Publications by authors named "Hyeonmok Kim"

27 Publications

  • Page 1 of 1

SLIT3 promotes myogenic differentiation as a novel therapeutic factor against muscle loss.

J Cachexia Sarcopenia Muscle 2021 Aug 22. Epub 2021 Aug 22.

Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.

Background: Sarcopenia and osteoporosis frequently co-occur in the elderly and have common pathophysiological determinants. Slit guidance ligand 3 (SLIT3) has been recently discovered as a novel therapeutic factor against osteoporosis, and a SLIT3 fragment containing the second leucine-rich repeat domain (LRRD2) had a therapeutic efficacy against osteoporosis. However, a role of SLIT3 in the skeletal muscle is unknown.

Methods: Skeletal muscle mass, strength, and/or physical activity were evaluated in Slit3 , ovariectomized, and aged mice, based on the measurements of muscle weight and grip strength, Kondziella's inverted hanging test, and/or wheel-running test. Skeletal muscles were also histologically evaluated by haematoxylin and eosin staining and/or immunofluorescence. The ovariectomized and aged mice were intravenously injected with recombinant SLIT3 LRRD2 for 4 weeks. C2C12 cells were used to know cellular effects of SLIT3, such as in vitro myogenesis, fusion, cell viability, and proliferation, and also used to evaluate its molecular mechanisms by immunocytochemistry, immunoprecipitation, western blotting, real-time PCR, siRNA transfection, and receptor-ligand binding ELISA.

Results: Slit3-deficient mice exhibited decreased skeletal muscle mass, muscle strength, and physical activity. The relative masses of gastrocnemius and soleus were lower in the Slit3 mice (0.580 ± 0.039% and 0.033 ± 0.003%, respectively) than those in the WT littermates (0.622 ± 0.043% and 0.038 ± 0.003%, respectively) (all, P < 0.05). Gastrocnemius of Slit3 mice showed the reduced number of Type I and Type IIa fibres (all, P < 0.05), but not of Type IIb and Type IIx fibres. SLIT3 activated β-catenin signalling by promoting its release from M-cadherin, thereby increasing myogenin expression to stimulate myoblast differentiation. In vitro experiments involving ROBO2 expression, knockdown, and interaction with SLIT3 indicated that ROBO2 functions as a SLIT3 receptor to aid myoblast differentiation. SLIT3 LRRD2 dissociated M-cadherin-bound β-catenin and up-regulated myogenin expression to increase myoblast differentiation, in a manner similar to full-length SLIT3. Systemic treatment with SLIT3 LRRD2 increased skeletal muscle mass in both ovariectomized and aged mice (all, P < 0.05). The relative masses of gastrocnemius and soleus were higher in the treated aged mice (0.548 ± 0.045% and 0.033 ± 0.005%, respectively) than in the untreated aged mice (0.508 ± 0.016% and 0.028 ± 0.003%, respectively) (all, P < 0.05). SLIT3 LRRD2 treatment increased the hanging duration of the aged mice by approximately 1.7-fold (P < 0.05).

Conclusions: SLIT3 plays a sarcoprotective role by activating β-catenin signalling. SLIT3 LRRD2 can potentially be used as a therapeutic agent against muscle loss.
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http://dx.doi.org/10.1002/jcsm.12769DOI Listing
August 2021

Association of Water Intake with Hand Grip Strength in Community-Dwelling Older Adults.

Nutrients 2021 May 21;13(6). Epub 2021 May 21.

Division of Endocrinology and Metabolism, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.

Although recent clinical studies have suggested that water intake enhances muscle mass, its impact on muscle strength remain unclear, especially in older adults. This cross-sectional, population-based study using a representative sample of Koreans investigated the relationship of water intake with hand grip strength (HGS) in 4443 older adults, including 2090 men aged ≥50 years and 2253 postmenopausal women. A digital grip strength dynamometer was used for HGS assessment. Low muscle strength was defined by the Korean-specific HGS cut-off value and adequate water intake was defined according to the Korean dietary reference intakes. In an unadjusted model, water intake was significantly higher in men and women without than with low muscle strength (both < 0.001), but this difference disappeared after adjustment for confounding variables in both men ( = 0.050) and women ( = 0.245). Similarly, the correlation between water intake and HGS, the difference in HGS depending on adequate water intake status, and the risk of low muscle strength depending on water intake quartile were significant only in the unadjusted model. These data indicate that factors such as age, body size, and resistance exercise contribute to improvements in HGS in older adults, whereas water intake may not.
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http://dx.doi.org/10.3390/nu13061756DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8224336PMC
May 2021

Changes in the glucose and insulin responses according to high-protein snacks for diabetic patients.

Nutr Res Pract 2021 Feb 12;15(1):54-65. Epub 2020 Oct 12.

Department of Nutritional Science and Food Management, Ewha Womans University, Seoul 03760, Korea.

Background/objectives: This study aimed to develop healthy, appetizing high-protein snacks with enhanced isolated soy protein for diabetic patients and determine the blood glucose and insulin response after being consumed by these patients.

Materials/methods: Thirty adult patients aged between 30 and 75 years, with a ≤ 10-year history of type 2 diabetes and hemoglobin A1c of < 7.5%, were enrolled in this study. They made 3 clinical visits at one-week intervals. The control group consumed 50 g carbohydrates (white bread), whereas the test groups consumed high-protein grain (HP_G) or high-protein chocolate (HP_C) after an 8-hrs fast. Blood (2 cm) was drawn at 15, 30, 45, 60, 90, and 120 min before and after consumption to analyze the blood glucose and insulin concentrations.

