metabolic Markers, Serum and Salivary Cortisol Concentration for Exercise Training Effect Analysis in Elderly with Osteoporosis Na-Young Ahn, Ki-Jin Kim Department of Physical Education, Keimyung University, Daegu, Korea PURPOSE: This study examined utility of bone metabolic markers, serum and salivary cortisol concentrations after exercise training the elderly with osteoporosis. METHODS: Subjects were 31 elderly people (ageave =76.90±2.11yr), and underwend an exercise program program 3 times a week over 12 weeks. The program consisted of yoga, elastic band resistance exercise and silver dance done three per week for 12 weeks. Participants were divided into 3 groups according to T scores: normal group (T=1.03±0.88, n=6), osteopenica group (T=-1.78±0.11, n=13) and osteoporotic group (T=-3.31±0.17, n=12). RESULTS: The osteoporotic group showed significant decrease of BMI (p<.01), increased BMC (p<.01) and decreased ALP (p<.01) concentration. There was a significant positive correlation found between serum cortisol and salivary cortisol concentrations (r=.265, p<0.05). whereas BMI showed an independent relationship with the osteoporosis group (β=.663, p=.038). ALP concentration was also found to be a useful prognostic factor of osteoporosis (Osteoporotic group: AUC=0.724, sensitivity=64.3%, specificity=58.8%). Serum cortisol and salivary cortisol concentrations were not significantly related in the osteoporotic group, but showed a significant positive correlation as predictors of osteoporosis. CONCLUSIONS: Changes in bone metabolic marker of normal and osteoporotic patients showed a different pattern. In addition, it had a positive effect on bone mineral density improvement, but not on cortisol concentration. Key words: Osteoporosis, Elderly people, Exercise, Salivary cortisol, Bone mineral density 서론 노인건강과관련해서골대사의중요성이강조되고있으며, 골다공증환자는전세계적으로증가하고있다 [1]. 골밀도가 10% 감소할때마다골절의위험은 배증가하며 [2,3], 골대사의가장기본적인지표에해당하는최대골량 (bone mineral content, BMC) 은골형성과골 흡수의균형과정에서인종, 유전적요인, 호르몬, 칼슘섭취정도및운동량등다양한요인의영향과복합적인과정을통해서조절된다 [4]. 신체활동의부족은골건강의생화학적요소를부정적으로변화시키고있지만 [5,6], 운동프로그램수행은골형성 [7-10], 골량증가 [11], 골밀도 (bone mineral density, BMD)[12], 골대사지표및코티졸농도등에서긍정적인효과를나타낸다. Corresponding author: Ki-Jin Kim Tel Fax kjk744@kmu.ac.kr Keywords 골다공증, 노인, 운동, 타액코티졸, 골밀도 Received 17 Nov 2015 Revised 28 Dec 2015 Accepted 11 Jan 2016 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Copyright 2016 Korean Society of Exercise Physiology 1

2 코티졸 (cortisol) 은부신피질에서분비되는호르몬으로서코티졸의과다분비는이차적골다공증을유발하며 [13], 코티졸분비초기에골소실이급속하게발생하여염증발현에의한골절의유발가능성을증가시킨다 [14]. 또한코티졸농도는근육량및골밀도의감소와밀접한관련성을나타내는데, 골다공증의진행과정에서글루코코티코이드 (glucocorticoids) 분비가증가하면서골밀도를급격하게감소시켜골절의위험을증가시킨다 [15]. 최근운동프로그램수행효과를살펴보기위한인체유래물의분석과정에서비침습적방법의모색이널리제시되고있는데, 특히노인의경우신체적침해성을최소화하고간편한방법인타액을이용하는진단법에대한관심이증대되고있다. 타액은호르몬, 펩타이드 (peptide), 전해질 (electrolytes), 점액 (mucous), 항박테리아성분 (antibacterial compounds) 및다양한효소 (enzyme) 등으로구성되어있다 [16]. 혈액에비해서비침습적인방법으로특별한장비의도움없이수집할수있으며, 부작용이적고비용및대규모검사를위하여매우효율적이어서아동이나노인의진단시효과적으로사용되어적극적으로활용될수있다. 