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Evaluation of the Laboratorial Profile of Elderlies with Proximal Femur Fracture by Low Energy Mechanism* * Work performed at Hospital Regional de São José Dr. Homero de Miranda Gomes, São José, SC, Brazil.

Abstract

Objective

This study aims to evaluate the laboratory results profile of elderly patients with proximal femoral fractures and to verify the relationship between these data, fracture outcome and death.

Methods

Cross-sectional study of patients admitted to the orthopedic emergency service of a referral hospital between February and April 2017 with proximal femoral fracture by low energy mechanism and submitted to laboratorial and imaging tests. Patients with suspected or confirmed pathological fracture were excluded fromthe study.

Results

Sixty-six individuals were evaluated, 44 of whom were women, all over 60 years old. Transtrochanteric fractures had the highest incidence in the study (36). Alterations of parathyroid hormone and albumin levels were significant for death (p ≤ 0.05). Length of hospital stay was not a significant factor for death.

Conclusions

Laboratory abnormalities were not related to the outcome of death. Albumin may be related to the risk of death. No laboratory result was pointed out as a facilitator in the generation of proximal femoral fractures. More studies are needed to better understand the laboratory influence on fractures and their consequences.

Keywords:
mortality; hip fractures; vitamin D; albumins; calcium

Resumo

Objetivo

Avaliar o perfil laboratorial de idosos com fratura de fêmur proximal e verificar a relação dos dados com o desfecho da própria fratura e como desfecho óbito.

Métodos

Estudo transversal de pacientes admitidos na emergência ortopédica de um hospital referência, entre os meses de fevereiro e abril de 2017, com fratura de fêmur proximal, por mecanismo de baixa energia, sendo coletados exames laboratoriais e de imagem. Foram excluídos do estudo pacientes comsuspeita ou confirmação de fratura patológica.

Resultados

Foram avaliados 66 indivíduos, sendo 44 mulheres, todos com idade superior a 60 anos. A fratura transtrocantérica apresentou maior incidência no estudo (36). Alterações do hormônio da paratireoide (PTH) e da albumina foram significativos para óbito (p ≤ 0,05). O tempo de internação não foi fator significativo para óbito.

Conclusões

Alterações laboratoriais não estavam relacionadas ao desfecho de óbito. A albumina pode estar relacionada ao risco de óbito. Nenhum resultado laboratorial foi apontado como facilitador na geração de fraturas de fêmur proximal. Mais estudos são necessários para poder entender melhor a influência do quadro laboratorial do paciente na ocorrência de fraturas e suas consequências.

Palavras-chave:
mortalidade; fraturas do quadril; vitamina D; albuminas; cálcio

Introduction

Populational aging is a reality that has been observed recently. Over the last 20 years, there was a 5% increase in people aged ≥ 60 years, reaching approximately 12% of the total live individuals. This statistic leads to the greater attention required in this age group, which includes higher risk of proximal femoral fractures, referred to as hip fracture.11 Sakaki MH, Oliveira AR, Coelho FF, Leme LEG, Suzuki I, Amatuzzi MM. Estudo da mortalidade na fratura do fêmur proximal em idosos. Acta Ortop Bras 2004;12(04):242-249 22 Mesquita GV, Lima M, Santos AM, Alves EL, Brito JNPO, Martins MC. Morbimortalidade em idosos por fratura proximal do fêmur. Texto Contexto Enferm 2009;18(01):67-73 33 Astur DC, Arliani GG, Balbachevsky D, Fernandes HJ, Reis FB. Fratura da extremidade proximal do fêmur tratadas no Hospital São Paulo/Unifesp: estudo epidemiológico. Rev BrasMed 2013;68 (04):11-15

