Journal of Shanghai Jiao Tong University (Medical Science) >

2022 , Vol. 42 >Issue 2: 166 - 172

DOI: https://doi.org/10.3969/j.issn.1674-8115.2022.02.005

Clinical research

Establishment of a nomogram clinical scoring system for the risk of heterotopic ossification in patients undergoing surgery after fracture

  • Yekai WANG ,
  • Wei CHEN ,
  • Yinghui YANG ,
  • Jingze WU ,
  • Heping WANG ,
  • Yanzhen YAO ,
  • Zhoujun BAO
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  • 1.Clinical Lab, Zhoushan Hospital, Zhejiang Province, Zhoushan 316021, China
    2.Department of Orthopaedics, Zhoushan Hospital, Zhejiang Province, Zhoushan 316021, China
    3.Radiology Diagnostic Center, Zhoushan Hospital, Zhejiang Province, Zhoushan 316021, China
WANG Yekai, E-mail: wangyekai@163.com.

Received date: 2021-08-04

  Online published: 2022-01-24

Supported by

General Project of Medical Science and Technology Plan of Health Commission of Zhejiang Province(2020KY340)

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Abstract

Objective

·To establish a nomogram scoring system to predict morbidity of heterotopic ossification (HO) in the patients undergoing surgery after fracture.

Methods

·From August 2018 to October 2020, 124 patients with fractures from department of orthopaedics or brain surgery, including 81 males and 43 females with an average age of (56.48±15.45) years old (ranging from 25?91 years old), were enrolled in the study. Clinical features including gender, age, with brain trauma or not, anesthetic mode, operation duration time, and blood loss during operation were collected. Peripheral blood samples were collected at three time points, i.e. 1 d, 7 d and 15 d after fracture, and the sera levels of bone morphogenetic protein 2 (BMP-2), BMP-4, BMP-5, BMP-7, interleukin 4 (IL-4), IL-6, IL-10, interferon γ (IFN-γ), and transforming growth factor-β (TGF-β) were detected by ELISA. All the patients were divided into HO group and non-HO group according to follow-up outcomes. The variables with statistically significant differences (α=0.15) between the two groups selected from clinical and laboratory indications were included in the univariate Cox regression model. Then the variables selected from univariate Cox regression model (α=0.05) were incorporated into multivariate Cox regression model to screen the independent risk factors of HO and calculate the risk ratios (HR). Finally, the nomogram scoring system was output through rms package in R language.

Results

·The follow-up observation found 13 HO cases after a median time of 71 (38, 292) d. Seven independent risk factors for HO, i.e. brain trauma (HR=2.932, P=0.038), operation duration time (HR=1.005, P=0.007), blood loss during operation (HR=1.004, P=0.022), BMP-2 (15d) (HR=1.009, P=0.044), BMP-4 (15 d) (HR=1.004, P=0.011), TGF-β (15 d) (HR=1.011, P=0.046), and BMP-7 (7 d) (HR=1.004, P=0.008), were selected by comparison between groups, univariate COX regression and multivariate COX regression sequentially. The nomogram to predict morbidity of HO after 90 d, 180 d, and 360 d was generated.

Conclusion

·The seven scoring indexes of nomogram scoring system for predicting the risk of HO in the patients undergoing surgery after fracture are with brain trauma or not, operation duration time, blood loss during operation, levels of BMP-2, BMP-4 and TGF-β in peripheral blood 15 d after fracture and BMP-7 7 d after fracture.

Key words： heterotopic ossification (HO); fracture; nomogram; brain trauma; bone morphogenetic protein (BMP)

Cite this article

Yekai WANG , Wei CHEN , Yinghui YANG , Jingze WU , Heping WANG , Yanzhen YAO , Zhoujun BAO . Establishment of a nomogram clinical scoring system for the risk of heterotopic ossification in patients undergoing surgery after fracture[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2022 , 42(2) : 166 -172 . DOI: 10.3969/j.issn.1674-8115.2022.02.005

References

1 KUSANO T, NAKATANI M, ISHIGURO N, et al. Desloratadine inhibits heterotopic ossification by suppression of BMP2-Smad1/5/8 signaling[J]. J Orthop Res, 2021, 39(6): 1297-1304.
2 PARK J O, LEE B H, KANG Y M, et al. Inflammatory cytokines induce fibrosis and ossification of human ligamentum flavum cells[J]. J Spinal Disord Tech, 2013, 26(1): E6-12.
3 WANG X, LI F F, XIE L, et al. Inhibition of overactive TGF-β attenuates progression of heterotopic ossification in mice[J]. Nat Commun, 2018, 9: 551.
4 RANGANATHAN K, LODER S, AGARWAL S, et al. Heterotopic ossification: basic-science principles and clinical correlates[J]. J Bone Joint Surg Am, 2015, 97(13): 1101-1111.
5 ?EGOSZ P, OTWOROWSKI M, SIBILSKA A, et al. Heterotopic ossification: a challenging complication of total hip arthroplasty: risk factors, diagnosis, prophylaxis, and treatment[J]. Biomed Res Int, 2019, 2019: 3860142.
6 高悠水, 孙玉强, 张长青. 获得性异位骨化预防和治疗策略的研究进展[J]. 上海交通大学学报(医学版), 2014, 34(6): 934-938.
7 THILAK J, PANAKKAL J J, KIM T Y, et al. Risk factors of heterotopic ossification following total hip arthroplasty in patients with ankylosing spondylitis[J]. J Arthroplasty, 2015, 30(12): 2304-2307.
8 赵萌. 全髋关节置换术5年随访研究[J]. 现代预防医学, 2014, 41(14): 2686-2688.
9 SUNG HSIEH H H, CHUNG M T, ALLEN R M, et al. Evaluation of salivary cytokines for diagnosis of both trauma-induced and genetic heterotopic ossification[J]. Front Endocrinol (Lausanne), 2017, 8: 74.
10 HAYASHI D, GOULD E S, HO C, et al. Severity of heterotopic ossification in patients following surgery for hip fracture: a retrospective observational study[J]. BMC Musculoskelet Disord, 2019, 20(1): 348.
11 LI L, JIANG Y, LIN H, et al. Muscle injury promotes heterotopic ossification by stimulating local bone morphogenetic protein-7 production[J]. J Orthop Translat, 2019, 18: 142-153.
12 LIU T, LI B, ZHENG X F, et al. Chordin-like 1 improves osteogenesis of bone marrow mesenchymal stem cells through enhancing BMP4-SMAD pathway[J]. Front Endocrinol (Lausanne), 2019, 10: 360.
13 SUUTRE S, TOOM A, AREND A, et al. Bone tissue content of TGF-β2 changes with time in human heterotopic ossification after total hip arthroplasty[J]. Growth Factors, 2009, 27(2): 114-120.
14 WANG L, WAN G, SHEN Y, et al. A nomogram to predict mortality in patients with severe fever with thrombocytopenia syndrome at the early stage: a multicenter study in China[J]. PLoS Negl Trop Dis, 2019, 13(11): e0007829.
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