타액이혈장을대체하는분석표본으로이용되기위해서는타액과혈장항목농도간의상호연관성이확인되어야한다. 타액성분은수집방법과자극의정도에비교적민감한반응을나타내기때문에채취및분석과정의차이에따라서그결과에다양한영향을미칠수있다. 타액분비속도율은노인 [17] 및여성 [18] 등개인에따라서현저한차이를나타내는데, 동일한개인의경우에도하루시간대 [19] 에따라서크게차이를나타낸다. 또한질병이나약물로인하여타액의양과성분이변화하여, 전체타액에포함되어있는단백분해효소들이특정한진단성분의안정성에영향을미칠수있다. 어떤분자들은타액으로확산되는과정에서분해될수도있다. 그러나이러한단점에도불구하고진단목적의타액사용은더욱증가하고있기때문에타액을이용한새로운실험이효과적으로진행되기위해서는민감성, 특정성, 성립되어있는진단기준과의연관성및재현성등이확인되어야할것이다. 타액과혈장항목간의상호연관성을확인한연구에서저항성운동을실시한그룹의타액과혈중코티졸농도는안정시와운동후모두유의한상관을나타내었으며 [20], 최대하사이클링운동시타액코티졸농도와혈중코티졸농도는유의한상관을나타내었으며, 코티졸농도는젖산축적의시작과함께동시에현저한증가를나타낸다 [21]. 타액코티졸 (salivary cortisol) 은순환하는혈중자유코티졸 (free cortisol) 농도와스테로이드호르몬의생리활성 (bioactive) 성분을모두반영함으로써 Moreira et al. [22] 은타액코티졸측정방법이스트레스반응에서혈중코티졸농도를측정하는것보다더욱정확한측정방법으로제시하였다. 대부분건강한성인을대상으로혈액과타액코티졸농도가관련성이있다고보고되어왔으나골다공증환자들은다양한병 리학적원인으로혈액과타액코티졸농도분비양상이정상인과차이를나타낼수있기때문에골다공증상태에서운동을수행하는경우코티졸농도의변화가어떤양상을나타내는지분석할필요성이있다. 폐경후여성의운동수행은골밀도를증가시키지만혈청 osteocalcin 수준은변화가없다 [23] 고보고한데반해서, 혈청 osteocalcin과 balp는폐경전후시점에서는골형성억제작용에의한보상과정에의해서증가한다 [24-26] 고보고되는등, 골다공증예후를가진폐경여성의운동처치에따른골형성지표의변화양상에대한분석결과는여전히명확하지않다. 근육은골조직의동화작용을위한물리적자극의중요한요인으로인식되어왔지만, 골다공증환자의골형성을유도하는자극의본질은정상인의골다공증발생시기의생리적반응과는다른변화를나타내기때문에논란의대상이되고있다. 이에본연구는골감소증및골다공증환자의비정상적인생화학적골대사지표와혈청및타액코티졸농도의변화양상을살펴보고, 아울러각요인간의관련성과골다공증예후인자로서혈청및타액코티졸농도의유용성을살펴봄으로써골다공증노인환자의생리적개선을위한운동수행효과와관련된중요한정보를제공하고자한다. 연구방법 1. 연구대상본연구의대상자는연령이평균 ± 2.11세인노인 31명 ( 남성 2명, 여성 29명 ) 을대상으로주 3회, 1일 1시간씩자율적인운동 ( 저항성탄성밴드운동, 노인댄스, 요가 ) 을 12주동안실시하였다. DEXA형식의골밀도를측정한결과 T 점수를기준으로정상 (T values= > -1, n= 6), 골감소증 (T values = -1.0~-2.5, n =13) 및골다공증 (T values = <-2.5, n =12) 으로구분하였다. 대상자들에게운동프로그램을적용하기전에는 T 점수를공개하지않았으며, 최대한약물복용을자제토록권고하였다. 2. 운동프로그램자율적인운동으로요가, 저항성탄성밴드운동 (elastic band resistance exercise) 및노인댄스 (silver dance) 를 12주간실시하였다. 요가의본운동은아사나 (Asana) 요가로실시하였으며, 저항성탄성밴드운동은앉아서하는동작과서서하는동작을구분하였고, 노인댄스는유산소운동을중심으로음악에맞춰실시하였다 (Table 1). 운동강도조절은심박수측정을주기적으로측정하여 beats/min, RPE 범위의중강도를유지토록하였다. 준비운동과정리운동은 RPE 9-10의강도로 5-10분간실시하였다. 3. 신체구성측정 InBody 3.0 (Biospace, Seoul, Korea) 을이용하여체중을측정하였으 2 Na-Young Ahn, et al. Exercise Training and Bone Metabolic Markers in the Ederly with Osteoporosis

3 Table 1. Exercise program Warm up (10 min) Main exercise type (40 min, RPE 12-14) Cool down (10 min) Breath, Stretch RPE 9-10 Yoga (Asana) sec, 2 repeat Tadasana, Pada-hastasana, Ardha-chandrasana, Trikanasana, Konasana, Ekapadasana, Paschimottanasana, Gomukhasana, Matsyendrasana, Ustrasana Breath, Stretch, Massage RPE 9-10 Elastic resistance exercise Upper Limbs Exercise (10 3 set) Seated rows, Overhead or military press, Biceps curls, Shoulder flexion to 90, PNF D2 flexion, Elbow flexion, Archery pull for posterior shoulder Lower Limbs Exercise (10 3 set) Hip flexion, Hip extention, Calf raise, Leg press, Standing hip adduction with knee extended, Standing hip abduction with external rotation, Long-sitting ankle plantar flexion Silver dance Light body movement, Dance with music and applause 며, 신체질량지수 (body mass index, BMI) 는 체중 / 신장 2 (kg/m 2 ) 의공 식으로산출하였다. 혈압은수은혈압계로측정하였다. 생성하고, 생성된 phenol 을산화제의촉매하에서 4-amino anti phyline 과축합하여적색의 quinon 이형성되는데, 이를비색정량하여활성도 를산출하였다 (Kind-king 법 ). 