Bone Mineral Density in Prediabetic Men

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1 Originl Article doi: /kdj pissn eissn Bone Minerl Density in Predibetic Men Ju Hee Lee 1, Yun Hyeong Lee 1, Kyoung Hye Jung 1, Min Kyeong Kim 1, Hye Won Jng 1, Te Kyun Kim 1, Hyun Jin Kim 1, Young Suk Jo 1, Minho Shong 1, Te Yong Lee 2, Bon Jeong Ku 1 Deprtments of 1 Internl Medicine, 2 Preventive Medicine, Chungnm Ntionl University School of Medicine, Dejeon, Kore Bckground: There re mny studies regrding the effects of insulin on bone metbolism nd chnges in bone minerl density (BMD) in the setting of dibetes. The effect of predibetes on BMD is not known. Methods: A totl of 802 men prticipted in the Kore Rurl Genomic Cohort Study (in Geumsn County). According to the results of n orl glucose tolernce test, subjects were clssified into norml, predibetic, nd dibetic ctegories. One hundred twenty-four subjects dignosed with type 2 dibetes were excluded, leving 678 subjects for the study inclusion. BMD ws estimted with quntittive ultrsonometer. Results: The verge BMD T scores of norml nd predibetic subjects were ± 1.42 nd ± 1.30, respectively; there ws no significnt difference in the BMD T scores between these groups. The BMD T score ws inversely ssocited with ge nd positively correlted with body weight, body mss index, totl cholesterol, low density lipoprotein cholesterol, nd HbA1c. On multiple liner regression nlysis, low density lipoprotein cholesterol ws the only sttisticlly significnt vrible for predibetes (β = 0.007, P = 0.005). On the stepwise regression nlysis, ge (β = , P < 0.001), the body mss index (β = 0.079, P < 0.001), nd low density lipoprotein cholesterol (β = 0.004, P = 0.016) were significnt vribles for predibetes. Conclusions: There ws no significnt difference in the BMD T score between the norml nd predibetic subjects. Further studies re needed regrding the ssocition of frcture risk nd chnges in BMD with the development of overt dibetes. Keywords: Bone density; Insulin; Predibetic stte INTRODUCTION The incidence of dibetes in Kore is on the rise. According to the Koren Ntionl Helth nd Nutrition Exmintion Survey (KNHNES) in 2007, the rte of dibetes reched 9.7% in dults older thn 30 yers; impired fsting glucose reched 16.1%. Additionlly, osteoporosis, nd consequent frctures, re on the rise. In the KNHNES in 2008, the incidence of osteoporosis in postmenopusl women nd mles older thn 50 yers hs been reported to be high s 19.3% [1]. Osteoporosis refers to the reduction of bone strength nd cuses n incresed risk of frcture. The World Helth Orgniztion (WHO) defines osteoporosis s bone minerl density (BMD) tht flls 2.5 stndrd devitions below the men for young helthy dults of the sme gender, lso referred to s T-score of -2.5 [2]. Severl studies hve reported on the effects of insulin nd dibetes on bone metbolism. A met-nlysis of the studies found tht BMD ws decresed in type 1 dibetes, but tht type 2 dibetes either did not significntly ffect the BMD or ws ssocited with slightly incresed BMD [3]. The mechnisms for these findings hve not yet been elucidted. It is thought tht insulin medites nbolic effects on bone metbolism nd tht insulin my exert synergistic effects together with other nbolic gents, such s insulin-like growth fctor (IGF)-I nd prthyroid hormone [4]. Therefore, bone metbolism my be ltered in ptients with impired fsting glucose (IFG) or impired glucose tolernce (IGT). However, studies of bone metbolism in predibetic ptients hve not yet been conducted. Corresponding uthor: Bon Jeong Ku Deprtment of Internl Medicine, Chungnm Ntionl University School of Medicine, 33 Munhw-ro, Jung-gu, Dejeon , Kore E-mil: bonjeong@cnu.c.kr Received: Mr. 31, 2010; Accepted: Jun. 29, 2010 This is n Open Access rticle distributed under the terms of the Cretive Commons Attribution Non-Commercil License ( which permits unrestricted non-commercil use, distribution, nd reproduction in ny medium, provided the originl work is properly cited. Copyright 2010 Koren Dibetes Assocition

