Drobinska N. Bone disorders in patients with liver cirrhosis: attack rate and nature; peculiarities of pathogenesis and clinical manifestations of bone mineral density changes; their diagnostic value; prediction of the probability of bone structure disorders

The dissertation presents a theoretical generalization and a new solution to an actual scientific task – to enhance diagnostics and ascertain the prognosis of bone structure disorders in patients with liver cirrhosis (LC) by: determining the frequency and characteristics of bone structure changes; clarifying the distinctive features of the pathogenesis and clinical manifestations of bone mineral density (BMD) disorders; ascertaining their diagnostic value; evaluating the risk of fractures and its diagnostic value; determining the post-test probability of bone structure disorders in general, and osteopenia and osteoporosis in particular. It was found that bone structure disorders and their manifestations were significantly more common among patients with LC (p < 0.010) than among relatively healthy individuals, and the prevalence of BMD disorders among patients with LC was 80.00 %. Of these, 51.11 % were manifested by osteopenia and 28.89 % by osteoporosis. Bone disorders in patients with LC have certain features of pathogenesis and clinical manifestations. Diagnostically valuable for osteopenia is highly sensitive decreased (dec) high-density lipoprotein (HDL) (sensitivity is 93.48 %; р < 0.001; coefficient of association is 0.87). Osteoporosis diagnostically valuable markers in patients with LC are medium sensitive constellation "dec RBC + increased (inc) RDWS" (sensitivity is 83.33 %; р = 0.045; coefficient of association is 0.63), highly specific constellation "dec RBC + dec MCV + inc RDWS ", which can combine with dec HGB and/or dec HCT and/or inc RDWC (specificity is 100.00 %; р = 0.029; contingency coefficient is 0.38), medium sensitive inc alkaline phosphatase (sensitivity is 80.77 %; р = 0.049; coefficient of association is 0.62), highly sensitive dec HDL (sensitivity is 100.00 %; р < 0.001; contingency coefficient is 0.61), highly specific simultaneous manifestation of five different LC laboratory syndromes out of six (specificity is 100.00 %; р = 0.031; contingency coefficient is 0.36), highly specific presence of previous fractures (specificity is 94.44 %; р = 0.002; coefficient of association is 0.89) and medium specific normal body weight (specificity is 72.22 %; р = 0.036; coefficient of association is 0.61). A low risk of fractures most often occurs in LC patients without bone structure disorders (p ≤ 0.005) and is most likely characteristic of BMD within the normal range (coefficient of association 0.74–0.90). The average risk of fractures is most often characteristic of LC patients with osteopenia and is a diagnostically valuable medium sensitive marker of osteopenia (sensitivity is 80.43 %; p = 0.028; coefficient of association is 0.61). A high risk of fractures is most often recorded in LC patients with osteoporosis and is a diagnostically valuable highly specific marker of osteoporosis (specificity is 94.44 %; p = 0.031; coefficient of association is 0.80). It has been observed that as bone structure disorders become more severe in patients with LC, the risk of fracture, being the most severe manifestation of bone damage, also increases (p < 0.001). Our identification of markers of bone damage based on their prevalence in patients with LC enables the prediction of the likelihood of bone structure disorders. The presence of previous fractures is most likely to indicate BMD disorders in general and osteoporosis in particular, and their absence – the absence of osteoporosis. The presence of a normal body weight is more valuable for predicting bone structure disorders in general and, in its absence, the absence of osteoporosis. If the erythrogram of LC patient does not contain the constellation "dec RBC + inc RDWS", then most likely he does not have osteoporosis, but the presence of the constellation "dec RBC + dec MCV + inc RDWS" or its combination with dec HGB and/or dec HCT and/or inc RDWC, most likely to confirm osteoporosis. Detection of dec HDL in LC patient will indicate BMD disorders in general, and if the marker is absent, bone structure disorders and osteoporosis in particular will be absent. If LC patient does not have inc alkaline phosphatase in the blood, then most likely he will not have osteoporosis. The simultaneous presence of five LC laboratory syndromes most likely indicates osteoporosis. Detection of a low fractures risk in LC patient after using Ukrainian FRAX® model will most likely rule out BMD disorder and its manifestations. An intermediate fractures risk will indicate osteopenia and the need to refer the patient for further examination of the bone tissue condition. Detection of a high fractures risk in patient with LC is most likely a sign of osteoporosis and it allows reasonable prescribtion of pathogenetic treatment.