혈액및타액코티졸농도는 Izawa et al. 4. 골밀도측정 DEXA 형식의골밀도측정기인 QDR-4500 (Hologic Inc., Waltham, [27] 의연구에서사용한 Cortisol EIA Kit 을사용하여 enzyme immunoassay 를적용하여분석하였다. MA, USA) 을이용하여요추 2-4 번의전 후에서골밀도를측정하였다. 골밀도검사결과 T 점수가 -1 이상이면정상, -1.0~-2.5 사이이면골감 소증, -2.5 이하는골다공증으로판정하였다. 7. 자료처리 모든자료는 SPSS 18.0 통계프로그램을이용하여측정변인의평균 과표준편차를산출하였다. 사전측정변인의각그룹별검정을위해 5. 타액채취피험자들은공복상태에서오전 9-10시의동일한시간대에측정하였으며온도는 22 를유지하였다. 측정당일양치질과식사를금지하고측정 30분전에음료수섭취를금지하였다. 피험자는안정상태를유지한상태에서타액수집이유를설명한후 100 ml의증류수로입안을 30초간행구고뱉어내기를 3회반복하였다. 입안에타액선에서침이충분히분비될때까지 5분간안정을취한후마지막으로입에있는침을삼키고약 1분동안천천히구령에맞춰서 salivette 용기의멸균솜을씹어타액이흡수되도록한후마지막으로입안에있는침을모은솜을 salivette 용기에뱉어내게하였으며, 타액수집한측정시간을 one-way ANOVA를이용하였으며, 사후검정은 Tukey를적용하였다. 12주운동후측정변인들에대한시기및그룹간상호작용을검정하기위하여 two-way ANOVA를이용하였으며상호작용효과가나타날경우각그룹별시기간 paired t-test를적용하였다. 또한골대사지표와코티졸농도의상호관련성을살펴보기위하여 Pearson의상관분석과다중회귀분석을실시하였다. 골다공증예후인자분석은 receiver operating characteristic (ROC) curve analysis를이용하여절단값 (cutoff value) 이유의하게나타났을때민감도 (sensitivity) 와특이도 (specificity) 를양성혹은음성의예측값으로설정하였다. 통계적유의수준은 5% (p <.05) 로설정하였다. 기록하였다. Salivette tube 를 4, 3,000 rpm 으로 5 분간원심분리한후 밑에가라앉은침을 e-tube 에넣고무게를재었다. 수집된타액을담은 e-tube 는분석시까지 -80 이하냉동보관하였으며, 솜통은냉장보관 토록하였다. 연구결과 1. 골대사지표와혈청및타액코티졸농도 신장및체중은 Table 2 에나타난바와같이골감소증및골다공증 6. ELISA (Blood & Saliva) 분석피험자로부터채취된혈액중 5 ml를 3,000 rpm에서 20분간원심분리하여혈청을분리하였으며, osteocalcin은 NovoClacin kit (Meta Biosystem Inc., USA) 를이용하여 enzyme-linked immunosorbent assay (ELISA) reader (Biotek Instrument Inc., Windoski, VT, USA) 로분석하였다. ALP는 phenyl-d-sodium phosphatase를가수분해하여 phenol을 그룹에서유의하게 (p <.001) 낮게나타났다. BMI는골다공증그룹이다른그룹에비해낮게나타났다. 또한 BMC 및 BMD도골감소증및골다공증그룹에서유의하게 (p <.001) 낮게나타났으며, T 점수는그룹간에유의한 (p <.001) 차이를나타냈다. 골감소증및골다공증그룹에서 osteocalcin 농도와 ALP 농도가높게나타났으나그룹간에유의차는나타나지않았다. 또한혈청및타액코티졸농도도골다공증그룹 안나영외 골다공증노인의운동과골대사지표 3

4 Table 2. Characteristic of bone mineral density in subjects Item Normal (n=6) Osteopenia (n=13) Osteoporosis (n=12) F p post-hoc Age (yr) ± ± ± Height (cm) ± ± ± a>b,c BW (kg) 70.72± ± ± a>b,c SBP (mmhg) ± ± ± DBP (mmhg) ± ± ± BMI (kg/cm 2 ) ± ± ± BMC (g) 77.97± ± ± a>b,c BMD (g/cm 2 ) 1.14 ± ± ± a>b,c T score 1.03± ± ± a>b>c Values are mean and SD. BW, body weight; SBP, systolic blood pressure; DBP, diastolic blood pressure; BMI, body mass index; BMC, bone mineral content; BMD, bone mineral density. Table 3. Characteristic of bone metabolic marker and serum and salivary cortisol concentration in subjects Item Normal (n=6) Osteopenia (n=13) Osteoporosis (n=12) F p Osteocalcin (ng/ml) 14.56± ± ± ALP (IU/L) 63.67± ± ± Cortisol (mg/dl) 7.79± ± ± SCortisol (ng/ml) 0.76± ± ± Values are mean and SD. ALP, alkaline phosphatase; SCortisol, salivary cortisol. Table 4. Change of bone mineral density, bone metabolic marker and serum and salivary cortisol concentration after 12 week exercise training Item Height (cm) BW (kg) BMI (kg/cm 2 ) BMC (g) BMD (g/cm 2 ) T score Osteocalcin (ng/ml) ALP (IU/L) Cortisol (mg/dl) SCortisol (ng/ml) Normal (n=6) Osteopenia (n=13) Osteoporosis (n=12) Pre Post Pre Post Pre Post ### ## ## ## ## F