2 Bone minerl density in predibetes Therefore, the current study exmined the chnges in BMD in ptients with IFG or IGT. METHODS Prticipnts Among the 1,993 individuls who prticipted in the Koren Rurl Genome Cohort Study from Jnury 2005 to December 2006, 802 mles were selected s the study subjects. Among these, we excluded 124 subjects who were dignosed s dibetic. The Koren Rurl Genome Cohort Study ws conducted on individuls between the ges of 40 to 70 yers nd who resided in Wonju-si, Pyeongchng-gun, nd Gngneung-si in Gngwon-do, Geumsn-gun in Chungcheong-do, nd Nju-si in Jeoll-do. The subjects of this study were recruited rndomly from Geumsn-gun. Bsed on the definition of the Americn Dibetes Assocition in 2004, subjects with either n IFG or n IGT were clssified s predibetic. Cses with fsting blood glucose between 100 mg/dl nd 126 mg/dl were dignosed s IFG. Cses with blood glucose ws between 140 mg/dl nd 200 mg/dl t 2 hours fter 75 g orl glucose loding were dignosed s IGT [5]. Methods Physicl mesurements Height nd weight were mesured by single individul. The wist nd hip circumference were mesured with the subject stnding stright. For obtining the wist circumference, ccording to the method recommended by the WHO, the ptients stood with legs cm prt nd, while distributing weight evenly, the middle re between the lowest rib nd the pelvic ilic crest ws mesured during the end-expirtion phse. The body mss index (BMI) ws clculted by the formul: weight (kg)/height (m 2 ). Body ft mesurement The ft mss (kg), percent body ft (%), viscerl ft (kg), nd percent viscerl ft (%) were mesured by body composition nlyzer (InBody 4.0; Biospce Co., Seoul, Kore). Evlution of glucose metbolism For ll subjects, the glycosylted hemoglobin ws mesured nd the blood glucose, s well s insulin, were mesured fter fsting (minimum 12 hours) nd 120 minutes fter the orl dministrtion of 75 g of glucose. Insulin ws mesured by rdioimmune ssy (Biosource, Fleurus, Belgium). The intrssy coefficient of vrition ws 2.41% nd the inter-ssy coefficient of vrition ws 2.93%. Blood chemistries In ll subject groups, fter fsting for more thn 12 hours, the blood ure nitrogen, serum cretine, serum cholesterol, triglyceride, low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol, sprtte minotrnsferse, nd lnine trnsminse were mesured. BMD In ll subjects, the BMD ws mesured in the clcneus using n ultrsonogrphic bone densitometer (ACHILLES Express; GE, Mdison, WI, USA). Additionlly, the T-score ws divided into three groups ccording to the clssifiction of the WHO s norml when greter thn -1.0, osteopeni when it ws between -2.5 nd -1.0, nd osteoporosis when it ws less thn Sttisticl nlysis All sttisticl procedures were crried out with SPSS for windows version 17.0 (SPSS Inc., Chicgo, IL, USA). All vlues re presented s the men ± stndrd devition. Student s t-test nd the chi-squre test were performed to compre the clinicl chrcteristic of the two groups clssified s the norml nd predibetic group. One-wy ANOVA ws pplied for comprtive nlysis of the BMD. The Person s correltion method ws pplied for nlysis of the correltion of BMD with the vrious clinicl chrcteristics. To determine the fctors hving the gretest effects on BMD, multiple regression nlysis ws performed nd confirmed by correltion nlysis; s less thn 0.05 were considered sttisticlly significnt. RESULTS Comprison of clinicl chrcteristics nd BMD Among the 678 study ptients, 406 were clssified s norml nd 272 were clssified s predibetic. Compred with the norml group, the predibetic group hd significntly higher vlues for fsting blood glucose concentrtion nd blood glucose concentrtion 2 hours fter 75 g orl glucose lod, serum insulin concentrtion 2 hours fter 75 g orl glucose lod, nd glycosylted hemoglobin ( ± mg/dl vs ± 6.47 mg/dl, ± mg/dl vs ± mg/dl, ± mu/l vs ± mu/l, nd 5.57 ±

