INCREASE IN SERUM CYTOKINE CONCENTRATION FOLLOWING GERIATRIC HIP FRACTURE – CLINICAL RELEVANCE

Authors

  • Marko Spasov University Clinic for Traumatology, Orthopaedic Diseases, Anaesthesia, Reanimation, Intensive Care and Emergency Centre - Skopje, Republic of North Macedonia Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, Republic of North Macedonia https://orcid.org/0000-0002-4553-7667
  • Stefan Krstevski University Clinic for Traumatology, Orthopaedic Diseases, Anaesthesia, Reanimation, Intensive Care and Emergency Centre - Skopje, Republic of North Macedonia
  • Oliver Arsovski University Clinic for Traumatology, Orthopaedic Diseases, Anaesthesia, Reanimation, Intensive Care and Emergency Centre - Skopje, Republic of North Macedonia Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, Republic of North Macedonia https://orcid.org/0000-0003-0595-288X
  • Ivan Eftimov Public General Hospital - Department for Orthopedics and Traumatology, Strumica, Republic of North Macedonia
  • Dino Hajradinovikj University Clinic for Traumatology, Orthopaedic Diseases, Anaesthesia, Reanimation, Intensive Care and Emergency Centre - Skopje, Republic of North Macedonia
  • Andreja Gavrilovski University Clinic for Traumatology, Orthopaedic Diseases, Anaesthesia, Reanimation, Intensive Care and Emergency Centre - Skopje, Republic of North Macedonia Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, Republic of North Macedonia https://orcid.org/0009-0003-3218-9194

Keywords:

hip, geriatrics, surgery, cytokine

Abstract

Introduction: Hip fractures are the most common operatively treated skeletal injuries, predominantly affecting individuals over 65 years of age who often have multiple comorbidities. A global increase in hip fracture incidence has been observed, accompanied by unfavorable outcomes, including reduced life expectancy. This study aimed to analyze the inflammatory response after hip fracture and surgery in patients aged over 65 years, and its association with functional outcomes. 

Methods: This prospective, non-randomized study included patients with AO type 31A and 31B hip fractures admitted for surgical treatment. Eligible participants had demographic and clinical parameters recorded, including ASA scores, pharmacological therapy, and Katz Index scores. Blood samples were collected at four time points: within 10 hours post-injury, 48-60 hours post-surgery, on postoperative day seven, and day 30. Laboratory analyses included IL-1β, IL-6, and IL-10 levels. Follow-up data, including survival, mobility, pain, and quality of life (SF-12), were collected at 12 months. 

Results: The study included 40 patients (median age: 78 years; 60% female). By the 12-month follow-up, 32 participants survived, while 8 died within 4-9 months. Deceased patients had significantly higher serum levels of IL-1β, IL-6, and IL-10 at all time-points. IL-6 was identified as an independent predictor of reduced mobility (p=0.013) and quality of life (p=0.009). 

Conclusion: Elevated serum inflammatory markers were associated with poorer quality of life, mobility, and survival. These findings suggest potential for targeted rehabilitation programs and preventive strategies to improve outcomes in geriatric hip fracture patients. 

References

Johnell O, Kanis JA. An estimate of the worldwide prevalence and disability associated with osteoporotic fractures. Osteoporos Int 2006; 17(12): 1726-1733. doi: 10.1007/s00198-006-0172-4.

Zorg LNA (2014) LTR factsheet 2012, acute hospitalizations for hip fractures. http://www.lnaz.nl/cms/LTR_2012_Factsheet-heupfracture_140611.pdf.

Kanis JA, Oden A, McCloskey EV, Johansson H, Wahl DA, Cooper C, et al. A systematic review of hip fracture incidence and probability of fracture worldwide. Osteoporos Int 2012; 23(9): 2239-2256. doi: 10.1007/s00198-012-1964-3.

Gullberg B, Johnell O, Kanis JA. World-wide projections for hip fracture. Osteoporos Int 1997; 7(5): 407-413. doi: 10.1007/pl00004148.

