Proteomic Insights into Osteoporosis: Unraveling Diagnostic Markers of and Therapeutic Targets for the Metabolic Bone Disease.

Osteoporosis (OP), a prevalent skeletal disorder characterized by compromised bone strength and increased susceptibility to fractures, poses a significant public health concern. This review aims to provide a comprehensive analysis of the current state of research in the field, focusing on the application of proteomic techniques to elucidate diagnostic markers and therapeutic targets for OP. The integration of cutting-edge proteomic technologies has enabled the identification and quantification of proteins associated with bone metabolism, leading to a deeper understanding of the molecular mechanisms underlying OP. In this review, we systematically examine recent advancements in proteomic studies related to OP, emphasizing the identification of potential biomarkers for OP diagnosis and the discovery of novel therapeutic targets. Additionally, we discuss the challenges and future directions in the field, highlighting the potential impact of proteomic research in transforming the landscape of OP diagnosis and treatment.

Development and internal validation of a clinical prediction model for osteopenia in Chinese middle-aged and elderly men: a prospective cohort study.

BACKGROUND: Early identification of patients at risk of osteopenia is an essential step in reducing the population at risk for fractures. We aimed to develop and validate a prediction model for osteopenia in Chinese middle-aged and elderly men that provides individualized risk estimates. METHODS: In this prospective cohort study, 1109 patients who attend regular physical examinations in the Second Medical Centre of Chinese PLA General Hospital were enrolled from 2015.03 to 2015.09. The baseline risk factors included dietary habits, exercise habits, medical histories and medication records. Osteopenia during follow-up were collected from Electronic Health Records (EHRs) and telephone interviews. Internal validation was conducted using bootstrapping to correct the optimism. The independent sample T-test analysis, Mann_Whitney U test, Chi-Square Test and multivariable Cox regression analysis were utilized to identify predictive factors for osteopenia in Chinese middle-aged and elderly men. A nomogram based on the seven variables was built for clinical use. Concordance index (C-index), receiver operating characteristic curve (ROC), decision curve analysis (DCA) and calibration curve were used to evaluate the efficiency of the nomogram. RESULTS: The risk factors included in the prediction model were bone mineral density at left femoral neck (LNBMD), hemoglobin (Hb), serum albumin (ALB), postprandial blood glucose (PBG), fatty liver disease (FLD), smoking and tea consumption. The C-index for the risk nomogram was 0.773 in the prediction model, which presented good refinement. The AUC of the risk nomogram at different time points ranged from 0.785 to 0.817, exhibiting good predictive ability and performance. In addition, the DCA showed that the nomogram had a good clinical application value. The nomogram calibration curve indicated that the prediction model was consistent. CONCLUSIONS: Our study provides a novel nomogram and a web calculator that can effectively predict the 7-year incidence risk of osteopenia in Chinese middle-aged and elderly men. It is convenient for clinicians to prevent fragility fractures in the male population.

Cutaneous Calcified Mass of Foot in Pseudohypoparathyoidism: Case Report.

Soft tissue calcifications frequently appear on imaging studies, representing a prevalent but non-specific discovery, varying from a local reaction without clear cause to suggesting an underlying systemic condition. Because calcifications like these can arise from various causes, an accurate differential diagnosis is crucial. Differential diagnosis entails a methodical assessment of the patient, encompassing clinical presentation, medical history, radiological and pathological findings, and other pertinent factors. Through scrutiny of the patient's medical and trauma history, we can refine potential causes of calcification to vascular, metabolic, autoimmune, neoplastic, or traumatic origins. Furthermore, routine laboratory assessments, including serum levels of calcium, phosphorus, ionized calcium, vitamin D metabolites, and parathyroid hormone (PTH), aid in identifying metabolic etiologies. We describe a rare occurrence of osteoma cutis in a 15-year-old female patient with a history of pseudohypoparathyroidism (PHP) and Albright's hereditary osteodystrophy (AHO). The patient presented with a painful mass on the lateral side of her left foot. The diagnosis was based on medical history, laboratory tests, and imaging, leading to an excisional biopsy and complete pain relief post-surgery. Understanding such rare occurrences and related conditions is crucial for accurate diagnosis and management.

