Perioperative changes of serum interleukin 6 levels in elderly male patients with intertrochanteric fracture_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

CHEN Xiangxu ^1,2,3,4 , ZHU Huanyi ^1,2,3,4 , WU Wei ^1,2,3,4 , TIAN Chuwei ^1,2,3,4 , SHI Liu ^1,2,3,4 , FAN Wenbin ^1,2,3,4 , ZHANG Cheng ^1,2,3,4 , LI Yingjuan ^3,4,5 , CHEN Hui ^1,2,3,4 , GAO Wei ^3,4,5 ,  RUI Yunfeng ^1,2,3,4

1. Trauma Center, Department of Orthopaedic Surgery, Zhongda Hospital Affiliated to Southeast University, Nanjing Jiangsu, 210009, P. R. China;
2. Institute of Trauma Orthopaedics, Southeast University, Nanjing Jiangsu, 210009, P. R. China;
3. Multidisciplinary Team for Geriatric Hip Fracture, Zhongda Hospital Affiliated to Southeast University, Nanjing Jiangsu, 210009, P. R. China;
4. School of Medicine, Southeast University, Nanjing Jiangsu, 210009, P. R. China;
5. Department of Geriatrics, Zhongda Hospital Affiliated to Southeast University, Nanjing Jiangsu, 210009, P. R. China;

Corresponding?author：

RUI Yunfeng, Email: ruiyunfeng@126.com

Keywords：

Osteoporosis; male; intertrochanteric fracture; fracture healing; interleukin 6; the elderly

DOI：

10.7507/1002-1892.202405057

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Objective To investigate the perioperative changes in serum interleukin 6 (IL-6) levels in elderly male patients with intertrochanteric fractures, and provide evidence for inflammatory control in this patient population. Methods The clinical data of 40 male patients aged more than 60 years with intertrochanteric fractures who met the selection criteria between January 2021 and December 2022 were retrospectively analyzed, including 25 non-osteoporosis patients (T value>?2.5, group A) and 15 osteoporosis patients (T value≤?2.5, group B). In addition, 40 healthy men aged more than 60 years old were included as controls (group C) according to the age matching rule. There was no significant difference in age, smoking history, drinking history, body mass index, complications (hypertension and diabetes), alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, creatinine, and total protein among the 3 groups (P>0.05). Serum samples were collected from group C subjects and from groups A and B patients preoperatively and on postoperative days 1, 3, 5, and 7. IL-6 levels were measured using ELISA assay. Pearson correlation analysis was used to assess the relationship between IL-6 levels and T values at various time points in groups A and B. Postoperative complications during hospitalization and 1-year mortality rates were recorded for groups A and B. Results Preoperative IL-6 levels were significantly higher in groups A and B than in group C (P<0.05), with group B being significantly higher than group A (P<0.05). In groups A and B, IL-6 levels increased significantly on postoperative day 1 compared to preoperative levels and then gradually decreased, approaching preoperative levels by postoperative day 7. IL-6 levels in group B were significantly higher than those in group A at all postoperative time points (P<0.05). Correlation analysis showed that IL-6 levels were negatively correlated with T values at all perioperative time points in all patients from groups A and B (P<0.05). Complications occurred in 4 patients (16.0%) in group A, including 2 cases of pulmonary infection, 1 case of urinary tract infection, and 1 case of heart failure, and in 3 patients (20.0%) in group B, including 2 cases of pulmonary infection and 1 case of gastrointestinal bleeding. There was no significant difference in the incidence of complications between the two groups (χ²=0.104, P=0.747). There were 2 cases (8.0%) and 4 cases (26.7%) died within 1 year after operation in groups A and B, respectively, and there was no significant difference in 1-year mortality rates between the two groups (χ²=2.562, P=0.109). Conclusion Serum IL-6 levels significantly increase in the early postoperative period in elderly male patients with intertrochanteric fractures, especially in those with osteoporosis. Monitoring the inflammatory state and promptly controlling the inflammatory response during the perioperative period, may reduce complications and improve postoperative survival in this patient population.

