Journal of Hainan Medical University 2017; 23(2): Journal of Hainan Medical University.

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1 Journl of Hinn Medicl University 2017; 23(2): Journl of Hinn Medicl University Reltionship between DEXA bone minerl density mesurement results nd serum cytokines s well s insulin resistnce in ptients with type 2 dibetes mellitus nd osteoporosis Bing Wng 1, Xun-Neng Yng 2 1 Rdiology Deprtment, Zigong Third People's Hospitl of Sichun Province, Zigong City, Sichun Province, Orthopedics Deprtment, Zigong Third People's Hospitl of Sichun Province, Zigong City, Sichun Province, ARTICLE INFO Article history: Received 7 Nov 2016 Received in revised form 17 Nov 2016 Accepted 12 Nov 2016 Avilble online 24 Nov 2016 Keywords: Type 2 dibetes mellitus Osteoporosis Inflmmtory fctors Insulin resistnce ABSTRACT Objective: To study the reltionship between DEXA bone minerl density mesurement results nd serum cytokines s well s insulin resistnce in ptients with type 2 dibetes mellitus nd osteoporosis. Methods: Ptients newly dignosed with type 2 dibetes were selected nd divided into norml bone mss group, osteopeni group nd osteoporosis group ccording to the DEXA femorl neck bone minerl density mesurement results, the bone minerl density of ll prts in of three groups of ptients were mesured, nd serum ws collected to determine the levels of bone metbolism indexes, cytokines nd insulin. Results: Femorl trochnter, Wrd's re s well s the 2-4th lumbr vertebr bone minerl density vlues of osteopeni group nd osteoporosis group were significntly lower thn those of norml bone mss group, nd the femorl trochnter, Wrd's re s well s the 2-4th lumbr vertebr bone minerl density vlues of osteoporosis group were significntly lower thn those of osteopeni group; serum N-MID, PINP nd BGP levels of osteopeni group nd osteoporosis group were significntly lower thn those of norml bone mss group while β-ctx, TRACP5b, Ins, Chemerin, TNF- 毩, IL-1β nd MCP-1 levels were significntly higher thn those of norml bone mss group; serum N-MID, PINP nd BGP levels of osteoporosis group were significntly lower thn those of osteopeni group while β-ctx, TRACP5b, Ins, Chemerin, TNF- 毩, IL-1β nd MCP-1 levels were significntly higher thn those of osteopeni group; serum Ins, Chemerin, TNF- 毩, IL-1β nd MCP-1 levels were negtively correlted with N-MID, PIN nd BGP levels, nd positively correlted with serum β-ctx nd TRACP5b levels. Conclusion: Excessively synthesized inflmmtory fctors nd compenstory hyperinsulinemi in ptients with type 2 dibetes mellitus nd osteoporosis cn promote bone resorption nd inhibit bone formtion, thus resulting in the osteopeni in multiple res of the body. 1. Introduction Type 2 dibetes mellitus is the most common clinicl endocrine system disese, insulin resistnce is its bsic pthologicl physiologicl chrcteristic, nd it is lso ccompnied by internl environment disturbnce s well s the bnorml synthesis nd secretion of vriety of cytokines. In recent yers, more nd more Corresponding uthor: Bing Wng, Rdiology Deprtment, Zigong Third People's Hospitl of Sichun Province, Zigong City, Sichun Province, Tel: Fund Project: Reserch Project of Sichun Provincil Helth Deprtment NO: clinicl evidences hve shown tht risk of osteoporosis hs gretly incresed in ptients with type 2 dibetes, nd the insulin resistnce nd bnorml secretion of cytokines cn ffect bone metbolism, thus resulting in osteopeni nd bone ultrstructure dmge[1,2]. However, the specific moleculr mechnisms of osteoporosis in ptients with type 2 dibetes re not cler t present, nd the relted fctors tht cuse osteopeni nd bone ultrstructure dmge during the chnge of type 2 dibetes hve not been fully elucidted. Lunr dul-energy X-ry bsorptiometry (DEXA) is the most common uxiliry method for clinicl bone minerl density mesurement nd osteoporosis evlution[3,4], nd in order to define the influence fctors of bone density in ptients with type 2 dibetes, the