Proximal femoral fractures in elderly patients result in high morbidity and mortality. In an observational study carried out in 2015 by Daniachi et al,44 Daniachi D, dos SantosNetto A, OnoNK,Guimarães RP, Polesello GC, Honda EK. Epidemiology of fractures of the proximal third of the femur in elderly patients. Rev Bras Ortop 2015;50(04):371-377 from 113 patients, 92.9% suffered fractures associated with low energy traumas, mostly occurring at home from fall from own height. In a literature review regarding the main associated risk factors, the variables most associated with fracture and/or death after fracture were advanced age, and changes in calcium, albumin and vitamin D metabolism.33 Astur DC, Arliani GG, Balbachevsky D, Fernandes HJ, Reis FB. Fratura da extremidade proximal do fêmur tratadas no Hospital São Paulo/Unifesp: estudo epidemiológico. Rev BrasMed 2013;68 (04):11-15 44 Daniachi D, dos SantosNetto A, OnoNK,Guimarães RP, Polesello GC, Honda EK. Epidemiology of fractures of the proximal third of the femur in elderly patients. Rev Bras Ortop 2015;50(04):371-377 55 Rocha MA, Azer HW, Nascimento VDG. Evolução funcional nas fraturas da extremidade proximal do fêmur. Acta Ortop Bras 2009;17(01):17-21 66 Cauley JA, Lacroix AZ,Wu L, Horwitz M, Danielson ME, Bauer DC, et al. Serum 25-hydroxyvitamin D concentrations and risk for hip fractures. Ann Intern Med 2008;149(04):242-250 77 Uzoigwe CE, Venkatesan M, Smith R, Burnand HG, Young PS, Cheesman CL, et al. Serum lactate is a prognostic indicator in patients with hip fracture. Hip Int 2012;22(05):580-584

A Chinese study by Li et al showed that patients with proximal femoral fractures had serum calcium levels lower than reference values.88 Li PF, LinZL, Pang ZH, ZengYR.Does serumcalciumrelate to different types of hip fracture? A retrospective study. Chin J Traumatol 2016; 19(05):275-277 Similarly, Ramason et al99 Ramason R, Selvaganapathi N, Ismail NH, Wong WC, Rajamoney GN, Chong MS. Prevalence of vitamin d deficiency in patientswith hip fracture seen in an orthogeriatric service in sunny singapore. Geriatr Orthop Surg Rehabil 2014;5(02):82-86 reported that these patients had vitamin D deficiency or insufficiency, and some fractures resulted in death. Another study showed that calcium and vitamin D alterations may influence parathyroid hormone (PTH) levels, which was also related to death.1010 Madsen CM, Jørgensen HL, Lind B, Ogarrio HW, Riis T, Schwarz P, et al. Secondary hyperparathyroidism and mortality in hip fracture patients compared to a control group from general practice. Injury 2012;43(07):1052-1057 Koval et al1111 Koval KJ,Maurer SG, Su ET, Aharonoff GB, Zuckerman JD. The effects of nutritional status on outcome after hip fracture. J Orthop Trauma 1999;13(03):164-169 believe that the nutritional status of the patient may influence mortality and that hypoalbuminemia may be a marker.

Although the relationship of laboratorial and radiological parameters of patients with proximal femoral fracture have been investigated, few studies have addressed this issue. This study aims to outline the bone metabolic profile of elderly patients with hip fracture and to evaluate possible causes that may facilitate its outcome.

Material and Methods

A cross-sectional study was conducted with 66 patients. These patients met the following inclusion criteria: proximal femoral fracture, aged 60 years old or more and visited the orthopedics and traumatology service of a reference hospital between February 02 and April 02, 2017.

The work was approved by the ethics committee of the institution.

Patients whose laboratory tests were not performed or registered at the hospital system, and those with history, suspicion, or confirmation of pathological fracture caused by tumors were excluded.

The information from these patients was collected from the electronic medical record of the hospital as authorized by the institution's medical records guardian. The variables analyzed included gender, age, fracture type, serum calcium level, serum PTH level, serum 25-hydroxy-vitamin D level and serum albumin level.

The material for laboratory tests was collected at the patient's arrival in the hospital and sent to a single laboratory, which analyzed all the samples from this study.

The collected data was entered into Excel (Microsoft Corp., Redmond, WA, USA) spreadsheets and then exported to SPSS Statistics for Windows, Version 15.0 (SPSS Inc., Chicago, IL, USA) for analysis. The data were presented using descriptive statistics; qualitative variables were expressed as absolute numbers and frequencies, whereas quantitative variables were expressed as mean and standard deviation. Categorical variables were tested by chi-squared test or Fisher exact test, when appropriate, while numerical variables were tested by Student t-test. The significance level was set as p≤ 0.05.

Results

The present study evaluated 66 individuals ˃ 60 years old. As shown in Table 1, 66.7% (n = 44) of the patients were female; their average age was 78.8 years old (n = 66), with a standard deviation (SD) of 9.2. Of the individuals studied, 15.2% (n = 10) died at admission, and the others were discharged after hospital treatment of the fracture.