Citation： CHEN Xiangxu, ZHU Huanyi, WU Wei, TIAN Chuwei, SHI Liu, FAN Wenbin, ZHANG Cheng, LI Yingjuan, CHEN Hui, GAO Wei, RUI Yunfeng. Perioperative changes of serum interleukin 6 levels in elderly male patients with intertrochanteric fracture. Chinese Journal of Reparative and Reconstructive Surgery, 2024, 38(10): 1249-1253. doi: 10.7507/1002-1892.202405057 Copy

1.	中華醫學會骨質疏松和骨礦鹽疾病分會. 中國骨質疏松癥流行病學調查及“健康骨骼”專項行動結果發布. 中華骨質疏松和骨礦鹽疾病雜志, 2019, 12(4): 317-318.
2.	《中國老年骨質疏松癥診療指南(2023)》工作組, 中國老年學和老年醫學學會骨質疏松分會, 中國醫療保健國際交流促進會骨質疏松病學分會, 等. 中國老年骨質疏松癥診療指南 (2023). 中華骨與關節外科雜志, 2023, 16(10): 865-885.
3.	中華醫學會骨質疏松和骨礦鹽疾病分會. 男性骨質疏松癥診療指南. 中華骨質疏松和骨礦鹽疾病雜志, 2020, 13(5): 381-395.
4.	Weitzmann M. Bone and the immune system. Toxicologic Pathology, 2017, 45(7): 911-924.
5.	Walsh MC, Kim N, Kadono Y, et al. Osteoimmunology: interplay between the immune system and bone metabolism. Annu Rev Immunol, 2006, 24: 33-63.
6.	Charles JF, Nakamura MC. Bone and the innate immune system. Curr Osteoporos Rep, 2014, 12(1): 1-8.
7.	Saribal D, Hocaoglu-Emre FS, Erdogan S, et al. Inflammatory cytokines IL-6 and TNF-α in patients with hip fracture. Osteoporos Int, 2019, 30(5): 1025-1031.
8.	張耀武, 陳平波, 洪漢剛, 等. 老年股骨粗隆間骨折患者血清炎性介質的表達與患者預后的關系. 中國老年學雜志, 2017, 37(4): 929-931.
9.	尚林強. 136例老年股骨粗隆間骨折患者血清TNF-α, IL-6及IL-10的表達及臨床意義. 創傷外科雜志, 2019, 21(4): 311-313.
10.	Shimazui T, Matsumura Y, Nakada TA, et al. Serum levels of interleukin-6 may predict organ dysfunction earlier than SOFA score. Acute Med Surg, 2017, 4(3): 255-261.
11.	Pesic G, Jeremic J, Nikolic T, et al. Interleukin-6 as possible early marker of stress response after femoral fracture. Mol Cell Biochem, 2017, 430(1-2): 191-199.
12.	Coates BA, McKenzie JA, Yoneda S, et al. Interleukin-6 (IL-6) deficiency enhances intramembranous osteogenesis following stress fracture in mice. Bone, 2021, 143: 115737. doi: 10.1016/j.bone.2020.115737.
13.	Prystaz K, Kaiser K, Kovtun A, et al. Distinct effects of IL-6 classic and trans-signaling in bone fracture healing. Am J Pathol, 2018, 188(2): 474-490.
14.	Jawa RS, Anillo S, Huntoon K, et al. Analytic review: Interleukin-6 in surgery, trauma, and critical care: part Ⅰ: basic science. J Intensive Care Med, 2011, 26(1): 3-12.