G: *** T: G T: G: *** T: *** G T: G: T: ** G T: G: *** T: 6.335* G T: G: *** T: G T: G: *** T: G T: G: T: G T: G: T: G T:0.748 G: T: G T: G: ** T: G T: Values are mean and SD. BW, body weight; SBP, systolic blood pressure; DBP, diastolic blood pressure; BMI, body mass index; BMC, bone mineral content; BMD, bone mineral density; ALP, alkaline phosphatase; SCortisol, salivary cortisol; G: group, T: time. *p<.05: significant different same time between groups; # p<.05: significant different between pre and post time in groups. 4 Na-Young Ahn, et al. Exercise Training and Bone Metabolic Markers in the Ederly with Osteoporosis

5 Table 5. Correlation between bone metabolic marker and cortisol concentration BMD (g) ALP (IU/L) Cortisol (μg/dl) SCortisol (ng/ml) Osteocalcin (ng/ml) BMC (g) 0.835** * BMD (g/cm 2 ) * ALP (IU/L) ** Cortisol (μg/dl) 0.265* SCortisol (ng/ml) BMC, bone mineral content; BMD, bone mineral density; ALP, alkaline phosphatase; SCortisol, salivary cortisol. Table 6. Results of multiple logistic regression analysis of the possible correlation for osteoporosis and osteopenia people Group Parameter β Lower 95% CI Upper F Osteoporosis (n=12) SCortisol (ng/ml) Osteocalcin (ng/ml) ALP (IUL) Cortisol (μg/dl) BMI (kg/cm 2 ) Age (yr) Osteopenia (n=13) SCortisol (ng/ml) Osteocalcin (ng/ml) ALP (IUL) Cortisol (μg/dl) BMI (kg/cm 2 ) Age (yr) BMI, body mass index; ALP, alkaline phosphatase; SCortisol, salivary cortisol. Table 7. Results of receiver operating characteristic analysis of bone metabolic marker and cortisol concentration in of patients with osteoporosis Parameters Cut off AUC Sensitivity (%) Specificity (%) NPV (%) PPV (%) ALP (IU/L) Cortisol (μg/dl) SCortisol (ng/ml) Osteocalcin (ng/ml) ALP, alkaline phosphatase; SCortisol, salivary cortisol. 에서높게나타났으나유의차는나타나지않았다 (Table 3). BMC 는 BMD 와유의한 (r =.835, p <.01) 정상관을나타냈으며, ALP 농 2. 12주간운동후신체구성, 골대사지표, 혈청및타액코티졸농도의변화 12주간자율적운동프로그램수행후골다공증그룹에서체중 (p <.001) 및 BMI (p <.01) 가유의하게감소하였다. 그러나골다공증그룹에서 12주운동후 BMC (p <.01) 와 T 점수 (p <.01) 가유의하게개선되었다. Osteocalcin 농도는운동후변화가없었으나 ALP 농도는골다공증그룹에서유의하게 (p <.01) 감소하였다. 혈청및타액코티졸농도는그룹및시기간유의차가나타나지않았으나골다공증그룹에서운동후감소한경향을나타냈다 (Table 4). 도와는유의한 (r = -.297, p <.05) 역상관을나타냈다. 또한 BMD 는 osteocalcin 농도와유의한 (r= -.294, p <.05) 역상관을나타냈으며, ALP 농도와 osteocalcin 농도는유의한 (r=.510, p <.01) 정상관을나타냈다. 혈청코티졸농도와타액코티졸농도는유의한 (r=.265, p <.05) 정상관을나타냈다. 그러나골대사지표와혈청및타액코티졸농도는관련성을나타내지않았다 (Table 5). 또한 Table 6에의하면골감소증과골다공증에영향을미칠수있는연령, BMI, 혈청코티졸, 타액코티졸, ALP 농도및 osteocalcin 농도를보정한다중회귀분석결과에서는 BMI가골다공증에독립적으로유의하게 (β =.663, p =.038) 관계하는것으로나타났으며, 골감소증에서는 ALP 농도 (β =1.056, p =.075) 와연령 (β =.783, p =.090) 에서관계의경향 3. 상관관계및다중회귀분석 성을보였다. 골대사지표와코티졸의관련성을알아보기위한상관분석결과 안나영외 골다공증노인의운동과골대사지표 5

