Lower Serum Creatinine Is Associated with Low Bone Mineral Density in Subjects without Overt Nephropathy

<div><p>Background</p><p>Low skeletal muscle mass is associated with deterioration of bone mineral density. Because serum creatinine can serve as a marker of muscle mass, we evaluated the relationship between serum creatinine and bone mineral density in an older population with normal renal function.</p><p>Methods</p><p>Data from a total of 8,648 participants (4,573 men and 4,075 postmenopausal women) aged 45–95 years with an estimated glomerular filtration rate >60 ml/min/1.73 m2 were analyzed from the Fourth Korea National Health and Nutrition Examination Survey (2008–2010). Bone mineral density (BMD) and appendicular muscle mass (ASM) were measured using dual-energy X-ray absorptiometry. Receiver operating characteristic curve analysis revealed that the cut points of serum creatinine for sarcopenia were below 0.88 mg/dl in men and 0.75 mg/dl in women. Subjects were divided into two groups: low creatinine and upper normal creatinine according to the cut point value of serum creatinine for sarcopenia.</p><p>Results</p><p>In partial correlation analysis adjusted for age, serum creatinine was positively associated with both BMD and ASM. Subjects with low serum creatinine were at a higher risk for low BMD (T-score ≤ –1.0) at the femur neck, total hip and lumbar spine in men, and at the total hip and lumbar spine in women after adjustment for confounding factors. Each standard deviation increase in serum creatinine was significantly associated with reduction in the likelihood of low BMD at the total hip and lumbar spine in both sexes (men: odds ratio (OR) = 0.84 [95% CI = 0.74−0.96] at the total hip, OR = 0.8 [95% CI = 0.68−0.96] at the lumbar spine; women: OR = 0.83 [95% CI = 0.73–0.95] at the total hip, OR=0.81 [95% CI = 0.67–0.99] at the lumbar spine).</p><p>Conclusions</p><p>Serum creatinine reflected muscle mass, and low serum creatinine was independently associated with low bone mineral density in subjects with normal kidney function.</p></div

Multivariate odds ratio and 95% confidence interval for low bone mineral density^a according to serum creatinine.

<p>^aLow bone mineral density: T-score ≤ –1.0</p><p>^bData are presented using a Chi-square test</p><p>Model 1: adjusted for age; Model 2: Model 1+ further adjusted for regular exercise, alcohol intake, current smoking status, 25(OH)D and estrogen replacement therapy (women); Model 3: Model 2+ further adjusted for HOMA-IR, daily calcium intake and body fat (%).</p><p>Multivariate odds ratio and 95% confidence interval for low bone mineral density<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0133062#t003fn001" target="_blank">^a</a> according to serum creatinine.</p

Adjusted odds ratios with 95% confidence interval for the presence of low bone mineral density for each standard deviation (SD) increase in serum creatinine.

<p>*Data were adjusted for age, current smoking status, regular exercise, daily calcium intake (mg/d), HOMA-IR, vitamin D, body fat (%) and estrogen replacement therapy (in women).</p

Adjusted odds ratios (ORs) with 95% confidence interval (CI) of metabolic syndrome and its components according to age at first delivery.

<p>Adjusted for age, current smoking, regular exercise, alcohol intake, number of pregnancies, age at menarche, hormone replacement therapy and daily total energy intake.</p><p>Adjusted odds ratios (ORs) with 95% confidence interval (CI) of metabolic syndrome and its components according to age at first delivery.</p

Characteristics of the study population according to the maternal age at first delivery.

<p>Data presented as age-adjusted mean ± standard error or n (%), except for age.</p><p>^a Non-adjusted values</p><p>BMI: body mass index; SBP: systolic blood pressure; DBP: diastolic blood pressure; HbA1c: Hemoglobin A1c; HOMA-IR: homeostasis model assessment-insulin resistance; LDL: low-density lipoprotein; HDL: high-density lipoprotein; ASM: appendicular skeletal mass</p><p>^†: The difference between ≤ 20 and 21–25: p<0.05 after post hoc comparison (Bonferroni test for continuous variables)</p><p>^‡: The difference between ≤ 20 and ≥26: p<0.05 after post hoc comparison (Bonferroni test for continuous variables)</p><p>^#: The difference between 21–25 and ≥26: p<0.05 after post hoc comparison (Bonferroni test for continuous variables)</p><p>Characteristics of the study population according to the maternal age at first delivery.</p

Adjusted mean trunk fat mass (A), waist circumference (B) and body mass index (BMI) (C) in the different age at first delivery groups.

