Jaewon Choe

Higher serum uric acid is associated with higher bone mass, lower bone turnover, and lower prevalence of vertebral fracture in healthy postmenopausal women

SummaryHigher serum uric acid (UA) was associated with higher bone mass, lower bone turnover, and lower prevalence of vertebral fracture in postmenopausal women. Furthermore, UA suppressed osteoclastogenesis and decreased production of reactive oxygen species in osteoclast precursors, indicating UA may have beneficial effects on bone metabolism as an antioxidant.IntroductionUA is known to play a physiological role as an antioxidant, and oxidative stress has detrimental effects on bone metabolism. In the present study, we investigated the association of serum UA level with the osteoporosis-related phenotypes and its direct effect on bone-resorbing osteoclasts using in vitro systems.MethodsThis is a large cross-sectional study, including 7,502 healthy postmenopausal women. Bone mineral density (BMD) and serum UA concentrations were obtained from all subjects. Data on bone turnover markers and lateral thoracolumbar radiographs were available for 1,023 and 6,918 subjects, respectively. An in vitro study investigated osteoclastogenesis and reactive oxygen species (ROS) levels according to UA treatment.ResultsAfter adjusting for multiple confounders, serum UA levels were positively associated with BMD at all sites (all pu2009<u20090.001). Compared with the participants in the highest UA quartile, the odds for osteoporosis were 40xa0% higher in those in the lowest quartile. The serum UA levels were inversely related to both serum C-terminal telopeptide of type I collagen and osteocalcin levels (pu2009<u20090.001 and pu2009=u20090.004, respectively). Consistently, subjects with vertebral fracture had lower serum UA levels, compared with those without it (pu2009=u20090.009). An in vitro study showed that UA decreased osteoclastogenesis in a dose-dependent manner and reduced the production of ROS in osteoclast precursors.ConclusionThese results provide epidemiological and experimental evidence that serum UA may have a beneficial effect on bone metabolism as an antioxidant in postmenopausal women.

Higher serum uric acid as a protective factor against incident osteoporotic fractures in Korean men: a longitudinal study using the National Claim Registry

SummaryIn this large longitudinal study of 16,078 Korean men aged 50xa0years or older, we observed that baseline elevation of serum uric acid level significantly associated with a lower risk of incident fractures at osteoporosis-related sites during an average follow-up period of 3xa0years.IntroductionMale osteoporosis and related fractures are becoming recognized as important public health concerns. Oxidative stress has detrimental effects on bone metabolism, and serum uric acid (UA) is known to be a strong endogenous antioxidant. In the present study, we performed a large longitudinal study with an average follow-up period of 3xa0years to clarify the role of UA on the risk of incident osteoporotic fractures (OFs).MethodsA total of 16,078 Korean men aged 50xa0years or older who had undergone comprehensive routine health examinations were enrolled. Incident fractures at osteoporosis-related sites (e.g., hip, spine, distal radius, and proximal humerus) that occurred after the baseline examinations were identified from the nationwide claims database of the Health Insurance Review and Assessment Service of Korea by using selected International Classification of Diseases, 10th revision codes.ResultsIn total, 158 (1.0xa0%) men developed incident OFs. The event rate was 33.1 per 10,000 person-years. Subjects without incident OFs had 6.0xa0% higher serum UA levels than subjects with OFs (Pu2009=u20090.001). Multivariable-adjusted Cox proportional hazard analyses adjusted for age, body mass index, glomerular filtration rate, lifestyle factors, medical and drug histories, and the presence of baseline radiological vertebral fractures revealed that the hazard ratio per standard deviation increase of baseline UA levels for the development of incident OFs was 0.829 (95xa0% CIu2009=u20090.695–0.989, Pu2009=u20090.038).ConclusionsThese data provide the epidemiological evidence that serum UA may act as a protective factor against the development of incident OFs in Korean men.

The association between serum osteocalcin levels and metabolic syndrome in Koreans.