Table 1
Sociodemographic and clinical characteristics of the patients seen during the study

Supplementary tests requested at the patient's admission are listed in Table 2, whereas their association with death outcome is presented in Table 3.

Table 2
Characteristics of supplementary test samples at patient's admission

Table 3
Comparison of average laboratorial test results regarding outcome variable (death and non-death)

When comparing the means of laboratory test results with death or non-death outcome, it was observed that PTH and albumin values were statistically significant (p0.05), with PTH showing a mean difference from 58.0 pg/mL, among those who did not die, to 93.1 pg/mL, among those who died; regarding albumin, those who died had a mean level of 2.7 pg/mL, and those that did not die, 3.3 pg/mL.

The length of hospital stay was not a determining cause for death in this sample.

The laboratorial values of vitamin D did not present variations when compared between genders.

There were no statistically significant differences (p> 0.05) when comparing the mean values of laboratory test results with fracture types, as shown in Table 4.

Table 4
Comparison of average laboratorial test results regarding fracture classification

There was no association between classification variables of the Dorr Index and the fracture type (p= 0.828). Similarly, the type of fracture showed no association with death (p= 0.555) or gender (p= 0.191).

Discussion

Studies researching the association between hip fractures and the results of laboratory tests are studied to try to estimate possible causes and thus avoid the consequences of this association.99 Ramason R, Selvaganapathi N, Ismail NH, Wong WC, Rajamoney GN, Chong MS. Prevalence of vitamin d deficiency in patientswith hip fracture seen in an orthogeriatric service in sunny singapore. Geriatr Orthop Surg Rehabil 2014;5(02):82-86 1010 Madsen CM, Jørgensen HL, Lind B, Ogarrio HW, Riis T, Schwarz P, et al. Secondary hyperparathyroidism and mortality in hip fracture patients compared to a control group from general practice. Injury 2012;43(07):1052-1057 1212 Roddam AW, Neale R, Appleby P, Allen NE, Tipper S, Key TJ. Association between plasma 25-hydroxyvitamin D levels and fracture risk: the EPIC-Oxford study. Am J Epidemiol 2007;166 (11):1327-1336 In the 66 individuals evaluated, mostly female, this work pointed out that transtrochanteric fractures are the most frequent in the studied age group (individuals ˃ 60 years old). There was no relationship between fracture type and death outcome. Regarding laboratory tests, it was observed that the patients who died had high levels of PTH and reduced albumin levels when compared to the patients who did not die. The length of stay was not related to mortality during hospitalization.

In a study conducted in Guangzhou, China, Li et al88 Li PF, LinZL, Pang ZH, ZengYR.Does serumcalciumrelate to different types of hip fracture? A retrospective study. Chin J Traumatol 2016; 19(05):275-277 observed that in patients hospitalized with proximal femoral fracture (196), those with intertrochanteric fractures presented serum calcium levels lower than the reference standard. Larrosa et al,1313 Larrosa M, Gomez A, Casado E, Moreno M, Vázquez I, Orellana C, et al. Hypovitaminosis D as a risk factor of hip fracture severity. Osteoporos Int 2012;23(02):607-614 in their sample of 128 patients with femoral neck fractures and 196 patients with intertrochanteric fractures, did not observe any evidence of laboratory abnormality in calcium levels at hospital admission. In the aforementioned studies, the mortality outcome was not cited. Our study noted that the laboratory calcium profile was not statistically significant in proximal femoral fractures and that the death outcome was not relevant either.

