Effect Of Metabolic Syndrome On Union Rate Of Fractures
Sadighi A, et al., J Anal Res Clin Med, 2015, 3(1): 37-42.doi: 10.15171/jarcm.2015.006, http://journals.tbzmed.ac.ir/JARCMEffect of metabolic syndrome on union rate of fractures1Associate Professor, Department of Orthopedics Surgery, School of Medicine, Shohada Educational Hospital, Tabriz University of MedicalSciences, Tabriz, Iran2Assistant Professor, Department of Orthopedics Surgery, School of Medicine, Shohada Educational Hospital, Tabriz University of MedicalSciences, Tabriz, Iran3Associate Professor, Department of Endocrinology, School of Medicine, Endocrine Research Center, Imam Reza Educational Hospital,Tabriz University of Medical sciences, Tabriz, Iran4Resident, Department of Orthopedics Surgery, School of Medicine, Shohada Educational Hospital, Tabriz University of Medical Sciences,Tabriz, IranMetabolic Syndrome,Nonunion,Inflammatory MarkersIncrease of inflammatory markers is the most important problem in metabolicsyndrome. C-reactive protein (CRP) is an undefined component of metabolic syndrome, andits increase is regarded as a dependent risk factor to cause complications. Considering the highprevalence of metabolic syndrome and relation of these diseases with different inflammatoryfactors, it is assumed this syndrome may affect fractured bone healing process. Therefore, thehypothesis is studied for the first time in analytical study.This analytical and descriptive study was conducted on 48 patients with isolatedfracture of tibia and femur shafts resulting from low-energy trauma. In this study, 24 patientswith metabolic syndrome criteria matched considering age, gender, type of fracture, andtreatment method were compared with 24 metabolically health persons. Level of highsensitivity hs-CRP (High-sensitivity CRP) inflammatory marker was also determined in thesepatients. Union rate and duration as well as a relation between inflammatory marker and unionrate were studied.Prevalence of nonunion and delayed union were seen in 8 (33.3%) and 3 (12.5%)patients with metabolic syndrome, respectively. However, there was not any case of nonunionin the metabolically health group. There was a statistically significant difference betweenthese groups. According to the regression model, hs-CRP level played a significant role withsensitivity of 95% considering nonunion prediction [P 0.001, OR (Odds ratio) 2.3 and CI(Confidence interval) 95% 1.4-3.8] while other factors of metabolic syndrome did not playany important role in nonunion prediction.Prevalence of nonunion in patients with metabolic syndrome suffering from afracture and undergoing orthopedic surgery is higher than healthy people. It seems that theincrease of inflammatory markers plays an important role in causing and predicting ofnonunion in these patients.Citation: Sadighi A, Bazavar M, Niafar M, Tabrizi A. Effect of metabolic syndrome on union rate offractures. J Anal Res Clin Med 2015; 3(1): 37-42.Metabolic syndrome is a known risk factor ofcardiovascular diseases. This syndromeincludes increase of abdominal fat,hypertension, increase of glucose andtriglycerides and decrease of abolic syndrome is defined as a set ofmetabolic disorders, which their concurrentoccurrence in every person is more possiblethan their single occurrence. In spite ofmedical advancements, prevalence of thissyndrome is increased. It has a close relationwith progression of cardiovascular diseases* Corresponding Author: Ali Tabrizi, Email: ali.tab.ms@gmail.com 2015 The Authors; Tabriz University of Medical SciencesThis is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), whichpermits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Metabolic syndrome in fractures healingand diabetes type II.2Prevalence rate of metabolic syndrome inasymptomatic persons has been reported 22.8and 40.0% respectively for American adults3and older-than-60 years persons.4 Prevalenceof metabolic syndrome is 12-21% for Chineseolder-than-20 years persons.5 According to thestudy conducted by Azizi et al. in Tehran,Iran, older than 20 years personsdemonstrated 33.7% of prevalence ofmetabolic syndrome. The older the persons ofboth genders, the higher the prevalence ofmetabolic syndrome.6 According to similarresults obtained by Zabetian et al. prevalenceof metabolic syndrome was reported 32.1%in Iran.7On the other hand, there is a close relationbetween metabolic syndrome and increase ofinflammatory