3 Lee JH, et l. mg/dl vs ± 0.36 mg/dl, respectively, P < 0.001). However, the fsting serum insulin concentrtion ws not significntly different between these groups (7.63 ± 3.60 mu/l vs ± 4.05 mu/l, respectively, P = 0.295). There ws no significnt difference in ge, BMI, percent body ft, nd wist circumference between the two groups. The men BMD T-score of the Tble 1. Chrcteristics ccording to norml nd predibetic sttus Group Norml (n = 406) IFG or IGT (n = 272) Age, yr ± ± Hypertension Negtive 331 (81.5) 206 (75.7) b Positive 75 (18.5) 66 (24.3) Dyslipidemi Negtive 387 (95.3) 254 (93.4) b Positive 19 (4.7) 18 (6.6) (40.2) 106 (38.5) b -1.0 > (42.2) 125 (45.5) < (17.6) 44 (16.0) BMD T score ± ± HbA1C, % 5.41 ± ± 0.45 < Fsting insulin, mu/l 7.31 ± ± Fsting glucose, mg/dl ± ± < hr-insulin, mu/l ± ± < hr- glucose, mg/dl ± ± < Height, cm ± ± Weight, kg ± ± Body mss index, kg/m ± ± Wist circumference, cm ± ± Percent body ft, % 21.5 ± ± Visecrl ft, kg 2.15 ± ± Percent viscerl ft, % ± ± Totl cholesterol, mg/dl ± ± Triglyceride, mg/dl ± ± HDL-C, mg/dl ± ± LDL-C, mg/dl ± ± BUN, mg/dl ± ± Cr, mg/dl 1.08 ± ± AST, IU/L ± ± ALT, IU/L ± ± Dt re expressed s men ± stndrd devition or number (%). 2 hr-insulin nd 2 hr-glucose represent the insulin nd glucose concentrtions 120 min fter n orl glucose tolernce test. IFG, impired fsting glucose; IGT, impired glucose tolernce; BMD, bone minerl density; HDL-C, high density lipoprotein cholesterol; LDL-C, low density lipoprotein cholesterol; ALT, lnine trnsminse; AST, sprtte minotrnsferse. s were clculted using n unpired T-test, b s were clculted by Person s chi-squre test. 296

4 Bone minerl density in predibetes norml group ws ± 1.42 while the BMD T-score of the predibetic group ws ± 1.30; this difference ws not significnt (P = 0.924). On chi-squre testing following clssifiction of the BMD T-score ccording to WHO stndrds, no significnt difference ws found between the two groups (P = 0.688, Tble 1). Among the 272 predibetic ptients, excluding 9 ptients who did not undergo the 75 g orl glucose tolernce test, totl of 263 ptients were divided to the three groups: cses with IFG only, cses with IGT only, nd cses with both IFG nd IGT. The BMD T-score of ech of these groups ws compred with the norml group; no significnt difference ws observed (Tble 2). Reltionship of blood glucose nd insulin with BMD No significnt difference in the BMD between the norml Tble 2. Subgroup nlysis of BMD T-scores in predibetics Group Norml (n = 406) IFG only (n = 80) IGT only (n = 114) IFG nd IGT (n = 69) BMD T score ± ± ± ± (40.2) 32 (40.0) 39 (34.2) 30 (43.5) b -1.0 > (42.2) 32 (40.0) 56 (49.1) 32 (46.4) < (17.6) 16 (20.0) 19 (16.7) 7 (10.1) Dt re expressed s men ± stndrd devition or number (%). BMD, bone minerl density; IFG, impired fsting glucose; IGT, impired glucose tolernce. s were clculted by one-wy ANOVA, b s were clculted by Person s chi-squre test. Tble 3. BMD T-scores in the norml, predibetic, nd dibetic subjects Group Norml (n = 406) Predibetes (n = 272) DM (n = 123) Tble 4. BMD T-scores ccording to the fsting insulin levels in norml, predibetic, nd dibetic subjects Fsting insulin level < 25% ( 5.2 mu/l ) 25-50% (5.2 < 6.6 mu/l) 50-75% (6.6 < 8.9 mu/l) > 75% (> 8.9 mu/l ) BMD T score ± ± ± (40.2) 106 (39.0) 48 (39.0) b -1.0 < (42.2) 126 (46.3) 57 (46.3) < (17.6) 40 (14.7) 18 (14.6) Dt re expressed s men ± stndrd devition or number (%). BMD, bone minerl density; DM, dibetes mellitus. s were clculted by one-wy ANOVA, b s were clculted by liner ssocition nlysis. BMD T score ± ± ± ± < b (31.7) 68 (34.2) 88 (43.9) 95 (47.5) -1.0 < (48.7) 92 (46.2) 86 (42.8) 77 (38.5) < (19.6) 39 (19.6) 27 (13.4) 28 (14.0) Dt re expressed s men ± stndrd devition or number (%). 2 hr-insulin represents the insulin concentrtions t 120 min fter n orl glucose tolernce test. BMD, bone minerl density. s were clculted by one-wy ANOVA, b s were clculted by liner ssocition nlysis. 297