Regarding vitamin D, the present study did not reveal significant relationships in the death and non-death outcomes, nor in relation to the several fracture types or gender. This laboratory profile has been studied and attributed as altered in patients with hip fracture. Ramason et al,99 Ramason R, Selvaganapathi N, Ismail NH, Wong WC, Rajamoney GN, Chong MS. Prevalence of vitamin d deficiency in patientswith hip fracture seen in an orthogeriatric service in sunny singapore. Geriatr Orthop Surg Rehabil 2014;5(02):82-86 in a sample of 412 patients with fractures, found out that 57.5% of the hospitalized patients had vitamin D deficiency, 34.5% showed vitamin D insufficiency, and 8% died. Another evidence of this study was that patients who live in nursing homes have lower vitamin D levels at admission. In another controlled study, Guerra et al1414 Guerra MT, Feron ET, Viana RD, Maboni J, Pastore SI, Castro CC. Elderly with proximal hip fracture present significantly lower levels of 25-hydroxyvitamin D. Rev Bras Ortop 2016;51(05): 583-588 evaluated 110 patients with hip fracture, 54.5% of whom presented vitamin D deficiency, and 18.2% with vitamin D insufficiency. The authors show that there was a statistically significant difference between the fracture and the control groups for patients older than 70 years, which did not occur in patients aged 60 to 65 years. Gumieiro et al,1515 Gumieiro DN, Pereira GJ, Minicucci MF, Ricciardi CE, Damasceno ER, Funayama BS. Associations of vitamin D deficiency with postoperative gait and mortality among patients with fractures of the proximal femur. Rev Bras Ortop 2015;50(02):153-158 in an analysis with 88 patients with hip fracture, found no difference between vitamin D values when fracture types and deambulation capacity were compared.

After evaluating serum PTH levels in a sample with 562 hip fractures, Madsen et al1010 Madsen CM, Jørgensen HL, Lind B, Ogarrio HW, Riis T, Schwarz P, et al. Secondary hyperparathyroidism and mortality in hip fracture patients compared to a control group from general practice. Injury 2012;43(07):1052-1057 believe that death is related to the sum of laboratory changes in vitamin D and calcium levels. These authors do not state that the single PTH alteration indicates a risk of death, but that this may be an indicator of poor health, generating an instability factor that results in death. Di Monaco et al1616 Di Monaco M, Vallero F, Di Monaco R, Tappero R, Cavanna A. 25- hydroxyvitamin D, parathyroid hormone, and functional recovery after hip fracture in elderly patients. J Bone MinerMetab 2006;24 (01):42-47 and Fischer et al1717 Fisher A, Goh S, SrikusalanukulW, Davis M. Elevated serumPTHis independently associated with poor outcomes in older patients with hip fracture and vitamin D inadequacy. Calcif Tissue Int 2009;85(04):301-309 corroborate the analysis that PTH alteration may be a risk factor for death, but their small sample is a limiting factor. In the present study, PTH alteration shows significant values for death; however, as in Monaco et al1616 Di Monaco M, Vallero F, Di Monaco R, Tappero R, Cavanna A. 25- hydroxyvitamin D, parathyroid hormone, and functional recovery after hip fracture in elderly patients. J Bone MinerMetab 2006;24 (01):42-47 and Fischer et al,1717 Fisher A, Goh S, SrikusalanukulW, Davis M. Elevated serumPTHis independently associated with poor outcomes in older patients with hip fracture and vitamin D inadequacy. Calcif Tissue Int 2009;85(04):301-309 the sample size may be a limitation.

Koval et al1111 Koval KJ,Maurer SG, Su ET, Aharonoff GB, Zuckerman JD. The effects of nutritional status on outcome after hip fracture. J Orthop Trauma 1999;13(03):164-169 correlated hypoalbuminemia with late mortality and state that these low levels are directly caused by an inadequate nutritional status. Grimes et al1818 Grimes JP, Gregory PM, Noveck H, ButlerMS, Carson JL. The effects of time-to-surgery on mortality and morbidity in patients following hip fracture. Am J Med 2002;112(09):702-709 did not relate hospitalization time to death in their analysis with 8,383 patients. Parker et al,1919 Parker MJ, Handoll HH, Bhargara A. Conservative versus operative treatment for hip fractures. Cochrane Database Syst Rev 2000; (04):CD000337 in a meta-analysis with 428 patients, demonstrated that surgical treatment does not decrease the risk of death when compared to the conservative treatment. Sakaki et al,11 Sakaki MH, Oliveira AR, Coelho FF, Leme LEG, Suzuki I, Amatuzzi MM. Estudo da mortalidade na fratura do fêmur proximal em idosos. Acta Ortop Bras 2004;12(04):242-249 in a literature review, concluded that there are four major influential factors in mortality, that is, advanced age, association of diverse comorbidities, male gender, and cognitive deficits. In our analysis, it was observed that albumin and PTH levels alterations are significantly related to death, while the hospitalization time did not have any significance.

