Identification of Novel Genetic Variants Related to Trabecular Bone Score in Community-Dwelling Older Adults

공성혜,윤지원,김정희,박주용,최지엽,이지현,홍아람,조남한,신찬수 대한내분비학회 2020 Endocrinology and metabolism Vol.35 No.4

Background: As the genetic variants of trabecular bone microarchitecture are not well-understood, we performed a genome-wide association study to identify genetic determinants of bone microarchitecture analyzed by trabecular bone score (TBS). Methods: TBS-associated genes were discovered in the Ansung cohort (discovery cohort), a community-based rural cohort in Korea, and then validated in the Gene-Environment Interaction and Phenotype (GENIE) cohort (validation cohort), consisting of subjects who underwent health check-up programs. In the discovery cohort, 2,451 participants were investigated for 1.42 million genotyped and imputed markers. Results: In the validation cohort, identified as significant variants were evaluated in 2,733 participants. An intronic variant in iroquois homeobox 3 (IRX3), rs1815994, was significantly associated with TBS in men (P=3.74E-05 in the discovery cohort, P=0.027 in the validation cohort). Another intronic variant in mitogen-activated protein kinase kinase 5 (MAP2K5), rs11630730, was significantly associated with TBS in women (P=3.05E-09 in the discovery cohort, P=0.041 in the validation cohort). Men with the rs1815994 variant and women with the rs11630730 variant had lower TBS and lumbar spine bone mineral density. The detrimental effects of the rs1815994 variant in men and rs11630730 variant in women were also identified in association analysis (β=–0.0281, β=–0.0465, respectively). Conclusion: In this study, the rs1815994 near IRX3 in men and rs11630730 near MAP2K5 in women were associated with deterioration of the bone microarchitecture. It is the first study to determine the association of genetic variants with TBS. Further studies are needed to confirm our findings and identify additional variants contributing to the trabecular bone microarchitecture.

Star-Shaped Intense Uptake of 131I on Whole Body Scans Can Reflect Good Therapeutic Effects of Low-Dose Radioactive Iodine Treatment of 1.1 GBq

공성혜,임정아,송영신,문신제,김예안,김민주,조선욱,문재훈,이가희,박도준,조보연,박영주 대한내분비학회 2018 Endocrinology and metabolism Vol.33 No.2

Background: After initial radioactive iodine (RAI) treatment in differentiated thyroid cancer patients, we sometimes observe a star-shaped region of intense uptake of 131I on whole body scans (WBSs), called a ‘star artifact.’ We evaluated the clinical implications of star artifacts on the success rate of remnant ablation and long-term prognosis. Methods: Total 636 patients who received 131I dose of 1.1 GBq for the initial RAI therapy and who did not show distant metastasis at the time of diagnosis were retrospectively evaluated. A negative second WBS was used for evaluating the ablation efficacy of the RAI therapy. Among them, 235 patients (36.9%) showed a star artifact on their first WBS. Results: In patients with first stimulated thyroglobulin (sTg) levels ≤2 ng/mL, patients with star artifacts had a higher rate of negative second WBS compared with those without star artifacts (77.8% vs. 63.9%, P=0.044), and showed significantly higher recurrence-free survival (P=0.043) during the median 8.0 years (range, 1.0 to 10.0) of follow-up. The 5- and 10-year recurrence rates (5YRR, 10YRR) were also significantly lower in patients with star artifacts compared with those without (0% vs. 4.9%, respectively, P=0.006 for 5YRR; 0% vs. 6.4%, respectively, P=0.005 for 10YRR). However, ablation success rate or recurrence-free survival was not different among patients whose first sTg levels >2 ng/mL regardless of star artifacts. Conclusion: Therefore, star artifacts at initial RAI therapy imply a good ablation efficacy or a favorable long-term prognosis in patients with sTg levels ≤2 ng/mL.

Effects of Dapagliflozin on Endothelial Function, Renal Injury Markers, and Glycemic Control in Drug-Naïve Patients with Type 2 Diabetes Mellitus

