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Lviv clinical bulletin 2018, 1(21)-2(22): 46-56

https://doi.org/10.25040/lkv2018.01.046

Peculiarities of Calcium-Phosphorus Metabolism and Bone State in Patients with Liver Cirrhosis: Diagnosis and Principles of Differential Treatment (Literature Rewiev and Clinical Case Description)

N. Drobinska, O. Abrahamovych, U. Abrahamovych, M. Farmaha

Danylo Halytsky Lviv National Medical University

Introduction. The disorders of calcium-phosphorus metabolism and bone tissue state, which leads to spontaneous fractures and limitation of motor activity in patients with liver cirrhosis (LC), require a deeper understanding of the etiology and pathogenesis, the use of laboratory-instrumental methods of diagnosis, taking into account risk factors and the appointment of effective treatment in order to improving quality of life. The conduction of additional research will give an impetus to the search for new methods of treatment both certain nosologies and comorbid, polymorbid diseases and will help to reduce the iatrogenic effect from the use of medicines.

The aim of the study. To review the literature on the peculiarities of calcium-phosphorus metabolism and bones state in patients with liver cirrhosis, diagnostic methods and principles of differentiated treatment and to describe a clinical case.

Materials and methods. The content analysis, the method of system and comparative analysis, the bibliosemantic method of studying the actual scientific research of the peculiarities of calcium-phosphorus metabolism and bones state in patients with LC, diagnostic methods and principles of differentiated treatment were used and the clinical case was described. 92 literary sources in Ukrainian, English and Russian have been analyzed. The search for the sources was carried out in the scientometric medical databases: PubMed-NCBI, Medline, ResearchGate, CochraneLibrary, EMBASE by keywords: liver cirrhosis, osteoporosis, hepatic osteodystrophy, densitometry, P1NP, osteocalcin, β-crossLaps, calcium, phosphorus, vitamin D, parathyroid hormone.

Results and clinical case description. Literature review. LC due to high mortality, low quality and expectancy of the life in patients is a serious problem of the XXI century over which scientists around the world work. More than 1 million people in the world died from the LC in 2010 (about 2.0 % of all deaths) [65]. The most common causes of LC are excessive use of alcohol, chronic HCV- and HBV-infection.

Hepatobiliary system damage in patients with LC is usually combined with damage of other organs and systems which requires a special ways for diagnosis and further treatment. The pathogenic processes occurring in the organism of patients with LC have a negative effect on the calcium-phosphorus metabolism (CPM) and bone tissue state, and may cause osteomalacia, osteoporosis and periosteal reactions united by the term “hepatic osteodystrophy” (HOD) [13, 25, 38, 47, 48, 68, 81].

Osteomalacia is characterized by disorders of mineralization of bones after the termination of their growth. There is a replacement of bone tissue with an osteoid tissue at the same time that shows itself in softening and deformation of the bones. Rickets unlike osteomalacia affects the mineralization of growing bones.

In the case of liver diseases osteomalacia is a rare occurrence. Its detection in patients with primary biliary cirrhosis requires additional research [26, 31, 46]. Hypocalcemia, hypophosphatemia, and vitamin D deficiency in patients with LC are not enough for diagnosis of osteomalacia. A bone biopsy is “gold standard” for diagnosing this disease.

The term of osteopenia is used to detecting a decrease in bone mineral density (BMD) and bone mass. It is an initial stage of osteoporosis and can exist for a long time without any manifestations. Osteoporosis is considered a common disease of the skeletal system in which there is a disbalance between formation and resorption of the bone. Its frequency among patients with LC varies from 20.0 % to 56.0 % in various literary sources [36, 38, 39, 47].

The risk factors for osteoporosis in patients with chronic liver disease and LC are long-term excessive use of alcohol, smoking, early climax (< 45 years), secondary amenorrhea (> 6 months), low body mass index (< 19.0 kg / m2), male hypogonadism, early osteoporosis fractures in a family history, long-term treatment with glucocorticoids (prednisolone 5.0 mg / day and more – more than three months) [44, 48].

