Bone mineral density and disorders of mineral metabolism in chronic liver disease

AIM： To estimate the prevalence and identify the risk factors for metabolic bone disease in patients with cirrhosis. METHODS： The study was performed on 72 Indian patients with cirrhosis （63 male, 9 female; aged 〈 50 years）. Etiology of cirrhosis was alcoholism （n = 37）, hepatitis B （n = 25） and hepatitis C （n = 10）. Twenty-three patients belonged to Child class A, while 39 were in class B and 10 in class C. Secondary causes for metabolic bone disease and osteoporosis were ruled out. Sunlight exposure, physical activity and dietary constituents were calculated. Complete metabolic profiles were derived, and bone mineral density （BMD） was measured using dual energy X ray absorptiometry. Low BMD was defined as a Z score below -2. RESULTS： Low BMD was found in 68% of patients. Lumbar spine was the most frequently and severely affected site. Risk factors for low BMD included low physical activity, decreased sunlight exposure, and low lean body mass. Calcium intake was adequate, with unfavorable calcium： protein ratio and calcium： phosphorus ratio. Vitamin D deficiency was highly prevalent （92%）. There was a high incidence of hypogonadism （41%）. Serum estradiol level was elevated significantly in patients with normal BMD. Insulin-like growth factor （IGF） 1 and IGF binding protein 3 levels were below the age-related normal range in both groups. IGF-1 was significantly lower in patients with low BMD. Serum osteocalcin level was low （68%） and urinary deoxypyridinoline to creatinine ratio was high （79%）, which demonstrated low bone formation with high resorption. CONCLUSION： Patients with cirrhosis have low BMD. Contributory factors are reduced physical activity, low lean body mass, vitamin D deficiency and hypogonadism and low IGF-1 level.

Long-Term Effect of Ferric Citrate Hydrate on Mineral Metabolism and Anemia in Maintenance Hemodialysis Patients

Background: Ferric citrate hydrate is a phosphate (P)-binder drug that is indicated for patients with chronic kidney disease (CKD) undergoing maintenance hemodialysis (MHD). Objectives: The objectives of this study were to evaluate the changes in the serum mineral metabolism biomarker levels and treatment status of anemia in MHD patients receiving ferric citrate hydrate. Methods: A total of 132 adult dialysis patients were enrolled in this study. Bone turnover marker levels, anemia status and iron biomarker levels over a period of 18 months after the start of the ferric citrate hydrate treatment were extracted from the medical records of the patients. Results: At enrollment, 14 (10.6%) patients were P-binder-naïve, and 118 (89.4%) patients were receiving other P-binders. The serum P level before the start of ferric citrate hydrate treatment was ≤5.5 mg/dL in 18.8% of the patients. After 18 months of ferric citrate hydrate treatment, the proportion of patients with serum P levels ≤ 5.5 mg/dL increased to 47.7%. The mean ± standard error of the mean (SEM) of the serum P level was 7.05 ± 0.14 mg/dL at the baseline, and decreased to 5.83 ± 0.17 mg/dL after 18 months of treatment with ferric citrate hydrate. The mean ± SEM of the serum hemoglobin (Hb), ferritin, and transferrin saturation (TSAT) levels were 11.96 ± 0.76 g/dL, 71.13 ± 6.09 ng/mL, and 25.19% ± 1.21%, respectively, at the baseline, and 11.45 ± 0.13 g/dL, 124.94 ± 8.62 ng/mL, and 26.18% ± 0.99%, respectively, after 18 months of ferric citrate hydrate treatment. Conclusions: These results suggest that the serum P and anemia biomarker levels observed in this study were similar to those reported in clinical trials.

Effect of Nitrogenous Fertilizer Treatment on Mineral Metabolism in Grazing Yaks

To assess the impact of N fertilization on contents of mineral elements in herbage and the effect of increased forage S on the copper metabolism of grazing yaks, study was conducted during the summer grazing season （2005, 2006, and 2007）. Pasture replicates （20 ha; n=3 per treatment） received the same fertilizer treatment in each growing season, consisting of i） 90 kg N ha^-1 from quickly available nitrogen, ii） 90 kg N ha^-1 from ammonium nitrate, iii） 90 kg N ha^-1 from ammonium sulfate, and iv） control （no fertilizer）. Forage sampling was collected at 60 days intervals following fertilization （10 samples per pasture） for Cu, Mo, Mn, Se, Fe, Zn, Ca, and P. To determine the effect of fertilizer treatment on mineral metabolism in grazing yaks, liver and blood samples were collected at the start and end of the study period in 2005, 2006, and 2007. Ammonium sulfate fertilization increased （P 〈 0.01） forage S concentration. Plant tissue N concentrations were increased by N fertilization, regardless of source in 2005, 2006, and 2007. Yaks grazing S fertilization pastures had lower （P〈0.05） liver and blood Cu concentrations at the end of the study period in 2005, 2006, and 2007, compared with urea, ammonium nitrate, and control. Nominal increases in forage in vitro organic matter digestibility were realized by fertilization, regardless of N source in each year.