Results: Compared to the commercial snacks, the developed high-protein snacks had below-average calorie, carbohydrate, and fat content and a 2.5-fold higher protein content. In diabetic patients who consumed these snacks, the postprandial blood glucose increased between 15 min and 2 h after consumption, which was significantly slower than the time taken for the blood glucose to increase in the patients who consumed the control food product ( < 0.001). Insulin secretion was significantly lower at 45 min after consumption ( < 0.05), showing that the high-protein snacks did not increase the blood glucose levels rapidly. The incremental area under the curve (iAUC), which indicated the degree of blood sugar and insulin elevation after food intake, was higher in the control group than the groups given the 2 developed snacks ( < 0.001), and there was no significant difference in insulin secretion.

Conclusions: The results of the postprandial blood glucose and insulin response suggest that high-protein snacks are potential convenient sources of high-quality protein and serve as a healthier alternative for patients with type 2 diabetes, who may have limited snack product choices. Such snacks may also provide balanced nutrition to pre-diabetic and obese individuals.
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http://dx.doi.org/10.4162/nrp.2021.15.1.54DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7838472PMC
February 2021

Clinical Experience with Use of Remdesivir in the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2: a Case Series.

Infect Chemother 2020 Sep 23;52(3):369-380. Epub 2020 Jul 23.

Department of Internal Medicine, Seoul Medical Center, Seoul, Korea.

Background: A novel antiviral agent, remdesivir (RDV), is a promising candidate treatment for coronavirus disease 2019 (COVID-19) in the absence of any proven therapy.

Materials And Methods: This retrospective case series included 10 patients with a clinically and laboratory confirmed diagnosis of severe COVID-19 pneumonia who had received RDV for 5 days (n = 5) or 10 days (n = 5) in the Phase III clinical trial of RDV (GS-US-540-5773) conducted by Gilead Sciences. The clinical and laboratory data for these patients were extracted.

Results: One patient in the 10-day group received RDV for only 5 days because of nausea and elevated liver transaminases. No patient had respiratory comorbidity. Seven patients had bilateral lesions and three had unilateral lesions on imaging. All patients had received other medications for COVID-19, including lopinavir/ritonavir and hydroxychloroquine, before administration of RDV. Five patients required supplemental oxygen and one required mechanical ventilation. All patients showed clinical and laboratory evidence of improvement. Half of the patients developed elevated liver transaminases and three had nausea. There were no adverse events exceeding grade 2.

Conclusion: Our experience indicates that RDV could be a therapeutic option for COVID-19. A well-designed randomized controlled clinical trial is now needed to confirm the efficacy of RDV in patients with COVID-19.
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http://dx.doi.org/10.3947/ic.2020.52.3.369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7533211PMC
September 2020

Differential association of dietary fat intake with DXA-based estimates of bone strength according to sex in the KNHANES IV population.

Arch Osteoporos 2020 04 25;15(1):62. Epub 2020 Apr 25.

Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul Medical Center, 156 Sinnae-ro, Jungnang-gu, Seoul, 02053, South Korea.

The higher the dietary fat intake is in men, the worse their bone strength. By contrast, in women, both low and high fat intakes have negative impacts on bone strength. Dietary fat intake may be a modifiable factor affecting bone health, but this needs to be reconfirmed in further studies.

Purpose: Despite the general belief that higher fat intake may be harmful for bone health, its impact on bone strength has not been thoroughly studied.

Methods: We conducted a population-based cross-sectional study derived from the Korea National Health and Nutrition Examination Surveys, including 2590 participants. Composite indices of femoral neck strength, such as the compression strength index (CSI), bending strength index (BSI), and impact strength index (ISI), were generated by combining bone mineral density, weight, and height with the femoral axis length and width. Nutritional status was assessed using a 24-h dietary recall questionnaire.

Results: Dietary fat intake (%: energy from fat intake/total energy intake × 100) was inversely related to CSI and ISI in men, but not in women. Men in the highest three fat intake quintiles had lower CSI, BSI, and/or ISI than those in the lowest quintile (P = 0.003-0.041). In women, compared with participants in the third fat intake quintile, those in the other four quintiles had lower CSI, BSI, and/or ISI (P = 0.004-0.049). When participants were allocated to three groups according to the dietary reference intake of fat in Koreans [low (< 15%), moderate (15-30%), or high (≥ 30%)], men with a moderate or high fat intake had significantly lower ISIs than those with a low fat intake (P = 0.045 and 0.040, respectively). By contrast, compared with women consuming a moderate amount of fat, those with a high intake had lower CSI, BSI, and ISI (P = 0.024-0.048).

Conclusion: Higher fat intake in men may contribute to deteriorations in bone strength. However, this finding and the observed sex differences need to be reconfirmed using established methods for assessment of dietary intake other than the 24-h dietary recall method employed in this study.
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http://dx.doi.org/10.1007/s11657-020-00737-0DOI Listing
April 2020

High circulating follistatin-like protein 1 as a biomarker of a metabolically unhealthy state.

Endocr J 2019 Mar 8;66(3):241-251. Epub 2019 Feb 8.

Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul 06591, Korea.

