Lviv clinical bulletin 2022, 1(37)-2(38): 41-52

Diagnostic Value, Predictive Value and Likelihood Ratio of Changes in Some Parameters of Laboratory Syndromes and Their Constellations in Patients with Liver Cirrhosis with Disorders of Bone Mineral Density

N. Drobinska, O. Abrahamovych, M. Abrahamovych, O. Fayura, M. Ferko, I. Korniychuk, R. Ivanochko

Danylo Halytsky Lviv National Medical University

Introduction. Changes in some laboratory blood parameters, the laboratory syndromes they appoint, and their constellations require investigation of their value for  clinicians to identify or exclude disorders of bone mineral density (DBMD) in patients with liver cirrhosis (LC).

The aim of the study. To investigate diagnostic value, predictive value and likelihood ratio of changes in certain parameters of laboratory syndromes and their constellations in patients with liver cirrhosis with disorders of bone mineral density.

Materials and methods. 90 patients with LC (27 women, 30.0 %), 63 men (70.0 %),18–66 years of age were randomly examined and stratified for bone lesions according to the T-score in accordance with WHO recommendations. 72 (80.0 %) patients combining LC with DBMD formed a research group (RG), out of which: 46 (63.9 %) patients combined LC with osteopenia (RG-A); 26 (36.1 %) patients combined LC with osteoporosis (RG-B). 18 (20.0 %) patients with LC without DBMD formed a comparison group (CG).

Laboratory syndromes were diagnosed on the basis of abnormalities detection in laboratory blood parameters, namely: cytolysis – in the case of increased levels of aspartate aminotransferase or alanine aminotransferase in blood plasma; mesenchymal-inflammatory syndrome – increased thymol test or gamma-globulins; hepatocellular insufficiency – decreased fibrinogen or prothrombin indeces, or total protein, or albumin; cholestasis – increased alkaline phosphatase (AP), or gamma-glutamyltranspeptidase or total bilirubin; portosystemic shunting – decreased sodium or potassium, or increased creatinine indeces; dyslipidemia – increased cholesterol or B-lipoproteins, triglycerides or low-density lipoproteins, or decreased high-density lipoproteins (HDL) levels.

The investigation was conducted in two stages. At the first stage the indicators of diagnostic value, predictive value and likelihood ratio of changes in laboratory parameters were figured out (first step of the first stage of research). Laboratory syndromes and their constellations  (second step), and simultaneous manifestation of a number of laboratory syndromes (third step), which exposed statistically significant differences, or had a significant direct stochastic relationship with the certain bone lesion were identified. The most informative of them, which were confirmed by both statistical criteria at the same time, were selected and therafter, during the second stage, the post-test probability of DBMD manifestations in case of their presence or absence was calculated and represented by the nomogram of Bayes’ theorem.

Results. At the first stage were identified markers of bone lesions that have higher sensitivity, negative predictive value, likelihood ratio of negative result, which could be of interest for excluding DBMD, or those that have higher specificity, positive predictive value, likelihood ratio of positive result, which could confirm the diagnosis.

During the first step the most characteristic laboratory blood parameters encompassing bone lesions were documented : for both types of DBMD – highly sensitive and most valuable decrease in HDL and highly specific increase in thymol test; only for osteopenia – highly specific increase in total cholesterol; only for osteoporosis – highly sensitive increase in aspartate aminotransferase, increase in gamma globulins and decrease in prothrombin index, moderately sensitive and most valuable increase in AP, and highly specific decrease in potassium.

At the second step were estimated constellations of laboratory syndromes as follows : for both types of DBMD – highly specific constellation of cytolysis, mesenchymal-inflammatory syndrome and dyslipidemia, that can be combined with hepatocellular insufficiency, or/and cholestasis; moderate-specific constellation mesenchymal-inflammatory syndrome and dyslipidemia, that can be combined with hepatocellular insufficiency; for osteopenia only – moderate-specific constellation of cytolysis, hepatocellular insufficiency and dyslipidemia; for osteoporosis only – cytolysis or its constellation with hepatocellular insufficiency, that can be combined by cholestasis.

At the third step it were revealed highly specific simultaneous manifestation of two different laboratory syndromes out of six characteristic of osteopenia, and highly specific and most valuable simultaneous manifestation of five out of six laboratory syndromes characteristic of osteoporosis.

The results obtained during the second stage of our investigation concerned the post-test probability of DBMD manifestations in the absence of a decreased HDL level in patient with LC indicate the possibility of its use in order to exclude any DBMD manifestation. The post-test probability of osteoporosis in the absence of increased LP values ​​is more valuable for excluding osteoporosis in patients with LC, and the maximum value of post-test probability of osteoporosis in a patient with simultaneous manifestation of five studied laboratory syndromes out of six is ​​the most valuable for osteoporosis confirmation.

Conclusions. Changes in the laboratory blood parameters of some laboratory syndromes and their constellations have been identified, which are of certain diagnostic value, predictable value and likelihood ratio, since can either confirm or deny the  disorders of bone mineral density. The most relevant were as follows : the highly sensitive decrease in high-density lipoproteins – to exclude both type disorders of bone mineral density; the moderately sensitive increase in alkaline phosphatase – to exclude osteoporosis; highly specific simultaneous manifestation of five studied laboratory syndromes out of six – to confirm osteoporosis in patients with liver cirrhosis.