5 Lee JH, et l. group, the predibetic group, nd the dibetic group ws observed (Tble 3). All subjects were divided into qurtiles bsed on the fsting insulin nd insulin levels 2 hours fter 75 g orl glucose lod, nd the BMD of ech group ws compred. As the concentrtion of fsting insulin incresed, the men BMD T-score lso incresed (P = 0.004). Additionlly, on chi-squre testing following clssifiction of the BMD ccording to WHO stndrds, the subjects with high concentrtions of fsting insulin belonged to the groups with higher BMD T-scores (P < 0.001, Tble 4). When compring these groups bsed on the insulin levels 2 hours fter orl dministrtion of 75 g glucose, no significnt difference in the men BMD T-score ws found. Tble 5. BMD T-scores ccording to the 2 hr-insulin levels in norml, predibetic, nd dibetic subjects 2 hr-insulin level < 25% ( 12.1 mu/l) 25-50% (12.1 < 20.5 mu/l ) 50-75% (20.5 < 35.4 mu/l ) > 75% (> 35.4 mu/l ) BMD T score ± ± ± ± b (35.1) 66 (35.1) 78 (41.1) 82 (43.6) -1.0 < (45.9) 89 (47.3) 74 (38.9) 87 (46.3) < (18.9) 33 (17.6) 38 (20.0) 19 (10.1) Dt re expressed s men ± stndrd devition or number (%). 2 hr-insulin represents the insulin concentrtions 120 min fter n orl glucose tolernce test. BMD, bone minerl density. s were clculted by one-wy ANOVA, b s were clculted by liner ssocition nlysis. Tble 6. Univrite nlysis of ssocitions between the BMD T-score nd clinicl nd lbortory prmeters in the predibetic subjects Correltion coefficient Prtil correltion coefficient R R Age, yr Height, cm Weight, kg Wist circumference, cm BMI, kg/m Fsting insulin, mu/l Fsting blood glucose, mg/dl hr-insulin, mu/l hr-glucose, mg/dl Percent body ft, % Visecrl ft, kg Percent viscerl ft, % HbA1C, % Totl cholesterol, mg/dl < Triglyceride, mg/dl HDL-C, mg/dl LDL-C, mg/dl < Dt re given s Person s correltion (R) coefficients with djustment for ge (r). 2 hr-insulin nd 2 hr-glucose represent the insulin nd glucose concentrtions 120 min fter n orl glucose tolernce test. BMD, bone minerl density; BMI, body mss index; HDL-C, high density lipoprotein cholesterol; LDL-C, low density lipoprotein cholesterol. P < 0.01, P <

6 Bone minerl density in predibetes Nonetheless, on chi-squre testing performed fter clssifying the BMD T-score ccording to WHO stndrds, ptients with higher insulin concentrtions belonged to the group with higher T-scores (P = 0.017, Tble 5). Correltion of BMD with clinicl chrcteristics in the predibetic group In the predibetic group, the BMD demonstrted sttisticlly significnt inverse correltion with ge (r = , P = 0.041) nd positive correltions with weight (r = 0.134, P = 0.027), BMI (r = 0.154, P = 0.011), percent body ft (r = 0.191, P = 0.002), percent viscerl ft (r = 0.151, P = 0.013), totl cholesterol (r = 0.185, P = 0.002), nd the LDL-C (r = 0.196, P = 0.001). However, the correltion coefficients for these ssocitions were between 0.1 nd 0.3, nd thus, the correltions were not very strong. No reltionship ws observed between the BMD nd fsting insulin levels, fsting blood glucose, nd the insulin nd blood glucose levels 2 hours fter orl dministrtion of 75 g of glucose. The BMD lso demonstrted positive correltion with glycosylted hemoglobin; gin, the correltion ws not strong (r = 0.133, P = 0.028). Adjustment for ge did not lter the results (Tble 6). As ge, BMI, glycosylted hemoglobin, nd LDL-C ll demonstrted correltion with BMD in the predibetic group, multiple regression nlysis with these vribles ws performed. Only the LDL-C ws found to be significnt vrible (β = 0.007, P = 0.005) (Tble 7). However, on step-wise multiple regression model, ge (β = , P < 0.001), BMI (β = 0.079, P < 0.001), nd LDL-C (β = 0.004, P = 0.016) were found to be significnt vribles (Tble 8). Tble 7. Vribles identified by multivrite liner regression nlysis s being predictive of the BMD T-score in predibetic subjects Unstndrdized coefficients R 2 β SD Age, yr