2 152 reltionship between DEXA bone minerl density mesurement results nd serum cytokines s well s insulin resistnce in ptients with type 2 dibetes mellitus nd osteoporosis ws nlyzed in the study. 2. Subjects nd methods 2.1 Reserch subjects A totl of 177 ptients dignosed with type 2 dibetes in our hospitl between My 2013 nd July 2015 were selected s the reserch subjects, nd ll ptients were dignosed with type 2 dibetes through OGTT test, were dignosed for the first time nd never received osteoporosis drug therpy before. The DEXA femorl neck bone minerl density mesurement results were referred to judge the bone minerl density, ptients with bone mss lower thn the pek bone mss by less thn 1 stndrd devition were with norml bone mss, those with bone mss lower thn the pek bone mss by stndrd devitions were with osteopeni nd those with bone mss lower thn the pek bone mss by more thn 2.5 stndrd devitions were with osteoporosis, nd they were enrolled in norml bone bss group, osteopeni group nd osteoporosis group respectively. Norml bone bss group (n=83) included 52 mle cses nd 31 femle cses tht were 52 yers old; osteopeni group (n=52) included 32 mle cses nd 20 femle cses tht were 52 yers old; osteoporosis group (n=42) included 27 mle cses nd 15 femle cses tht were 53 yers old. The three groups of ptients were not significntly different in generl informtion (P>0.05). 2.2 Bone minerl density mesurement methods Three groups of ptients received bone minerl density mesurement by Lunr dul-energy X-ry bsorptiometry fter dmission, the instrument ccurcy ws 1%, the error of repliction ws <1%, nd the femorl neck, femorl trochnter, Wrd's re s well s the 2-4th lumbr vertebr (L2-L4) bone minerl density were mesured respectively. 2.3 Serum index detection methods About 8 ml of fsting peripherl blood ws collected from the three groups fter dmission nd centrifuged to get serum, nd enzymelinked immunosorbent ssy kits were used to determine N-terminl osteoclcin (N-MID), N-terminl propeptide of procollgen type I (PINP), 毬 -collgen degrdtion product ( 毬 -CTX), bone gl protein (BGP), trtrte-resistnt cid phosphtse 5b (TRACP5b), Chemerin, tumor necrosis fctor α (TNF- 毩 ), interleukin-1 毬 (IL-1 毬 ), IL-6 nd monocyte chemottrctnt protein-1 (MCP-1) content. 2.4 Sttisticl methods SPSS 20.0 softwre ws used to input nd nlyze dt, mesurement dt nlysis mong three groups ws by vrince nlysis, pir-wise comprison ws by LSD-t test nd P<0.05 indicted sttisticl significnce in differences. 3. Results 3.1 DEXA bone minerl density mesurement vlues of three groups of ptients Anlysis of femorl trochnter, Wrd's re s well s the 2-4th lumbr vertebr bone minerl density vlues mong three groups of ptients ws s follows: femorl trochnter, Wrd's re s well s the 2-4th lumbr vertebr bone minerl density vlues of osteopeni group nd osteoporosis group were significntly lower thn those of norml bone mss group, nd the femorl trochnter, Wrd's re s well s the 2-4th lumbr vertebr bone minerl density vlues of osteoporosis group were significntly lower thn those of osteopeni group. Differences in pir-wise comprison of femorl trochnter, Wrd's re s well s the 2-4th lumbr vertebr bone minerl density vlues were sttisticlly significnt mong three groups of ptients (P<0.05). 3.2 Serum bone metbolism indexes of three groups of ptients Anlysis of serum bone metbolism indexes N-MID, PINP, 毬 -CTX, BGP nd TRACP5b mong three groups of ptients ws s follows: serum N-MID, PINP nd BGP levels of osteopeni group nd osteoporosis group were significntly lower thn those of Tble 1. Comprison of bone minerl density vlues of vrious prts mong three groups of ptients. Groups n femorl trochnter Wrd s region L2 L3 L4 Norml ± ± ± ± ±0.11 Osteopeni ± ± ± ± ±0.08 Osteoporosis ±0.07 b 0.52±0.06 b 0.82±0.08 b 0.79±0.08 b 0.75±0.08 b : compred with norml bone mss group, P<0.05; b : compred with osteopeni group, P<0.05.