Use of data-independent acquisition mass spectrometry to identify an objective serum indicator of the need for osteoporotic therapeutic intervention.

Osteoporosis is characterized by weakened bone microstructure and loss of bone mass. Current diagnostic criteria for osteoporosis are based on the T-score, which is a measure of bone mineral density. However, osteoporotic fragility fractures can occur regardless of the T-score, underscoring the need for additional criteria for the early detection of patients at fracture risk. To identify indicators of reduced bone strength, we performed serum proteomic analysis using data-independent acquisition mass spectrometry with serum samples from two patient groups, one with osteoporosis but no fractures and the other with osteopenia and fragility fractures. Collective evaluation of the results identified six serum proteins that changed to a similar extent in both patient groups compared with controls. Of these, extracellular matrix protein 1 (ECM1), which contributes to bone formation, showed the most significant increase in serum levels in both patient groups. An ELISA-based assay suggested that ECM1 could serve as a serum indicator of the need for therapeutic intervention; however, further prospective studies with a larger sample size are necessary to confirm these results. The present findings may contribute to the provision of early and appropriate therapeutic strategies for patients at risk of osteoporotic fractures. SIGNIFICANCE: This study aimed to identify objective serum indicators of the need for therapeutic intervention in individuals at risk of osteoporotic fracture. Comprehensive proteome analyses of serum collected from patients with osteoporosis but no fractures, patients with osteopenia and fragility fractures, and controls were performed by data-independent acquisition mass spectrometry. Collective evaluation of the proteome analysis data and ELISA-based assays identified serum ECM1 as a potential objective marker of the risk of fragility fractures in patients with osteoporosis or osteopenia. The findings are an important step toward the development of appropriate bone health management methods to improve well-being and maintain quality of life.

Bone health screening practices with dual-energy X-ray absorptiometry and prediction of abnormal results in pediatric inflammatory bowel disease.

OBJECTIVES: Pediatric patients diagnosed with inflammatory bowel disease (IBD) are at risk of suboptimal peak bone mass attainment. This study aimed to understand rates of bone health screening adherence, describe factors associated with dual-energy X-ray absorptiometry (DXA) acquisition, and identify factors associated with abnormal DXA. METHODS: We performed a retrospective cohort study of pediatric IBD patients over a 10-year time frame. We included IBD patients (2-20 years of age) enrolled in ImproveCareNow and excluded patients with primary metabolic bone disease. Time-to-event methods and multivariable logistic regression were employed to identify factors associated with DXA acquisition and abnormal DXA. RESULTS: In 676 patients, 464 (68.63%) pediatric patients with IBD had a risk factor for low bone mineral density (BMD); 137 (29.53%) underwent an initial DXA scan. Quiescent disease was significantly associated with a reduced likelihood of DXA (hazard ratio [HR]: 0.48; 95% confidence interval [CI]: 0.24-0.97), while weight z-score <-2 was significantly associated with DXA performance (HR: 2.07; 95% CI: 1.08-3.98). Abnormal DXA results (BMD z-score ≤-1) occurred in 59 (35.54%) individuals. After adjusting for visit diagnosis, delayed puberty, severe disease course, 6 months or greater of steroid exposure, and history of fracture, BMI z-score <-1 (odds ratio: 5.45; 95% CI: 2.41-12.33) was associated with abnormal DXA. CONCLUSIONS: DXA screening occurred in less than one-third of eligible pediatric IBD patients. Compliance was more common in patients with a weight z-score <-2 and less common in those with quiescent disease. BMI strongly predicted abnormal DXA results when adjusting for risk factors for abnormal BMD.

Association between monocyte to high-density lipoprotein-cholesterol ratio and osteoporosis: An analysis of the National Health and Nutrition Examination Survey 2013-2014.

