Association between leukocyte-based inflammatory indices and bone mineral density in hemodialysis patients

Year 2025, Volume: 6 Issue: 2, 131 - 137, 23.03.2025

Javid Mohammadzadeh Azarabadi , Neveen Shalalfa

https://doi.org/10.47582/jompac.1642972

Abstract

Aims: Osteoporosis and osteopenia are common among hemodialysis (HD) patients, yet current methods for risk stratification remain limited. This study aimed to investigate the relationship between leukocyte-based inflammatory indices and osteoporosis and osteopenia in HD patients and to assess their diagnostic performance in differentiating these conditions.
Methods: A retrospective analysis was conducted on 168 HD patients classified into normal bone mineral density (BMD) (n=43), osteopenia (n=70), and osteoporosis (n=55) based on T-scores by dual-energy X-ray absorptiometry measurements. The leukocyte-based inflammatory indices were calculated as follows: Platelet to lymphocyte ratio (PLR)=platelet count/ lymphocyte count ratio; neutrophil o lymphocyte ratio (NLR)=neutrophil count/ lymphocyte count ratio; systemic immune inflammation index (SII)=platelet count×neutrophil count / lymphocyte count ratio, and systemic inflammation response index (SIRI)=neutrophil count×monocyte count/ lymphocyte count ratio.
Results: Osteopenia and osteoporosis were identified in 41.7% and 32.7% of patients, respectively. Patients with osteoporosis exhibited higher neutrophil and monocyte counts and lower lymphocyte count (p<0.001). All inflammatory indices were higher in osteoporosis group compared to other group. Also, these indices were higher in osteopenia group compared to normal BMD group. SIRI showed the strongest discriminative power for differentiating osteopenia from normal BMD (AUC=0.84; sensitivity=81.4%; specificity=79.2%, p<0.001) and osteoporosis from osteopenia (AUC=0.86; sensitivity=82.5%; specificity=78.6%; p<0.001).
Conclusion: Leukocyte-based inflammatory indices, particularly SIRI, are significantly associated with reduced BMD in HD patients and may serve as accessible biomarkers for identifying those at heightened risk of osteopenia and osteoporosis.

Keywords

Bone mineral density, hemodialysis, osteoporosis, systemic inflammation

Ethical Statement

The study was performed in accordance with the Declaration of Helsinki, and was approved by the Başkent University Institutional Review Board (Date: 22/10/2024, Project no: KA24/346).).

Supporting Institution

The authors declared that this study has supported by Başkent University Research Fund (Project no: KA24/346).

Hemodiyaliz hastalarında lökosit bazlı enflamatuar indeksler ile kemik mineral yoğunluğu arasındaki ilişki

Abstract

Amaç: Osteoporoz ve osteopeni, hemodiyaliz (HD) hastalarında yaygın olarak görülmektedir, ancak mevcut risk sınıflandırma yöntemleri sınırlıdır. Bu çalışma, HD hastalarında lökosit bazlı enflamatuar indeksler ile osteoporoz ve osteopeni arasındaki ilişkiyi araştırmayı ve bu indekslerin bu durumları ayırt etmedeki tanısal performansını değerlendirmeyi amaçladı.
Yöntemler: İkili enerji X-ray absorbsiyometri ölçümleri ile T skorlarına göre normal kemik mineral yoğunluğu (KMY) (n=43), osteopeni (n=70) ve osteoporoz (n=55) olarak sınıflandırılan 168 hemodiyaliz hastası üzerinde retrospektif bir analiz yapıldı. Lökosit bazlı enflamatuar indeksler aşağıdaki şu şekilde hesaplandı: Trombosit-Lenfosit Oranı (PLR) = trombosit sayısı / lenfosit sayısı; Nötrofil-Lenfosit Oranı (NLR) = nötrofil sayısı / lenfosit sayısı; Sistemik İmmün Enflamasyon İndeksi (SII) = trombosit sayısı × nötrofil sayısı / lenfosit sayısı; Sistemik Enflamasyon Yanıt İndeksi (SIRI) = nötrofil sayısı × monosit sayısı / lenfosit sayısı.
Bulgular: Hastaların %41,7’sinde osteopeni, %32,7’sinde osteoporoz tespit edildi. Osteoporozu olan hastalarda nötrofil ve monosit sayıları daha yüksek, lenfosit sayıları ise daha düşüktü (p < 0,001). Tüm enflamatuar indeksler, osteoporoz grubunda diğer gruplara kıyasla daha yüksek bulundu. Ayrıca, osteopeni grubunda da normal KMY grubuna göre daha yüksek değerler gözlendi. SIRI, osteopeniyi normal KMY’den ayırt etmede en güçlü belirleyici olarak tespit edildi (AUC = 0,84; duyarlılık = %81,4; özgüllük = %79,2; p < 0,001). Osteoporozu osteopeniden ayırt etmede de güçlü bir performans gösterdi (AUC = 0,86; duyarlılık = %82,5; özgüllük = %78,6; p < 0,001).
Sonuç: Lökosit bazlı enflamatuar indeksler, özellikle SIRI, HD hastalarında düşük KMY ile anlamlı şekilde ilişkilidir ve osteopeni ve osteoporoz riski yüksek olan hastaları belirlemede kolay erişilebilir biyogöstergeler olarak kullanılabilir.