  1. Abrahamovych MO, Farmaha ML. Treatment of the liver cirrhosis: modern principles, considering syntropic co- and multimorbid lesions of other organs and systems of organs. Lviv Clinical Bulletin. 2013;2(2):37-45 (Ukrainian)
  2. Abrahamovych UO, Abrahamovych OO, Tsyhanyk LV, Synenkyi OV, Guta SI. Сomparative evaluation of bone mineral density based upon the results of ultrasound osteodensitometry, X-ray Osteodensitometry, and dual-energy X-ray Absorptiometry tests in premenopausal women with systemic lupus erythematosus. Lviv Clin Bull. 2017;1(17):32-37 (Ukrainian)
  3. Drobinska NV, Abrahamovych OO, Bilous ZO, Ferko MR, Ivanochko RB, Zavadka MO. Features of Changes in Blood Parameters of Some Laboratory Syndromes and their Constellations in Patients with Liver Cirrhosis with Disorders of Bone Mineral Density. Lviv Clin Bull. 2022;2-3(35-36):23-26 (Ukrainian)
  4. Povoroznyuk VV, Balacka NI. The role of markers of bone remodeling in diagnosing systemic osteoporosis. Art of Treatment. 2013;2-3(98-99):12-14 (Ukrainian)
  5. Povoroznyuk VV, Grygorieva NV, Dzerovych NI, Balatska NI, Bystrytska MA, Povoroznyuk VV et al. Information letter. On innovations in the health care system. Algorithm for the diagnosis of osteoporosis and its complications at the secondary (specialized) level of medical care. Pain Joints Spine. 2018;8(1):54-55 (Ukrainian)
  6. Povoroznyuk VV, Grygoryeva NV, Povoroznyuk VV. Ultrasound Densitometry in the Assessment of Structural and Functional Bone. Pain Joints Spine. 2013;0(4.12):5-12 (Ukrainian)
  7. Nakaz N 271 vid 13.06.2005 Pro zatverdzhennia protokoliv nadannia medychnoi dopomohy za spetsialnistiu “Hastroenterolohiia”).
  8. Abushouk AI. Evolution of Fagan’s Nomogram; a Commentary. Emerg (Tehran). 2016;4(3):114-115.
  9. Alpaslan M, Ozkacmaz S, Bora A. The comparison of computed tomography densitometry and DEXA for diagnosis of osteoporosis. Ann Clin Anal Med. 2020;11(3):201-206.
  10. Bukhari T, Jafri L, Majid H, Khan AHH, Siddiqui I. Determining bone turnover status in patients with chronic liver disease. Cureus. 2021;13(4):e14479.
  11. Cipriani C, Colangelo L, Santori R, Renella M, Mastrantonio M, Minisola S et al. The interplay between bone and glucose metabolism. Vol. 11, Frontiers in Endocrinology. Frontiers; 2020. 122 p.
  12. Gamma Coefficient (Goodman and Kruskal’s Gamma) & Yule’s Q [Internet].
  13. Gokcan H, Akdogan M, Demir SO, Kacar S, Cam P, Kaplan M et al. Prevalence and characteristics of bone disease in cirrhotic patients. Hepatol Forum. 2020;2:48-52.
  14. Guañabens N, Parés A. Osteoporosis in chronic liver disease. Liver Int. 2018;38(5):776-785.
  15. Hammond I, Lyons DJ. Bone Mineral Densitometry Reporting and the CAR Technical Standards: Tips for the Radiologist. Can Assoc Radiol J. 2020;71(2):134-135.
  16. Iftikhar A, Ahmed ST, Asim T. Review of Bone Turn over Biomarkers for Early Diagnose of Osteoporosis. J Adv Med Med Res. 2018;26(8):1-8.
  17. Jeong H, Kim D. Bone Diseases in Patients with Chronic Liver Disease. Int J Mol Sci. 2019;20(17):4270.
  18. Khadim M, Mubashir W, Irshad A, Hospital S, Khan RY. Prevalence of Osteoporosis in Liver Cirrhosis. Asian J Multidiscip Stud. 2019;7(9):2348-7186.
  19. Marasco J, Beach P, Doerfler R, Roschier L. Doc, What Are My Chances? UMAP Journal. 2011;32:279-98.
  20. McDonald JH. Fisher’s Exact Test [Internet]. 2021.
  21. McGee DL. Understanding Medical Tests and Test Results [Internet]. Merck Manual Professional Version. 2018.
  22. Park SY, Ahn SH, Yoo J Il, Chung YJ, Jeon YK, Yoon BH et al. Position statement on the use of bone turnover markers for osteoporosis treatment. J Bone Metab. 2019;26(4):213-224.
  23. Refining Clinical Diagnosis With Likelihood Ratios | Basicmedical Key [Internet].
  24. Saeki C, Takano K, Oikawa T, Aoki Y, Kanai T, Takakura K et al. Comparative assessment of sarcopenia using the JSH, AWGS, and EWGSOP2 criteria and the relationship between sarcopenia, osteoporosis, and osteosarcopenia in patients with liver cirrhosis. BMC Musculoskelet Disord. 2019;20(1):1-12.
  25. WHO Study Group Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. World Health Organ Tech Rep. 1994;843:5-6.
  26. Wu CH, Chang YF, Chen CH, Lewiecki EM, Wüster C, Reid I et al. Consensus Statement on the use of bone turnover markers for short-term monitoring of osteoporosis treatment in the Asia-pacific region. J Clin Densitom. 2021;24(1):3-13.
  27. Yule GU. On the methods of measuring association between two attributes. J R Stat Soc. 1912;75(6):579.
  28. Zheng JP, Miao HX, Zheng SW, Liu W Le, Chen CQ, Zhong HB et al. Risk factors for osteoporosis in liver cirrhosis patients measured by transient elastography. Medicine (Baltimore). 2018;97(20):e10645.