Meessen JM, Pisani S, Gambino ML, Bonarrigo D, van Schoor NM, Fozzato S, et al. Assessment of mortality risk in the elderly patients after proximal femoral fracture. Orthopedics 2014; 37(2):e194-e200. doi: 10.3928/01477447-20140124-25.

Hu F, Jiang C, Shen J, Tang P, Wang Y. Preoperative predictors for mortality following hip fracture surgery: a systematic review and metaanalysis. Injury 2012; 43(6): 676-685. doi: 10.1016/j.injury.2011.05.017.

Cree M, Soskolne CL, Belseck E, Hornig J, McElhaney JE, Brant R, et al. Mortality and institutionalization following hip fracture. J Am Geriatr Soc 2000; 48(3): 283-288. doi: 10.1111/j.1532-5415.2000.tb02647.x.

Kistler EA, Nicholas JA, Kates SL, Friedman SM. Frailty and short-term outcomes in patients with hip fracture. Geriatr Orthop Surg Rehabil 2015; 6(3): 209-214. doi: 10.1177/2151458515591170.

Endo A, Baer HJ, Nagao M, Weaver MJ. Prediction model of in-hospital mortality after hip fracture surgery. J Orthop Trauma 2018; 32(1): 34-38. doi: 10.1097/BOT.0000000000001026.

Kalmet PH, Koc BB, Hemmes B, Ten Broeke RH, Dekkers G, Hustinx P, et al. Effectiveness of a multidisciplinary clinical pathway for elderly patients with hip fracture: a multicenter comparative cohort study. Geriatric Orthop Surg Rehabil 2016; 7(2):81–85. https://doi.org/10.1177/2151458516 . 645633 .

Makridis KG, Karachalios T, Kontogeorgakos VA, Badras LS, Malizos KN. The effect of osteoporotic treatment on the functional outcome, re-fracture rate, quality of life and mortality in patients with hip fractures: a prospective functional and clinical outcome study on 520 patients. Injury 2015; 46(2): 378-383. doi: 10.1016/j.injury.2014.11.031.

Rosell PA, Parker MJ. Functional outcome after hip fracture. A 1-year prospective outcome study of 275 patients. Injury 2003; 34(7): 529-532. doi: 10.1016/s0020-1383(02)00414-x.

Kammerlander C, Gosch M, Kammerlander-Knauer U, Luger TJ, Blauth M, Roth T. Long-term functional outcome in geriatric hip fracture patients. Arch Orthop Trauma Surg 2011; 131(10): 1435-1444. doi: 10.1007/s00402-011-1313-6.

Petros RSB, Ferreira PEV, Petros RSB. Influence of proximal femur fractures in the autonomy and mortality of elderly patients submitted to osteosynthesis with cephalomedullary nail. Rev Bras Ortop 2017; 52(Suppl 1): 57-62. doi: 10.1016/j.rboe.2017.08.014.

Aarden JJ, van der Esch M, Engelbert RHH, van der Schaaf M, de Rooij SE, Buurman BM. Hip fractures in older patients: trajectories of disability after surgery. J Nutr Health Aging 2017; 21(7): 837-842. doi: 10.1007/s12603-016-0830-y.

Al-Ani AN, Samuelsson B, Tidermark J, Norling A, Ekström W, Cederholm T, et al. Early operation on patients with a hip fracture improved the ability to return to independent living. A prospective study of 850 patients. J Bone Joint Surg Am 2008; 90(7): 1436-1442. doi: 10.2106/JBJS.G.00890.

Haentjens P, Magaziner J, Colon-Emeric CS, Vanderschueren D, Milisen K, Velkeniers B, et al. Meta-analysis: excess mortality after hip fracture among older women and men. Ann Intern Med 2010; 152(6): 380-390. doi: 10.7326/0003-4819-152-6-201003160-00008.

Rushton PR, Reed MR, Pratt RK. Independent validation of the Nottingham Hip Fracture Score and identification of regional variation in patient risk within England. Bone Joint J 2015; 97-B(1): 100-103. doi: 10.1302/0301-620X.97B1.34670.