markers in the patients.According to the findings, high inflammatorymarkers and C-reactive protein (CRP) has adirect relation with high risk of fractures.Some studies referred to the relation foundbetween CRP and decrease of bone mineraldensity.8Nonunion is an important problemencountered by orthopedic surgeons. It isdetected relying on the lack of unionsymptoms in two radiographic plans andclinical evidences during a specific period.9There is different healing time consideringthe involved bones. Nonunion may beattributed to injury velocity, intensity of softtissue damage, type of fracture (open orclosed), crushed bone, and bone loss. Thereare other factors involved in the unionprocessincludingtreatmentmethod,10infection and associated diseases.Metabolic and endocrine diseases, e.g.thyroid, parathyroid and osteomalaciadiseases, estrogen deficiency, Cushingdiseases, Paget’s diseases, and Malabsorptionsyndrome, are regarded as important factorsin delay of bone formation and fracturehealing process.11 The present study aims atevaluating effects of metabolic syndrome asan important and prevalent metabolicdisease on fractures healing process anddetermining the relation between unionrate and inflammatory markers, which are38JARCM/ Winter 2015; Vol. 3, No. 1increasing in this syndrome. This is the firststudy in this regard, and there are onlysome studies about role of metabolicsyndrome in increasing fractures risk,especially vertebra fractures.This analytical and descriptive study wasconducted on 48 patients with fracture oftibia and femur shafts referring toorthopedic trauma center of TabrizUniversity of Medical Sciences, Iran, from2010-2013. The traumatic patients sufferedfrom isolated and non-comminuted fracturesin their tibia and femur shafts due to lowenergy trauma resulting from falling. Thepatients were matched considering type offracture, surgical treatment, age, and gender.In this study, 24 patients with metabolicsyndrome criteria were placed in one groupand there were other 24 patients withfactures, but without any other disease orproblem in the control group. Metabolicsyndrome is detected based on the latestcriteria of National Cholesterol EducationProgram Adult Treatment Panel III orsuffering from one of three cases ofabdominal fat ( 102 cm for men and 88 cmfor women), HDL 40 mg/dl for men and 50 mg/dl for women, hypertriglyceridemia 150 mg/dl, hypertension (blood pressure 130/85 mmHg), or glucose disorder in theform of fast blood glucose 100 mg/dl. Thegroups were compared considering theunderstudy variables.Patients with open fractures, crushedfractures, soft tissue damage, any systemicdiseases as well as patients with history ofsmoking, consumption of alcohol andmineral supplements during last 6 monthsand older-than-50 years patients wereexclude from the study. To attend the study,informed letter of satisfaction was receivedfrom the patients and the study wasconfirmed by Ethics Committee of the TabrizUniversity of Medical Sciences. Consideringsimilar method and their indications, thepatients underwent orthopedic surgeryincluding open reduction and internalfixation using intramedullary nails. Before
Sadighi, et al.surgery, antibiotic prophylaxis was done forall patients through intravascular injection ofcefazolin which continued at least for 24 hafter surgery.The patients were continuously followedup for 9 months (biweekly during the 1stmonth and every month for 8 months)considering union based on radiographicevidences and clinical examinations. Thepatients of both groups demonstrated thesame rehabilitation during the 1st week, andrelative weight tolerance was seen in lowerlimb fractures after 2 days. Radiographicevidences confirmed union if it is seen at leastin two plans and clinical examinations.Nonunion cases were studied consideringinfection as the first step such that whiteblood cell, erythrocyte sedimentation rate,and CRP were checked and the patients wereexcluded from the study in case of observingany signs of infection.A volume of 20 ml venous blood samplewas taken from every participant after anovernight fast ( 8h) by a certifiedphlebotomist using standard laboratorytechniques. Blood samples were collectedinto a Vacutainer serum separator tube(SST) for analysis of lipids and glucose. Aftercomplete coagulation (30-45 min), the SSTwas centrifuged at 2500 RPM (Revolutionsper minute) for 30 min. The serum wastransferred from the spun