15.	陳聰, 毋凡, 覃茂鑫, 等. 嚴重創傷后免疫炎癥反應機制及相關臨床干預研究進展. 中華創傷雜志, 2019, 35(10): 953-960.
16.	Emami AJ, Toupadakis CA, Telek SM, et al. Age dependence of systemic bone loss and recovery following femur fracture in mice. J Bone Miner Res, 2019, 34(1): 157-170.
17.	M?rs K, Wagner N, Sturm R, et al. Enhanced pro-inflammatory response and higher mortality rates in geriatric trauma patients. Eur J Trauma Emerg Surg, 2021, 47(4): 1065-1072.
18.	楊明園, 李超, 李明. 細胞因子與絕經后骨質疏松癥關系的研究進展. 中國骨質疏松雜志, 2014, 20(6): 698-705.
19.	McLean RR. Proinflammatory cytokines and osteoporosis. Curr Osteoporos Rep, 2009, 7(4): 134-139.
20.	Liu S, Li J, Zhang M. Determination of immune factor levels in serum and local hematoma samples of osteoporotic fracture patients and clinical study of the effect of active vitamin D3 treatment on immune factor levels. J Orthop Surg Res, 2023, 18(1): 291. doi: 10.1186/s13018-023-03777-7.
21.	Fischer V, Kalbitz M, Müller-Graf F, et al. Influence of menopause on inflammatory cytokines during murine and human bone fracture healing. Int J Mol Sci, 2018, 19(7): 2070. doi: 10.3390/ijms19072070.
22.	Sedlár M, Kudrnová Z, Trca S, et al. Inflammatory response in patients undergoing hip surgery due to osteoarthrosis or different types of hip fractures. Osteoarthritis Cartilage, 2008, 16(1): 26-33.
23.	Kristek G, Rado? I, Kristek D, et al. Influence of postoperative analgesia on systemic inflammatory response and postoperative cognitive dysfunction after femoral fractures surgery: a randomized controlled trial. Reg Anesth Pain Med, 2019, 44(1): 59-68.
24.	Malysch T, Reinhold JM, Becker CA, et al. In vivo immunomodulation of IL6 signaling in a murine multiple trauma model. Immunol Res, 2023, 71(2): 164-172.
25.	Devlin RD, Reddy SV, Savino R, et al. IL-6 mediates the effects of IL-1 or TNF, but not PTHrP or 1, 25(OH)2D3, on osteoclast-like cell formation in normal human bone marrow cultures. J Bone Miner Res, 1998, 13(3): 393-399.
26.	Zhang D, Huang Y, Huang Z, et al. FTY-720P suppresses osteoclast formation by regulating expression of interleukin-6 (IL-6), interleukin-4 (IL-4), and matrix metalloproteinase 2 (MMP-2). Med Sci Monit, 2016, 22: 2187-2194.