It is important to note that, without vitamin D, only 10 to 15% of dietary calcium will be absorbed at the intestinal level, resulting in a forced elevation of PTH levels and a rebound effect at the renal tubular level, generating calcium reabsorption. The increased PTH level causes bone resorption due to osteoclasts stimulation, leading to osteopenia and osteoporosis, which increases the risk of fractures.2020 Holick MF. Vitamin D deficiency. N Engl J Med 2007;357(03): 266-281 One study showed that 3,270 elderly individuals who received 800 IU of vitamin D and 1,200 mg of calcium in a daily replacement dose for 3 years had a 43% reduction in hip fractures incidence.2121 ChapuyMC, Arlot ME, Duboeuf F, Brun J, Crouzet B, Arnaud S, et al. Vitamin D3 and calcium to prevent hip fractures in elderly women. N Engl J Med 1992;327(23):1637-1642 In a meta-analysis comparing the daily replacement with 400 IU or 700 to 800 IU of vitamin D, it was observed that low doses did not alter fracture outcomes, but that high doses (700–800 IU) reduced the relative risk of hip fracture by 26%.2222 Bischoff-Ferrari HA, Giovannucci E,WillettWC, Dietrich T,Dawson- Hughes B. Estimation of optimal serum concentrations of 25- hydroxyvitamin D for multiple health outcomes. Am J Clin Nutr 2006;84(01):18-28. [Erratum. Am J Clin Nutr 2006;84:1253 This shows that there is an intimate bone metabolic relationship; therefore, the isolated analysis of PTH, vitamin D, and calcium can generate a false negative result and a misinterpretation of laboratorial findings. The dietary relationship with hypoalbuminemia agrees with the aforementioned alterations, corroborating the malnutrition picture and reduced calcium ingestion.

These profile parameters were analyzed because they are the most studied variables describe in the literature as death-related complications. The literature also associates such parameters with cognitive diseases and multiple clinical comorbidities, but this correlation was not studied because of the difficulty in performing a multidisciplinary follow-up in our service due to scientific reasons. The present study may be confined to limited outcomes because of the small number of patients studied and the lack of long-term follow-up. Blood collection for laboratory analysis was performed in a similar way for all patients, and, therefore, it is not a limiting source in their results. Data analysis was performed by a single trained professional, with no bias. The average time of hospitalization may present divergent results from the literature, and, in our service, the reservation of intensive care beds, when necessary, is difficult due to the large number of polytrauma patients admitted.

Conclusions

The death outcome indicates that albumin level changes, possibly related to malnutrition, may increase the risk. In the present study, the increased PTH level showed a tendency to death, but the low number of patients studied may limit this result. Hip fracture-related bone metabolic analyses need further studies to complement the results already described in the literature for a better understanding of the relationship of laboratory results with fractures and their consequences.

