Focused Issue J Korean Diabetes 2017;18: Vol.18, No.4, 2017 ISSN 당뇨병과골다공증 진흥용전북대학교의과대학내분비대사

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1 J Korean Diabetes 2017;18: Vol.18, No.4, 2017 ISSN 진흥용전북대학교의과대학내분비대사내과, 전북대학교병원의생명연구원 Diabetes Mellitus and Osteoporosis Heung Yong Jin Division of Endocrinology and Metabolism, Department of Internal Medicine, Chonbuk National University Medical School, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Korea Abstract Diabetes mellitus, which is a well-known chronic metabolic disorder with diverse complications, affects over 10% and up to nearly 20% of older adults; its prevalence is increasing rapidly. Fracture is also important issue in a large proportion of older adults and osteoporosis is a common cause of fracture. Therefore, both diabetes and increased fracture risks due to osteoporosis have become serious concerns and health problems in aging societies these days. However, the mechanisms of and exact relationship between diabetes and bone conditions are not fully understood and remain controversial issues because observational and animal studies do not show consistent results. Nonetheless, we should not overlook that bone quality and fractures are also important in older diabetic patients just as in the non-diabetic general population. Therefore, we need a better understanding of how diabetes and its treatment relate to bone health; this will improve morbidity and mortality in older diabetic and osteoporosis patients. Until these questions are answered, we should continue treating diabetic patients for osteoporosis with wellknown current medications to improve bone mineral density besides including optimal glucose control and management of micro and macro vascular complications. Keywords: Bone and bones, Diabetes, Osteoporosis Corresponding author: Heung Yong Jin Division of Endocrinology and Metabolism, Department of Internal Medicine, Chonbuk National University Medical School, 20 Geonji-ro, Deokjin-gu, Jeonju 54907, Korea, mdjinhy@jbnu.ac.kr Received: Oct. 10, 2017; Accepted: Oct. 12, 2017 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 c 2017 Korean Diabetes Association 248 The Journal of Korean Diabetes

2 진흥용 서론 평균수명이늘어나고이에따라노인인구가증가하면서다양한만성질환이사회적문제가되고있다. 이중하나가고령의당뇨병환자들이골다공증및골절과동반되는문제이다. 수십년전부터꾸준하게증가해오고있는당뇨병환자의유병률은고령에서는최근에거의 20% 에다다르며, 고령에서는여러가지합병증이추가적으로동반될수있기에더욱사회적문제가되는만성질환이다. 골격계의질환은이러한고령층에서더욱중요한건강과삶의질문제가될수있고이중에서골절은연령의증가와함께급격하게증가하는것으로보고되고있다. 따라서골절이동반된고령의당뇨병환자는당뇨병의합병증과함께골절의치유가지연될수있고이로인해수명기간의단축과사망률증가라는문제가제기될수있다 [1-3]. 골다공증은골량의감소뿐만아니라골질의감소로인하여전반적인골강도가저하되고이로인해골절의위험성이증가되는질환으로정의되고있다 [4]. 이러한골다공증의증가가전세계적으로나타나고있는고령화와함께당뇨병환자에서도문제가될수있는연관성이있어당뇨병과골절의위험성을증가시키는골다공증간의관계는역학적인연관성외에병태생리학적인인과관계에대해더많은이해의필요성이요구된다. 따라서본종설에서는당뇨병환자에서골질환특히골다공증의발생과골절의위험이증가될수있는원인과기전에대해보고된연구결과들에대해간략하게정리해보고자한다. 가가남녀각각 1.84, 1.73배증가하고, 특히 50~64세연령대의당뇨병환자에서남녀각각 2.7, 2.54배증가한다는연구결과는당뇨병환자에서골다공증과골절의증가가더는간과해서는안되는중요한문제임을강조하고있다. 제1형당뇨병에서는골밀도의감소가관찰되고이와함께고관절의골절위험도증가되는것으로알려져있으나모든연구결과들이일관된결과를보여주고있지는않다 [8,9]. 동물실험에서보여주는골표지자들이감소된조골세포및파골세포들의상태를시사하는것과달리임상연구결과들에서는연구결과들마다골표지자들의결과들이일관되게나타나지않는점은앞으로도많은연구들이필요함을제시하고있다. 물론제2형당뇨병환자들에서는골밀도가감소하지않고오히려증가되어있다고보고되었기때문에골절의위험이증가되리라고는여겨지지않았다. 그러나고관절의증가뿐만아니라근위상완골과발목등다른부위에서도골절의위험이증가되는것으로보고되면서제2형당뇨병을가지고있는고령의환자에서는특정부위골절의위험성에대한경각심을제시하고있다. 물론이러한골밀도증가가관찰되는제2형당뇨병환자에서의골절증가라는역설적인개념은고령의제2형당뇨병환자에서신경병증과시력의저하, 뇌졸증등동반된여러가지문제로인한낙상의증가및골밀도로설명되지않는골질의문제등추가적으로고려되어야될점이많음을간과해서는안되겠다. 2. 당뇨병환자에서골다공증발생의병태생리학적관계 본론 1. 당뇨병환자에서골다공증및골절의위험도당뇨병환자에서는주로족부질환과관련된국소적인골질환의문제들이제기되어왔으나이외에도전반적인골질환및골다공증에대한경각심을가지고개별적인골다공증과골절의위험도평가가필요하다 [5,6]. 최근 Kim 등 [7] 이발표한한국인제2형당뇨병환자에서의고관절골절의증 당뇨병과골밀도및골질과의관계를살펴보면당뇨병이골에미치는영향을여러가지면에서생각해볼수있다. 물론골밀도가감소하지않고오히려증가하는것으로알려진제2형당뇨병과골밀도가감소되는제1형당뇨병이다를수있으나공통적으로고혈당으로인한부산물의증가특히 advanced glycation end products (AGEs) 의높은농도는골강도의감소를초래할수있다 [10]. 당뇨와연관된고칼슘뇨증도골소실을야기할수있고 [11], 골생성에관여할수있는 insulin-like growth factor-1의감소도골질변 249