There is a large loss of bone mass and decreases the BMD in case of osteoporosis and therefore bone fragility increases and osteoporotic fractures may occur. As a result, the quality and expectancy of the life in patients with LC decrease [68].

Osteoporosis and fractures occur more often in patients with LC than in the usual population. Older age, cholestasis, alcohol use and other risk factors for osteoporosis even more provoke bone fractures especially after liver transplantation [21, 46, 78].

The main functions of bone tissue is mechanical, protective and metabolic.  The metabolic function essence is to support the calcium-phosphorus homeostasis [12].

The main amount of phosphorus and calcium is deposited in bone tissue (approximately 80.0 % and 99.0 % respectively) [4]. Important is the biologically active ionized calcium that is not bound to proteins [4, 12].

The exchange of calcium and phosphorus and their constant concentration in the blood are regulated mainly by calcium-regulating hormones – parathyroid hormone (PTH), vitamin D, and calcitonin [4, 12].

The bone tissue consists of osteoblasts, osteocytes, osteoclasts, a matrix of collagen and non-collagen proteins (osteoid) and inorganic mineral salts. It is characterized by a dynamic restructuring that lasts continuously throughout its life. An important role in this process belongs to osteoblasts responsible for the formation and mineralization of bone tissue, as well as osteoclasts which ensure its resorption. Remodeling is the main mechanism for maintaining the mechanical integrity of the skeleton by removing the old bone and restoring damaged bone only where needed [46, 82]. This process is carefully controlled by molecules of calcium-regulating hormones, cytokines and various systemic proteins [69].

In childhood due to the prevalence of osteogenesis over resorption grow teeth and skeleton. This process changes with ages and under the influence of adverse factors destructive processes are much more prevalent, as a result the bone tissue is lost, osteopenia and osteoporosis are formed [82]. Osteocytes, which are terminally differentiated osteoblasts embedded in the matrix, act as the main regulators of phosphate homeostasis and bone resorption. They regulate the amount of osteoclasts with the formation of bone tissue by modifying the osteoblastic induced bone mineralization in response to mechanical damage [23].

Mechanisms that lead to pathological changes in bone tissue in patients with LC have been studied insufficiently. Despite this, there are a number of common factors associated with chronic liver disease that affect bone metabolism: calcium and vitamin D metabolism disorders, vitamin K deficiency, hormonal dysregulation, cytokine release, insulin-like growth factor 1 (IGF-1) deficiency, etc [48].

Vitamin D3 is hydroxylated in the liver into 25-hydroxyvitamin D (25-OH-vitamin D) and then with the participation of PTH in the kidneys – into 1,25-hydroxyvitamin D. Reduced production of 25-OH-vitamin D is due to changes in the liver functioning. As a result osteoclast-induced bone resorption and osteoblast-induced bone mineralization are disordered and resorption of calcium in the gastrointestinal tract is reduced. Also due to bile secretion disorders the absorption of fats decreases and this leads to excessive absorption of vitamin D.

In patients with jaundice due to a 25-hydroxylation disorder, intestinal malabsorption and a decrease the skin synthesis the metabolism of calcium and vitamin D is disordered [87]. With the increase in portal hypertension and the degree of liver dysfunction, the level of vitamin D in blood gradually decreases. Its deficiency can be a prognostic factor in the mortality rate in patients with LC [75].

Another factor in osteoblastic function disorder is the insufficiency of IGF-1. The deficiency of IGF-1 in patients with chronic liver disease can be explained by its production in the liver under the influence of a growth hormone. The activity of osteoblasts decreases, collagen synthesis on the bone matrix and mineralization of bones are reduced [35, 81]. In patients with LC with confirmed osteoporosis the level of IGF-1 is lower than in patients without osteoporosis and may depend on the degree of liver failure [35].

Interleukin-1, interleukin-6 and tumor necrosis factor α are involved in the inflammatory process, cholestasis and fibrosis [8, 20, 53]. These cytokines also increase the osteoclasts activity and lead to the formation of HOD. Interleukin-6, as an osteoclastogenesis inducer, is produced by osteoblasts in response to PTH, which is one of the key regulators of calcium homeostasis and is synthesized by the parathyroid glands and capable of stimulating osteoblasts to bone formation and osteoclasts to bone resorption [40, 67]. In patients with LC, caused by HCV- and HBV-infection,  the concentration of PTH in the blood may increase. This indicate the formation of secondary hyperparathyroidism [14].