Keywords

emik Mineral Yoğunluğu, Hemodiyaliz, Osteoporoz, Sistemik Enflamasyon

References

• Waziri B, Duarte R, Naicker S. Chronic kidney disease-mineral and bone disorder (CKD-MBD): current perspectives. Int J Nephrol Renovasc Dis. 2019;12:263-276. doi:10.2147/IJNRD.S191156
• Huang GS, Chu TS, Lou MF, Hwang SL, Yang RS. Factors associated with low bone mass in the hemodialysis patients--a cross-sectional correlation study. BMC Musculoskelet Disord. 2009;10(1):60. doi:10.1186/ 1471-2474-10-60
• Hu L, Napoletano A, Provenzano M, et al. Mineral bone disorders in kidney disease patients: the ever-current topic. Int J Mol Sci. 2022;23(20): 12223. doi:10.3390/ijms232012223
• Nich C, Takakubo Y, Pajarinen J, et al. Macrophages-key cells in the response to wear debris from joint replacements. J Biomed Mater Res A. 2013;101(10):3033-3045. doi:10.1002/jbm.a.34599
• Charles JF, Nakamura MC. Bone and the innate immune system. Curr Osteoporos Rep. 2014;12(1):1-8. doi:10.1007/s11914-014-0195-2
• Loi F, Cordova LA, Pajarinen J, Lin TH, Yao Z, Goodman SB. Inflammation, fracture and bone repair. Bone. 2016;86:119-30. doi:10. 1016/j.bone.2016.02.020
• Mazzaferro S, Cianciolo G, De Pascalis A, et al. Bone, inflammation and the bone marrow niche in chronic kidney disease: what do we know? Nephrol Dial Transplant. 2018;33(12):2092-2100. doi:10.1093/ndt/gfy115
• Qian Q. Inflammation: a key contributor to the genesis and progression of chronic kidney disease. Contrib Nephrol. 2017;191:72-83. doi:10.1159/ 000479257
• Zhou P, Zheng T, Zhao B. Cytokine-mediated immunomodulation of osteoclastogenesis. Bone. 2022;164:116540. doi:10.1016/j.bone.2022. 116540
• D'Amelio P, Sassi F. Osteoimmunology: from mice to humans. Bonekey Rep. 2016;5:802. doi:10.1038/bonekey.2016.29
• Jiang Y, Bao X. Systemic immune-inflammatory indicators and bone mineral density in chronic kidney disease patients: a cross-sectional research from NHANES 2011 to 2018. PLoS One. 2024;19(4):e0302073. doi:10.1371/journal.pone.0302073
• Şen Uzeli Ü, Doğan M. The relationship between neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), hemoglobin albumin lymphocyte and platelet (HALP) score and bone mineral density in hemodialysis Patients. J Orthop Res Rehab. 2024;2(1):5-8. doi:10.51271/JORR-0023
• Chen S, Sun X, Jin J, Zhou G, Li Z. Association between inflammatory markers and bone mineral density: a cross-sectional study from NHANES 2007-2010. J Orthop Surg Res. 2023;18(1):305. doi:10.1186/s13018-023-03795-5
• Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clinical Chemistry. 1972;18(6): 499-502. doi:10.1093/clinchem/18.6.499
• Siris ES, Adler R, Bilezikian J, et al. The clinical diagnosis of osteoporosis: a position statement from the National Bone Health Alliance Working Group. Osteoporos Int. 2014;25(5):1439-1443. doi:10.1007/s00198-014-2655-z
• Slouma M, Sahli H, Bahlous A, et al. Mineral bone disorder and osteoporosis in hemodialysis patients. Adv Rheumatol. 2020;60(1):15. doi:10.1186/s42358-020-0118-0
• Polymeris A, Doumouchtsis K, Grapsa E. Bone mineral density and bone metabolism in hemodialysis patients. Correlation with PTH, 25OHD3 and leptin. Nefrologia. 2012;32(1):73-78. doi:10.3265/Nefrologia.pre2011.Jul.10916
• Tamimi R, Bdair A, Shratih A, et al. Bone mineral density and related clinical and laboratory factors in peritoneal dialysis patients: implications for bone health management. PLoS One. 2024;19(5):e0301814. doi:10. 1371/journal.pone.0301814