3 화의원인중의하나로고려될수있다 [12,13]. 물론당뇨병에서흔하게발생하는신기능의저하나미세혈관합병증들도골소실과골강도의약화에관여될수있다 [14,15]. 최근 Fujiwara-kyo osteoporosis risk in men (FORMEN) 연구에서는인슐린저항성과관련되어감소된 trabecular bone score와골다공증의위험을보고하고있기도하다 [16]. 그러나당뇨병환자에서골다공증발생과골절의위험을증가시키는경로와정도에대한근거들이아직은부족하고, 또한여러관찰연구나기초연구를통해당뇨병환자에서골다공증유병률및골절발생정도를분석하고, 이를통해실제환자들에서발생하는빈도를규명할수있는연구들이필요한실정이다. 3. 관리의연관성당뇨병환자들은이미잘알려져있는급성합병증외에도다양한혈관계와신경계의만성합병증으로삶의질과수명기간에영향을받고있다. 이와더불어골다공증과골절등을포함한골질환들은잘알려진당뇨병합병증의악화와함께이러한합병증들에의해치유가지연되거나발생할수있는상호간의연관성에대해인지되고포괄적으로함께관리되어야한다. 당뇨병환자에서골질환은당뇨발에관련된골수염이나샤르코관절염이잘알려져있으나이외당뇨병합병증에따른낙상의위험성은골절의위험을증가시킨다는것에대해환자나의료진모두잘인지하고있다. 당뇨병환자에서골다공증은이상혈당이나고혈당이골질및골강도에영향을줄수있는지여부와동반된미세혈관합병증이골상태에어떠한영향을줄수있는지가규명되어야골다공증에미치는영향을판단해볼수있다. 앞에서언급한기전중의하나인당뇨병환자에서의고혈당은 AGEs가뼈의콜라겐에축적됨으로써골강도의약화가초래될수있고이와함께연령증가에따른당뇨병환자에서의체중감소와이에따른골소실의증가도골밀도의감소없이도골절이증가되는부분적인원인으로추정되고있기때문에당뇨병의치료인엄격한혈당조절을포함한적절한영양관 리와운동요법이당뇨병환자에서골다공증을포함한골질환의발생및악화예방에도효과가있을것으로판단해볼수있다 [17,18]. 4. 당뇨병환자에서골다공증의치료및관리당뇨병치료와합병증의적극적인관리가골질환및골다공증의치료에도움이되는지여부는명확하지않으나당뇨병이없는환자에서의골다공증치료와관리방법은당뇨병이있는환자에서도동일하게적용될수있고유사한효과를기대해볼수있다. 다만당뇨병환자들은혈당조절을위해인슐린을포함한여러약제들을복용하고있고당뇨병의진행에따른합병증을고려해서좀더세심하게약제선택이이루어져하겠다. 제1형과 2형당뇨병환자들모두특정부위골절위험이증가할수있고이는혈당조절뿐만아니라저혈당및고령으로인한낙상의예방이중요함을환자들에게교육해야한다. 물론현재사용하고있는약제들이당뇨병환자에서도동일한효과를보이고있는지여부에대해서는더많은연구들이진행되어야하겠으나골밀도에근거해골보존의정도는유사한효과를기대할수있기에 [19,20] 당뇨병환자에서도동일하게적극적인골다공증약제사용과함께다양한골질환에대한치료와예방을고려해야되겠다. 결론 제1형과 2형당뇨병환자에서골다공증은잘알려진당뇨병의만성합병증과함께연령을고려해서정기적인검사를통해조기에진단되고혈당조절과함께지속적으로관리되어야한다. 이를위해고령화, 당뇨병, 골다공증, 골절이라는복잡하게얽혀진여러위험인자및질환들의관계가더명확하게규명되어야하겠다. 또한당뇨병환자에서고혈당및고혈당의조절방법이골다공증과골절에미치는영향뿐만아니라골성분의변화에미치는효과등다양한연구들도당뇨병환자에서골다공증을포함한여러가지골질환의 250