SST into threelabeled plastic tubes: the first tube was usedfor glucose analysis, the second for lipidpanel, and the third one was stored at -70 Cto be used later for high sensitivity hs-CRP(High-sensitivityCRP).hs-CRPwasmeasured using an immunoturbidimetricassay system while other laboratorymetabolic components measured by Hitachi911 instrument produced by Japan. The waistcircumference was measured midwaybetween the lowest lib and iliac crest with aflexible anthropometric tape.The body mass index (BMI) was calculatedas weight (kg) divided by height (m). Initialexaminations of the patients included heightmeasurement (cm) using a wall-mountedheight testing instrument with the scale of 1cm and weight measurement (kg) with a Segascale. BMI was calculated in accordance withthe formula of weight (kg)/height (m2). Thepatients completed a food frequencyquestionnaire, which was designed andstandardized by Iranian Nutrition Institute.The data were statistically analyzed usingthe SPSS statistical package for Windows(version 16, SPSS Inc., Chicago, IL, USA) andwas demonstrated as mean SD (Standarddeviation) and 95% confidence interval (CI).Normality of the distribution was checked foreach variable (one sample KolmogorovSmirnov test). Independent T-test was usedto check the difference found between meansof the groups. Sensitivity of the factors wasestimated by area under the receiveroperating characteristic curve. Logisticregression model was used to determinefactors role in fractures union. Chi-squareand Fisher’s exact tests were used todetermine statistical difference of qualitativevariables. P 0.050 was considered asstatistically significant.The present study was conducted on48 patients including 32 (66.7%) male and16 (33.3%) female with age average of39.5 14.8 years. The groups were the sameconsidering age, gender, and type offracture. There were 8 women and 16 men inevery group. Furthermore, there were 14cases of tibia and 10 cases of femur isolatedfractures all treated through open reductionand internal fixation methods usingintramedullary nails. Table 1 refers tolaboratory findings of both groups.According to this table, there wasstatistically significant difference betweentwo groups considering metabolic syndromecriteria, hs-CRP level, and measuredinflammatory markers.In patients with metabolic syndromecriteria, there were 8 (33.3%) cases ofnonunion and 3 (12.5%) cases of delayedunion. However, there was not seen any caseof nonunion in the control group, but onecase of delayed union. There was statisticallysignificant difference between two groupsconsidering union rate (P 0.002).JARCM/ Winter 2015; Vol. 3, No. 139
Metabolic syndrome in fractures healingTable 1. Comparison of qualitative and laboratory findings measured in two groupsVariableAge (year)TG (mg/dl)HDL (mg/dl)SBP (mmHg)DBP (mmHg)Waist circumference (cm)FBSWeight (Kg)Height (cm)BMIhs-CRP (mg/dl)Metabolic syndrome (n 24)38.8 8.0202.5 58.538.7 11.4142.8 14.588.2 8.3109.4 12.899.8 13.6100.8 12.4156.9 4.332.9 4.24.2 1.7Normal patients (n 24)40.1 7.896.5 42.251.8 12.6106.1 9.268.7 7.270.0 22.287.7 9.487.7 9.2165.5 6.522.7 4.30.9 .010 0.001TG: Triglyceride; HDL: High-density lipoprotein; SBP: Systolic blood pressure; DBP: Diastolic blood pressure;FBS: Fasting blood sugar; BMI: Body mass index; hs-CRP: Highly sensitive C-reactive proteinAccording to the regression model,hs-CRP level played a significant role inpredicting of nonunion (P 0.001, OR 2.3and CI 95% 1.4-3.8) with sensitivity of 95%shown in figure 1 while other factors ofmetabolic syndrome did not play anyimportant role in nonunion prediction.Figure 1. Sensitivity of highly sensitive C-reactiveprotein in prediction of metabolic syndromeIn lower limbs, nonunion may occur in anybone, and it has been reported 3-8% for tibiaand femur fractures. However, open andcrushed fractures and fractures with moredislocation demonstrate a higher rate ofnonunion.9,12 There are different factorsinvolved in nonunion such as mechanicalfactors involved in fixation method of fracture.Appropriate stabilization plays an important40JARCM/ Winter 2015; Vol. 3, No. 1role in preventing from nonunion.13Metabolic, endocrine, and even nutritionalfactors may affect healing of fracturedbones.13 According to the observational data,there were controversies about the relationfound between metabolic syndrome andfractures within recent 10 years.14 Findings ofmeta-analysis studies