BMI, kg/m HbA1c, % LDL-C, mg/dl Dt re expressed s stndrdized coefficients (β) using multivrite regression nlysis. BMD, bone minerl density; SD, stndrd devition; BMI, body mss index; LDL-C, low density lipoprotein cholesterol. P < DISCUSSION It is well known tht insulin plys criticl role in glucose metbolism. Upon recognition tht it lso exerts nbolic effects on bone metbolism, dibetes hs become subject of interest in bone metbolism studies. The direct effect of insulin on bone metbolism hs not yet been determined, but high level of expression of insulin receptors on osteoblsts hs been reported [6]. It ws observed tht the binding of insulin to insulin receptors ccelerted cell prolifertion, collgen synthesis, production of lkline phosphtse, nd glucose intke [7-10]. In ddition to the direct effects of insulin on osteoblsts, insulin hs been found to render osteoblsts more sensitive to IGF by the suppression of IGFBP-1; this induces synergistic effect with the ctions of prthyroid hormone nd induces indirect synergistic effects with other substnces tht medite nbolic effects on bone metbolism [11,12]. The nbolic effects of insulin on bone metbolism cn be confirmed in nimls with experimentlly induced dibetes. Mor et l. [13] observed tht IGF-1, IGF-1 receptor, nd insulin receptor were reduced in the skeletl growth centers of dibetic rts. Insulin receptor trnsduces intrcellulr signls through insulin receptor substrte (IRS), nd IRS-1 nd IRS-2 hve been reveled to ply n importnt role in bone turnover nd bone formtion, respectively [14]. With the observtions tht the insulin receptor ws lso detected in osteoclsts nd tht insulin suppresses osteoclst ctivity, the effects of insulin on reducing bone resorption could be predicted nd studied [15]. Additionlly, non-osmotic hyperclciuri ws observed in dibetic rts, nd hs been reported to induce the effects of clcium deficiency [16]. It hs lso been reported tht when hy- Tble 8. Vribles identified by stepwise regression nlysis s being predictive of the BMD T-score in predibetic subjects Unstndrdized coefficients R 2 β SD Age, yr < BMI, kg/m < LDL-C, mg/dl Dt re expressed s stndrdized coefficients (β) using multivrite regression nlysis. BMD, bone minerl density; SD, stndrd devition; BMI, body mss index; LDL-C, low density lipoprotein cholesterol. P < 0.01, P <

7 Lee JH, et l. perglycemi is persistent, dvnced glyction end-products ccumulte nd result in the reduction of bone formtion by osteoblsts nd n increse in bone resorption by osteoclsts [17]. Severl studies focusing on chnges in BMD nd risks for bone frcture hve been conducted in dibetic ptients. Prior studies hve found tht BMD ws decresed in type 1 dibetes though it ws unchnged or incresed in type 2 dibetes. In type 2 dibetes, djustment for BMI did not lter these results. Insulin secretion is decresed in type 1 dibetes, but incresed in type 2 dibetes. Therefore, the nbolic effects of insulin could be confirmed. However, in both type 1 nd type 2 dibetes, the reltive risk for hip frcture ws incresed by times nd times, respectively. In type 2 dibetes, the BMD ws incresed s did the risk for frcture. A possible explntion for this my be n incresed number of flls due to deteriortion of visul cuity or proprioception cused by dibetes [18]. We conducted comprtive studies on the chnges in BMD in the norml nd predibetic groups using n ultrsonogrphic bone densitometer. We noted no significnt difference in BMD between these groups. The BMD demonstrted significnt correltions with ge, BMI, percent of body ft, percent viscerl ft, nd cholesterol. The subjects were divided into qurtiles ccording to the concentrtion of insulin in the norml, predibetic, nd dibetic groups. The BMD T-scores were divided to three groups ccording to the WHO stndrds. Chi-squre nlysis ws performed between the insulin groups nd the BMD T-score groups. Interestingly, s the concentrtion of insulin incresed, more ptients