3 153 Tble 2. Comprison of serum bone metbolism indexes mong three groups of ptient. Groups n N-MID (ng/ml) PINP (ng/ml) 毬 -CTX (pg/ml) BGP (ng/ml) TRACP5b (U/L) Norml ± ± ± ± ±0.53 Osteopeni ± ± ± ± ±0.77 Osteoporosis ±1.03 b 24.27±3.17 b ±63.32 b 12.31±1.42 b 7.31±0.89 b : compred with norml bone mss group, P<0.05; b : compred with osteopeni group, P<0.05. Tble 3. Comprison of serum cytokine levels mong three groups of ptients. Groups n Chemerin (ng/ml) TNF- 毩 (pg/ml) IL-6 (pg/ml) MCP-1 (ng/ml) Norml ± ± ± ±2.26 Osteopeni ± ± ± ±3.86 Osteoporosis ±10.37 b 13.27±1.89 b 7.91±0.93 b 44.65±6.14 b : compred with norml bone mss group, P<0.05; b : compred with osteopeni group, P<0.05. norml bone mss group while the 毬 -CTX nd TRACP5b levels were significntly higher thn those of norml bone mss group; serum N-MID, PINP nd BGP levels of osteoporosis group were significntly lower thn those of osteopeni group while 毬 -CTX nd TRACP5b levels were significntly higher thn those of osteopeni group. Differences in pir-wise comprison of serum N-MID, PINP, 毬 -CTX, BGP nd TRACP5b content were sttisticlly significnt mong three groups of ptients (P<0.05). 3.2 Serum cytokine levels of three groups of ptients 3.5 Correltion between serum insulin levels s well s cytokine levels nd bone metbolism indexes Person test results of the correltion between serum Ins, Chemerin, TNF- 毩, IL-1 毬 s well s MCP-1 levels nd bone metbolism indexes N-MID, PINP, BGP, β-ctx s well s TRACP5b were s follows: serum Ins, Chemerin, TNF- 毩, IL-1 毬 nd MCP-1 levels were negtively correlted with N-MID, PIN nd BGP levels, nd positively correlted with serum 毬 -CTX nd TRACP5b levels. Anlysis of serum cytokines Chemerin, TNF- 毩, IL-1 毬 nd MCP-1 mong three groups of ptients ws s follows: serum Chemerin, TNF- 毩, IL-1 毬 nd MCP-1 levels of osteopeni group nd osteoporosis group were significntly higher thn those of norml bone mss group; serum Chemerin, TNF- 毩, IL-1 毬 nd MCP-1 levels of osteoporosis group were significntly higher thn those of osteopeni group. Differences in pir-wise comprison of serum Chemerin, TNF- 毩, IL-1 毬 nd MCP-1 content were sttisticlly significnt mong three groups of ptients (P<0.05). 3.4 Serum insulin levels of three groups of ptients Serum insulin level of norml bone mss group ws (9.31±1.03) U/ ml, serum insulin level of osteopeni group ws (16.57±2.18) U/ ml, serum insulin level of osteoporosis group ws (25.34±3.78) U/ ml, nd the specific sttisticl nlysis ws s follows: serum insulin levels of osteopeni group nd osteoporosis group were significntly higher thn tht of norml bone mss group; serum insulin level of osteoporosis group ws significntly higher thn tht of osteopeni group. Differences in pir-wise comprison of serum insulin levels were sttisticlly significnt mong three groups of ptients (P<0.05). 4. Discussion In recent yers, the reltionship between type 2 dibetes nd osteoporosis hs received more nd more ttention. During the development nd chnge of the type 2 dibetes, insulin resistnce s well s the internl environment disturbnce nd bnorml secretion of cytokines cn ffect bone metbolism, which further increses the risk of osteoporosis[5,6]. In order to define the bone mss chnges of vrious res of ptients with type 2 dibetes mellitus nd osteoporosis, the DEXA femorl neck bone density mesurement vlues were used in the study s the stndrd to judge osteoporosis nd divide the ptients with newly dignosed type 2 dibetes into norml bone mss group, osteopeni group nd osteoporosis group, nd the nlysis of bone minerl density vlues of different res mong the groups showed tht femorl trochnter, Wrd's re s well s the 2-4th lumbr vertebr bone minerl density vlues of osteopeni group nd osteoporosis group were significntly lower thn those of norml bone mss group, nd the femorl trochnter, Wrd's re s well s the 2-4th lumbr vertebr bone minerl density vlues of osteoporosis group were significntly lower thn those of osteopeni group. This mens tht DEXA bone minerl density mesurement is with good consistency, the osteopeni nd osteoporosis process of vrious res of ptients with type 2