Doherty WJ, Stubbs TA, Chaplin A, Reed MR, Sayer AA, Witham MD, Sorial AK. Prediction of postoperative outcomes following hip fracture surgery: independent validation and recalibration of the Nottingham hip fracture score. JAMDA 22 (2021) 663e669 https://doi.org/10.1016/j.jamda.2020.07.013 .

Johns WL, Strong B, Kates S, Patel NK. POSSUM and P-POSSUM scoring in hip fracture mortalities. Geriatr Orthop Surg Rehabil 2020; 11: 2151459320931674. doi: 10.1177/2151459320931674.

Jonsson MH, Bentzer P, Turkiewicz A, Hommel A. Accuracy of the Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity score and the Nottingham risk score in hip fracture patients in Sweden - A prospective observational study. Acta Anaesthesiol Scand 2018; 62(8): 1057-1063. doi: 10.1111/aas.13131.

Nijmeijer WS, Folbert EC, Vermeer M, Slaets JP, Hegeman JH. Prediction of early mortality following hip fracture surgery in frail elderly: the Almelo Hip Fracture Score (AHFS). Injury 2016; 47(10): 2138-2143. doi: 10.1016/j.injury.2016.07.022.

Karres J, Heesakkers NA, Ultee JM, Vrouenraets BC. Predicting 30-day mortality following hip fracture surgery: evaluation of six risk predictions models. Injury 2015; 46(2): 371-377. doi: 10.1016/j.injury.2014.11.004.

Kenzora JE, McCarthy RE, Lowell JD, Sledge CB. Hip fracture mortality. Relation to age, treatment, preoperative illness, time of surgery, and complications. Clin Orthop Relat Res 1984;(186): 45-56. PMID: 6723159.

Mimoz O, Benoist JF, Edouard AR, Assicot M, Bohuon C, Samii K. Procalcitonin and C-reactive protein during the early posttraumatic systemic inflammatory response syndrome. Intensive Care Med 1998; 24(2): 185-188. doi: 10.1007/s001340050543.

Fox KM, Magaziner J, Hebel JR, Kenzora JE, Kashner TM. Intertrochanteric versus femoral neck hip fractures: differential characteristics, treatment, and sequelae. J Gerontol A Biol Sci Med Sci 1999; 54(12): M635-M640. doi: 10.1093/gerona/54.12.m635.

Cornwall R, Gilbert MS, Koval KJ, Strauss E, Siu AL. Functional outcomes and mortality vary among different types of hip fractures: a function of patient characteristics. Clin Orthop Relat Res 2004; (425): 64-71. doi: 10.1097/01.blo.0000132406.37763.b3.

Shah MR, Aharonoff GB, Wolinsky P, Zuckerman JD, Koval KJ. Outcome after hip fracture in individuals ninety years of age and older. J Orthop Trauma 2001; 15(1): 34-39. doi: 10.1097/00005131-200101000-00007.

Sharma H, Vashishtha P, Sharma R. Gender differences in patients with hip fracture: a greater risk of morbidity and mortality in men. J Orthop Trauma 2005;19(5): 365-366. PMID: 15891551.

Rosencher N, Vielpeau C, Emmerich J, Fagnani F, Samama CM; ESCORTE group. Venous thromboembolism and mortality after hip fracture surgery: the ESCORTE study. J Thromb Haemost 2005; 3(9): 2006-2014. doi: 10.1111/j.1538-7836.2005.01545.x.

de Luise C, Brimacombe M, Pedersen L, Sørensen HT. Chronic obstructive pulmonary disease and mortality following hip fracture: a population-based cohort study. Eur J Epidemiol 2008; 23(2): 115-122. doi: 10.1007/s10654-007-9211-5.

Casaletto JA, Gatt R. Post-operative mortality related to waiting time for hip fracture surgery. Injury. 2004;35(2):114-20. doi: 10.1016/s0020-1383(03)00210-9. PMID: 14736466.

Huang YS, Yang ZC, Liu XS, Chen FM, He BB, Li A, et al. Serial experimental and clinical studies on the pathogenesis of multiple organ dysfunction syndrome (MODS) in severe burns. Burns 1998; 24(8): 706-716. doi: 10.1016/s0305-4179(98)00123-5.