References

  • 1
    Sakaki MH, Oliveira AR, Coelho FF, Leme LEG, Suzuki I, Amatuzzi MM. Estudo da mortalidade na fratura do fêmur proximal em idosos. Acta Ortop Bras 2004;12(04):242-249
  • 2
    Mesquita GV, Lima M, Santos AM, Alves EL, Brito JNPO, Martins MC. Morbimortalidade em idosos por fratura proximal do fêmur. Texto Contexto Enferm 2009;18(01):67-73
  • 3
    Astur DC, Arliani GG, Balbachevsky D, Fernandes HJ, Reis FB. Fratura da extremidade proximal do fêmur tratadas no Hospital São Paulo/Unifesp: estudo epidemiológico. Rev BrasMed 2013;68 (04):11-15
  • 4
    Daniachi D, dos SantosNetto A, OnoNK,Guimarães RP, Polesello GC, Honda EK. Epidemiology of fractures of the proximal third of the femur in elderly patients. Rev Bras Ortop 2015;50(04):371-377
  • 5
    Rocha MA, Azer HW, Nascimento VDG. Evolução funcional nas fraturas da extremidade proximal do fêmur. Acta Ortop Bras 2009;17(01):17-21
  • 6
    Cauley JA, Lacroix AZ,Wu L, Horwitz M, Danielson ME, Bauer DC, et al. Serum 25-hydroxyvitamin D concentrations and risk for hip fractures. Ann Intern Med 2008;149(04):242-250
  • 7
    Uzoigwe CE, Venkatesan M, Smith R, Burnand HG, Young PS, Cheesman CL, et al. Serum lactate is a prognostic indicator in patients with hip fracture. Hip Int 2012;22(05):580-584
  • 8
    Li PF, LinZL, Pang ZH, ZengYR.Does serumcalciumrelate to different types of hip fracture? A retrospective study. Chin J Traumatol 2016; 19(05):275-277
  • 9
    Ramason R, Selvaganapathi N, Ismail NH, Wong WC, Rajamoney GN, Chong MS. Prevalence of vitamin d deficiency in patientswith hip fracture seen in an orthogeriatric service in sunny singapore. Geriatr Orthop Surg Rehabil 2014;5(02):82-86
  • 10
    Madsen CM, Jørgensen HL, Lind B, Ogarrio HW, Riis T, Schwarz P, et al. Secondary hyperparathyroidism and mortality in hip fracture patients compared to a control group from general practice. Injury 2012;43(07):1052-1057
  • 11
    Koval KJ,Maurer SG, Su ET, Aharonoff GB, Zuckerman JD. The effects of nutritional status on outcome after hip fracture. J Orthop Trauma 1999;13(03):164-169
  • 12
    Roddam AW, Neale R, Appleby P, Allen NE, Tipper S, Key TJ. Association between plasma 25-hydroxyvitamin D levels and fracture risk: the EPIC-Oxford study. Am J Epidemiol 2007;166 (11):1327-1336
  • 13
    Larrosa M, Gomez A, Casado E, Moreno M, Vázquez I, Orellana C, et al. Hypovitaminosis D as a risk factor of hip fracture severity. Osteoporos Int 2012;23(02):607-614
  • 14
    Guerra MT, Feron ET, Viana RD, Maboni J, Pastore SI, Castro CC. Elderly with proximal hip fracture present significantly lower levels of 25-hydroxyvitamin D. Rev Bras Ortop 2016;51(05): 583-588
  • 15
    Gumieiro DN, Pereira GJ, Minicucci MF, Ricciardi CE, Damasceno ER, Funayama BS. Associations of vitamin D deficiency with postoperative gait and mortality among patients with fractures of the proximal femur. Rev Bras Ortop 2015;50(02):153-158
  • 16
    Di Monaco M, Vallero F, Di Monaco R, Tappero R, Cavanna A. 25- hydroxyvitamin D, parathyroid hormone, and functional recovery after hip fracture in elderly patients. J Bone MinerMetab 2006;24 (01):42-47
  • 17
    Fisher A, Goh S, SrikusalanukulW, Davis M. Elevated serumPTHis independently associated with poor outcomes in older patients with hip fracture and vitamin D inadequacy. Calcif Tissue Int 2009;85(04):301-309
  • 18
    Grimes JP, Gregory PM, Noveck H, ButlerMS, Carson JL. The effects of time-to-surgery on mortality and morbidity in patients following hip fracture. Am J Med 2002;112(09):702-709
  • 19
    Parker MJ, Handoll HH, Bhargara A. Conservative versus operative treatment for hip fractures. Cochrane Database Syst Rev 2000; (04):CD000337
  • 20
    Holick MF. Vitamin D deficiency. N Engl J Med 2007;357(03): 266-281
  • 21
    ChapuyMC, Arlot ME, Duboeuf F, Brun J, Crouzet B, Arnaud S, et al. Vitamin D3 and calcium to prevent hip fractures in elderly women. N Engl J Med 1992;327(23):1637-1642
  • 22
    Bischoff-Ferrari HA, Giovannucci E,WillettWC, Dietrich T,Dawson- Hughes B. Estimation of optimal serum concentrations of 25- hydroxyvitamin D for multiple health outcomes. Am J Clin Nutr 2006;84(01):18-28. [Erratum. Am J Clin Nutr 2006;84:1253
  • *
    Work performed at Hospital Regional de São José Dr. Homero de Miranda Gomes, São José, SC, Brazil.

Publication Dates

  • Publication in this collection
    07 Oct 2019
  • Date of issue
    Jul-Aug 2019

History

  • Received
    21 Mar 2018
  • Accepted
    17 July 2018
Sociedade Brasileira de Ortopedia e Traumatologia Al. Lorena, 427 14º andar, 01424-000 São Paulo - SP - Brasil, Tel.: 55 11 2137-5400 - São Paulo - SP - Brazil
E-mail: rbo@sbot.org.br