SummaryThe association between serum osteocalcin levels and metabolic syndrome (MS) in Korean individuals was investigated. Serum osteocalcin levels are significantly lower in subjects with MS than in those without the disease, regardless of glucose metabolism.IntroductionOsteocalcin was recently shown to affect energy metabolism. In the present study, we investigated the possible association between serum osteocalcin concentrations and MS.MethodsA cross-sectional community-based survey was conducted. Serum osteocalcin, type 1 collagen C-telopeptide (CTX) and total alkaline phosphatase (ALP) concentrations were determined in 567 subjects. MS was defined according to NCEP-ATP III criteria.ResultsSerum osteocalcin concentrations were significantly lower in subjects with MS than those without MS in postmenopausal women (18.923u2009±u20097.685 vs 22.513u2009±u20097.344xa0ng/ml, Pu2009<u20090.001) and marginally lower in subjects with MS than those without MS in men (14.550u2009±u20095.090 vs 16.125u2009±u20094.749xa0ng/ml, Pu2009=u20090.086) after adjustment for age and BMI. Further controlling with CTX or ALP did not affect this association in postmenopausal women; however, controlling with osteocalcin abolished the association between CTX and MS. Significant differences in serum osteocalcin levels by MS status were noted in subjects with normal glucose tolerance as well as those with abnormal glucose tolerance (Pu2009=u20090.032 and Pu2009<u20090.001, respectively). Compared with subjects with the highest quartile of osteocalcin, those in the lower quartile groups (Q1–Q3) had significantly increased risks of MS (ORsu2009=u20095.18, CIsu2009=u20091.15–23.42) in men. In postmenopausal women, the ORs for MS were significantly higher in the lowest quartile than in the highest quartile (ORsu2009=u20095.25, CIsu2009=u20092.42–11.36).ConclusionsThese findings suggest that osteocalcin is associated with MS, independently of glucose metabolism.

Risk stratification for advanced proximal colon neoplasm and individualized endoscopic screening for colorectal cancer by a risk-scoring model

BACKGROUNDnOnly 30% to 40% of patients with advanced proximal neoplasms (APN) have distal colon neoplasms.nnnOBJECTIVEnTo develop a risk score model for APN and propose an individualized screening protocol for colorectal cancer.nnnDESIGNnRetrospective cohort study.nnnSETTINGnTertiary-care center.nnnPATIENTSnDerivation cohort (6200 adults) and validation cohort (1389 adults).nnnINTERVENTIONnScreening colonoscopy.nnnMAIN OUTCOME MEASUREMENTSnAn APN risk score model was developed from the derivation cohort (6200 adults) and was tested in the validation cohort (1389 adults), who underwent screening colonoscopy.nnnRESULTSnAge, male sex, and smoking were clinical risk factors for APN. The presence of a distal neoplasm was a sigmoidoscopic risk factor for APN. We calculated APN risk scores (0-8) based on these variables and classified patients as low risk (0-2) or high risk (3-8). In the validation cohort, the relative risk of APN was 3.5-fold higher in the high-risk group than in the low-risk group. Our model suggests that colonoscopy should be performed as an initial screening test in patients with a high clinical risk for APN. Sigmoidoscopy should be performed initially in patients with low clinical risk for APN followed by supplementary colonoscopy in those with high APN risk scores based on both clinical and sigmoidoscopic risk factors. This protocol detected APN in 22 of 34 APN+ patients (64.7%) with little increase in the endoscopy burden, whereas only 16 of 34 APN+ patients (47.1%) would be identified by initial sigmoidoscopy followed by colonoscopy only in cases with distal neoplasms.nnnLIMITATIONSnRetrospective design.nnnCONCLUSIONnOur APN risk score model provides an algorithm for efficient screening of colorectal cancer by sigmoidoscopy and colonoscopy.

Isolated terminal ileal ulcerations in asymptomatic individuals: natural course and clinical significance

BACKGROUNDnAlthough isolated terminal ileal ulcerations (ITIUs) are occasionally observed on colonoscopic examination of asymptomatic individuals, their clinical course and guidelines for treatment are unclear.nnnOBJECTIVEnTo evaluate the clinical course and significance of ITIUs in asymptomatic individuals.nnnDESIGNnSingle-center retrospective analysis.nnnSETTINGnUniversity hospital.nnnPATIENTS AND INTERVENTIONSnAll patients diagnosed with ITIUs on colonoscopy from July 2001 to December 2007 were identified. Patients with colorectal symptoms, a history of nonsteroidal anti-inflammatory drug consumption, a history of colorectal surgery, oral or genital ulcerations, and coincidental ulceration in the ileocecal valve or colon were excluded.nnnMAIN OUTCOME MEASUREMENTSnColonoscopic findings and clinical courses of patients were analyzed.nnnRESULTSnOf the 148 included patients, 93 were followed (mean duration, 29.9 months). Of these, 62 showed resolution of ITIU on follow-up colonoscopy, including 60 who resolved without any treatment and 2 who resolved after antituberculosis medication. Follow-up colonoscopy continued to show ITIUs in the remaining 31 patients, only 1 of whom developed typical Crohns disease, whereas the other 30 showed no significant changes in the lesions (n = 22), partial improvement (n = 6), or waxing and waning endoscopic appearance (n = 2).nnnLIMITATIONSnRetrospective design, relatively short-term follow-up.nnnCONCLUSIONSnMost ITIUs incidentally observed in asymptomatic individuals resolve without any treatment. Even if these lesions persist, it is unusual for them to progress or to cause any symptoms.