6 Sensitivity ROC 곡선을이용한민감도와특이도측정 골다공증지표의양분된결과를예측하는테스트의정확도를평가 하기위하여 ALP 농도, osteocalcin 농도, 혈액및타액코티졸농도를 ROC 곡선을이용하였다. ALP 농도의 AUC (area under the ROC curve) 는.724 로나타났으며민감도도 64.3% 로나타나 IU/L 이상 일때골다공증예후인자로정확한것으로나타났다. Osteocalcin 농 도의 AUC 는.659 로나타나절단값 (cut-off value) 은 ng/ml 이었다. 그러나혈청및타액코티졸농도의 AUC 는.599 및.578 로나타나골 다공증예후인자로서정확도가낮은것으로나타났다 (Table 7). 특히 골다공증환자의타액코티졸의민감도는 32.1% 로낮게나타났으며, 특이도는 61.8% 로나타났다 (Fig. 1). 논의 ROC curve Specificity ALP Cortisol Scortisol Osteocalcin Reference line Fig. 1. Receiver operating characteristic curve analysis results of patients with osteoporosis. 미국류마티스학회 (American College of Rheumatology, ACR) 는 FRAX (WHO Fracture Risk Assessment Tool) 를이용하여 10 년내골 절절대위험도를평가한결과 10% 미만이면저위험군, 10-20% 는중등 도위험군, 20% 초과혹은 T 점수가 -2.5 이하혹은취약골절병력이있 을때고위험군으로정의하였다 [28]. 골밀도검사결과 T 점수가 -1.0 이 면젊은성인의정상최대골밀도에비해 10-15% 정도골밀도가감소 하는것을의미하여 1.0 감소할수록정상인에비해골절발생위험이 2-3 배증가한다 [2]. 본연구에서는 T 점수가 -2.5 이하일때골다공증 환자로정의를내렸으며, 평균 T 점수는 ± 0.17 로나타나취약골절 위험및고위험군인것으로나타났다. 또한 BMI 는골다공증그룹이 정상및골감소증그룹보다낮게나타났으며, 다중회귀분석결과에서 도골다공증에독립적으로유의하게관련성이있는것으로나타나골다공증예후요인으로 BMI는중요한요인인것으로생각된다. ALP는골아세포의활성도를반영하는대표적인지표이며, talp는대표적인골형성지표이다 [29]. 조골세포는 ALP를생성하여조골세포막의소포에저장하며일부가혈액내로유리되어나온다. Delmas et al. [30] 은 talp의활성도는간에서 55%, 조골세포에서 40%, 장에서 5% 가분비되기때문에이지표는특이도및민감도가낮은것으로주장하였다. 그러나 Takahashi et al. [31] 은 talp가 bone specific ALP를잘반영하기때문에간장질환이나대사성질환이없는대상자의경우골대사지표로이용될수있다고보고하였다. Osteocalcin은조골세포에서분비되고골기질에많이존재하며, 골조직과치아조직에만특이하게발견된다. 주로조골세포에서합성된후뼈세포의기질에결합되며일부는혈액내로유입됨으로써조골세포의활동성과골형성의지표로유용한데, 골흡수과정에서유리되는 Osteocalcin은골흡수를반영한다 [32]. 또한 osteocalcin은제1형골다공증의평가에유용하며척추골밀도의변화와도상관관계가높고 [33], 골무기질인수산화인회석 (hydroxyapatite) 에높은친화력을가지는것으로나타남으로써골형성에중추적인역할을담당하는것으로간주되어왔으나 [34] 골형성에실제로관여하지않는다는상반된주장도제시되었다 [35]. 본연구결과에서, ALP 농도는유의한차이는나타나지않았으나골감소증및골다공증그룹이정상그룹보다높게나타난경향을보였으며, osteocalcin 농도는골다공증에서높은경향을나타냄으로써폐경전후를기점으로혈청 osteocalcin과 balp가골흡수를지연시키기위하여증가한다는연구결과 [23-26] 와폐경후여성의운동처치가혈청 osteocalcin 수준에서는변화가없다고보고한연구결과 [36] 와거의동일하게나타냈다. 그러나본연구결과에서 ALP 농도는모두정상범위 ( IU/L) 에분포되어있기때문에 ALP를골다공증의진단을포함한골대사의분석지표로활용하기위해서는많은사례수를포함해서보다추가적인분석이요구된다. 운동수행은골형성 [37-40] 과골미네랄밀도 [12] 개선에많은영향을미친다. 운동과 osteocalcin 농도의관련성에관한선행연구를살펴보면, 무산소성운동을 1-2개월동안실시한결과 osteocalcin 농도가증가하였으며 [41], 성숙된수컷쥐를대상으로 6주간저강도와고강도사다리운동을실시한결과, 혈청 osteocalcin 농도가대조군에비하여두그룹모두유의하게증가하였으나골밀도는고강도운동그룹에서만유의하게증가하였다고보고하였다 [42]. 본연구의 12주간운동수행결과 BMC와 T 점수는유의하게 (p <.01) 향상되어최대골량및골밀도는개선된것으로간주되었다. 그러나 ALP 농도는골다공증그룹에서유의하게 (p <.01) 감소하였으며, osteocalcin 농도는변화가없었다. 이러한결과는운동수행이골다공증환자의골밀도향상에도움을줄수있다는것을확인할수있었으나, osteocalcin 농도의변화에대한영향은 6 Na-Young Ahn, et al. Exercise Training and Bone Metabolic Markers in the Ederly with Osteoporosis

7 보다추가적인분석이요구된다고생각된다. 타액과혈장항목간의상호관련성을분석한연구에서 Cadore et al. [20] 은저항성운동을실시한그룹의타액과혈중의코티졸농도는안정시 (r=.52, p =.05) 와운동후 (r =.62, p =.01) 모두유의한상관을나타냈다고보고하였으며, Port [21] 도최대하사이클링운동시에서도타액과혈중의코티졸농도는유의한 (p <.001) 상관 (r=.86) 을나타내면서코티졸농도는젖산축적의시작과함께동시에일어난다고하였다. 본연구에서도혈청및타액의코티졸농도는유의하게 (r =.265, p <.05) 정상관을나타냄으로써상호관련성이높다는것을확인할수있었다. Nass & Thorner [43] 는노인을대상으로한연구결과에서혈중코티졸농도의증가는근육량의감소와동시적으로나타나는현상을확인하면서고코티졸혈증이근육감소증의요인 [43] 으로간주한바있는데, 본연구결과에서골다공증노인환자가운동프로그램실시후타액코티졸농도에유의차는나타나지않았지만감소하는경향을나타냈다. 골대사지표에부정적인영향을미치는코티졸의과다분비는골소실을유발할수있다는관점에서노인들의골다공증예방을위하여코티졸과다분비를방지할수있는운동프로그램의적용가능성을제시할수있을것이다. 본연구에서골대사지표들간의관련성을분석한결과, ALP와 osteocalcin 농도는유의한정상관을나타냈으며, ALP는 BMC와역상관, osteocalcin 농도는 BMD와역상관을각각나타내었으나혈청및타액코티졸농도는골밀도및골대사지표와관련성을나타내지않았다. 골감소증을일으키는독립적인변인은다중회귀분석결과연령과 ALP 농도가관련성을가지는경향성을나타냈다. 