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Prognostic Value of Bone Formation and Resorption Proteins in Heterotopic Ossification in Critically-Ill Patients. A Single-Centre Study Cover

Prognostic Value of Bone Formation and Resorption Proteins in Heterotopic Ossification in Critically-Ill Patients. A Single-Centre Study

The Journal of Critical Care Medicine
Volume 7 (2021): Issue 1 (January 2021)
By: Alice Georgia Vassiliou,  Edison Jahaj,  Zafeiria Mastora,  Ioannis Karnezis,  Ioanna Dimopoulou,  Stylianos E. Orfanos and  Anastasia Kotanidou  
Open Access
|Jan 2021

Figures & Tables

Fig. 1

Study enrolment flow chart
Study enrolment flow chart

Fig. 2

BMP-2, RANKL and Osteoprotegerin levels on admission. a) BMP-2, b) RANKL, c) Osteoprotegerin and d) RANKL: Osteoprotegerin ratio were measured in 28 critically ill, initially non-septic patients on ICU admission. Patients were subsequently categorised as heterotopic ossification-positive (those who subsequently developed heterotopic ossification, yes, N= 9) and heterotopic ossification -negative (those who did not develop heterotopic ossification, no, N= 19). Two-group comparisons were performed with the non-parametric Mann-Whitney test, * p< 0.05. Data are presented as box plots. Line in the box, median value; box edges, 25th to 75th centiles; whiskers, range of values; bullet points, outliers. BMP-2= bone-morphogenetic protein 2, RANKL= receptor activator of nuclear factor kappa-Β ligand, OPG= osteoprotegerin.
BMP-2, RANKL and Osteoprotegerin levels on admission. a) BMP-2, b) RANKL, c) Osteoprotegerin and d) RANKL: Osteoprotegerin ratio were measured in 28 critically ill, initially non-septic patients on ICU admission. Patients were subsequently categorised as heterotopic ossification-positive (those who subsequently developed heterotopic ossification, yes, N= 9) and heterotopic ossification -negative (those who did not develop heterotopic ossification, no, N= 19). Two-group comparisons were performed with the non-parametric Mann-Whitney test, * p< 0.05. Data are presented as box plots. Line in the box, median value; box edges, 25th to 75th centiles; whiskers, range of values; bullet points, outliers. BMP-2= bone-morphogenetic protein 2, RANKL= receptor activator of nuclear factor kappa-Β ligand, OPG= osteoprotegerin.

Fig.3

Time course of BMP-2, RANKL and OPG levels during ICU stay and the follow-up period in the patients who developed heterotopic ossification. a) BMP-2, b) RANKL, c) OPG and d) RANKL: OPG ratio were measured in 9 patients who developed heterotopic ossification on ICU admission (0), and thereafter seven days post-admission (7) and 30 days following ICU discharge (30). Data are presented with box plots. Line in the box, median value; box edges, 25th to 75th centiles; whiskers, range of values. Comparisons were performed using one-way ANOVA followed by Dunn’s multiple comparisons. BMP-2= bone-morphogenetic protein 2, RANKL= receptor activator of nuclear factor kappa-Β ligand, OPG= osteoprotegerin.
Time course of BMP-2, RANKL and OPG levels during ICU stay and the follow-up period in the patients who developed heterotopic ossification. a) BMP-2, b) RANKL, c) OPG and d) RANKL: OPG ratio were measured in 9 patients who developed heterotopic ossification on ICU admission (0), and thereafter seven days post-admission (7) and 30 days following ICU discharge (30). Data are presented with box plots. Line in the box, median value; box edges, 25th to 75th centiles; whiskers, range of values. Comparisons were performed using one-way ANOVA followed by Dunn’s multiple comparisons. BMP-2= bone-morphogenetic protein 2, RANKL= receptor activator of nuclear factor kappa-Β ligand, OPG= osteoprotegerin.