Association between metabolic syndrome and bone loss at various skeletal sites in postmenopausal women: a 3-year retrospective longitudinal study.

SummaryAlthough the presence of metabolic syndrome (MetS) and increasing numbers of MetS components were associated with attenuated bone loss at various skeletal sites in postmenopausal women, this beneficial effect of MetS on bone mass can be mainly explained by higher mechanical loading in the affected subjects.IntroductionPrevious cross-sectional epidemiological studies reported the inconsistent results regarding the combined effects of MetS on bone mass. In our present report, we performed a large, longitudinal study to evaluate MetS in relation to annualized bone mineral density (BMD) changes in postmenopausal Korean women.MethodsThe study cohort consisted of 1,218 postmenopausal women who had undergone comprehensive routine health examinations with an average follow-up interval of 3xa0years. The BMD at the lumbar spine and proximal femur sites was measured with dual-energy X-ray absorptiometry using the same equipment at baseline and at follow-up.ResultsFollowing adjustment for age, baseline BMD, and lifestyle factors, the women with MetS had 21.7, 17.0, 26.7, and 31.1xa0% less bone loss at the total femur, femur neck, trochanter, and lumbar spine, respectively, compared with MetS-free women (Pu2009=u20090.004 to 0.041). Consistently, the rates of bone loss at all skeletal sites were linearly attenuated with increasing numbers of MetS components (Pu2009=u20090.004 to <0.001). Importantly, when weight and height were added as confounding factors, the differences and trends of annualized BMD changes according to the MetS status disappeared.ConclusionOur current results indicate that the beneficial effects of MetS on bone mass can be mainly explained by higher mechanical loading in the affected subjects. Consequently, MetS per se may not be a meaningful concept for predicting future bone loss and for explaining associations between osteoporosis and cardiovascular diseases.

Prevalence and Risk Factors of Early-Stage Age-Related Macular Degeneration in Patients Examined at a Health Promotion Center in Korea

We evaluated the prevalence and risk factors for early age-related macular degeneration (AMD) in Koreans 50 yr of age or older who were examined at a single health promotion center. We retrospectively reviewed the records of 10,449 subjects who visited the center over a 6-month period. Fundus photography was performed on all subjects, and systematic risk factor analysis was conducted using a structured questionnaire. All patients (n = 322) were initially diagnosed with drusen or early AMD using fundoscopy; the control group (n = 10,127) were those yielding normal fundoscopy findings. The age- and gender-adjusted prevalence of early AMD was 3.08%. Advanced age, male gender, smoking status, hyperlipidemia, working outdoors, and residence in rural areas were all significantly associated with an increased risk for development of early AMD. Higher-level ingestion of fruit or herbal medication and an increased amount of exercise were associated with a lower risk of early AMD development. In our Korean cohort, consisting principally of relatively healthy, middle-class urban adults, the prevalence of early AMD was 3.08% that is similar to that reported in earlier epidemiological studies. Several modifiable risk factors such as smoking and hyperlipidemia are associated with the prevalence of early AMD in our cohort.

Association between non-alcoholic fatty liver disease and cancer incidence rate

BACKGROUND & AIMSnLittle is known about the association between non-alcoholic fatty liver disease (NAFLD) and cancer development. This study investigated the cancer incidence rates in NAFLD and analysed the association between NAFLD and cancer development.nnnMETHODSnThis historical cohort study included subjects who were followed up for >1u202fyear after having a heath checkup at a tertiary hospital in Korea from September 1, 2004 to December 31, 2005. NAFLD was diagnosed by ultrasonographic detection of hepatic steatosis in the absence of other known liver disease, including alcoholic or viral hepatitis. Cox proportional hazards regression model was conducted to assess the association between NAFLD and cancer development.nnnRESULTSnOf 25,947 subjects, 8,721 (33.6%) had NAFLD. During the total follow-up of 164,671 person-years (median 7.5u202fyears), the cancer incidence rate of the NAFLD group was higher than that of the non-NAFLD group (782.9 vs. 592.8 per 100,000 person-years; hazard ratio [HR] 1.32; 95% confidence interval [CI] 1.17-1.49; pu202f<0.001). When demographic and metabolic factors were adjusted for, NAFLD showed a strong association with three cancers: hepatocellular carcinoma ([HCC]; HR 16.73; 95% CI 2.09-133.85; pu202f=u202f0.008), colorectal cancer in males (HR 2.01; 95% CI 1.10-3.68; pu202f=u202f0.02), and breast cancer in females (HR 1.92; 95% CI 1.15-3.20; pu202f=u202f0.01). A high NAFLD fibrosis score (NFS) and a high fibrosis-4 (FIB-4) score were associated with the development of all cancers and HCC.nnnCONCLUSIONnNAFLD was associated with the development of HCC, colorectal cancer in males, and breast cancer in females. A high NFS and a high FIB-4 score showed a strong association with the development of all cancers and HCC.nnnLAY SUMMARYnNon-alcoholic fatty liver disease (NAFLD) is associated with developing hepatocellular carcinoma (HCC). There have been limited data on the association between NAFLD and extrahepatic cancers. This study demonstrated that patients with NAFLD showed a higher association with the development of HCC, colorectal cancer in males, and breast cancer in females. A high NAFLD fibrosis score and a high fibrosis-4 score showed a strong association with the development of all cancers and HCC.