Keel M, Trentz O. Pathophysiology of polytrauma. Injury 2005; 36(6): 691-709. doi: 10.1016/j.injury.2004.12.037.

Visser T, Pillay J, Koenderman L, Leenen LP. Postinjury immune monitoring: can multiple organ failure be predicted? Curr Opin Crit Care 2008; 14(6): 666-672. doi: 10.1097/MCC.0b013e3283196522.

Dimopoulou I, Orfanos S, Kotanidou A, Livaditi O, Giamarellos-Bourboulis E, Athanasiou C, et al. Plasma pro- and anti-inflammatory cytokine levels and outcome prediction in unselected critically ill patients. Cytokine 2008; 41(3): 263-267. doi: 10.1016/j.cyto.2007.11.019.

McDaniel DO, Hamilton J, Brock M, May W, Calcote L, Tee LY, et al. Molecular analysis of inflammatory markers in trauma patients at risk of postinjury complications. J Trauma 2007; 63(1): 147-57; discussion 157-8. doi: 10.1097/TA.0b013e31806bf0ab.

Oda S, Hirasawa H, Shiga H, Nakanishi K, Matsuda K, Nakamua M. Sequential measurement of IL-6 blood levels in patients with systemic inflammatory response syndrome (SIRS)/sepsis. Cytokine 2005; 29(4): 169-175. doi: 10.1016/j.cyto.2004.10.010.

Rodríguez-Gaspar M, Santolaria F, Jarque-López A, González-Reimers E, Milena A, de la Vega MJ, et al. Prognostic value of cytokines in SIRS general medical patients. Cytokine 2001; 15(4): 232-236. doi: 10.1006/cyto.2001.0932.

Meinberg EG, Agel J, Roberts CS, Karam MD, Kellam JF. Fracture and Dislocation Classification Compendium-2018. J Orthop Trauma 2018; 32(Suppl 1): S1-S170. doi: 10.1097/BOT.0000000000001063.

Doyle DJ, Garmon EH. American Society of Anesthesiologists Classifcation (ASA Class). In: StatPearls Publishing LLC., Treasure Island (FL) 2018.

Katz S, Akpon CA. A measure of primary sociobiological functions. Int J Health Serv 1976; 6(3): 493-508. doi: 10.2190/UURL-2RYU-WRYD-EY3K.

Jakobsson U. Using the 12-item Short Form health survey (SF-12) to measure quality of life among older people. Aging Clin Exp Res 2007; 19(6): 457-464. doi: 10.1007/BF03324731.

Baëhl S, Garneau H, Le Page A, Lorrain D, Viens I, Svotelis A, et al. Altered neutrophil functions in elderly patients during a 6-month period follow-up period after a hip fracture. Exp Gerontol 2015; 65: 58-68. https://doi.org/10.1016/j.exger.2015.03.009.

Ginaldi L, De Martinis M, Ciccarelli F, Saitta S, Imbesi S, Mannucci C, et al. Increased levels of interleukin 31 (IL-31) in osteoporosis. BMC Immunol 2015; 16: 60. doi: 10.1186/s12865-015-0125-9.

Shi H, Na Q, Zhang X, Jiang X. Correlations between the levels of acute infection markers and serum albumin in elderly patients with hip fracture. Aging Clin Exp Res 2017; 29(3): 435-441. doi: 10.1007/s40520-016-0585-7.

Stojanović D, Bůžková P, Mukamal KJ, Heckbert SR, Psaty BM, Fink HA, et al. Soluble inflammation markers and risk of incident fractures in older adults: the cardiovascular health study. J Bone Miner Res 2018; 33(2): 221-228. https://doi.org/10.1002/jbmr.3301.

Beloosesky Y, Hendel D, Weiss A, Hershkovitz A, Grinblat J, Pirotsky A, et al. Cytokines and C-reactive protein production in hip-fracture-operated elderly patients. J Gerontol A Biol Sci Med Sci 2007; 62(4): 420-426. doi: 10.1093/gerona/62.4.420.

Downloads

Published

2025-04-11

Issue

Section

Original Articles