The monocyte to high-density lipoprotein-cholesterol (HDL-C) ratio (monocyte-to-HDL-C ratio) was proposed as a marker of atherosclerosis. Osteoporosis and atherosclerosis share common risk factors and pathophysiological mechanisms. This study aimed to assess the relationship between monocyte-to-HDL-C ratio and osteoporosis. Participants aged ≥50 years with complete bone mineral density (BMD), monocyte, and HDL-C examination data from the National Health and Nutrition Examination Survey (NHANES) 2013-2014 were included. Descriptive analysis was performed separately according to males and females. Weight linear regression and weight logistic regression analyses were used to analyze the association between the monocyte-to-HDL-C ratio and BMD and osteopenia and osteoporosis and vertebral fracture. A total of 1804 participants were included. Among the participants with osteopenia, 398 (48.31%) were males and 466 (51.91%) were females. Among those with osteoporosis, 38 (2.77%) were males and 95 (9.50%) were females. In females, monocyte-to-HDL-C ratio was negatively associated with femoral neck BMD (regression coefficient (ß) = -0.18; 95% confidence interval (CI): (-0.29, -0.07)) and high monocyte-to-HDL-C ratio was associated with higher odds of osteopenia (odds ratio (OR) = 1.22; 95% CI: (1.01, 1.47)) and osteoporosis (OR = 1.68; 95% CI: (1.13, 2.49)) after adjusting for confounders. In males, only monocyte-to-HDL-C ratio >0.35 was observed to be associated with higher odds of osteoporosis (OR = 1.96; 95% CI: (1.02, 3.79)). Stratified analyses showed that similar results were also found in different populations. This study showed that the monocyte-to-HDL-C ratio was negatively associated with BMD and the risk of osteopenia and osteoporosis in females. The monocyte-to-HDL-C ratio may be a new marker of osteoporosis or osteopenia.

Bone health in children undergoing solid organ transplantation.

PURPOSE OF REVIEW: Pediatric solid organ transplant recipients are a unique and growing patient population who are at risk for metabolic bone disease both before and after transplantation. RECENT FINDINGS: The odds of sustaining a fracture in adulthood are significantly higher if an individual has sustained at least one childhood fracture, therefore, close monitoring before and after transplant is essential. Emerging data in patients with chronic kidney disease mineral and bone disorder (CKD-MBD) and hepatic osteodystrophy highlights the role of fibroblast growth factor 23 in the pathogenesis of metabolic bone disease in these conditions. While dual X-ray absorptiometry (DXA) is the most widely used imaging modality for assessment of bone mass in children, quantitative computer tomography (QCT) is an emerging modality, especially for patients with glucocorticoid-induced osteoporosis. SUMMARY: Solid organ transplantation improves organ function and quality of life; however, bone mineral density can decline following transplantation, particularly during the first three to six months. Immunosuppressive medications, including glucocorticoids, are a major contributing factor. Following transplant, treatment should be tailored to achieve mineral homeostasis, correct nutritional deficiencies, and improve physical conditioning. In summary, early identification and treatment of metabolic bone disease can improve the bone health status of pediatric transplant recipients as they enter adulthood. VIDEO ABSTRACT: http://links.lww.com/MOP/A71.

A Novel Risk Score to Predict Hungry Bone Syndrome After Parathyroidectomy for Renal Hyperparathyroidism.