Prevalence of coronary atherosclerosis in an Asian population: findings from coronary computed tomographic angiography

We sought to estimate the prevalence of coronary atherosclerosis by coronary computed tomographic angiography (CCTA) and to identify risk factors attributable to the development of coronary atherosclerosis in an asymptomatic Asian population. We analyzed 6,311 consecutive asymptomatic individuals aged 40 and older with no prior history of coronary artery disease (CAD) who voluntarily underwent CCTA evaluation as part of a general health examination. The mean age of study participants was 54.7xa0±xa07.4xa0years, and 4,594 (72.8xa0%) were male. After age and gender adjustment using the population census of the National Statistical Office, the prevalence of plaque was 40.5xa0% [95xa0% confidence interval (CI) 38.1–42.9], and significant CAD (diameter stenosis ≥50xa0%) was observed in 9.0xa0% (95xa0% CI 7.7–10.2). Individuals with significant CAD were significantly older than those without (59.2xa0±xa08.8 vs. 54.0xa0±xa07.1xa0years, pxa0<xa00.001). Compared with individuals with no cardiovascular risk factors, there was a higher prevalence of significant CAD in individuals with diabetes mellitus [standardized rate ratio (SRR) 2.66; 95xa0% CI 1.93–3.68; pxa0<xa00.001], hypertension (SRR 2.24; 95xa0% CI 1.69–2.97; pxa0<xa00.001), or hyperlipidemia (SRR 1.65; 95xa0% CI 1.25–2.17; pxa0<xa00.001). There was also a greater prevalence of significant CAD in individuals with an intermediate or high Framingham risk score (SRR 5.91; 95xa0% CI 2.34–14.95; pxa0<xa00.001) or a high atherosclerotic cardiovascular disease risk score (SRR 8.04; 95xa0% CI 3.04–21.23; pxa0<xa00.001). The prevalence of coronary atherosclerosis in this Asian population was not negligible and was associated with known cardiovascular risk factors and high-risk individuals.

Comparison of Coronary Computed Tomographic Angiographic Findings in Asymptomatic Subjects With Versus Without Diabetes Mellitus

There are limited data on the impact of diabetes mellitus (DM) on the risk of subclinical atherosclerosis. Therefore, we sought to investigate the impact of DM on the risk of subclinical atherosclerosis in asymptomatic subjects. We analyzed 2,034 propensity score-matched asymptomatic subjects who underwent coronary computed tomographic angiography (mean age 55.9 ± 8.2xa0years; men 1,725 [84.8%]). Coronary artery calcium score, degree and extent of coronary artery disease (CAD), and clinical outcomes were assessed. High-risk CAD was defined as at least 2-vessel coronary disease with proximal left anterior descending artery involvement, 3-vessel disease, or left main disease. Compared with subjects without DM, those matched with DM had higher coronary artery calcium score (89.9 ± 240.4 vs 62.8 ± 179.5, pxa0= 0.004) and more significant CAD (≥50% diameter stenosis, 15.2% vs 10.2%, pxa0= 0.001), largely in the form of 1-vessel disease (10.8% vs 7.3%, pxa0= 0.007). However, there were no significant differences between matched pairs in significant CAD in the left main or proximal left anterior descending artery (5.3% vs 3.8%, pxa0= 0.138), multivessel disease (4.4% vs 2.9%, pxa0= 0.101), and high-risk CAD (4.3% vs 2.7%, pxa0= 0.058). During the follow-up period (median 21.8, interquartile range 15.2 to 33.4 months), there was no significant difference in the composite of all-cause death, myocardial infarction, acute coronary syndrome, and coronary revascularization between 2 groups (hazard ratio 1.438, 95% confidence interval 0.844 to 2.449, pxa0= 0.181). In asymptomatic subjects, those matched with DM have more subclinical atherosclerosis, mainly confined to non-high-risk CAD, than those matched without DM, and there are no differences in high-risk CAD and clinical outcomes.