<p>Data are expressed as estimated marginal mean and standard error (*, P<0.05 by ANCOVA after controlling for adjusted for age, number of pregnancies, age at menarche, total energy intake, regular exercise and hormone replacement therapy with Bonferroni correction). Box and whisker plots of the trunk fat mass (D), waist circumference (E) and BMI (F) among different age at first delivery groups. Boxes show interquartile range with median indicated, and the whiskers indicate the minimum and maximum value (#, P<0.05 by ANOVA with Bonferroni correction).</p

High Dietary Sodium Intake Assessed by Estimated 24-h Urinary Sodium Excretion Is Associated with NAFLD and Hepatic Fibrosis

<div><p>Background</p><p>Although high sodium intake is associated with obesity and hypertension, few studies have investigated the relationship between sodium intake and non-alcoholic fatty liver disease (NAFLD). We evaluated the association between sodium intake assessed by estimated 24-h urinary sodium excretion and NAFLD in healthy Koreans.</p><p>Methods</p><p>We analyzed data from 27,433 participants in the Korea National Health and Nutrition Examination Surveys (2008–2010). The total amount of sodium excretion in 24-h urine was estimated using Tanaka’s equations from spot urine specimens. Subjects were defined as having NAFLD when they had high scores in previously validated NAFLD prediction models such as the hepatic steatosis index (HSI) and fatty liver index (FLI). BARD scores and FIB-4 were used to define advanced fibrosis in subjects with NAFLD.</p><p>Results</p><p>The participants were classified into three groups according to estimated 24-h urinary excretion tertiles. The prevalence of NAFLD as assessed by both FLI and HSI was significantly higher in the highest estimated 24-h urinary sodium excretion tertile group. Even after adjustment for confounding factors including body fat and hypertension, the association between higher estimated 24-h urinary sodium excretion and NAFLD remained significant (Odds ratios (OR) 1.39, 95% confidence interval (CI) 1.26–1.55, in HSI; OR 1.75, CI 1.39–2.20, in FLI, both <i>P</i> < 0.001). Further, subjects with hepatic fibrosis as assessed by BARD score and FIB-4 in NAFLD patients had higher estimated 24-h urinary sodium values.</p><p>Conclusions</p><p>High sodium intake was independently associated with an increased risk of NAFLD and advanced liver fibrosis.</p></div

Characteristics of the study population according to tertiles of estimated 24-h sodium excretion.

<p>Data presented as mean ± standard deviation or n (%) for categorical variables</p><p>^§: The difference between 1^st and 2^nd: p <0.05 after ANOVA followed by Scheffé post hoc comparison</p><p>^†: The difference between 1^st and 3^rd: p <0.05 after ANOVA followed by Scheffé post hoc comparison</p><p>^‡ The difference between 2^nd and 3^rd: p <0.05 after ANOVA followed by Scheffé post hoc comparison</p><p>E24UNA, Estimated 24-hour urine sodium excretion; BMI, body mass index; ASM, appendicular skeletal mass; SBP, systolic blood pressure; DBP, diastolic blood pressure; LDL, low-density lipoprotein; HDL, high-density lipoprotein; AST, aspartate aminotransaminase; ALT, alanine aminotransferase; GGT, gamma-glutamyl transferase; HTN, hypertension; FLI, fatty liver; HSI, hepatic steatosis index</p><p>Characteristics of the study population according to tertiles of estimated 24-h sodium excretion.</p

Association of estimated 24-h sodium excretion with prevalence of NAFLD assessed by FLI and elevated serum ALT levels.

<p>Elevated ALT levels were defined as >33 IU/L for males and >25 IU/L for females. * P-value < 0.05.</p

Differences in estimated 24-h urinary sodium excretion levels among groups with and without hepatic fibrosis defined by BARD score (A) and FIB-4 (B) in subjects with NAFLD.

<p>** Data presented as mean + standard deviation.</p