OBJECTIVE: Hungry bone syndrome (HBS) is a known complication of parathyroidectomy. Patients with renal hyperparathyroidism are particularly vulnerable to HBS because of their prolonged exposure to electrolyte abnormalities and elevated parathyroid hormone (PTH). However, in-depth characterization of predictive factors for HBS in these patients is lacking. METHODS: A retrospective analysis was performed of patients with renal hyperparathyroidism who underwent parathyroidectomy at a single institution from 2011-2021. Patient demographics, clinical characteristics, and biochemical data were collected and analyzed. Boruta and binary logistic regression analyses were used to develop a scoring system. RESULTS: Thirty-three patients were identified; 16 (48%) developed HBS. Patients with HBS had significantly higher preoperative levels of serum PTH (mean difference [MS] = 2167.2 pg/mL, P <.001), phosphorus (MD = 3.5 mg/dl, P <.001), and alkaline phosphatase (ALP) (MD = 344.2 U/L, P =.002) and significantly lower levels of preoperative serum calcium (MD = -0.96 mg/dL, P =.004). Stepwise regression analysis identified elevated ALP (>150 U/L) and markedly elevated PTH (>1000 pg/mL) as positive predictors of HBS. A two-point scoring system with these 2 variables had overall diagnostic accuracy of 96.8% (sensitivity 100% and specificity 94.1%) with 1 point conferring 93.8% positive predictive value and 2 points conferring 100% positive predictive value. CONCLUSION: Preoperative serum PTH and ALP are significantly associated with HBS in patients with renal hyperparathyroidism undergoing parathyroidectomy for renal hyperparathyroidism. A scoring system with these 2 variables may be of clinical utility in predicting patients at high risk of HBS.

Prenatal and Neonatal Bone Health: Updated Review on Early Identification of Newborns at High Risk for Osteopenia.

Bone health starts with maternal health and nutrition, which influences bone mass and density already in utero. The mechanisms underlying the effect of the intrauterine environment on bone health are partly unknown but certainly include the 'foetal programming' of oxidative stress and endocrine systems, which influence later skeletal growth and development. With this narrative review, we describe the current evidence for identifying patients with risk factors for developing osteopenia, today's management of these populations, and screening and prevention programs based on gestational age, weight, and morbidity. Challenges for bone health prevention include the need for new technologies that are specific and applicable to pregnant women, the foetus, and, later, the newborn. Radiofrequency ultrasound spectrometry (REMS) has proven to be a useful tool in the assessment of bone mineral density (BMD) in pregnant women. Few studies have reported that transmission ultrasound can also be used to assess BMD in newborns. The advantages of this technology in the foetus and newborn are the absence of ionising radiation, ease of use, and, above all, the possibility of performing longitudinal studies from intrauterine to extrauterine life. The use of these technologies already in the intrauterine period could help prevent associated diseases, such as osteoporosis and osteopenia, which are characterised by a reduction in bone mass and degeneration of bone structure and lead to an increased risk of fractures in adulthood with considerable social repercussions for the related direct and indirect costs.

Bone health in inflammatory bowel disease.

INTRODUCTION: Inflammatory bowel disease (IBD) is a chronic disease characterized by the presence of systemic inflammation, manifesting not only as gastrointestinal symptoms but also as extraintestinal bone complications, including osteopenia and osteoporosis. However, the association between IBD and osteoporosis is complex, and the presence of multifactorial participants in the development of osteoporosis is increasingly recognized. Unlike in adults, delayed puberty and growth hormone/insulin-like growth factor-1 axis abnormalities are essential risk factors for osteoporosis in pediatric patients with IBD. AREAS COVERED: This article reviews the potential pathophysiological mechanisms contributing to osteoporosis in adult and pediatric patients with IBD and provides evidence for effective prevention and treatment, focusing on pediatric patients with IBD. A search was performed from PubMed and Web of Science inception to February 2023 to identify articles on IBD, osteoporosis, pediatric, and fracture risk. EXPERT OPINION: A comprehensive treatment pattern based on individualized principles can be used to manage pediatric IBD-related osteoporosis.

Bone mineral density and its influential factors in Chinese patients with newly diagnosed Crohn's disease.