Interleukin-6 can lead to bone loss due to the induction of receptor activator of nuclear factor kappa β ligand (RANKL), which is a member of the tumor necrosis factor family [30]. The receptor activator of nuclear factor kappa β (RANK) activates osteoclasts increasing bone resorption. Osteoprotegerin (OPG) inhibits the binding of RANKL with RANK preventing loss of bone mass.

In patients with primary biliary cirrhosis the level of OPG in the blood is greater and RANKL is lower than in healthy people. In patients with chronic hepatitis C the concentration of RANKL and OPG in the blood is greater than in control group [85].

Sclerostin is an inhibitor of the Wnt/β-catenin signal pathway, which is produced by osteocytes and suppresses the differentiation of osteoblasts, limiting the formation of bone tissue. There is no information about the mechanism of increasing level sclerostin in patients with LC. However, some publications point to the possible role of the liver in the sclerostin metabolism with the formation of pathological changes in bone tissue [45, 63, 79].

The liver is involved in the exchange of sex hormones (estrogens and testosterone) that support the bone system in a healthy state. Hypogonadism is quite common in patients with LC and decrease the serum  testosterone levels is an independent predictor of mortality [41]. Hypogonadism arises from the rapid loss of bone tissue, mainly due to increased osteoclast activity, especially in patients with hemochromatosis [32, 81].

Vitamin K has an anti-apoptotic effect on osteoblasts. Its deficiency does not inhibit the differentiation of osteoclasts (due to the expression of RANKL) and disrupts the ability of osteoblastic cells to synthesize bone matrix proteins – osteonetin and osteocalcin (OK). This can provoke osteopenia and loss of bone mass in patients with LC [57, 59, 70].

OK – a hormone produced by osteoblasts. It participates in homeostasis of calcium, mineralization of bone matrix and proliferation of osteoblasts [76]. Reducing its level is an important indicator of bone formation disorder and may be a manifestation of HOD in patients with LC [13, 24].

The  procollagen type I N-terminal propeptide (P1NP) is a specific marker for the formation of type I collagen and its incorporation into the bone matrix. It is responsible for bone formation. Increase the P1NP level in the blood is characteristic not only for diseases of the bone system, but may also have a prognostic value in the liver diseases and LC, because, as some studies suggest, it correlates with the degree of liver fibrosis [60, 88]. Probably, this is due to the fact that P1NP clearance is carried out by endothelial liver cells using macrophages (receptors-absorbers that recognize and capture modified proteins) [64].

The isomerized C-terminal telopeptide, which is specific for degradation of type I collagen in bone tissue and is formed by converting α-aspartic acid into β-form (β-CTx, β-crossLaps), is responsible for bone resorption. Despite the fact that P. Qvist et al. [77] found that β-crossLaps did not participate in the hepatic metabolism, it is impossible to exclude its role in the pathogenesis of bone tissue damage in patients with LC.

In study by V.Culafic-Vojinovic and colleagues [29] in patients with LC, the increase  β-crossLaps and the decrease OC levels correlated with a degree of liver failure, which may indicate an osteoblastic disorder with the decrease synthesis of collagen matrix and increased osteoclast activity.

In addition, high levels of β-crossLaps in patients before and after liver transplantation and increased bone-specific alkaline phosphatase (AP) after liver transplantation served as predictors of bone loss and risk of fracture [58].

The largest amount of AP is synthesized in bone tissue (50.0%), the rest – in the liver and other organs. In the case of osteoblast activation, the bone-specific isoferment of AP, which is responsible for the mineralization of the bone matrix is excreted from the osteoblast membrane in the total flow where determines the total AP. Increasing its level indicates the activation of bone remodeling processes [15, 39].

Hyperbilirubinemia is often found in patients with LC with osteopenia and osteoporosis. C. Janes et al. [50] noticed that an increase in the concentration of unconjugated bilirubin negatively affects the proliferation of osteoblasts. However, D. Smith et al. [84] denied the relationship between increasing the concentration of bilirubin and loss of bone mass in patients with chronic liver disease, which requires further study of its involvement in the etiopathogenesis of HOD.