The inflammatory biomarkers that fully characterize the metabolically unhealthy (MU) state-which is a risk factor for cardiovascular disease (CVD)-remain unclear. Recent studies suggest follistatin-like protein 1 (FSTL1) could be used as a biomarker for inflammation and CVD, however there is little information on FSTL1 levels in the MU state. We aimed to evaluate the associations between FSTL1, the presence of MU state and subclinical coronary atherosclerosis. In a cross-sectional study, we evaluated FSTL1 levels and their relationship with the presence of MU state and coronary artery plaques in 230 Korean patients. Significant increase in FSTL1 levels was observed in subjects with MU state (p = 0.020), but not those with obesity state according to body mass index criteria (p = 0.790). After adjusting for confounders, the odd ratio (OR) for the MU state among patients in the highest FSTL1 tertile (T3) was higher in comparison with the lowest tertile (T1) (OR = 3.60, 95% confidence interval [95% CI] = 1.20-10.83). In a subgroup (n = 66), FSTL1 levels were also marginally higher in patients with plaques (p = 0.098). The OR for plaque presence in patients with T3 was significantly higher in comparison with T1 after adjusting for confounders (OR = 12.51, 95% CI = 1.15-135.73). Plasma FSTL1 may be a useful biomarker for the risk of MU state and CVD.
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http://dx.doi.org/10.1507/endocrj.EJ18-0352DOI Listing
March 2019

Change of skeletal muscle mass in patients with pheochromocytoma.

J Bone Miner Metab 2019 Jul 20;37(4):694-702. Epub 2018 Sep 20.

Division of Endocrinology and Metabolism, Department of Medicine, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, South Korea.

The effects of catecholamine excess due to pheochromocytoma on body composition, including skeletal muscle mass, are unknown. Here, we investigated the effects of catecholamine metabolites on body composition in subjects with pheochromocytoma. After body compositions using bioelectrical impedance analysis, urinary metanephrine (UM), and urinary normetanephrine (UNM) were measured in 16 patients with pheochromocytoma and 224 patients with nonfunctioning adrenal incidentaloma (NFAI), we compared skeletal muscle mass and fat mass (FM) between the two groups. After adjustments for confounders, UM (β = - 0.171, P = 0.006) and UNM (β = - 0.249, P < 0.001) levels were correlated inversely with skeletal muscle mass index (SMI), but not FM or percentage FM (pFM), in all subjects. Patients with pheochromocytoma had lower ASM by 7.7% (P = 0.022) and SMI by 6.6% (P = 0.001) than patients with NFAI. Conversely, FM and pFM were not statistically different between the two groups. The odds ratio for low skeletal muscle mass in the presence of pheochromocytoma was 10.33 (95% confidence interval, 2.65-40.22). Our results indicate that patients with pheochromocytoma have a reduced skeletal muscle mass and suggest that catecholamine excess has adverse effects on skeletal muscle metabolism.
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http://dx.doi.org/10.1007/s00774-018-0959-3DOI Listing
July 2019

A clinical prediction model to estimate the metastatic potential of pheochromocytoma/paraganglioma: ASES score.

Surgery 2018 09 19;164(3):511-517. Epub 2018 Jun 19.

Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. Electronic address:

Background: Malignant pheochromocytoma and paraganglioma can be defined only after the development of metastases in nonchromaffin tissues. There is no single clinical parameter that is sufficiently reliable to predict metastatic potential, so our goal was to develop a prediction model based on multiple clinical parameters.

Methods: The baseline age, size, extra-adrenal location, secretory type score was calculated in a retrospective cohort study comprising 333 patients with pheochromocytoma and paraganglioma. In each patient, each variable for age ≤35 years, tumor size ≥ 6.0 cm, extra-adrenal, and norepinephrine-secretory type was coded as 1 point (otherwise 0 point); these points were summed to yield age, size, extra-adrenal location, secretory type score.

Results: Metastases occurred in 23 of 333 patients (6.9%). Metastatic pheochromocytoma and paraganglioma was associated with age ≤35 years (hazard ratio [HR] 2.74, 95% confidence interval [95% CI] 1.19-6.35), tumor size ≥6.0 cm (HR 2.43, 95% CI 1.06-5.56), extra-adrenal location (HR 2.73, 95% confidence interval 1.10-7.40), and tumor producing only norepinephrine (HR 2.96, 95% CI 1.30-6.76). The area under the curve of the age, size, extra-adrenal location, secretory type score was 0.735. There was a significant difference in metastasis-free survival between participants with age, size, extra-adrenal location, secretory type score ≥2 and score <2 (P < .0001 by the log rank test). The negative predictive value of this system was 96.5% for a cutoff point of 2.

Conclusion: We developed a new prediction model, the age, size, extra-adrenal location, secretory type score, based on multiple clinical parameters to assess the metastatic potential of pheochromocytoma and paraganglioma.
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http://dx.doi.org/10.1016/j.surg.2018.05.001DOI Listing
September 2018

Characteristics of Adrenal Incidentalomas in a Large, Prospective Computed Tomography-Based Multicenter Study: The COAR Study in Korea.

Yonsei Med J 2018 Jun;59(4):501-510

Division of Endocrinology and Metabolism, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea.

Purpose: Previous studies on adrenal incidentalomas (AIs) are limited by their retrospective design, small numbers of patients, Western populations, or use of an outdated imaging technique. We investigated the characteristics of AIs in Korean patients and compared them with those reported in the largest retrospective study in Italy to discover the effects of improved imaging techniques and ethnicity differences.

Materials And Methods: This was a prospective, multicenter, cross-sectional observational study including 1005 Korean patients. Levels of plasma adrenocorticotrophic hormone, 24-h urinary free cortisol (UFC), serum cortisol after a 1 mg-dexamethasone suppression test, 24-h urinary fractionated metanephrine, and plasma aldosterone and plasma renin activity were measured. All AIs were characterized using computed tomography (CT).