Fig. 4

Time course of BMP-2, RANKL and OPG levels during ICU stay and the follow-up period in the patients who did not develop heterotopic ossification. a) BMP-2, b) RANKL, c) OPG and d) RANKL: OPG ratio were measured in 19 patients who did not develop heterotopic ossification on ICU admission (0), and thereafter seven days post-admission (7) and 30 days following ICU discharge (30). Data are presented with box plots. Line in the box, median value; box edges, 25th to 75th centiles; whiskers, range of values; bullet points, outliers. Comparisons were performed using one-way ANOVA followed by Dunn’s multiple comparisons. BMP-2= bone-morphogenetic protein 2, RANKL= receptor activator of nuclear factor kappa-Β ligand, OPG= osteoprotegerin.
Time course of BMP-2, RANKL and OPG levels during ICU stay and the follow-up period in the patients who did not develop heterotopic ossification. a) BMP-2, b) RANKL, c) OPG and d) RANKL: OPG ratio were measured in 19 patients who did not develop heterotopic ossification on ICU admission (0), and thereafter seven days post-admission (7) and 30 days following ICU discharge (30). Data are presented with box plots. Line in the box, median value; box edges, 25th to 75th centiles; whiskers, range of values; bullet points, outliers. Comparisons were performed using one-way ANOVA followed by Dunn’s multiple comparisons. BMP-2= bone-morphogenetic protein 2, RANKL= receptor activator of nuclear factor kappa-Β ligand, OPG= osteoprotegerin.

Fig. 5

Receiver operating characteristic (ROC) curve analysis. ROC curves were generated to determine the prognostic accuracy of a) BMP-2 and b) RANKL; the corresponding areas under the curve (AUC) and 95% confidence intervals (CI) were estimated as follows: BMP-2 at 0.823 (0.623-1.023, p= 0.038); RANKL at 0.767 (0.557-0.977, p= 0.048). The levels of both molecules were estimated on ICU admission. BMP-2= bone-morphogenetic protein 2, RANKL= receptor activator of nuclear factor kappa-Β ligand.
Receiver operating characteristic (ROC) curve analysis. ROC curves were generated to determine the prognostic accuracy of a) BMP-2 and b) RANKL; the corresponding areas under the curve (AUC) and 95% confidence intervals (CI) were estimated as follows: BMP-2 at 0.823 (0.623-1.023, p= 0.038); RANKL at 0.767 (0.557-0.977, p= 0.048). The levels of both molecules were estimated on ICU admission. BMP-2= bone-morphogenetic protein 2, RANKL= receptor activator of nuclear factor kappa-Β ligand.

Demographics on ICU admission and important outcomes of the patients who developed heterotopic ossification (HO) (HO-positive) versus those who did not (HO-negative)_

Demographics/OutcomesHO-positive patientsHO-negative patientsp-value
Number of patients (N)919
Age51(19)51(14)ns
Sex ns
         Male 14
         Female 5
APACHE II, mean (SD)16(6)17(5)ns
SOFA, mean (SD)7(1)7(2)ns
CRP (mg/dl), (median, IQR)5.1 (1.6-12.0)5.5 (1.1-8.8)ns
PCT (ng/ml), (median, IQR)1.1 (0.2-2.5)0.1 (0.1-0.8)ns
Creatinine (mg/dl), mean (SD)0.7(0.2)0.9(0.3)ns
Vitamin D (ng/ml), (median, IQR)6.8 (4.2-13.6)12.7 (6.5-16.8)ns
Diagnosis ns
         Medical0%15.8%
         Surgery/Trauma100%84.2%
Medical03
         Cerebral abscess-1
         Subarachnoid haemorrhage-1
         Cerebral haemorrhage-1
Surgical Emergency58
         Thoracic00
         Neurosurgery58
         Abdominal00
Trauma48
Comorbidities37ns
         CAD
         Arterial Hypertension
         Hypothyroidism
Mechanical ventilation (days)20 (17-25)22 (16-30)ns
ICU Length of Stay (days)29 (21-35)30 (22-40)ns
Sepsis66.7%84.2%ns
Day of sepsis10 (7-12)8 (5-10)ns
DOI: https://doi.org/10.2478/jccm-2020-0046 | Journal eISSN: 2393-1817 | Journal ISSN: 2393-1809
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Language: English
Page range: 37 - 45
Submitted on: Aug 26, 2020
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Accepted on: Nov 26, 2020
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Published on: Jan 29, 2021
Published by: University of Medicine, Pharmacy, Science and Technology of Targu Mures
In partnership with: Paradigm Publishing Services
Publication frequency: 4 issues per year
Keywords:
bone morphogenetic proteins,
critically-ill,
heterotropic ossification,
osteoprotegerin,
receptor activator of nuclear factor kappa-Β ligand
Related subjects:
Medicine,
Clinical medicine,
Internal medicine,
Internal medicine, other,
Surgery,
Surgery, other,
Anaesthesiology,
Emergency medicine and intensive-care medicine

© 2021 Alice Georgia Vassiliou, Edison Jahaj, Zafeiria Mastora, Ioannis Karnezis, Ioanna Dimopoulou, Stylianos E. Orfanos, Anastasia Kotanidou, published by University of Medicine, Pharmacy, Science and Technology of Targu Mures
This work is licensed under the Creative Commons Attribution 4.0 License.

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