OBJECTIVES: Bone loss is a common morbidity in patients with inflammatory bowel disease (IBD). Bone mineral density (BMD) measurement is recommended for IBD patients at a high risk of osteoporosis. However, there is a lack of evidence in the need of BMD measurement in patients who are young at the first disease onset. In this study we aimed to investigate the prevalence of low BMD in patients with newly diagnosed Crohn's disease (CD) at 20-50 years of age and the potential risk factors. METHODS: A single-center, retrospective cross-sectional study was conducted. Medical records of the patients were reviewed and their demographics, clinical characteristics and laboratory test results were collected. Dual energy X-ray absorptiometry (DEXA) scan was performed for BMD measurements; low BMD was defined as Z-score or T-score <-1.0 standard deviation (SD). Univariate and multivariate logistic regression analyses were used to determine the risk factors for low BMD. RESULTS: A total of 221 patients with CD were included; osteopenia and osteoporosis were identified in 23.1% and 8.6%, and 39.4% and 7.2% of the patients using Z-score and T-score, respectively. Female gender and a higher BMI at diagnosis were protective factors for low BMD. CONCLUSIONS: Low BMD is common in patients with newly diagnosed CD aged 20-50 years. Female gender and a higher BMI at diagnosis might protect CD patients from bone loss. Therefore, BMD measurement and early intervention with calcium and vitamin D are recommended for these patients.

INDICATORS OF BONE METABOLISM IN PATIENTS WITH RHEUMATOID ARTHRITIS WITH IMPAIRED BONE MINERAL DENSITY: CHARACTERISTICS, THEIR FEATURES AND DIAGNOSTIC VALUE.

Rheumatoid arthritis (RA) is an autoimmune disease with a chronic inflammatory process that affects bone metabolism and leading to impaired bone mineral density (BMD). Therefore, the determination of laboratory markers of bone metabolism contributes to a better understanding of the pathogenesis of metabolic bone diseases. The aim of the study - to characterize the bone metabolism parameters in rheumatoid arthritis patients with impaired bone mineral density, to find out their features and diagnostic value. The study included 76 patients randomly stratified by RA status who were treated in the Rheumatology Department of Lviv Regional Clinical Hospital, a municipal non-profit enterprise of Lviv Regional Council, from 2013 to 2019. The goal was achieved by performing three consecutive stages of the study. At the first stage, markers of bone formation and bone resorption were characterized. At the second stage, the peculiarities of these indicators were determined. The third stage was to determine the diagnostic value of the content of the markers of OCN formation, P1NP and resorption marker ß-CrossLaps. According to the results of the study at the first stage, it was found that, in RA patients with osteopenia, the serum content of markers of osteoblastic bone function OCN (p=0.000) and P1NP (p=0.035) was significantly lower compared to the healthy individuals of CG, while the content of the marker of bone resorption ß-CrossLaps was significantly higher (p=0. 021); in RA patients with OP, the serum content of both markers of osteoblastic bone function OCN (p=0.000) and P1NP (p=0.001) is significantly lower, while ß-CrossLaps (p>0.050) is only slightly higher compared to healthy CG subjects. According to the results obtained at the second stage of the study, it can be stated that the content of OCN and P1NP in the blood serum is significantly lower in RA patients both with osteopenia and OP compared to RA patients without BMD disorders. At the third stage of the study, it was found significant relationship between the content of P1NP and belonging to SG1 (AC -0.52). A confirmed relationship was found between the content of OCN and belonging to the group with OP (direct direction of AC 0.57; p=0.017). Bone structure disorders in rheumatoid arthritis patients with osteopenia are characterized by a weakening of bone formation and increased resorption processes; in rheumatoid arthritis patients with osteoporosis, the weakening of osteoblastic bone function is more pronounced compared to rheumatoid arthritis patients with osteopenia. For rheumatoid arthritis patients with unimpaired bone mineral density, the highest diagnostic value is provided by procollagen type I N-terminal propeptide. For rheumatoid arthritis patients with osteoporosis, osteocalcin is a diagnostically valuable marker.

Recommendations of the Spanish Society of Nephrology for the management of mineral and bone metabolism disorders in patients with chronic kidney disease: 2021 (SEN-MM).