1. 中華醫學會骨質疏松和骨礦鹽疾病分會. 中國骨質疏松癥流行病學調查及“健康骨骼”專項行動結果發布. 中華骨質疏松和骨礦鹽疾病雜志, 2019, 12(4): 317-318.
2. 《中國老年骨質疏松癥診療指南(2023)》工作組, 中國老年學和老年醫學學會骨質疏松分會, 中國醫療保健國際交流促進會骨質疏松病學分會, 等. 中國老年骨質疏松癥診療指南 (2023). 中華骨與關節外科雜志, 2023, 16(10): 865-885.
3. 中華醫學會骨質疏松和骨礦鹽疾病分會. 男性骨質疏松癥診療指南. 中華骨質疏松和骨礦鹽疾病雜志, 2020, 13(5): 381-395.
4. Weitzmann M. Bone and the immune system. Toxicologic Pathology, 2017, 45(7): 911-924.
5. Walsh MC, Kim N, Kadono Y, et al. Osteoimmunology: interplay between the immune system and bone metabolism. Annu Rev Immunol, 2006, 24: 33-63.
6. Charles JF, Nakamura MC. Bone and the innate immune system. Curr Osteoporos Rep, 2014, 12(1): 1-8.
7. Saribal D, Hocaoglu-Emre FS, Erdogan S, et al. Inflammatory cytokines IL-6 and TNF-α in patients with hip fracture. Osteoporos Int, 2019, 30(5): 1025-1031.
8. 張耀武, 陳平波, 洪漢剛, 等. 老年股骨粗隆間骨折患者血清炎性介質的表達與患者預后的關系. 中國老年學雜志, 2017, 37(4): 929-931.
9. 尚林強. 136例老年股骨粗隆間骨折患者血清TNF-α, IL-6及IL-10的表達及臨床意義. 創傷外科雜志, 2019, 21(4): 311-313.
10. Shimazui T, Matsumura Y, Nakada TA, et al. Serum levels of interleukin-6 may predict organ dysfunction earlier than SOFA score. Acute Med Surg, 2017, 4(3): 255-261.
11. Pesic G, Jeremic J, Nikolic T, et al. Interleukin-6 as possible early marker of stress response after femoral fracture. Mol Cell Biochem, 2017, 430(1-2): 191-199.
12. Coates BA, McKenzie JA, Yoneda S, et al. Interleukin-6 (IL-6) deficiency enhances intramembranous osteogenesis following stress fracture in mice. Bone, 2021, 143: 115737. doi: 10.1016/j.bone.2020.115737.
13. Prystaz K, Kaiser K, Kovtun A, et al. Distinct effects of IL-6 classic and trans-signaling in bone fracture healing. Am J Pathol, 2018, 188(2): 474-490.
14. Jawa RS, Anillo S, Huntoon K, et al. Analytic review: Interleukin-6 in surgery, trauma, and critical care: part Ⅰ: basic science. J Intensive Care Med, 2011, 26(1): 3-12.
15. 陳聰, 毋凡, 覃茂鑫, 等. 嚴重創傷后免疫炎癥反應機制及相關臨床干預研究進展. 中華創傷雜志, 2019, 35(10): 953-960.
16. Emami AJ, Toupadakis CA, Telek SM, et al. Age dependence of systemic bone loss and recovery following femur fracture in mice. J Bone Miner Res, 2019, 34(1): 157-170.
17. M?rs K, Wagner N, Sturm R, et al. Enhanced pro-inflammatory response and higher mortality rates in geriatric trauma patients. Eur J Trauma Emerg Surg, 2021, 47(4): 1065-1072.
18. 楊明園, 李超, 李明. 細胞因子與絕經后骨質疏松癥關系的研究進展. 中國骨質疏松雜志, 2014, 20(6): 698-705.
19. McLean RR. Proinflammatory cytokines and osteoporosis. Curr Osteoporos Rep, 2009, 7(4): 134-139.
20. Liu S, Li J, Zhang M. Determination of immune factor levels in serum and local hematoma samples of osteoporotic fracture patients and clinical study of the effect of active vitamin D3 treatment on immune factor levels. J Orthop Surg Res, 2023, 18(1): 291. doi: 10.1186/s13018-023-03777-7.
21. Fischer V, Kalbitz M, Müller-Graf F, et al. Influence of menopause on inflammatory cytokines during murine and human bone fracture healing. Int J Mol Sci, 2018, 19(7): 2070. doi: 10.3390/ijms19072070.
22. Sedlár M, Kudrnová Z, Trca S, et al. Inflammatory response in patients undergoing hip surgery due to osteoarthrosis or different types of hip fractures. Osteoarthritis Cartilage, 2008, 16(1): 26-33.
23. Kristek G, Rado? I, Kristek D, et al. Influence of postoperative analgesia on systemic inflammatory response and postoperative cognitive dysfunction after femoral fractures surgery: a randomized controlled trial. Reg Anesth Pain Med, 2019, 44(1): 59-68.
24. Malysch T, Reinhold JM, Becker CA, et al. In vivo immunomodulation of IL6 signaling in a murine multiple trauma model. Immunol Res, 2023, 71(2): 164-172.
25. Devlin RD, Reddy SV, Savino R, et al. IL-6 mediates the effects of IL-1 or TNF, but not PTHrP or 1, 25(OH)2D3, on osteoclast-like cell formation in normal human bone marrow cultures. J Bone Miner Res, 1998, 13(3): 393-399.
26. Zhang D, Huang Y, Huang Z, et al. FTY-720P suppresses osteoclast formation by regulating expression of interleukin-6 (IL-6), interleukin-4 (IL-4), and matrix metalloproteinase 2 (MMP-2). Med Sci Monit, 2016, 22: 2187-2194.

Chinese Journal of Reparative and Reconstructive Surgery

Perioperative changes of serum interleukin 6 levels in elderly male patients with intertrochanteric fracture

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