• Binici DN, Gunes N. Risk factors leading to reduced bone mineral density in hemodialysis patients with metabolic syndrome. Ren Fail. 2010;32(4):469-474. doi:10.3109/08860221003675260
• Sprague SM, Martin KJ, Coyne DW. Phosphate balance and CKD-mineral bone disease. Kidney Int Rep. 2021;6(8):2049-2058. doi:10.1016/j.ekir.2021.05.012
• Hsu CY, Chen LR, Chen KH. Osteoporosis in patients with chronic kidney diseases: a systemic review. Int J Mol Sci. 2020;21(18):6846. doi: 10.3390/ijms21186846
• Feng X, McDonald JM. Disorders of bone remodeling. Annu Rev Pathol. 2011;6(1):121-145. doi:10.1146/annurev-pathol-011110-130203
• Aguilar A, Gifre L, Urena-Torres P, et al. Pathophysiology of bone disease in chronic kidney disease: from basics to renal osteodystrophy and osteoporosis. Front Physiol. 2023;14:1177829. doi:10.3389/fphys. 2023.1177829
• Cobo G, Lindholm B, Stenvinkel P. Chronic inflammation in end-stage renal disease and dialysis. Nephrol Dial Transplant. 2018;33(suppl_3): iii35-iii40. doi:10.1093/ndt/gfy175
• Lorenzo J, Horowitz M, Choi Y. Osteoimmunology: interactions of the bone and immune system. Endocr Rev. 2008;29(4):403-440. doi:10.1210/er.2007-0038
• Mazzaferro S, De Martini N, Rotondi S, et al. Bone, inflammation and chronic kidney disease. Clinica Chimica Acta. 2020;506:236-240. doi: 10.1016/j.cca.2020.03.040
• Hong J, Luo F, Du X, Xian F, Li X. The immune cells in modulating osteoclast formation and bone metabolism. Int Immunopharmacol. 2024;133:112151. doi:10.1016/j.intimp.2024.112151
• Li Y, Hao W, Guan J, et al. Relationship between indices of circulating blood cells and bone homeostasis in osteoporosis. Front Endocrinol (Lausanne). 2022;13:965290. doi:10.3389/fendo.2022.965290
• Valderrabano RJ, Lui LY, Lee J, et al. Bone density loss is associated with blood cell counts. J Bone Miner Res. 2017;32(2):212-220. doi:10.1002/jbmr.3000
• Su YJ, Chen CT, Tsai NW, et al. The role of monocyte percentage in osteoporosis in male rheumatic diseases. Am J Mens Health. 2017;11(6): 1772-1780. doi:10.1177/1557988317721642
• Schyrr F, Marques-Vidal P, Hans D, Lamy O, Naveiras O. Differential blood counts do not consistently predict clinical measurements of bone mineral density and microarchitecture at homeostasis. JBMR Plus. 2022;6(9):e10669. doi:10.1002/jbm4.10669
• Liu YC, Yang TI, Huang SW, Kuo YJ, Chen YP. Associations of the neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio with osteoporosis: a meta-analysis. Diagnostics (Basel). 2022;12(12):2968. doi:10.3390/diagnostics12122968
• Ban TH, Choi BS, Yoon SA, et al. Clinical significance of neutrophil-to-lymphocyte ratio on the risk of abdominal aortic calcification and decreased bone mineral density in patients with end-stage kidney disease. PLoS One. 2023;18(10):e0286612. doi:10.1371/journal.pone. 0286612
• Xue J, Xu L, Zhu H, et al. CD14(+)CD16(-) monocytes are the main precursors of osteoclasts in rheumatoid arthritis via expressing Tyro3TK. Arthritis Res Ther. 2020;22(1):221. doi:10.1186/s13075-020-02308-7
• Ma H, Cai X, Hu J, et al. Association of systemic inflammatory response index with bone mineral density, osteoporosis, and future fracture risk in elderly hypertensive patients. Postgrad Med. 2024;136(4):406-416. doi: 10.1080/00325481.2024.2354158
• Chen Y, Yu J, Shi L, et al. Systemic inflammation markers associated with bone mineral density in perimenopausal and postmenopausal women. J Inflamm Res. 2023;16:297-309. doi:10.2147/JIR.S385220