CYTOKINE DYNAMICS AND LONG-TERM OUTCOMES IN GERIATRIC HIP FRACTURE PATIENTS
Keywords:
hip fracture, geriatrics, C-reactive protein, tumor necrosis factor-alpha, functional recoveryAbstract
Introduction: Hip fractures in the elderly are associated with high morbidity, mortality, and reduced quality of life. This study investigated the role of systemic inflammation, measured through serum levels of C-reactive protein (CRP) and tumor necrosis factor-alpha (TNF-α), in predicting outcomes following operatively treated hip fractures in patients over 65 years of age.
Materials and Methods: A prospective, nonrandomized study was conducted involving 40 patients with hip fractures classified as 31A or 31B (AO classification). Blood samples were collected at four time points: within 10 hours post-injury, 48–60 hours post-surgery, on the seventh postoperative day, and on the 30th postoperative day. Serum levels of CRP and TNF-α were measured using ELISA. Functional outcomes, including quality of life (SF-12), mobility, and pain, were assessed at 12 months post-injury.
Results: Elevated serum levels of CRP and TNF-α were significantly associated with reduced quality of life, mobility, and survival. Deceased patients exhibited significantly higher cytokine levels compared to survivors at all time points. Multivariate regression analysis identified CRP (p<0.0001) and TNF-α (p=0.017) as independent predictors of quality of life, while TNF-α was significantly associated with mobility (p=0.043).
Conclusion: CRP and TNF-α may serve as valuable biomarkers for identifying high-risk patients and guiding postoperative care. Monitoring inflammatory markers could improve outcomes in geriatric hip fracture patients by enabling targeted interventions and rehabilitation programs.
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. LTR factsheet 2012, acute hospitalizations for hip fractures. 2014. Available from: http://www.lnaz.nl/cms/LTR_2012_Factsheet-heupfracture_ 140611.pdf. Accessed August 31, 2018.
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): e194-200. 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):283–8. 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. doi: 10.1177/2151458516645633.
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 Classification (ASA Class). In: StatPearls. Treasure Island (FL): StatPearls Publishing; 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.
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.
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 follow-up period after a hip fracture. Exp Gerontol 2015; 65: 58-68. doi: 10.1016/j.exger.2015.03.009.
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.
Stojanović D, Bůžková P, Mukamal KJ, Heckbert SR, Psaty BM, Fink HA, et al. Soluble Inflammatory Markers and Risk of Incident Fractures in Older Adults: The Cardiovascular Health Study. J Bone Miner Res 2018; 33(2): 221-228. doi: 10.1002/jbmr.3301.
Shi H, Na Q, Zhang X, Jiang X. Correlations between the levels of acute infection markers and serum albumin in the elderly patients with hip fracture. Aging Clin Exp Res 2017; 29(3): 435-441. doi: 10.1007/s40520-016-0585-7.
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. https://doi.org/10.1186/s12865-015-0125-9.
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. eCollection 2017.
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, Colón-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): 380-90. 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, et al. Prediction of postoperative outcomes following hip fracture surgery: independent validation and recalibration of the Nottingham Hip Fracture Score. J Am Med Dir Assoc. 2020;21(10):1418–24.
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. eCollection 2020.
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(4):451–9.
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.