The cholestasis, the influence of alcohol and iron on osteoblasts can also contribute to the pathogenesis of metabolic disorders in the sceletal system with the formation of osteoporosis and the occurrence of osteoporotic fractures in patients with LC  [44, 68].

Studies in rats have shown that γ-glutamyltranspeptidase (γ-GTP) can serve as a predictor of HOD. Y. Kawazoe et al. [51] found that increasing the level of γ-GTP increases osteoclast formation and intensifies bone resorption, and loss of bone tissue decreases in the case of the use of anti-γ-GTP antibodies.

In contrast, osteopenic changes may occur not only when increased but decreased of γ-GTP level due to inhibition of osteogenesis (bone formation). It is associated with cysteine deficiency, which is regulated by γ-GTP and corrected by N-acetylcysteine [49].

L. Fisher and A. Fisher [34] confirmed the involvement of γ-GTP in the bone metabolism of elderly people without liver disease.

Study of CPM and bone tissue state in patients with LC requires the use of various diagnostic methods that will help to choose the right treatment tactics, to avoid spontaneous fractures, to improve the life quality. Today, a variety of diagnostic methods are used for this purpose: clinical laboratory methods, X-ray absorptiometry, ultrasound densitometry (USDM), radiogrammetry, quantitative computer tomography, morphometric and histomorphometric methods, etc.

An important role belongs to the study of biochemical markers of bone metabolism with the study of osteoblastic (P1NP, OC, bone-specific AP) and osteoclastic activity (β-crossLaps), on the basis of which one can estimate the rate of bone remodeling and the effectiveness of the prescribed treatment [13, 15, 24, 29, 39, 58, 60, 88, 90]. The value of β-crossLaps is informative after 3-6 months of antiresorptive therapy [15, 71].

To evaluate the functional state of bone tissue it is also necessary to study calcium, phosphorus, vitamin D, PTH [15, 18, 19, 31, 64, 75, 87].

State BMD is assessed in accordance with the WHO guidelines for the T-score (BMD above the lower mean for young adult) and the Z-score (BMD below or above the mean for the corresponding age group), expressed in standart deviation (SD). When the deviation of the T-score from -1.0 to -2.5 SD is diagnosed osteopenia (from -1.0 to -1.5 SD – 1st degree; from -1.5 to -2.0 SD – second degree; from -2.0 to -2.5 SD – III degree), from -2.5 SD – osteoporosis.

Dual energy X-ray absorptiometry (DXA) is considered a “gold standard” for the determination of BMD [11]. However, in patients with LC with severe ascites this study may produce false results, which creates some difficulties, because the reliability of the DXA result requires prior puncture [42, 61].

In contrast, the USDM characterizes a BMD similar to DXA, but uses indicators of ultrasound vibration velocity, providing noninvasiveness, lack of X-ray irradiation, scan speed and ease of conduction of the study [11, 16].

A. Borsukov and D. Moiseev [3] examined patients with LC and found a correlation between the results of USDM of the heel bone, which is represented mainly by trabecular (spongy) bone tissue, and DXA of the bones of the lower third of the forearm (r = 0.73; p <0.05). This indicates the possibility of using USDM to study the BMD in them. The high sensitivity and specificity of USDM is proved also in studies by U. Abrahamovych et al. [1].

Recently, in clinical practice, the FRAX algorithm is used to determine the 10-year probability of osteoporotic fractures with or without information about BMD, taking into account risk factors individually for people over 40 years of age [16, 17, 83]. The use of FRAX in combination with the results of USDM increases the specificity of the indicators of evaluation of bone state disorders and predict the probability of osteoporotic fractures [16].

In the scientific literature, an active discussion is continuing on the treatment and prevention of disorders of CPM and BMD in patients with LC. All efforts are aimed at minimizing loss of bone mass, preventing fractures and reducing bone pain. Іt is important to persuade the patient to stop smoking, drink alcohol, exercise regularly and maintain a balanced diet with high levels of calcium and vitamin D.