공성혜,구보경,문민경 대한당뇨병학회 2019 Diabetes and Metabolism Journal Vol.43 No.5

Background: The study aimed to evaluate the effects of dapagliflozin and metformin on vascular endothelial function and renalinjury markers. Methods: This prospective, randomized, open-label, crossover study included drug-naïve patients with type 2 diabetes mellitus,who were randomized to receive 8 weeks of initial treatment using metformin or dapagliflozin and crossed over for another 8weeks of treatment after a 1-week washout period. Systemic endothelial function was evaluated via the reactive hyperemic index(RHI). Results: The 22 participants included 10 males (45.5%) and had a median age of 58 years. The RHI values were not significantlychanged during both 8-week treatment periods and there was no significant difference between the treatments. Relative to themetformin group, 8 weeks of dapagliflozin treatment produced significantly higher median N-acetyl-beta-D-glucosaminidaselevels (10.0 ng/mL [interquartile range (IQR), 6.8 to 12.1 ng/mL] vs. 5.6 ng/mL [IQR, 3.8 to 8.0 ng/mL], P=0.013). Only the dapagliflozingroup exhibited improved homeostatic model assessment of insulin resistance and body weight, while serum ketone andβ-hydroxybutyrate levels increased. Conclusion: Dapagliflozin treatment did not affect systemic endothelial function or renal injury markers except N-acetyl-beta-D-glucosaminidase.

갑상선기능항진증과 열결절로 나타난 갑상선유두암 1예

공성혜,이서영,양예슬,문재훈 대한갑상선학회 2016 International Journal of Thyroidology Vol.9 No.1

We report a case of a 74-year-old woman who was incidentally found to have a single thyroid nodule. Laboratory evaluation showed undetectable serum thyroid stimulating hormone and elevated free thyroxine levels. 99mTc thyroid scan showed a hyperfunctioning autonomous nodule in a right lobe of the thyroid. Thyroid ultrasonography showed a 2.2 cm sized nonhomogeneous spiculated nodule with microcalcification, and which was identical with the hyperfunctioning nodule confirmed in thyroid scan by 99mTc single photon emission computed tomography/computed tomography. Fine needle aspiration was done, and cytology reported as suspicious of malignancy. The patient underwent total thyroidectomy with central neck dissection, and pathology was consistent with papillary thyroid carcinoma. This case report demonstrates that diagnosis of a hyperfunctioning autonomous thyroid nodule does not preclude the possibility of thyroid cancer. Clinicians should consider further evaluation such as ultrasonography and fine needle aspiration in patients with hyperfunctioning autonomous nodules.

Efficacy of Moderate Intensity Statins in the Treatment of Dyslipidemia in Korean Patients with Type 2 Diabetes Mellitus

공성혜,구보경,문민경 대한당뇨병학회 2017 Diabetes and Metabolism Journal Vol.41 No.1

Background: There has been evidences of ethnic differences in the low density lipoprotein cholesterol (LDL-C) lowering effect of statin. We aimed to evaluate the efficacy of moderate-intensity statins in the treatment of dyslipidemia among Korean patients with type 2 diabetes mellitus (T2DM). Methods: We analyzed a retrospective cohort that consisted of Korean patients with T2DM aged 40 to 75 years who had been prescribed any of the moderate-intensity statins (atorvastatin 10 or 20 mg, rosuvastatin 5 or 10 mg, pitavastatin 2 mg, or pravastatin 40 mg). Among them, only patients with baseline lipid profiles before starting statin treatment were selected, and changes in their lipid profiles before and 6 months after statin therapy were analyzed. Results: Following the first 6 months of therapy, the overall LDL-C reduction was −47.4% (interquartile range, −56.6% to −34.1%). In total, 92.1% of the participants achieved an LDL-C level of <100 mg/dL, 38.3% had a 30% to 50% reduction in their LDL-C levels, and 42.3% had a reduction in their LDL-C levels greater than 50%. The response rates of each drug for achieving a LDL-C level <100 mg/dL were 81.7%, 93.1%, 95.0%, 95.0%, 96.5%, and 91.7% for treatment with atorvastatin doses of 10 or 20 mg, rosuvastatin 5 or 10 mg, pitavastatin 2 mg, and pravastatin 40 mg, respectively. Conclusion: In conclusion, the use of moderate-intensity statins reduced LDL-C levels less than 100 mg/dL in most of the Korean patients studied with T2DM. The efficacies of those statins were higher than expected in about 42% of Korean patients with T2DM.