do not strongly supportrole of metabolic syndrome in increasingfracture risk.14 According to Sun et al.metabolic syndrome does not play any role inincreasing fracture risk.14 In contrary, thestudy conducted by Everson-Rose et al.indicates to role of metabolic syndrome inphysical and functional condition of patients,which may be involved in fractures process.15Sedlár et al. evaluated role ofinflammatoryreactionsinpatientsunderwent orthopedic surgery. In this study,inflammatory reactions and inflammatorymarkers, especially CRP was increasedsignificantly.16 del Prete et al. studied 68patients with hip fracture and indicated topost-treatment increase of interleukin-6 andtumor necrosis factor alpha ory markers are increased due toinfectious nonunion and have high sensitivityin detecting infectious nonunion.18,19 Fractureand surgical treatment are involved inreactive response. Increase of CRP level seenin metabolic syndrome is associated withsome complications.20According to our findings, there is asignificant difference between the controlgroup and the patients with metabolic
Sadighi, et al.syndrome criteria considering prevalencerate of nonunion of 33.0%, which is higherthan the mentioned general prevalence rateof nonunion. In similar findings, Wright andKhan21 suggested that inflammatory markersand CRP level was associated with anincrease of complications of fracturestreatment and nonunion rate. Our study alsoreferred to the important role of CRP inpredicting nonunion with sensitivity of 95%.According to Brinker et al., metabolic andendocrine abnormalities play a significantrole in progressing and causing of nonunionin some patients.11 Pourfeizi et al. suggestthat metabolic and endocrine disordersshould be considered in nonunion oflow-energy and unjustifiable fractures.13In this study, unjustifiable nonunion inpatientswithmetabolicsyndrome(in comparison with other patients sufferingfrom similar fractures and taking benefitfrom the same treatment methods) may beattributed to metabolic disorders whereincrease of inflammatory markers levelplayed a significant role.and undergoing orthopedic surgery is higherthan healthy persons. It seems that theincrease of inflammatory markers plays asignificant role in causing and predictingnonunion in these patients.LimitationsThe present study tried to completely matchtwo groups to have results with highreliability. Considering that nonunioncauses are multifactorial, however, it wasnot possible to exactly match the groups.Nutritional condition of people is aninvolved variable, which may affect theresults.Usingafoodfrequencyquestionnaire, which was designed andstandardized by Iranian Nutrition Institute,it was tried to minimize differences inthis regard.Authors have no conflict of interest.Prevalence of nonunion in patients withmetabolic syndrome suffering from a fractureThis study was supported by students’research committee of the Tabriz Universityof Medical Sciences. Endocrine and metabolicdisease departments of the medical facultyand research vice-dean of the faculty areappreciated for their cooperation.1. Isomaa B, Almgren P, Tuomi T, Forsen B, Lahti K,Nissen M, et al. Cardiovascular morbidity andmortality associated with the metabolic syndrome.Diabetes Care 2001; 24(4): 683-9.2. Cho LW. Metabolic syndrome. Singapore Med J2011; 52(11): 779-85.3. Sumner AD, Khalil YK, Reed JF. The relationship ofperipheral arterial disease and metabolic syndromeprevalence in asymptomatic US adults 40 years andolder: results from the National Health and NutritionExamination Survey (1999-2004). J Clin Hypertens(Greenwich) 2012; 14(3): 144-8. Available 580.x4. Jia WP, Xiang KS. Current studies on newparameters of metabolic syndrome. Zhongguo YiXue Ke Xue Yuan Xue Bao 2006; 28(6): 737-9.5. Ford ES, Giles WH, Dietz WH. Prevalence of themetabolic syndrome among US adults: findings fromthe third National Health and Nutrition ExaminationSurvey. JAMA 2002; 287(3): 356-9.6. Azizi F, Salehi P, Etemadi A, Zahedi-Asl S.Prevalence of metabolic syndrome in an urbanpopulation: Tehran Lipid and Glucose Study.Diabetes Res Clin Pract 2003; 61(1): 29-37.7. Zabetian A, Hadaegh F, Azizi F. Prevalence ofmetabolic syndrome in Iranian adult population,concordance between the IDF with the ATPIII andthe WHO definitions. Diabetes Res Clin Pract 2007;77(2): 251-7. Available 018. Ishii S, Cauley JA, Greendale GA, Crandall CJ,Danielson ME, Ouchi Y, et al. C-reactive protein,bone strength, and nine-year fracture risk: data fromthe Study of Women's Health Across the Nation(SWAN). J Bone Miner Res 2013; 28(7): 1688-98.Available from: http://dx.doi.org/10.1002/jbmr.19159. Csongradi JJ, Maloney WJ. Ununited lower limbfractures. West J Med 1989; 150(6): 675-80.10. Drosos GI, Bishay M, Karnezis IA, Alegakis ary nailing of the tibial diaphysis forclosed and grade I open fractures. J Bone Joint SurgBr 2006; 88(2): 227-31. Available 6JARCM/ Winter 2015; Vol. 3, No. 141