were ssigned to the groups with higher BMD T-scores. Therefore, it ws confirmed tht insulin exerts nbolic effects on bone metbolism. However, there ws no significnt difference in BMD between the predibetic nd norml group. There hve been conflicting reports in the previous studies of type 2 dibetic; in some studies, the BMD ws reduced while in others it ws incresed or unchnged [19]. This is thought to be secondry to numerous fctors, other thn insulin, ffecting BMD [3]. Additionlly, in study tht exmined the differences in BMD between mles nd femles with type 2 dibetes ptients, the BMD ws found to be incresed in femles, while the BMD of mles ws not significntly chnged; this result is consistent with the current study which included only mles [20]. In the Rotterdm study, the BMD nd risk of frcture were exmined in 792 mle nd femle dibetic ptients older thn 55 yers. They compred subjects with type 2 dibetes with the subjects without dibetes. Subset nlyses were performed, dividing the subjects on the bsis of the glucose tolernce test, into lredy treted dibetes, newly dignosed dibetes, IGT, nd norml glucose tolernce groups. Even fter djustment for ge nd gender, the femur neck BMD of the dibetic nd IGT groups ws significntly incresed [21], yet in the IGT group, the chnge in the lumbr spine BMD ws not sttisticlly significnt. Similrly, the chnge in femur BMD ws not significnt fter djustment for BMI, impirment of the lower extremities, smoking, nd the use of diuretics, in ddition to djustments for ge nd gender. Tht study included both mles nd femles nd reserchers used dul energy X-ry bsorptiometry (DXA) for ssessing the BMD. Strotmeyer et l. [22] exmined BMD nd frcture risk in 2,797 mles nd femles between 70 nd 79 yers of ge using DXA. These investigtors found tht in both mles nd femles, the BMD of the hip joint ws sttisticlly incresed in the IFG group. Koren studies on the correltion of dibetes with osteoporosis re rre. Kim et l. [23] exmined the correltion of noninsulin dependent dibetes with osteoporosis in 63 postmenopusl women using DXA. These uthors found tht the lumbr spine nd femur BMD of the dibetic group ws significntly higher thn tht of the norml group. Even fter djustment for BMI nd postmenopusl sttus, the BMD differences remined significnt. Prk et l. [24] mesured the BMD of 30 mle nd 30 femle dibetic ptients suspected s hving dibetic foot disese s well 30 mle nd 30 femle norml individuls using DXA. They found tht the forefoot BMD of the dibetic group ws significntly lower thn tht of the control group. Yet, in this study, the foot BMD of the ptients suspected s hving dibetic foot disese ws evluted, nd so the study my hve limittions in ssessing the ssocition of dibetes with osteoporosis. Although it is well known tht ge nd weight re fctors tht medite effects on BMD, there re no studies tht hve nlyzed the fctors mediting effects on BMD in predibetics. In the current study, correltion nlysis performed in the predibetic group found tht ge, BMI, glycosylted hemoglobin, nd LDL-C re fctors tht medite effects on BMD. In multiple regression nlysis, only the LDL-C levels were found to be significntly correlted fctor. In step-wise multiple regression model, ge nd weight were found to be significntly ssocited fctors with BMD. It is nticipted tht if n incresed number of subjects re included in future studies, ge my lso be found to be significnt fctor. Depending on the prticulr study, cholesterol hs been re- 300