Mineral metabolism disturbances are associated with the presence and severity of calcific aortic valve disease

Objective：We investigated whether disturbance of calcium and phosphate metabolism is associated with the presence and severity of calcific aortic valve disease （CAVD） in patients with normal or mildly impaired renal function. Methods：We measured serum levels of calcium, phosphate, alkaline phosphatase （AKP）, intact parathyroid hormone （iPTH）, 25-hydroxyvitamin D （25-OHD）, and biomarkers of bone turnover in 260 consecutive patients with normal or mildly impaired renal function and aortic valve sclerosis （AVSc） （n=164） or stenosis （AVS） （n=96） and in 164 age- and gender-matched controls. Logistic regression models were used to determine the association of mineral metabolism parameters with the presence and severity of CAVD. Results：Stepwise increases were observed in serum levels of calcium, phosphate, AKP, and iPTH from the control group to patients with AVS, and with reverse changes for 25-OHD levels （al P〈0.001）. Similarly, osteocalcin, procol agen I N-terminal peptide, andβ-isomerized type I col agen C-telopeptide breakdown products were significantly increased stepwise from the control group to patients with AVS （al P〈0.001）. In patients with AVS, serum levels of iPTH were positively, in contrast 25-OHD levels were negatively, related to trans-aortic peak flow velocity and mean pressure gradient. After adjusting for relevant confounding varia-bles, increased serum levels of calcium, phosphate, AKP, and iPTH and reduced serum levels of 25-OHD were in-dependently associated with the presence and severity of CAVD. Conclusions： This study suggests an association between mineral metabolism disturbance and the presence and severity of CAVD in patients with normal or mildly impaired renal function. Abnormal bone turnover may be a potential mechanism.

Effects of Different Hemodialysis Treatments on Abnormal Mineral and Bone Metabolism in Patients with Chronic Renal Failure

Objective:To investigate the effects of different hemodialysis treatments on abnormal mineral and bone metabolism in patients with chronic renal failure.Methods:A random number table was used to divide 80 patients with chronic renal failure admitted to our hospital from January 2018 to January 2019 into 2 groups,with 40 cases in each group.Group A was treated with low-flux hemodialysis,and group B was treated with high-flux hemodialysis.The related indicators of mineral and bone metabolism of the two groups were compared.Results:Before treatment,the blood calcium,blood phosphorus,intact parathyroid hormone(iPTH),type I procollagen amino terminal peptide(PINP),fibroblast growth factor 23(FGF23),serum creatinine(Scr)indicators of the two groups were compared.The difference was not statistically significant(P>0.05);After treatment,the blood calcium levels of the two groups were higher than before treatment,the blood phosphorus,iPTH,PINP,FGF23,and Scr levels were lower than before treatment,and the blood calcium level of group B was higher than that of group A,while blood phosphorus,iPTH,PINP,FGF23,and Scr levels were lower than group A,the difference was statistically significant(P<0.05).Conclusion:Compared with low-flux hemodialysis,patients with chronic renal failure treated with highflux hemodialysis have better results,which can correct abnormal bone metabolism and improve Scr levels.

Bone Remodeling and Energy Metabolism:New Perspectives

Bone mineral, adipose tissue and energy metabolism are interconnected by a complex and multilevel series of networks. Calcium and phosphorus are utilized for insulin secretion and synthesis of high energy compounds. Adipose tissue store lipids and cholecalciferol, which, in turn, can influence calcium balance and energy expenditure. Hormones long-thought to solely modulate energy and mineral homeostasis may influence adipocytic function. Osteoblasts are a target of insulin action in bone. Moreover, endocrine mediators, such as osteocalcin, are synthesized in the skeleton but regulate carbohydrate disposal and insulin secretion. Finally, osteoblasts and adipocytes originate from the same mesenchymal progenitor. The mutual crosstalk between osteoblasts and adipocytes within the bone marrow microenvironment plays a crucial role in bone remodeling. In the present review we provide an overview of the reciprocal control between bone and energy metabolism and its clinical implications.

Contribution of Musculoskeletal Disorders to Chronic Lumbago in Parkinson’s Disease

Purpose: To clarify the impact of bone metabolism disorder on lumbago in Parkinson’s Disease (PD). Methods: Data was retrospectively analyzed from 52 patients with PD in our outpatient clinic for more than 1 year (mean age, 63 ± 4 years old;mean duration from onset, 6.3 ± 0.8 years). Patients’ characteristics, comorbid musculoskeletal disorders, serum bone metabolism biomarkers, and bone mineral density were examined. Results: Twenty-one PD patients (40.2%) had chronic lumbago. Severe comptocormia and scoliosis were the most common musculosketal disorders in this group (47.6%) affected by lumbago, followed by osteoporosis (14.3%), compression fracture (4.8%). There was no significant difference in the duration of PD, body mass index, frequency of falls, bone mineral density, tartrate-resistant acid phosphatase-5b, osteocalcin, and N-terminal telopeptide between PD patients with or without chronic lumbago. Multivaritae logistic regression analysis identified the independent predictors of chroni lumbago in PD patients as Hoen-Yahr stage (odds ration [OR] = 2.794, 95%CI 1.103 - 7.076), and elevated serum 1,25-OH2 vitamin D level ([OR] = 0.92, 95%CI 0.86 - 98). Conclusion: Bone metabolism disorders are found to be associated with chronic lumbago in PD patients.