As in 2011, when the Spanish Society of Nephrology (SEN) published the Spanish adaptation to the Kidney Disease: Improving Global Outcomes (KDIGO) universal Guideline on Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD), this document contains an update and an adaptation of the 2017 KDIGO guidelines to our setting. In this field, as in many other areas of nephrology, it has been impossible to irrefutably answer many questions, which remain pending. However, there is no doubt that the close relationship between the CKD-MBD/cardiovascular disease/morbidity and mortality complex and new randomised clinical trials in some areas and the development of new drugs have yielded significant advances in this field and created the need for this update. We would therefore highlight the slight divergences that we propose in the ideal objectives for biochemical abnormalities in the CKD-MBD complex compared to the KDIGO suggestions (for example, in relation to parathyroid hormone or phosphate), the role of native vitamin D and analogues in the control of secondary hyperparathyroidism and the contribution of new phosphate binders and calcimimetics. Attention should also be drawn to the adoption of important new developments in the diagnosis of bone abnormalities in patients with kidney disease and to the need to be more proactive in treating them. In any event, the current speed at which innovations are taking place, while perhaps slower than we might like, globally drives the need for more frequent updates (for example, through Nefrología al día).

Establishment of a nomogram model for predicting metabolic bone disease in preterm infants: A case‒control study.

OBJECTIVE: To investigate risk factors for metabolic bone disease (MBD) in preterm infants and establish a nomogram model for predicting MBD risk. METHODS: A total of 1104 preterm infants were enrolled, among whom 809 were included in the modelling set and 295 were included in the validation set. The modelling set was divided into MBD (n = 185) and non-MBD (n = 624) groups. A multivariate logistic regression analysis was used to investigate the independent risk factors for MBD. R software was used to plot the nomogram model, which was then validated by the data of the validation set. Receiver operating characteristic (ROC) and calibration curves were used to evaluate the nomogram model's performance, and the clinical decision curve was used to assess the clinical practicability of the model. RESULTS: Gestational age, time of trophic feeding initiation, parenteral nutrition duration, necrotizing enterocolitis, bronchopulmonary dysplasia, cholestasis and sepsis were independent risk factors for MBD in preterm infants (P < 0.05). The ROC curve of the modelling set had an area under the curve (AUC) of 0.801; the risk prediction value of 0.196 corresponding to the maximum Youden index was the best value, and the prediction critical value was 125 points. The ROC curve of the validation set had an AUC of 0.854. The calibration curve analysis showed good accuracy and consistency between the model's predicted and actual values. CONCLUSIONS: The nomogram model provides an efficient tool for the early assessment of MBD risk. Preterm infants with scores ≥ 125 should receive close attention and interventions in the early stage. WHAT IS KNOWN: • The incidence and severity of MBD are inversely proportional to gestational age and birth weight. Bone loss can lead to prolonged hospital stay, ventilator dependence, pathological fractures and short stature. WHAT IS NEW: • Gestational age, time of trophic feeding initiation, parenteral nutrition duration, necrotizing enterocolitis, bronchopulmonary dysplasia, cholestasis and sepsis were independent risk factors for MBD in preterm infants. The nomogram model provides an efficient tool for the early assessment of MBD risk.

Trends in incidence of recorded diagnosis of osteoporosis, osteopenia, and fragility fractures in people aged 50 years and above: retrospective cohort study using UK primary care data.

This study used primary care data to estimate the incidence of recorded diagnosis of osteoporosis, osteopenia, and fragility fracture in the UK during 2000-2018 accounting for age, sex, calendar year and social deprivation. More than 3 million people aged 50-99 years were included. We found that men living in the most deprived areas had a 45% higher risk of being diagnosed with osteoporosis and 50% higher risk of fragility fracture compared to men living in the least deprived areas. PURPOSE: a) To estimate the incidence trends of a recorded diagnosis of osteoporosis, osteopenia, and fragility fracture in the UK over time; b) to describe differences according to age, sex, and social deprivation. METHODS: This is a longitudinal population-based cohort study using routinely collected primary care data obtained via IQVIA Medical Research Database (IMRD). All patients aged 50-99 years registered with a practice participating in THIN (The Health Improvement Network) between 2000-2018 were included. The first recorded diagnosis of osteoporosis, osteopenia, or fragility fracture was used to estimate incidence rates (IR) per 10,000 person-years at risk. Poisson regression was used to provide Incidence Rate Ratios (IRR) adjusted by age, sex, social deprivation, calendar year, and practice effect. RESULTS: The year-specific adjusted IRR of recorded osteoporosis was highest in 2009 in women [IRR 1.44(95%CI 1.38-1.50)], whereas in men it was highest in 2013-2014 [IRR 1.94(95%CI 1.72-2.18)] compared to 2000. The year-specific adjusted IRR of fragility fracture was highest in 2012 in women [IRR 1.77(95%CI 1.69-1.85)], whereas in men it was highest in 2013 [IRR 1.64(95%CI 1.51-1.78)] compared to 2000. Men in the most deprived areas had a higher risk of being diagnosed with osteoporosis [IRR 1.45(95%CI 1.38-1.53)], osteopenia [IRR 1.17(95%CI 1.09-1.26)], and fragility fracture [IRR 1.50(95%CI 1.44-1.56)] compared to those living in the least deprived areas, but smaller differences were seen in women. CONCLUSION: Use of fracture risk assessment tools may enhance the detection of osteoporosis cases in primary care. Further research is needed on the effect of social deprivation on diagnosis of osteoporosis and fractures.