4 154 dibetes re consistent, nd the bone minerl density of vrious res mesured by DEXA cn ll reflect the osteopeni nd osteoporosis process. In the development of osteoporosis, the chnges of the bone ultrstructure is the bsic pthologicl chrcteristic, nd the blnce between bone resorption nd bone formtion is n importnt mechnism tht regultes bone ultrstructure. Bone resorption process is minly medited by osteoclsts, the TRACP5b secreted by osteoclsts cn cuse bone collgen degrdtion nd bone minerl density decrese[7]; 毬 -CTX is the intermedite product in the process of bone collgen degrdtion, nd serum 毬 -CTX cn reflect the ctivity of osteoclsts nd the ctive degree of bone resorption[8]. In the study, nlysis of the levels of these bone resorption mrker molecules showed tht serum 毬 -CTX nd TRACP5b levels of osteopeni group nd osteoporosis group were significntly higher thn those of norml bone mss group, nd serum 毬 -CTX nd TRACP5b levels of osteoporosis group were significntly higher thn those of osteopeni group. This mens tht the excessive ctivity of bone resorption process is closely relted to the process of type 2 dibetes combined with osteoporosis. The bone formtion process is minly medited by osteoblsts, nd the N-MID nd BGP secreted by osteoblsts cn deposit in bone mtrix nd form bone ultrstructure[9,10]; PINP is the intermedite product in the process of type I collgen synthesis nd deposition in the bone, nd serum PINP levels cn reflect the ctive degree of bone formtion[11,12]. In the study, nlysis of the levels of these bone formtion mrker molecules showed tht serum N-MID, PINP nd BGP levels of osteopeni group nd osteoporosis group were significntly lower thn those of norml bone mss group, nd serum N-MID, PINP nd BGP levels of osteoporosis group were significntly lower thn those of osteopeni group. This mens tht the reltive inhibition of bone formtion process is closely relted to the process of type 2 dibetes combined with osteoporosis. At present, the bnorml bone metbolism in ptients with type 2 dibetes mellitus nd osteoporosis hs been unnimously recognized, but the mechnism cusing bnorml bone metbolism is not totlly cler. Insulin resistnce is the most bsic pthologicl chrcteristic in ptients with type 2 dibetes, long-term insulin resistnce cn cuse compenstory hyperinsulinemi, nd under the combined ction of hyperinsulinemi nd insulin resistnce, the bone metbolism process will be significntly ffected[13-15]. In the study, nlysis of the reltionship between blood insulin levels nd bone metbolism indexes showed tht serum Ins levels of osteopeni group nd osteoporosis group were significntly higher thn those of norml bone mss group, serum Ins level osteoporosis group ws significntly higher thn tht of osteopeni group, nd Ins levels were negtively correlted with N-MID, PINP nd BGP levels, nd positively correlted with serum 毬 -CTX nd TRACP5b levels. This mens tht the insulin resistnce nd hyperinsulinemi in ptients with type 2 dibetes mellitus nd osteoporosis will ffect the process of bone formtion nd bone resorption. The insulin resistnce sttus in ptients with type 2 dibetes is closely relted to inflmmtion, nd vriety of inflmmtory fctors will ffect the insulin sensitivity nd lso cuse the imblnce between bone formtion nd bone resorption[16,17]. Serum Chemerin, TNF- 毩, IL-1 毬 nd MCP-1 levels of osteopeni group nd osteoporosis group were significntly higher thn those of norml bone mss group, serum Chemerin, TNF- 毩, IL-1 毬 nd MCP-1 levels of osteoporosis group were significntly