Results: Compared with the results of the Italian study, AIs in Korean patients were observed more frequently in men and predominantly on the left side. Korean patients with AIs were slightly younger, and fewer patients underwent surgery. Most AIs were nonfunctional in both studies, while fewer subclinical hypercortisolism and more primary aldosteronism (PA) cases were detected in Korean patients. In our study, high UFC levels showed very low sensitivity, compared to those in the Italian study. In pheochromocytoma or PA cases, there were no hormonal differences between the studies. AIs in Korean patients were smaller, such that a lower cutoff size for detecting adrenocortical carcinoma (ACC) could be warranted.

Conclusion: Recent advances in CT technology were leveraged to provide accurate characteristics of AIs and to detect smaller ACCs.
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http://dx.doi.org/10.3349/ymj.2018.59.4.501DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5949292PMC
June 2018

Alteration in skeletal muscle mass in women with subclinical hypercortisolism.

Endocrine 2018 07 1;61(1):134-143. Epub 2018 May 1.

Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Korea.

Purpose: Despite the well-known deleterious effects of cortisol on skeletal muscle, whether subtle cortisol excess in subclinical hypercortisolism (SH) affects skeletal muscle mass is unknown. Our objective was to understand the effects of the cortisol level on skeletal muscle mass in patients with SH.

Methods: We compared skeletal muscle mass and fat mass (FM) between 21 patients with SH (12 women and 9 men) and 224 controls (67 women and 157 men) with nonfunctioning adrenal incidentaloma (NFAI). Medical records were reviewed, and we measured body composition parameters using bioelectrical impedance analysis and serum cortisol levels after the overnight 1-mg dexamethasone suppression test (DST).

Results: After adjusting for confounding factors, 1-mg DST levels were inversely correlated with appendicular skeletal muscle mass (ASM) (γ = -0.245, P = 0.040), lower limb ASM (γ = -0.244, P = 0.040), and appendicular skeletal muscle index (ASMI; height-adjusted ASM) (γ = -0.229, P = 0.048) in all women, but not men. ASM and ASMI were significantly lower by 6.2% (P = 0.033) and 5.9% (P = 0.046), respectively, in women with SH compared with those with NFAI, but not men. Conversely, FM and percent fat mass were similar between the two groups. Compared with women with NFAI, among those with SH, lower limb, but not upper limb, ASM was lower by 6.8% (P = 0.020).

Conclusions: This study showed that women with SH had lower skeletal muscle mass, especially of the lower limb, and suggested that subtle cortisol excess also has adverse effects on skeletal muscle metabolism.
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http://dx.doi.org/10.1007/s12020-018-1598-0DOI Listing
July 2018

Osteoclast-secreted SLIT3 coordinates bone resorption and formation.

J Clin Invest 2018 04 5;128(4):1429-1441. Epub 2018 Mar 5.

Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.

Coupling is the process that links bone resorption to bone formation in a temporally and spatially coordinated manner within the remodeling cycle. Several lines of evidence point to the critical roles of osteoclast-derived coupling factors in the regulation of osteoblast performance. Here, we used a fractionated secretomic approach and identified the axon-guidance molecule SLIT3 as a clastokine that stimulated osteoblast migration and proliferation by activating β-catenin. SLIT3 also inhibited bone resorption by suppressing osteoclast differentiation in an autocrine manner. Mice deficient in Slit3 or its receptor, Robo1, exhibited osteopenic phenotypes due to a decrease in bone formation and increase in bone resorption. Mice lacking Slit3 specifically in osteoclasts had low bone mass, whereas mice with either neuron-specific Slit3 deletion or osteoblast-specific Slit3 deletion had normal bone mass, thereby indicating the importance of SLIT3 as a local determinant of bone metabolism. In postmenopausal women, higher circulating SLIT3 levels were associated with increased bone mass. Notably, injection of a truncated recombinant SLIT3 markedly rescued bone loss after an ovariectomy. Thus, these results indicate that SLIT3 plays an osteoprotective role by synchronously stimulating bone formation and inhibiting bone resorption, making it a potential therapeutic target for metabolic bone diseases.
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http://dx.doi.org/10.1172/JCI91086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5873876PMC
April 2018

Lower Trabecular Bone Score in Patients With Primary Aldosteronism: Human Skeletal Deterioration by Aldosterone Excess.

J Clin Endocrinol Metab 2018 02;103(2):615-621

Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Context: Despite the potential detrimental effects of aldosterone excess on bone metabolism, discrepancies exist between fracture risk and bone mass in patients with and without primary aldosteronism (PA).

Objective: To clarify the possibility that aldosterone excess might mainly affect bone properties not explained by the bone mineral density (BMD).

Design, Setting, And Patients: Among 625 consecutive patients with newly diagnosed adrenal incidentaloma (AI), 72 with biochemically confirmed PA and 335 with nonfunctional AI were defined as cases and controls, respectively.

Results: In women, although no statistically significant differences in lumbar spine BMD were found between groups, the lumbar spine trabecular bone score (TBS) was significantly lower in patients with PA than in controls after adjustment for confounders (P = 0.007). Consistently, the plasma aldosterone concentration (PAC) correlated inversely with the lumbar spine TBS (P = 0.028) but not with bone mass in women. Compared with women in the lowest PAC quartile, those in the highest PAC quartile had significantly lower lumbar spine TBSs (P = 0.004). Importantly, all these observations in women remained statistically significant after additional adjustment for the lumbar spine BMD in the multivariable model. However, BMD and TBS at the lumbar spine did not differ according to the presence of PA and the level of PAC in men.