또한 ROC 곡선을이용한골다공증지표의양분된결과를예측하는테스트의정확도평가에서는 ALP 농도의 AUC가비교적정확하게나타남으로써골다공증예후인자로간주되며, 혈청및코티졸농도의 AUC는낮게나타나골다공증환자에서예후인자로제시하기에는다소미흡한것으로생각된다. 그러나본연구대상자의사례수가적은것을고려하여추후추가적인연구를통해서보다명확한결과를얻어제시할수있을것이다. 본연구에서골다공증노인환자가운동프로그램을수행하는과정에서골대사관련지표들의변화양상은정상인과다른결과를나타낸다는것을확인하였다. 또한운동프로그램수행이골다공증환자의골밀도향상에긍정적인영향을미치지만코티졸분비의개선에는유의한영향을미치지못하는것으로나타났다. 그러나골다공증노인환자가운동프로그램수행후코티졸농도가감소한경향을나타냄으로써장기간에걸친규칙적인운동은골다공증노인환자의코티졸분비개선에도움을줄수있을것으로생각된다. 아울러골다공증의판정및예후과정에서골밀도 T 점수의고려뿐만아니라연령과체중변화에따른골절위험도의변화를임상진단과정에서함께고려되어야할것으로간주된다. 결론 본연구는노인을대상으로 12주간자율적인운동 ( 저항성탄성밴드운동, 노인댄스, 요가 ) 을실시한후골다공증환자의 BMI 감소, BMC 증가및 ALP 농도가감소하였으며, 골밀도및혈중 ALP 농도는혈중코티졸농도와상관이있으며, 혈청코티졸농도와타액코티졸농도는유의한정상관을나타냈으나측정결과의특이도와민감도는낮은것으로나타났다. 따라서 12주간자율적운동프로그램수행은노인의골다공증과코티졸분비개선에효과적인것으로간주되었으며, 혈중 ALP 및 osteocalcin 농도는노인의골다공증과관련된정확한예후인자로나타났다. 또한골다공증노인환자가운동프로그램을수행하는과정에서골대사관련지표들의변화양상은정상인과다른결과를나타내며, 혈청코티졸농도와타액코티졸농도는노인의골건강관련진단지표로서의활용가능성은제시되었으나그신뢰성을높이기위해서는계속적인연구가요구된다. REFERENCES 1. World Health Organization. WHO scientific group on the assessment of osteoporosis at primary health care level: summary meeting report Belgium WHO, Marshall D, Johnell O, Wedel H. Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures. British Medical Journal 1996;312(7041): Peeters G, van Schoor NM, Lips P. Fall risk: the clinical relevance of falls and how to integrate fall risk with fracture risk. Best Practice & Research Clinical Rheumatology 2009;23(6): Goldman L, Ausiello D. Cecil Textbook of medicine. 23rd ed. Philadelphia: Elsevier online Eser P, Frotzler A, Zehnder Y, Wick L, Knecht H, et al. Relationship between the duration of paralysis and bone structure: a pqct study of spinal cord injured individuals. Bone 2004;34(5): Lang T, LeBlanc A, Evans H, Lu Y, Genant H, et al. Cortical and trabecular bone mineral loss from the spine and hip in long-duration spaceflight. Journal of Bone and Mineral Research2004;19(6): Bemben DA, Buchanan TD, Bemben MG, Knehans AW. Influence of type of mechanical loading, menstrual status, and training season on bone density in young women athletes. Journal of Strength and Conditioning Research 2004;18(2): Marques EA, Wanderley F, Machado L, Sousa F, Viana JL, et al. Effects of resistance and aerobic exercise on physical function, bone mineral 안나영외 골다공증노인의운동과골대사지표 7

8 density, OPG and RANKL in older women. Experimental Gerontology 2011;46(7): Kohrt WM, Bloomfield SA, Little KD, Nelson ME, Yingling VR. American College of Sports Medicine. American college of sports medicine position stand: physical activity and bone health. Medicine and Science in Sports and Exercise 2004;36: Taaffe DR, Marcus R. The muscle strength and bone density relationship in young women: dependence on exercise status. The Journal of Sports Medicine and Physical Fitness 2004;44(1): Riggs BL, Khosla S, Melton LJ. Sex steroids and the construction and conservation of the adult skeleton. Endocrine Reviewrs 2002;23(3): Marques EA, Mota J, Viana JL, Tuna D, Figueiredo P, et al. Response of bone muneral density, inflammatory cytokines, and