CHARACTERISTICS OF CALCIUM-PHOSPHORUS METABOLISM AND BONE TURNOVER INDICATORS IN PATIENTS WITH LIVER CIRRHOSIS AND THEIR DIAGNOSTIC VALUE FOR ASSESSING BONE STRUCTURES DISORDER.

Information about calcium-phosphorus metabolism (CPM) and bone turnover in patients with liver cirrhosis (LC), as well as clarifying their diagnostic value for assessing bone structure disorder, will help doctors to detect their lesions in timely manner and, based on the information received, to choose well-founded comprehensive treatment strategy. Aim - to characterize the indicators of calcium-phosphorus metabolism and bone turnover in patients with liver cirrhosis, and to find out their diagnostic value for detecting bone structure disorder. In randomized manner 90 patients with LC (27 women and 63 men of age from 18 to 66), who were treated at the Lviv Regional Hepatological Center (Communal Non-Commercial Enterprise of Lviv Regional Council "Lviv Regional Clinical Hospital") between 2016 and 2020, were included in the research. The research was carried out in two stages. The purpose of the first stage was to obtain information that would allow characterizing indicators of CPM (total calcium, ionized calcium, phosphorus, total vitamin D (25-hydroxyvitamin D), and parathyroid hormone) and bone turnover (osteocalcin, P1NP, alkaline phosphatase (bone formation markers), and ß-Cross Laps (bone resorption marker)) in patients with LC, and the purpose of the second stage was to find out their diagnostic value for assessing bone structure disorder of them. To perform research, an experimental group (EG) (72 patients with impaired bone mineral density (BMD)), which was divided into EG A (46 patients with osteopenia) and EG B (26 patients with osteoporosis), and a comparison group (18 patients with normal BMD) were formed. The control group consisted of 20 relatively healthy people. At the first stage, it was established that the frequency of cases of increased alkaline phosphatase content was statistically significantly different in LC patients with osteopenia and osteoporosis (p=0.002), as well as with osteoporosis and normal BMD (p=0.049). Impaired BMD in general had significant direct stochastic relationship with vitamin D deficiency, decrease in osteocalcin content and increase in P1NP content in serum (Yule's Coefficient of Association (YCA))>0.50); osteopenia - with decrease in phosphorus content, vitamin D deficiency and increase in P1NP content (YCA>0.50); and osteoporosis - with vitamin D deficiency, decrease in osteocalcin content, increase in P1NP content, and increase in alkaline phosphatase content in serum (YCA>0.50). Significant inverse stochastic relationship was recorded between vitamin D insufficiency and each of the impaired BMD manifestations (YCA<-0.50), which most likely indicates that it is characteristic of normal BMD. At the second stage, it was found that among indicators of CPM and bone turnover, only increase in alkaline phosphatase content in serum can be diagnostically valuable marker of osteoporosis in patients with LC (р<0.050; YCA>0.50; coefficient contingency=0.32), which has medium sensitive (80.77%) and positive predictive value (70.00%) for it. Although other indicators of CPM and bone turover did not confirm their diagnostic value in our research, they may be useful for monitoring pathogenetic changes in bone structure disorder and evaluating the effectiveness of their treatment in patients with LC. Indicators of calcium-phosphorus metabolism and bone turnover, which are characteristic of bone structure disorder and its absence in patients with liver cirrhosis, were revealed. Among them, an increase in alkaline phosphatase content in serum, which is a moderately sensitive marker of osteoporosis, is diagnostically valuable.