O. Synenkyi [18] in patients with rheumatoid arthritis with vitamin D deficiency used the basic antireumatic treatment and individual targeted treatment of vitamin D deficiency, which contributed to the reduction of pain syndrome.

Despite the conflicting evidence of the effectiveness of drugs calcium and vitamin D in patients with LC, their appointment is necessary and lengthy [27, 44, 81].

Bisphosphonates inhibit bone resorption by increasing apoptosis of osteoclasts [11]. They are considered to be the drugs of choice for the treatment of osteoporosis and the most safe and effective for improving the BMD today.

Bisphosphonates, unlike other antiosteoporosis drugs, can be embedded in the bone and have been stored there for a long time. In order to avoid side effects from prolonged use, bisphosphonates should not be used for more than 3-5 years [6]. It is also necessary to clearly adhere to the recommendations for use [9].

Among the side effects of oral administration of bisphosphonates, the most frequent are erosive ulcerative changes, bleeding from the gastrointestinal tract, esophagitis, etc. [2, 10, 56].

There are certain reports of osteonecrosis of the jaw that are associated with both oral and parenteral bisphosphonates (alendronate, pamidronate, zolendronate), which are most commonly seen in cancer patients and as a result of prolonged use [54, 62, 72, 80]. After occurrence of jaw osteonecrosis as a result of prolonged use of alendronate W. Pan et al. [72] used strontium ranelate as an alternative to continuing postmenopausal osteoporosis treatment.

In the case of use risedronate (17.5 mg once a week) in combination with a proton pump inhibitor rabeprazole (10.0 mg daily) in patients ascertained a significant improvement healthy, including reduction of bodyly pain, compared with risedronate treatment only [86].

The few cases of bisphosphonates for the treatment of HOD in patients with LC are described in the scientific literature. R. Bansal et al. [22] used ibandronic acid (150.0 mg once a month) in combination with calcium and vitamin D for the treatment of osteoporosis in 19 patients with LC. There was a significant improvement in BMD and levels of calcium and vitamin D after six months of treatment. Side effects have not been detected. Other studies also confirm the positive results of using ibandronic acid (150.0 mg once a month) and alendronic acid (70.0 mg once a week) in combination with calcium and vitamin D in patients with LC [19, 22, 43, 44 73, 81, 91]. Despite the lack of clear achievement in preventing fractures these results demonstrate their safety and effectiveness.

Recent study by X. Zhou et al. [92] show new possibilities for using zolendronate and its analogue of lipophilic bisphosphonate ВРН-1236 in combination with Vγ9Vδ2 T-cells for the treatment of liver fibrosis, LC and hepatocellular carcinoma by the destruction of active stellate liver cells.

Another achievement in modern medicine was the invention of monoclonal antibodies that are used in various medical fields, especially for the treatment of oncological and many autoimmune diseases.

An important finding was the discovery of participation of the janus kinase (JAK) and the JAK/STAT signaling system in the occurrence of osteoporosis and the possibility to improve the bone tissue using inhibitors of JAK that affect the aging cells [33, 37].

Even more interest is the participation of JAK2 in the formation of LC and the occurrence of portal hypertension. The use of AG490, which is the specific inhibitor of JAK2/STAT3 signalling,  in rats with LC contributed to the reduction of manifestations of portal hypertension [55, 89]. The obtained results give impetus for additional researches and intensive search of methods of treatment of diseases not only as separate nosologies, but also as co- and polymorbide damages.

Significant success in the treatment of osteoporosis was achieved through the use of an inhibitor of RANKL (denazumab) and anti-sclerostin antibodies (romosozumab, blosozumab), based on the target mechanism of action [6, 7, 28, 63]. The use of romosozumab or denazumab for the treatment of postmenopausal osteoporosis significantly reduces the risk of fractures [5, 28].

Teriparatide is an analogue of PTH that has the ability to rapidly stimulate bone formation by increasing the number and activity of osteoblasts, but after its abolition bone mass continues to be lost. Its requiring an additional appointment of antiresorptive treatment for the preservation or improvement of the BMD [6].