Interleukin-1 gene polymorphism disease activity and bone mineral metabolism in rheumatoid arthritis

Objective To determine whether interleukin-1α and 1β gene polymorphism is associated with rheumatoid arthritis disease activity and bone mineral metabolism, and whether there is any relationship between IL-1β and rheumatoid arthritis (RA) motif gene. Methods IL-1 gene polymorphisms were analyzed in 65 RA patients who met American College of Radiology (ACR) criteria and 60 controls. From genomic DNA, 2 polymorphisms in each gene for IL1α-889 and IL-1β+3953 were typed by PCR-RFLP and HLA-DRB1 allele typing was also undertaken by PCR-SSOP. Some clinical and laboratory parameters were collected. The allelic frequencies and carriage rates were compared between RA patients and controls and between patients with active and quiescent disease. Comparison was also made between IL-1 polymorphism and parameters of bone mineral metabolism and between patients with the HLA-DRB1 RA motif plus IL-1β 2 and patients without the two alleles. Fisher test and the analysis of variance was used to analyze the data.Results There was no significant difference in the frequency and carriage rate of IL-1α polymorphisms between RA patients and the controls. The β2/2 genotype of IL-1β was more common in female RA patients compared with controls (P=0.001). A lower carriage rate of IL-1β 2 occurred in male RA patients (P=0.001). A higher carriage rate of IL-1α2 is associated with a higher ESR (P=0.008), HAQ score (P=0.03), and vit-D 3 (P【0.001), but conversely a lower SJC (p=0.002), a lower RF (P=0.002) and a lower BMD at the lumbar spine (P=0.001). A higher frequency of IL-1α1 is associated with a lower CRP value (P=0.009). An increased IL-1β2 carriage is associated with active rheumatoid disease as indicated by a higher CRP (P【0.001), ESR (P【0.001) and pain score (P=0.001) and a higher BMD at the lumbar spine (P=0.007), lower vit-D 3 and. Udpd/Crea level The presence of the HLA DRB1 RA motif and IL-1β allele 2 at same time did not contribute to disease activity.Conclution Polymorphisms of the IL-β gene may affect the RA occurrence. Carriage of IL-1β2 polymorphisms is associated with more active disease in RA and the presence of both the IL-1α2 and the IL-1β1 allele in RA influences bone resorption.

Effects of raloxifene hydrochloride on bone mineral density,bone metabolism and serum lipids in postmenopausal women:a randomized clinical trial in Beijing

Objective To determine the effects of raloxifene hydrochloride (RLX) on bone mineral density (BMD),bone metabolism markers and serum lipids in healthy postmenopausal women in Beijing.Methods A multicenter,randomized,double-blind,placebo-controlled study was conducted in a total of 204 healthy postmenopausal women (age 59.5±5.0 years and weight 62.8±8.7 kg) treated with either RLX 60 mg (n=102) or placebo (n=102) daily for 12 months. BMD,serum lipids,and bone markers were measured before and after drug administration.Results Compared with placebo,RLX produced a significant increase in both total lumbar spine and total hip BMD. For the lumbar spine,percentage increase in total BMD was 2.3% with RLX compared with a decrease of 0.1% with placebo ( P <0.001). Corresponding values for total hip BMD were a 2.5% increase for RLX and a 1.1% increase for placebo ( P =0.011). For biochemical markers of bone metabolism,serum osteocalcin and C-telopeptide,percentage decreases were 27.65% and 24.02% in RLX-treated subjects. Corresponding values in placebo were a 10.64% decrease and a 15.75% increase (RLX compared with placebo,both P <0.001). For total cholesterol and low-density lipoprotein cholesterol levels,percentage decreases were 6.44% and 34.58% in the RLX-treated group. Corresponding values in placebo-treated patients were a 1.44% increase and a 19.07% decrease (RLX compared with placebo,both P <0.001). No differences were found for high-density lipoprotein cholesterol or triglyceride levels between the two groups. Only 5 subjects discontinued early owing to an adverse event (3 in the RLX group and 2 in the placebo group). Conclusions This study confirms that RLX exerts positive effects on the skeleton,increasing BMD and decreasing biochemical markers of bone metabolism,and has a positive effect on the overall serum lipid profile in postmenopausal women in China.