Early elevated alkaline phosphatase as a surrogate biomarker of ongoing metabolic bone disease of prematurity.

Very low birth weight (VLBW) neonates present a high risk of metabolic bone disease (MBD). Our main objective was to determine the easiest way to make an early diagnosis of this disease by identifying surrogate biomarkers before any radiological signs occurred. We conducted in our NICU a 6-month observational prospective study, with inclusion of all singleton VLBW neonates. We collected clinical and biological data, and nutritional intakes during hospitalization. We defined biological MBD (bMBD) as alkaline phosphatase (ALP) levels superior to 600 UI/L at day of life 30 (DOL30) and performed a case-control analysis. Nine out of 30 patients (30%) exhibited bMBD. All have extremely low birth weight and were significantly younger in gestational age (GA) and smaller at birth. There was no statistically significant difference in nutritional intake between bMBD and control groups. In the bMBD group, phosphatemia was lower since DOL3. ALP was already significantly higher at DOL15, and way beyond normal range. CONCLUSIONS: Our results showed that even the strict respect of nutritional guidelines cannot completely prevent bMBD in high-risk patients and suggest that an early screening from DOL15, with ALP levels greater than 500 UI/L, could be sufficient for detection of upcoming MBD. WHAT IS KNOWN: • Metabolic bone disease of prematurity (MBD) definition is not consensual, but biological changes appear earlier than radiological signs of rickets. • MBD management relies on biological evidence. Treatment is based on phosphate and/or calcium and calcitriol supplementation. WHAT IS NEW: • Studying phosphocalcic biological assessment in very low birth weight neonates, we showed respect of nutritional guidelines could not protect from biological MBD. • Increase in alkaline phosphatase (ALP), about 500 UI/l at day of life 15, could be a biomarker of MBD with no need of X-ray evaluation and sufficient to begin a treatment to prevent osteopenia.

A Novel Frailty Grade Combined with Cachexia Index and Osteopenia in Esophagectomy.

BACKGROUNDS: The optimal method for evaluating frailty grade in patients with cancer has not been established in patients undergoing esophagectomy for esophageal cancer. This study aimed to clarify the impact of cachexia index (CXI) and osteopenia on survival in esophagectomized patients for esophageal cancer to develop frailty grade for risk stratification of the prognosis. METHODS: A total of 239 patients who underwent esophagectomy were analyzed. CXI was calculated as follows: skeletal muscle index × serum albumin/neutrophil-to-lymphocyte ratio. Meanwhile, osteopenia was defined as below the cutoff value of bone mineral density (BMD) calculated by the receiver operating characteristic curve. We evaluated the average Hounsfield unit within a circle in the lower midvertebral core of the 11th thoracic vertebra on preoperative computed tomography as BMD. RESULTS: Multivariate analysis revealed that low CXI (Hazard ratio [HR], 1.95; 95% confidence interval [CI], 1.25-3.04) and osteopenia (HR, 1.86; 95% CI, 1.19-2.93) were independent prognostic factors for overall survival. Meanwhile, low CXI (HR, 1.58; 95% CI, 1.06-2.34) and osteopenia (HR, 1.57; 95% CI, 1.05-2.36) were also significant prognostic factors for relapse-free survival. A frailty grade combined with CXI and osteopenia stratified into four groups by their prognosis. CONCLUSIONS: Low CXI and osteopenia predict poor survival in patients undergoing esophagectomy for esophageal cancer. Furthermore, a novel frailty grade combined with CXI and osteopenia stratified the patients into four groups according to their prognosis.