Remosozumab and teriparatide are anabolic agents, but differently affect bone markers. The serum level of β-crossLaps (indicating bone resorption) decreases and P1NP (responsible for bone formation) increases when remosozumab is used. When using teriparatide the levels of P1NP and β-crossLaps increased [7].

Strontium ranelate, which is also recognized as an effective  drugs for preventing osteoporosis fractures, has the ability to control both of the processes of remodeling at the same time – stimulating the formation of bone tissue and reducing the intensity of resorption [11]. The use of strontium ranelate in patients with LC has not yet been studied which may be due to the risk of side effects [5, 11, 52].

Hormonal treatment, calcitonin and other drugs to prevent fractures and improve the state of BMD despite their effectiveness in some patients with LC after the occurrence of bisphosphonates are used uncommonly [44, 74, 81].

Description of the clinical case. A patient, 51 years old, was hospitalized with complaints of heaviness in the right and left hypochondrium, nausea, one-time vomiting after taking fried food, lack of appetite, general weakness, periodic pain in the lower extremities.

The patient considers himself ill for about a year, when the first time there was a gastrointestinal bleeding and diagnosed “liver cirrhosis”. Before that he abused alcohol. Approximately two months before hospitalization, the patient experienced nausea, general weakness, heaviness in the right hypochondrium, pain in the lower extremities. He came to a doctor at his place of residence, where he was sent for hospitalization in the gastroenterology department of the Lviv Regional Clinical Hospital.

Anamnesis of life. Suffered parotitis and varicella in childhood. Tuberculosis, venereal diseases, parasitosis in himself and his family denies. It is known about a fracture of the right collarbone due to the fall (date does not remember), with subsequent suppuration and surgical removal. Heredity is not burdened. There were no allergic reactions. Parenteral interventions for the last 6 months were performed with disposable syringes.

Results of physical examination. General status of the patient is moderate. Consciousness is clear. Position in bed is active. Structure of the body is correct, constitution is normosthenic. Height – 164 cm, weight – 74 kg. Skin is moist, of normal color, traces of combing on the shins and hands; visible mucous membranes is subicteric, moist. Peripheral lymph nodes are not palpable.

Breathing through the nose is free; there is no discharge from the nose. The chest is regular in shape, symmetrical. Breathing is mixed. Voice tremor is of medium intensity; percussion sound clear pulmonary; auscultation of the lungs: vesicular breathing, wheezing is not heard.

The area of the heart is unchanged; apical push in the V intercostal space at 1.5 cm inward from the left mid-clavicular line, medium strength, resistant. Pulse on the radial arteries is the same, 68 in 1 min, rhythmic. The heart rate is 68 / min. The blood pressure is 140/85 mm Hg. Percussion: the borders of the heart are not enlarged. Auscultation: heart sounds are rhythmical, sonorous, clean, additional noises are not listened.

Tongue is moist, with a white layer; teeth need sanitation. The abdomen is soft, bloated, palpation sensitive in the right and left hypochondrium; at auscultation – weakened peristaltic sounds. Liver is palpated to 3.0-4.0 cm below the costal margin, the dimensions according to M. Kurlov are 13 × 10 × 9 cm; spleen is palpated, enlarged, approximately 2.0 cm below the costal margin. F. Pasternatsky symptom is negative in both sides. Peripheral edema is absent. Joints configuration is unchanged, active and passive movements in full. Muscles are developed satisfactorily. Behavior is adequate, orientation in space and time is not violated. Thyroid gland is painless, not enlarged.

Patient underwent laboratory and instrumental examinations: 1) in the general blood test – a low level of hemoglobin (90.0 g / l); 2) in the general analysis of urine – traces of protein, accumulation of leukocytes to 15.0 in the field of vision, bacteria +, single oxalates; 3) in the coprogram – stool is unformed, the reaction to оccult blood is positive, moderate creatorrhea, moderate amount of non-digestible vegetable fiber, a significant amount of fatty acids, a small amount of soap, a small amount of fungus; 4) in the biochemical blood analysis – іncrease concentratіon of totаl bilirubin (27.6 μmol / l), direct bilirubin (13.8 μmol / l), indices of thymol test (13.0), AST (61.0 units / l) , γ-GTP (573.0 units / l), decrease concentratіon of albumin (up to 46.2%), increase of g-globulin (up to 25.0%); 5) in the coagulogram – prolongation of prothrombin time (18.0 sec) and INR (1.34), decrease of prothrombin index (up to 72.0%). Patient underwent immunological analysis of total antibodies to HCV (not detected), HBcore (not detected), HBeAg (not detected), HBsAg (not detected). Urine analysis by A. Nechiporenko – without deviations from the norm.