Effect of Vitamin D Supplementation on Risk of Fractures and Falls According to Dosage and Interval: A Meta-Analysis

공성혜,장한나,김정희,김상완,신찬수 대한내분비학회 2022 Endocrinology and metabolism Vol.37 No.2

Background: Although recent studies comparing various dosages and intervals of vitamin D supplementation have been published,it is yet to be elucidated whether there is an appropriate dose or interval to provide benefit regarding fracture risk. We aimed to assessthe published evidence available to date regarding the putative beneficial effects of vitamin D supplements on fractures and falls according to various dosages and intervals. Methods: We performed a meta-analysis of randomized controlled studies reporting associations between vitamin D supplementation and the risks of fractures and falls in PubMed, EMBASE, and Cochrane library. Studies with supplements of ergocalciferol orcalcitriol, those with a number of event ≤10, or those with a follow-up duration of less than 6 months were also excluded. Results: Thirty-two studies were included in the final analysis. Vitamin D supplementation with daily dose of 800 to 1,000 mg wasassociated with lower risks of osteoporotic fracture and fall (pooled relative risk [RR], 0.87; 95% confidence interval [CI], 0.78 to0.97 and RR, 0.91; 95% CI, 0.85 to 0.98), while studies with <800 or >1,000 mg/day did not. Also, among intervals, daily administration of vitamin D was associated with the reduced risk of falls, while intermittent dose was not. Also, patients with vitamin D deficiency showed a significant risk reduction of falls after vitamin D supplementation. Conclusion: Daily vitamin D dose of 800 to 1,000 IU was the most probable way to reduce the fracture and fall risk. Further studiesdesigned with various regimens and targeted vitamin D levels are required to elucidate the benefits of vitamin D supplements.

Effects of Dapagliflozin on Endothelial Function, Renal Injury Markers, and Glycemic Control in Drug-Naïve Patients with Type 2 Diabetes Mellitus (Diabetes Metab J 2019:43:711-7)

공성혜,구보경,문민경 대한당뇨병학회 2019 Diabetes and Metabolism Journal Vol.43 No.6

Efficacy of Moderate Intensity Statins in the Treatment of Dyslipidemia in Korean Patients with Type 2 Diabetes Mellitus (Diabetes Metab J 2017;41:23-30)

공성혜,구보경,문민경 대한당뇨병학회 2017 Diabetes and Metabolism Journal Vol.41 No.2

Development of a Spine X-Ray-Based Fracture Prediction Model Using a Deep Learning Algorithm

공성혜,이재원,배병욱,성진경,정규환,김정희,신찬수 대한내분비학회 2022 Endocrinology and metabolism Vol.37 No.4

Background: Since image-based fracture prediction models using deep learning are lacking, we aimed to develop an X-ray-basedfracture prediction model using deep learning with longitudinal data. Methods: This study included 1,595 participants aged 50 to 75 years with at least two lumbosacral radiographs without baselinefractures from 2010 to 2015 at Seoul National University Hospital. Positive and negative cases were defined according to whethervertebral fractures developed during follow-up. The cases were divided into training (n=1,416) and test (n=179) sets. A convolutional neural network (CNN)-based prediction algorithm, DeepSurv, was trained with images and baseline clinical information (age,sex, body mass index, glucocorticoid use, and secondary osteoporosis). The concordance index (C-index) was used to compare performance between DeepSurv and the Fracture Risk Assessment Tool (FRAX) and Cox proportional hazard (CoxPH) models. Results: Of the total participants, 1,188 (74.4%) were women, and the mean age was 60.5 years. During a mean follow-up period of40.7 months, vertebral fractures occurred in 7.5% (120/1,595) of participants. In the test set, when DeepSurv learned with imagesand clinical features, it showed higher performance than FRAX and CoxPH in terms of C-index values (DeepSurv, 0.612; 95% confidence interval [CI], 0.571 to 0.653; FRAX, 0.547; CoxPH, 0.594; 95% CI, 0.552 to 0.555). Notably, the DeepSurv method withoutclinical features had a higher C-index (0.614; 95% CI, 0.572 to 0.656) than that of FRAX in women. Conclusion: DeepSurv, a CNN-based prediction algorithm using baseline image and clinical information, outperformed the FRAXand CoxPH models in predicting osteoporotic fracture from spine radiographs in a longitudinal cohort.

The Impact of COVID-19 on the Optimal Management of Osteoporosis

공성혜,황보권,윤병호 대한골대사학회 2021 대한골대사학회지 Vol.28 No.2

Osteoporosis does not take a break while Coronavirus disease 2019 (COVID-19) stunned and overtook everyone’s lives. Medical resources were immediately shifted, self-isolation and telemedicine were expanded, ambulatory care services such as bone densitometry and osteoporosis-centered clinics came to a near halt. Progress with fracture prevention has been challenged because osteoporotic fracture with low energy injury is more prevalent even though restriction of people’s movement. Thus we must re-engage with chronic bone health concerns and fracture prevention. This review discusses challenges in management of osteoporosis during the COVID-19 pandemic and reinforces the need to implementing recommendations concerning the importance of bone fragility care with at least those patients who are already treated with antiosteoporotic drugs maintaining their adherence to treatments.