8 Bone minerl density in predibetes ported s hving positive, inverse, or no correltion with BMD [25-27]. It hs recently been reported tht 3-hydroxy-3-methylglutryl (HMG)-CoA reductse inhibitors increse BMD nd id in frcture heling; this hs been demonstrted to be independent of lipid reductions nd rther due to enhncing the expression of osteoblsts through bone morphogenetic protein-2. Additionlly, HMG-CoA reductse inhibitor suppresses osteoclst ctivity nd my ct s n nti-bone resorption gent [28]. As cholesterol increses, it my be mrker for reltively good nutrition nd so my be fctor tht increses the BMI. Hence, the effects of cholesterol on BMD need to be considered. The positive correltion of cholesterol with BMD observed in our study wrrnts further investigtion. The current study hs severl limittions. This is crosssectionl study. Ultrsonogrphy ws used to determine BMD insted of DXA. Additionlly, bone turnover mrkers nd ndrogen concentrtions were not mesured. Finlly, the mjor risk fctors for mle osteoporosis (drinking, smoking, nd physicl ctivity) were not nlyzed. Our study is importnt s it is the first Koren study tht hs exmined the chnges in BMD in predibetic ptients. Further studies re required to elucidte the ssocitions between the risk level of ctul frcture nd chnges in BMD during the progression from predibetic stte to frnk dibetes. REFERENCES 1. Ministry for Helth, Welfre nd Fmily Affirs: The Third Kore Ntionl Helth nd Nutrition Exmintion Survey (KNHANES III). Avilble from: (updted 2009 Mr 19). 2. World Helth Orgniztion. Assessment of frcture risk nd its ppliction to screening for postmenopusl osteoporosis. Genev: World Helth Orgniztion; Vestergrd P. Discrepncies in bone minerl density nd frcture risk in ptients with type 1 nd type 2 dibetes: metnlysis. Osteoporos Int 2007;18: Thrilkill KM, Lumpkin CK Jr, Bunn RC, Kemp SF, Fowlkes JL. Is insulin n nbolic gent in bone? Dissecting the dibetic bone for clues. Am J Physiol Endocrinol Metb 2005;289: E Americn Dibetes Assocition. Dignosis nd clssifiction of dibetes mellitus. Dibetes Cre 2004;27(Suppl 1):S Thoms DM, Hrds DK, Rogers SD, Ng KW, Best JD. Insulin receptor expression in bone. J Bone Miner Res 1996;11: Wergedl JE, Bylink DJ. Chrcteriztion of cells isolted nd cultured from humn bone. Proc Soc Exp Biol Med 1984;176: Cnlis EM, Dietrich JW, Min DM, Risz LG. Hormonl control of bone collgen synthesis in vitro. Effects of insulin nd glucgon. Endocrinology 1977;100: Cnlis E. Effect of hormones nd growth fctors on lkline phosphtse ctivity nd collgen synthesis in cultured rt clvrie. Metbolism 1983;32: Hhn TJ, Westbrook SL, Sullivn TL, Goodmn WG, Hlsted LR. Glucose trnsport in osteoblst-enriched bone explnts: chrcteriztion nd insulin regultion. J Bone Miner Res 1988; 3: Conover CA, Lee PD, Riggs BL, Powell DR. Insulin-like growth fctor-binding protein-1 expression in cultured humn bone cells: regultion by insulin nd glucocorticoid. Endocrinology 1996;137: Suzuki K, Miykoshi N, Tsuchid T, Ksukw Y, Sto K, Itoi E. Effects of combined tretment of insulin nd humn prthyroid hormone (1-34) on cncellous bone mss nd structure in streptozotocin-induced dibetic rts. Bone 2003;33: Mor G, Krnieli E. The insulin-sensitive glucose trnsporter (GLUT4) is involved in erly bone growth in control nd dibetic mice, but is regulted through the insulin-like growth fctor I receptor. Endocrinology 1999;140: Ogt N, Chikzu D, Kubot N, Teruchi Y, Tobe K, Azum Y, Oht T, Kdowki T, Nkmur K, Kwguchi H. Insulin receptor substrte-1 in osteoblst is indispensble for mintining bone turnover. J Clin Invest 2000;105: Kitmur T, Kitmur Y, Nke J, Giordno A, Cinti S, Khn CR, Efstrtidis A, Accili D. Mosic nlysis of insulin receptor function. J Clin Invest 2004;113: Wrd DT, Yu SK, Mee AP, Mwer EB, Miller CA, Grlnd HO, Riccrdi D. Functionl, moleculr, nd biochemicl chrcteriztion of streptozotocin-induced dibetes. J Am Soc Nephrol 2001;12: Ymgishi S, Nkmur K, Inoue H. Possible prticiption of dvnced glyction end products in the pthogenesis of osteoporosis in dibetic ptients. Med Hypotheses 2005;65: Rkel A, Sheehy O, Rhme E, LeLorier J. Osteoporosis mong ptients with type 1 nd type 2 dibetes. Dibetes Metb 2008; 34: Brrett-Connor E, Holbrook TL. Sex differences in osteoporosis in older dults with non-insulin-dependent dibetes mellitus. JAMA 1992;268:

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