On the electrocardiogram – the likely hypertrophy of the left atrium. Ultrasound examination of internal organs: liver is enlarged by 4.0 cm, the structure is heterogeneous, echogenicity is elevated; portal vein – 14,0-15,0 mm; holedoh – 5,0; gallbladder is stagnated, its wall – 5,0-6,0 mm, without concrements; pancreas: structure is heterogeneous, echogenicity is elevated, contour is tuberous; spleen – 209.0 × 85.0 mm; v. lienalis – 13.0 mm. Esophagogastroduodenofibroscopy – varicose veins of the esophagus: II degree; focal gastropathy; papular bulbitis. Ultrasound dopplerofluometric examination of the vessels of the abdominal cavity – portal hypertension: II degree.

Consultations of other doctors: neuropathologist – dyscirculatory encephalopathy: І degree; toxic polyneuropathy of the lower extremities, I degree, with pain syndrome; ophthalmologist – central retinal degeneration of both eyes; dermatologist – onychomycosis with transition to smooth skin; dentist – chronic periodontitis of the 4th upper right tooth.

To study the CPM and the state of bone tissue in this patient, the following examinations were carried out: ionized calcium – 1.22 mmol / l (N 1.15-1.27 mmol / l), total calcium – 2.33 mmol / l (N 2.15-2.50 mmol / l), phosphorus – 1.61 mmol / l (N 0.87-1.45 mmol / l), vitamin D – 25.6 ng / ml (N 30.0-100.0) ng / ml), PTH – 33.8 pg / ml (N 15.0 – 65.0 pg / ml), OK – <2.0 ng / ml (N 2.0-22.0 ng / ml), Total P1NP – 92.27 ng / ml (N 16.27-73.87 ng / ml), β-CrossLaps – 0.186 ng / ml (N to 0.700 ng / ml), USDM – ultrasound signs of osteoporosis (bone quality index – 52.8; T-Score – -2.8; Z-Score – -2.0; the velocity of ultrasound waves through the bone tissue – 1467.4 m / s; broadband ultrasound attenuation – 27.5 dB / MHz; T-coefficient – 50.3%; Z-coefficient – 57,4%).

Based on the results of the examination, the patient has a clinical diagnosis: “Cirrhosis of the liver: toxic-alimentary etiology, stage II: 2nd degree of damage to the liver (hepatic-cellular insufficiency of the 2nd degree; portal hypertension of the 2nd degree), with a damage of the central and peripheral nervous system (dyscirculatory encephalopathy of the 1st degree; toxic polyneuropathy of the lower extremities of the 1st degree, with pain syndrome); digestive system (varicose veins of the esophagus: II degree; status after bleeding (2016); focal gastropathy; papular bulbitis); hematopoietic system (chronic anemia of moderate severity, coagulopathy); osteoarticular system (osteoporosis); rapid movement with negative dynamics, FCCP II; chronic pancreatitis in the phase of exacerbation, digestion insufficiency of the II degree; chronic cholecystitis: non-calculous, in remission phase; chronic periodontitis of the 4th upper right tooth. Сentral retinal degeneration of both eyes. Оnychomycosis with transition to smooth skin. FCTP ІІ”.

The patient was given a comprehensive pathogenetic treatment, taking into account damage to the bone and joint system, which contributed to the improvement of his status and reduction of pain in the lower extremities.

The patient was prescribed a complex pathogenetic treatment taking into account the damage of the osteoarticular system, which helped to improve his status and reduce pain in the lower extremities.

Notes: FCCP – functional class of cirrhotic patient; FCTP – functional class of therapeutic patient.

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