Conclusion: These findings provide clinical evidence that aldosterone excess in PA might contribute to deteriorated bone quality through weak microarchitecture, regardless of bone mass, especially in women.
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http://dx.doi.org/10.1210/jc.2017-02043DOI Listing
February 2018

Validation of pathological grading systems for predicting metastatic potential in pheochromocytoma and paraganglioma.

PLoS One 2017 8;12(11):e0187398. Epub 2017 Nov 8.

Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Purpose: The Grading system for Adrenal Pheochromocytoma and Paraganglioma (GAPP) was proposed for predicting the metastatic potential of pheochromocytoma and paraganglioma to overcome the limitations of the Pheochromocytoma of the Adrenal Scaled Score (PASS). However, to date, no study validating the GAPP has been conducted, and previous studies did not include mutations in the succinate dehydrogenase type B (SDHB) gene in the score calculation. In this retrospective cohort study, we validated the prediction ability of GAPP and assessed whether it would be improved by inclusion of the loss of SDHB immunohistochemical staining.

Methods: We divided the tumors into non-metastatic and metastatic groups based on the presence of synchronous or metachronous metastases. The GAPP score and PASS at the initial operation were measured. Moreover, we combined some GAPP parameters with the immunohistochemical staining of SDHB to obtain a modified GAPP (M-GAPP) score.

Results: Metastasis occurred in 15/72 (20.8%) patients, with a mean follow-up of 43.5 months. Loss of SDHB staining was more frequent (P = 0.044) in the metastatic group. The GAPP score (P = 0.006), PASS (P = 0.003), and M-GAPP score (P<0.001) were all higher in the metastatic group. Twelve of 40 (30.0%) moderately or poorly differentiated tumors, as defined by the GAPP score, and 12/34 (35.3%) tumors with a PASS ≥4 were metastatic. Conversely, 10/19 (52.6%) tumors with an M-GAPP score ≥3 were metastatic. The area under the curve of the M-GAPP score (0.822) was significantly higher than that of the GAPP (0.728) (P = 0.012), but similar to that of the PASS (0.753) (P = 0.411). The GAPP (P = 0.032) and M-GAPP scores (P = 0.040), but not PASS (P = 0.200), negatively correlated with metastasis-free survival.

Conclusion: The GAPP was validated, and M-GAPP, a combination of some GAPP parameters and loss of SDHB staining, might be useful for the prediction of the metastatic potential of pheochromocytoma and paraganglioma.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0187398PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5678867PMC
November 2017

Lower Bone Mass and Higher Bone Resorption in Pheochromocytoma: Importance of Sympathetic Activity on Human Bone.

J Clin Endocrinol Metab 2017 08;102(8):2711-2718

Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.

Context: Despite the apparent biological importance of sympathetic activity on bone metabolism in rodents, its role in humans remains questionable.

Objective: To clarify the link between the sympathetic nervous system and the skeleton in humans.

Design, Setting, And Patients: Among 620 consecutive subjects with newly diagnosed adrenal incidentaloma, 31 patients with histologically confirmed pheochromocytoma (a catecholamine-secreting neuroendocrine tumor) and 280 patients with nonfunctional adrenal incidentaloma were defined as cases and controls, respectively.

Results: After adjustment for confounders, subjects with pheochromocytoma had 7.2% lower bone mass at the lumbar spine and 33.5% higher serum C-terminal telopeptide of type 1 collagen (CTX) than those without pheochromocytoma (P = 0.016 and 0.001, respectively), whereas there were no statistical differences between groups in bone mineral density (BMD) at the femur neck and total hip and in serum bone-specific alkaline phosphatase (BSALP) level. The odds ratio (OR) for lower BMD at the lumbar spine in the presence of pheochromocytoma was 3.31 (95% confidence interval, 1.23 to 8.56). However, the ORs for lower BMD at the femur neck and total hip did not differ according to the presence of pheochromocytoma. Serum CTX level decreased by 35.2% after adrenalectomy in patients with pheochromocytoma, whereas serum BSALP level did not change significantly.

Conclusions: This study provides clinical evidence showing that sympathetic overstimulation in pheochromocytoma can contribute to adverse effects on human bone through the increase of bone loss (especially in trabecular bone), as well as bone resorption.
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http://dx.doi.org/10.1210/jc.2017-00169DOI Listing
August 2017

Symptom-dependent cut-offs of urine metanephrines improve diagnostic accuracy for detecting pheochromocytomas in two separate cohorts, compared to symptom-independent cut-offs.

Endocrine 2016 Oct 2;54(1):206-216. Epub 2016 Aug 2.

Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

The development of advanced imaging techniques has increased the detection of subclinical pheochromocytomas. Because of the substantial proportions of subclinical pheochromocytomas, measurement of urine metanephrine concentrations is crucial due to detect or exclude pheochromocytoma. Although urine metanephrines are elevated in symptomatic subjects, diagnostic cut-offs according to the presence of adrenergic symptoms have not been studied. Pheochromocytomas patients who underwent adrenalectomy at Samsung Medical Center and a control group were compared to determine cut-off concentrations of urine metanephrines. An independent population was analyzed for urine metanephrines with different kits to validate the improvement in diagnostic accuracy using adjusted cut-offs. Symptom-dependent cut-offs of urine metanephrines were higher for symptomatic patients (307 μg/day in males, 235 μg/day in females for urine metanephrine, and 1,045 μg/day in males and 457 μg/day in females for urine normetanephrine) than for asymptomatic patients (206 μg/day in males, 199 μg/day in females for urine metanephrine, and 489 μg/day in males and 442 μg/day in females for urine normetanephrine). Symptom-dependent cut-offs of urine metanephrines improved a specificity from 92.7 % to 96.3 % and a high sensitivity of 97.8 % was maintained. Using the Symptom-dependent cut-offs raised diagnostic accuracy by 5.5 % (p <0.001). Similar trend was also observed in an independent population using different hormone kits. Using symptom-dependent cut-offs of urine metanephrines in symptomatic patients for pheochromocytomas resulted in a significant improvement in diagnostic accuracy in two separate cohorts.
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http://dx.doi.org/10.1007/s12020-016-1049-8DOI Listing
October 2016

The Association of Higher Plasma Macrophage Migration Inhibitory Factor Levels with Lower Bone Mineral Density and Higher Bone Turnover Rate in Postmenopausal Women.

Endocrinol Metab (Seoul) 2016 Sep 26;31(3):454-461. Epub 2016 Jul 26.

Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Background: Despite evidence from animal and clinical studies showing the detrimental effects of macrophage migration inhibitory factor (MIF) on bone metabolism, there are no clinical studies relating circulating MIF levels to osteoporosis-related phenotypes. This cross-sectional study investigated the association of plasma MIF with bone mineral density (BMD), bone turnover markers (BTMs), and prevalence of osteoporosis in postmenopausal Korean women.

Methods: A total of 246 women not taking any medications or diagnosed with any diseases that could affect bone metabolism were enrolled. BMD values at the lumbar spine, femoral neck, and total femur, and blood levels of MIF and BTMs were measured in all subjects. Osteoporosis was defined by World Health Organization criteria.

Results: Before and after adjustment for confounding variables, higher MIF levels were significantly associated with lower BMD values at all measured sites and higher levels of all BTMs. All BMD values and BTMs significantly changed in a dose-dependent fashion across increasing MIF quartile. When participants were divided into two groups according to osteoporosis status, postmenopausal women with osteoporosis demonstrated 24.2% higher plasma MIF levels than those without osteoporosis (P=0.041). The odds ratio per each standard deviation increment of MIF levels for prevalent osteoporosis was 1.32 (95% confidence interval, 1.01 to 1.73).

Conclusion: This study provides the first epidemiological evidence that higher plasma MIF may be associated with higher risk of osteoporosis resulting from lower bone mass and higher bone turnover rate, and thus it could be a potential biomarker of poor bone health outcomes in postmenopausal women.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5053059PMC
http://dx.doi.org/10.3803/EnM.2016.31.3.454DOI Listing
September 2016

New diagnostic criteria for subclinical hypercortisolism using postsurgical hypocortisolism: the Co-work of Adrenal Research study.

Clin Endocrinol (Oxf) 2017 Jan 29;86(1):10-18. Epub 2016 Jul 29.

Division of Endocrinology and Metabolism, Department of Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Objective: There is no consensus on the biochemical diagnostic criteria for subclinical hypercortisolism (SH). Using parameters related to the hypothalamic-pituitary-adrenal axis, we aimed to develop a diagnostic model of SH for predicting postsurgical hypocortisolism and metabolic complications.

Design: Prospective and cross-sectional, observational, multicentre study in Korea.

Methods: After exclusion of overt Cushing's syndrome, adrenal incidentaloma (AI) patients who underwent unilateral adrenalectomy (n = 99) and AI patients (n = 843) were included. Primary outcome was defined as the presence of postsurgical hypocortisolism; secondary outcome was the presence of ≥4 complications (components of the metabolic syndrome and low bone mass). Postsurgical hypocortisolism was determined on the fifth postsurgery day using the ACTH stimulation test.

Results: Thirty-three of the 99 patients developed postsurgical hypocortisolism. Analysis of the presurgery overnight 1-mg dexamethasone suppression test (1-mg DST) showed that all patients with cortisol levels of >138 nmol/l experienced postsurgical hypocortisolism, whereas those with levels of ≤61 nmol/l did not. The models of (i) 1-mg DST >138 nmol/l or (ii) >61 nmol/l with the presence of one among low levels of ACTH and dehydroepiandrosterone-sulphate had the highest accuracy (89·9%, P < 0·001) and odds ratio [OR 111·62, 95% confidence interval (CI) 21·98-566·74, P < 0·001] for predicting postsurgical hypocortisolism. Finally, patients with the same criteria in the 843 AI patients showed the highest risk for having ≥4 complications (OR 3·51, 95% CI 1·84-6·69, P < 0·001), regardless of gender, age, body mass index and bilaterality.

Conclusions: Our proposed model is able to accurately predict subtle cortisol excess and its chronic manifestations in AI patients.
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http://dx.doi.org/10.1111/cen.13145DOI Listing
January 2017

Decreased Plasma Levels of Sclerostin But Not Dickkopf-1 are Associated with an Increased Prevalence of Osteoporotic Fracture and Lower Bone Mineral Density in Postmenopausal Korean Women.

Calcif Tissue Int 2016 10 11;99(4):350-9. Epub 2016 Jun 11.

Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea College of Medicine, 222 Banpo-daero, Seocho-gu, Seoul, 137-701, Korea.