biochemical bone markers to a 32-week combined loading exercise programme in older men and women. Archives of Gerontology and Geriatrics 2013;57(2): Kok C, Sambrook PN. Secondary osteoporosis in patients with an osteoporotic fracture. Best Practice & Research: Clinical Rheumatology 2009;23(6): Roux C. Osteoporosis in inflammatory joint diseases. Osteoporosis International 2011;22(2): Briot K, Roux C. Glucocorticoid-induced osteoporosis Rheumatic & Musculoskeletal Diseases Open 2015;1(e000014): Chicharo JL, Lucia A, Perez M, Vaquero A F, Ureña R. Saliva composition and exercise. Sports Medicine 1998;26(1): Percival RS, Challacombe SJ, Marsh PD. Flow rates of resting whole and stimulated parotid saliva in relation to age and gender. Journal of Dentistry Research 1994;73(8): Inoue H, Ono K, Masuda W, Morimoto Y, Tanaka T, et al. Gender difference in unstimulated whole saliva flow rate and salivary gland sizes. Archives of Oral Biology 2006;51(12): Palmai G, Blackwell B. The diurnal pattern of salivary flow in normal and depressed patients. The British Journal of Psychiatry 1965;111(473): Cadore E, Lhullier F, Brentano M, Silva E, Ambrosini M, et al. Correlations between serum and salivary hormonal concentrations in response to resistance exercise. Journal of Sports Sciences 2008;26(10): Port K. Serum and saliva cortisol responses and blood lactate accumulation during incremental exercise testing. International Journal of Sports Medicine 1991;12(5): Moreira A, Arsati F, de Oliveira Lima Arsati YB, da Silva DA, de Araújo VC. Salivary cortisol in top-level professional soccer players. European Journal of Applied Physiology 2009;106(1): Kohrt WM, Snead DB, Slatopolsky E, Birge SJ. Additive effects of weight-bearing exercise and estrogen on bone mineral density in older women. Journal of Bone and Mineral Research 1995;10(9): Gundberg CM, Looker AC, NieMan SD, Calvo MS. Patterns of osteocalcin and bone specific alkaline phosphatase by age, gender, and race or ethnicity. Bone 2002;31(6): Delmas PD. Biochemical markers of bone turnover for the clinical investigation of osteoporosis. Osteoporosis 1993;3(1): Van Hoof VO, De Broe ME. Interpretation and clinical significance of alkaline phosphatase isoenzyme patterns. Critical Reviews in Clinical Laboratory Sciences 1994;31(3): Izawa S, Kim K, Akimoto T, Ahn N, Lee H, et al. Effects of cold environment exposure and cold acclimatization on exercise-induced salivary cortisol response. Wilderness and Environmental Medicine 2009; 20(3): Grossman JM, Gordon R, Ranganath VK, Deal C, Caplan L, et al. American College of Rheumatology 2010 recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis. Arthritis Care & Research 2010;62(11): Leung KS, Fung KP, Sher AH, Li CK, Lee KM. Plasma bone-specific alkaline phosphatase as an indicator of osteoblastic activity. Journal of Bone and Joint Surgery British 1993;75(2): Delmas PD, Stenner D, Wahner HW, Mann KG, Riggs BL. Increase in serum bone gamma- carboxyglutamic