higher thn those of osteopeni group, nd the bove inflmmtory fctor levels were negtively correlted with N-MID, PINP nd BGP levels, nd positively correlted with serum 毬 -CTX nd TRACP5b levels. This mens tht the micro-inflmmtion stte in ptients with type 2 dibetes mellitus nd osteoporosis cn ffect the process of bone formtion nd bone resorption. Bsed on bove discussion nd nlysis, the conclusion of the study ws obtined: there re excessive ctivity of bone resorption process nd reltive inhibition of bone formtion process in ptients with type 2 dibetes mellitus nd osteoporosis, nd the excessively synthesized inflmmtory fctors nd compenstory hyperinsulinemi in vivo cn ffect the bone formtion nd bone resorption process, thus resulting in the osteopeni in multiple res of the body. References [1] Heilmeier U, Ptsch JM. Dibetes nd Bone. Semin Musculoskelet Rdiol 2016; 20(3): [2] Xi JW, Tn SJ, Zhng XL, Jun T, Sun XK, Ling W. Correltion of serum testosterone with insulin resistnce in elderly mle type 2 dibetes mellitus ptients with osteoporosis. J Dibetes Investig 2015; 6(5): [3] Epnov VV, Plshin GA, Epnov AA, Komissrov AN, Tomsky MI, Sedunov VF, et l. X-ry densitometry nd frx model in predicting the risk of osteoporosis nd low-energy frctures in postmenopusl women. Wid Lek 2015; 68(4): [4] Jung HJ, Prk HY, Kim JS, Yoon JO, Jeon IH. Bone minerl density nd prevlence of osteoporosis in postmenopusl koren women with lowenergy distl rdius frctures. J Koren Med Sci 2016; 31(6): [5] Strup-Linde J, Vestergrd P. Mngement of endocrine disese: Dibetes nd osteoporosis: cuse for concern? Eur J Endocrinol 2015; 173(3): [6] Wongdee K, Chroenphndhu N. Updte on type 2 dibetes-relted osteoporosis. World J Dibetes 2015; 6(5): [7] Neem ST, Hussin R, Rheem A, Siddiqui I, Ghni F, Khn AH. Bone turnover mrkers for osteoporosis sttus ssessment t bseline

5 155 in postmenopusl pkistni femles. J Coll Physicins Surg Pk 2016; 26(5): [8] Chvssieux P, Portero-Muzy N, Roux JP, Grnero P, Chpurlt R. Are biochemicl mrkers of bone turnover representtive of bone histomorphometry in 370 postmenopusl women? J Clin Endocrinol Metb 2015; 100(12): [9] Wei QS, Hung L, Tn X, Chen ZQ, Chen SM, Deng WM. Serum osteopontin levels in reltion to bone minerl density nd bone turnover mrkers in postmenopusl women. Scnd J Clin Lb Invest 2016; 76(1): [10] Arntes HP, Gimeno SG, Ching AY, Bilezikin JP, Lzretti-Cstro M. Incidence of vertebrl frctures in clcium nd vitmin D-supplemented postmenopusl Brzilin women with osteopeni or osteoporosis: dt from Arzoxifene Genertions Tril. Arch Endocrinol Metb 2016; 60(1): [11] Shetty S, Kpoor N, Din Bondu J, Antonismy B, Thoms N, Pul TV. Bone turnover mrkers nd bone minerl density in helthy motherdughter pirs from South Indi. Clin Endocrinol (Oxf) 2016; 85(5): [12] Bndeir F, Cost AG, Sores Filho MA, Pimentel L, Lim L, Bilezikin JP. Bone mrkers nd osteoporosis therpy. Arq Brs Endocrinol Metbol 2014; 58(5): [13] liwick E, Nowk A, Zep W, Leszczyński P, Pilczyńsk-Szcześnik Ł. Bone mss nd bone metbolic indices in mle mster rowers. J Bone Miner Metb 2015; 33(5): [14] Xu F, Dong Y, Hung X, Li M, Qin L, Ren Y, et l. Decresed osteoclstogenesis, osteoblstogenesis nd low bone mss in mouse model of type 2 dibetes. Mol Med Rep 2014; 10(4): [15] Al-Dghri NM, Al-Ajln AS, Alfwz H, Ykout SM, Aljohni N, Kumr S, et l. Serum cytokine, chemokine nd hormone levels in Sudi dults with pre-dibetes: one-yer prospective study. Int J Clin Exp Pthol 2015; 8(9): [16] Engin-Üstün Y, Çğlyn EK, Göçmen AY, Polt MF. Postmenopusl osteoporosis is ssocited with serum chemerin nd irisin but not with polipoprotein M levels. J Menopusl Med 2016; 22(2): [17] Roy B, Curtis ME, Fers LS, Nhshon SN, Fentress HM. Moleculr mechnisms of obesity-induced osteoporosis nd muscle trophy. Front Physiol 2016; 29(7): 439.