Although sclerostin (SOST) and Dickkopf-related protein 1 (DKK1) are major regulators in bone metabolism, their associations with osteoporotic fracture (OF) in Asians are inconclusive. Furthermore, there have been no clinical studies separately considering non-vertebral and vertebral fractures in terms of the blood levels of SOST and DKK1. Among 513 consecutive postmenopausal Korean women, we identified 103 cases defined as subjects with OF (i.e., non-vertebral and/or vertebral fractures). The controls were randomly selected from the remaining 410 subjects and matched 1:1 to cases according to both age and body mass index. Non-vertebral and morphological vertebral fractures were identified by an interviewer-assisted questionnaire and lateral thoracolumbar radiographs, respectively. Bone mineral density (BMD) and plasma levels of SOST and DKK1 were measured. Plasma SOST levels were lower in subjects with OF than in the control group. Each standard deviation decrement of plasma SOST concentration was associated with a multivariable-adjusted odds ratio of 1.77 for any prevalent OF type. The odds for OF was 2.97-fold higher in subjects in the lowest SOST tertile compared with subjects in the highest SOST tertile. These associations remained significant when the non-vertebral and vertebral fractures were analyzed separately. However, prevalent OF was not associated with plasma DKK1 levels, regardless of the type of fracture and the adjustment model employed. Consistently, plasma SOST levels were positively related with BMD values at all measured skeletal sites, although this was not observed for DKK1. Circulating SOST but not DKK1 may be a potential biomarker for predicting bone health in Asians.
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http://dx.doi.org/10.1007/s00223-016-0160-4DOI Listing
October 2016

Free Fatty Acid Receptor 4 (GPR120) Stimulates Bone Formation and Suppresses Bone Resorption in the Presence of Elevated n-3 Fatty Acid Levels.

Endocrinology 2016 07 4;157(7):2621-35. Epub 2016 May 4.

Department of Endocrinology and Metabolism (S.H.A.), Inha University Hospital, Inha University School of Medicine, Incheon 402-751, South Korea; Asan Institute for Life Sciences (S.-Y.P., J.-E.B., S.-Youn.L., W.-.Y.B., S.-Young.L., Y.-S.L.) and Biomedical Research Center (H.J.Y.) and Division of Endocrinology and Metabolism (H.K., S.H.L., B.-J.K., J.-M.K.), Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, South Korea; Molecular Inflammation Research Center for Aging Intervention and College of Pharmacy (D.-S.I.), Pusan National University, Busan 609-735, South Korea; and UConn Center on Aging (S.-K.L.), University of Connecticut Health Center, Farmington, Connecticut 06030-1601.

Free fatty acid receptor 4 (FFA4) has been reported to be a receptor for n-3 fatty acids (FAs). Although n-3 FAs are beneficial for bone health, a role of FFA4 in bone metabolism has been rarely investigated. We noted that FFA4 was more abundantly expressed in both mature osteoclasts and osteoblasts than their respective precursors and that it was activated by docosahexaenoic acid. FFA4 knockout (Ffar4(-/-)) and wild-type mice exhibited similar bone masses when fed a normal diet. Because fat-1 transgenic (fat-1(Tg+)) mice endogenously converting n-6 to n-3 FAs contain high n-3 FA levels, we crossed Ffar4(-/-) and fat-1(Tg+) mice over two generations to generate four genotypes of mice littermates: Ffar4(+/+);fat-1(Tg-), Ffar4(+/+);fat-1(Tg+), Ffar4(-/-);fat-1(Tg-), and Ffar4(-/-);fat-1(Tg+). Female and male littermates were included in ovariectomy- and high-fat diet-induced bone loss models, respectively. Female fat-1(Tg+) mice decreased bone loss after ovariectomy both by promoting osteoblastic bone formation and inhibiting osteoclastic bone resorption than their wild-type littermates, only when they had the Ffar4(+/+) background, but not the Ffar4(-/-) background. In a high-fat diet-fed model, male fat-1(Tg+) mice had higher bone mass resulting from stimulated bone formation and reduced bone resorption than their wild-type littermates, only when they had the Ffar4(+/+) background, but not the Ffar4(-/-) background. In vitro studies supported the role of FFA4 as n-3 FA receptor in bone metabolism. In conclusion, FFA4 is a dual-acting factor that increases osteoblastic bone formation and decreases osteoclastic bone resorption, suggesting that it may be an ideal target for modulating metabolic bone diseases.
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http://dx.doi.org/10.1210/en.2015-1855DOI Listing
July 2016

Higher serum ferritin level and lower femur neck strength in women at the stage of bone loss (≥ 45 years of age): The Fourth Korea National Health and Nutrition Examination Survey (KNHANES IV).

Endocr Res 2016 Nov 4;41(4):334-342. Epub 2016 Apr 4.

b Division of Endocrinology and Metabolism , Asan Medical Center, University of Ulsan College of Medicine , Seoul , Republic of Korea.

Purpose: Despite the clear effect of iron on bone metabolism, most clinical studies related to bone health have only focused on bone mineral density (BMD). In the present study, we investigated the relationship between serum ferritin and composite indices of femur neck strength via a population-based, cross-sectional study using the Korea National Health and Nutrition Examination Survey (KNHANES).

Methods: Our study series included 693 women at the stage of bone loss (≥ 45 years of age), defined based on the observed patterns of age-related BMD changes in the KNHANES. Geometric bone structure properties, including hip axis length (HAL) and femur neck width (FNW), were measured using hip dual-energy X-ray absorptiometry scans and were combined with BMD, body weight, and height to create composite indices of femur neck strength relative to load in three different failure modes: compression (CSI), bending (BSI), and impact strength indices (ISI).