Metabolic syndrome in fractures healing11. Brinker MR, O'Connor DP, Monla YT, EarthmanTP. Metabolic and endocrine abnormalities inpatients with nonunions. J Orthop Trauma 2007;21(8): 557-70. Available 612. Van Demark RE, Allard B, Van Demark REJ.Nonunion of a distal tibial stress fracture associatedwith vitamin D deficiency: a case report. S D Med2010; 63(3): 87-91, 93.13. Pourfeizi HH, Tabriz A, Elmi A, Aslani H.Prevalence of vitamin D deficiency and secondaryhyperparathyroidism in nonunion of traumaticfractures. Acta Med Iran 2013; 51(10): 705-10.14. Sun K, Liu J, Lu N, Sun H, Ning G. Associationbetween metabolic syndrome and bone fractures: ameta-analysis of observational studies. BMC EndocrDisord 2014; 14: 13. Available from:http://dx.doi.org/10.1186/1472-6823-14-1315. Everson-Rose SA, Paudel M, Taylor BC, Dam T,Cawthon PM, Leblanc E, et al. Metabolic syndromeand physical performance in elderly men: theosteoporotic fractures in men study. J Am GeriatrSoc 2011; 59(8): 1376-84. Available 518.x16. (16). Sedlár M, Kudrnová Z, Trca S, MazochJ, MalíkováI,KvasnickaJ,etal.Inflammatory response in
Increase of inflammatory markers is the most important problem in metabolic syndrome. C-reactive protein (CRP) is an undefined component of metabolic syndrome, and its increase is regarded as a dependent risk factor to cause complications. Considering the high
ment of the metabolic syndrome (Table 1) [10]. Prevalence of the Metabolic Syndrome and Risk for Cardiovascular Events It is estimated that approximately one fifth of the US population has the metabolic syndrome, and prevalence increases with age. The prevalence of the metabolic syndrome in a healthy American population is approxi-mately 24% [11].
relation between nut consumption and metabolic syndrome (MetS). Metabolic Syndrome is a group of cardio-metabolic risk factors, which comprise of type 2 diabetes, high fasting plasma glucose, hyperglycemia, hyper-triglycerides, low HDL cholesterol and abdominal obesity [21]. Metabolic syndrome raises the risk of diabetes by 5 times and that of
year. Metabolic syndrome (MetS) is known as an independent risk factor of coronary artery disease and stroke. Aim of the work: To investigate the relationship between metabolic syndrome and risk of ischemic stroke, whether stroke patients with metabolic syndrome differ from other ischemic stroke patients in demographic
Metabolic Syndrome and Obesity Metabolic syndrome refers to a group of risk factors that raise a person’s risk of heart disease, stroke, and other illnesses. Abdominal obesity is one component of metabolic syndrome. Other components of metabolic syndrome like high blood pressure and high blo
REVIEW Trans Fats and Metabolic Syndrome Patrick Sundin 1 Two issues affecting health today are metabolic syndrome and trans fats. Metabolic syndrome is a common condition that has no single known cause. Trans fats are fatty acids that can be artificially made and added t
latent metabolic syndrome that warrants clinic al evaluation and risk factor modification. Though intricate and still incompletely understood, the gradual expansion of knowledge about inter-relationships between the metabolic syndrome, GDM and T2DM may provide us with opportunities to screen for and detect metabolic dysfunction at various stages of
on risk of metabolic syndrome Metabolic syndrome is defined as the cluster of central obesity, insulin resistance, hyper-tension, and dyslipidemia. Metabolic syn-drome increases a patient’s risk of diabetes 5-fold and cardiovascular disease 3-fold.1 Physical inactivity and eating
A third type of stroke, known as metabolic stroke, begins with metabolic dys-function and leads to a rapid onset of lasting focal brain lesions in the absence of large vessel rupture or occlu-sion [3-5]. The mechanism by which global metabolic dysfunction leads to focal brain injury in metabolic stroke is not well understood. Pure metabolic .