acid protein with aging in women. Implications for the mechanism of age-related bone loss. Journal of Clinical Investigation 1983;71(5): Takahashi M, Kushida K, Hoshino H, Ohishi T, Inoue T. Evaluation of bone turnover in postmenopause, vertebral fracture, and hip fracture using biochemical markers for bone formation and resorption. Journal of Endocrinological Investigation 1997;20(3): Slovik DM, Gundberg CM, Neer RM, Lian JB. Clinical evaluation of bone turnover by serum osteocalcin measurements in a hospital setting. The Journal of Clinical Endocrinology & Metabolism 1984;59(2): Brown JP, Delmas PD, Malaval L, Edouard C, Chapuy MC, et al. Serum bone Gla-protein: a specific marker for bone formation in postmenopausal osteoporosis. Lancet 1984;323(8386): Hauschka PV, Lian JB, Cole DE, Gundberg CM. Osteocalcin and ma- 8 Na-Young Ahn, et al. Exercise Training and Bone Metabolic Markers in the Ederly with Osteoporosis

9 trix Gla protein: vitamin K-dependent proteins in bone. Physiological Reviews 1989;69(3): Murshed M, Schinke T, McKee MD, Karsenty G. Extracellular matrix mineralization is regulated locally;different roles of two gla-containing proteins. Journal of Cell Biology 2004;165(5): Yasumura S, Aloia JF, Gundberg CM, Yeh J, Vaswani AN, et al. Serum osteocalcin and total body calcium in normal pre-and postmenopausal women and postmenopausal osteoporotic patients. Journal of Clinical Endocrinol Metablism 1987;64(4): Kohrt WM, Bloomfield SA, Little KD, Nelson ME, Yingling VR. American College of Sports Medicine. American college of sports medicine position stand: physical activity and bone health. Medicine and Science in Sports and Exercise 2004;36: Taaffe DR, Marcus R. The muscle strength and bone density relationship in young women: dependence on exercise status. The Journal of Sports Medicine and Physical 2004;44(1): Bemben DA, Buchanan TD, Bemben MG, Knehans AW. Influence of type of mechanical loading, menstrual status, and training season on bone density in young women athletes. Journal of Strength and Conditioning Research 2004;18(2): Kirchner EM, Lewis RD, O Connor PJ. Bone mineral density and dietary intake of female college gymnasts. Medicine and Science in Sports and Exercise 1995;27(4): Banfi G, Lombardi G, Colombini A, Lippi G. Bone metabolism markers in sports medicine. Sports Medicine 2010;40(8): Smith MZ, Goettsch BM, Van Ramshorst RD, O Brien JA, Jaque SV, et al. Resistance training and bone mineral density during growth. International Journal of Sports Medicine 2008;29: Nass R, Thorner MO. Impact of the GH-cortisol ratio on the age-dependent changes in body composition. Growth Hormone & IGF Research 2002;12(3): 안나영외 골다공증노인의운동과골대사지표 9

전립선암발생률추정과관련요인분석 : The Korean Cancer Prevention Study-II (KCPS-II)

전립선암발생률추정과관련요인분석 : The Korean Cancer Prevention Study-II (KCPS-II) 전립선암발생률추정과관련요인분석 : The Korean Cancer Prevention Study-II (KCPS-II) - i - - ii - - iii - - iv - - v - - vi - - vii - - viii - - ix - -