4 진흥용 예방과뼈의건강증진을휘해필요할것으로생각된다. REFERENCES 1. Lieberman D, Fried V, Castel H, Weitzmann S, Lowenthal MN, Galinsky D. Factors related to successful rehabilitation after hip fracture: a case-control study. Disabil Rehabil 1996;18: Dubey A, Aharonoff GB, Zuckerman JD, Koval KJ. The effects of diabetes on outcome after hip fracture. Bull Hosp Jt Dis 2000;59: Loder RT. The influence of diabetes mellitus on the healing of closed fractures. Clin Orthop Relat Res 1988;(232): Kanis JA. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis: synopsis of a WHO report. WHO Study Group. Osteoporos Int 1994;4: Leidig-Bruckner G, Ziegler R. Diabetes mellitus a risk for osteoporosis? Exp Clin Endocrinol Diabetes 2001;109 Suppl 2:S Isidro ML, Ruano B. Bone disease in diabetes. Curr Diabetes Rev 2010;6: Kim SH, Kim YM, Yoo JS, Choe EY, Kim TH, Won YJ. Increased risk of hip fractures in Korean patients with type 2 diabetes: a 6-year nationwide population-based study. J Bone Miner Metab doi: /s z. [Epub ahead of print] 8. Nicodemus KK, Folsom AR; Iowa Women's Health Study. Type 1 and type 2 diabetes and incident hip fractures in postmenopausal women. Diabetes Care 2001;24: Melchior TM, Sørensen H, Torp-Pedersen C. Hip and distal arm fracture rates in peri- and postmenopausal insulin-treated diabetic females. J Intern Med 1994;236: Paul RG, Bailey AJ. Glycation of collagen: the basis of its central role in the late complications of ageing and diabetes. Int J Biochem Cell Biol 1996;28: Raskin P, Stevenson MR, Barilla DE, Pak CY. The hypercalciuria of diabetes mellitus: its amelioration with insulin. Clin Endocrinol (Oxf) 1978;9: Dills DG, Allen C, Palta M, Zaccaro DJ, Klein R, D'Alessio D. Insulin-like growth factor-i is related to glycemic control in children and adolescents with newly diagnosed insulin-dependent diabetes. J Clin Endocrinol Metab 1995;80: Jehle PM, Jehle DR, Mohan S, Böhm BO. Serum levels of insulin-like growth factor system components and relationship to bone metabolism in Type 1 and Type 2 diabetes mellitus patients. J Endocrinol 1998;159: Wientroub S, Eisenberg D, Tardiman R, Weissman SL, Salama R. Is diabetic osteoporosis due to microangiopathy? Lancet 1980;2: Vogt MT, Cauley JA, Kuller LH, Nevitt MC. Bone mineral density and blood flow to the lower extremities: the study of osteoporotic fractures. J Bone Miner Res 1997;12: Iki M, Fujita Y, Kouda K, Yura A, Tachiki T, Tamaki J, Winzenrieth R, Sato Y, Moon JS, Okamoto N, Kurumatani N. Hyperglycemia is associated with increased bone mineral density and decreased trabecular bone score in elderly Japanese men: The Fujiwara-kyo osteoporosis risk in men (FORMEN) study. Bone 2017;105: Vashishth D, Gibson GJ, Khoury JI, Schaffler MB, Kimura J, Fyhrie DP. Influence of nonenzymatic glycation on biomechanical properties of cortical bone. Bone 2001;28: Arakaki H, Owan I, Kudoh H, Horizono H, Arakaki K, Ikema Y, Shinjo H, Hayashi K, Kanaya F. Epidemiology 251

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A 617 Special Issue Diabetic Retinopathy Won Ki Lee, M.D. Department of Ophthalmology The Catholic University of Korea College of Medicine Kangnam St. Mary s Hospital E mail : wklee@catholic.ac.kr Abstract R