Results: After adjustment for age, body mass index (BMI), lifestyle factors, serum 25-hydroxyvitamin D, calcium and phosphorus intake, diabetes, and menopause status, multiple regression analyses revealed that serum ferritin was inversely associated with the BMD values at the lumbar spine and femur neck, and the femur neck cortical thickness. Importantly, in all adjustment models, higher serum ferritin was consistently associated with the lower values for all three femur neck composite indices, such as CSI, BSI, and ISI.

Conclusions: These data provide the first clinical evidence that increased total body iron stores reflected by higher serum ferritin may be associated with the decrease of bone strength relative to load.
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http://dx.doi.org/10.3109/07435800.2016.1155600DOI Listing
November 2016

Insulin resistance and composite indices of femoral neck strength in Asians: the fourth Korea National Health and Nutrition Examination Survey (KNHANES IV).

Clin Endocrinol (Oxf) 2016 Feb 5;84(2):185-193. Epub 2015 Nov 5.

Division of Endocrinology and Metabolism, Asan Medical Centre, University of Ulsan College of Medicine, Seoul, Korea.

Objective: Fracture risk in type 2 diabetes mellitus with insulin resistance is increased, despite relatively preserved bone mineral density (BMD). In this study, we investigated the relationship between insulin resistance and composite indices of femoral neck strength in Koreans.

Design: A population-based, cross-sectional study from the Korea National Health and Nutrition Examination Survey PARTICIPANTS: About 1243 men and 1433 women MEASUREMENTS: Insulin resistance was evaluated using the homoeostasis model assessment-estimated insulin resistance (HOMA-IR) index. Femoral neck width and axis length were measured from hip dual-energy X-ray absorptiometry scans and combined with BMD, weight and height to calculate composite indices of femoral neck strength relative to load: compression (CSI), bending (BSI) and impact strength indices (ISI).

Results: HOMA-IR showed an inverse relationship with CSI, BSI and ISI in both genders before and after adjusting for confounders (P < 0·001-0·029). CSI was more strongly associated with HOMA-IR than BSI and/or ISI in both genders (P < 0·001-0·013). When men were stratified according to HOMA-IR quartiles, all strength indices decreased as the quartile increased, after adjusting for all potential confounders (P for trend <0·001-0·001), whereas CSI and ISI did in women (P for trend = 0·012 and 0·002, respectively). Fasting insulin levels, but not glucose levels, were negatively associated with all strength indices regardless of confounders (P < 0·001-0·044).

Conclusions: Insulin resistance is associated with low femoral neck strength, particularly against the compressive load. These findings suggest a better approach to evaluate bone health in insulin-resistant individuals.
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http://dx.doi.org/10.1111/cen.12958DOI Listing
February 2016

Plasma periostin associates significantly with non-vertebral but not vertebral fractures in postmenopausal women: Clinical evidence for the different effects of periostin depending on the skeletal site.

Bone 2015 Dec 19;81:435-441. Epub 2015 Aug 19.

Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736, Republic of Korea. Electronic address:

Background: Periostin is preferentially expressed by the periosteum, which mainly covers the long bones. Therefore, the role of periostin in osteoporotic fracture (OF) may differ depending on bone type. We performed a case-control study to investigate whether periostin can serve as a predictor of OF risk, particularly after dividing OFs into non-vertebral and vertebral fractures.

Methods: Among 532 consecutive postmenopausal women not taking any drug or without any disease that could affect bone metabolism, 133 cases with OF (i.e., non-vertebral and/or vertebral fractures) and 133 age- and body mass index-matched controls were enrolled. Non-vertebral (i.e., forearm, humerus, hip, and pelvis; n=81) and morphological vertebral (n=62) fractures were identified by an interviewer-assisted questionnaire and lateral thoracolumbar radiographs, respectively. Bone mineral density (BMD) and plasma periostin levels were also measured.

Results: Plasma periostin was markedly higher in subjects with non-vertebral fracture than their controls even after adjustment for BMD and potential confounders (P=0.006). Each standard deviation increment of plasma periostin was associated with a multivariable-adjusted odds ratio of 1.59 for non-vertebral fracture. The odds for non-vertebral fracture were 2.48-fold higher in subjects in the highest periostin tertile compared with those in the lowest periostin tertile (95% confidence interval=1.10-5.61). However, associations between plasma periostin and vertebral fracture were not observed, regardless of the adjustment model used. Consistently, plasma periostin levels were inversely associated with proximal femur BMD (P=0.007 to 0.030) but not lumbar spine BMD. In subgroup analyses, plasma periostin had no correlation with the levels of classical bone turnover markers.

Conclusions: Plasma periostin may be a potential biomarker of the risk of OF, especially in non-spinal skeletal sites, such as the limbs, rather than spine.
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http://dx.doi.org/10.1016/j.bone.2015.08.014DOI Listing
December 2015

The Association of Vitamin D With Femoral Neck Strength: An Additional Evidence of Vitamin D on Bone Health.

J Clin Endocrinol Metab 2015 Aug 28;100(8):3118-25. Epub 2015 May 28.

Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736, Korea.

Context: Although bone mineral density (BMD) is a strong predictor of fracture risk, additional parameters, such as bone strength, are needed to predict future fracture risk because of the low sensitivity of BMD for predicting fracture risk.

Objective: The objective was to study the association of vitamin D with femoral neck (FN) strength.

Design And Setting: This was a population-based, cross-sectional study from Korea National Health and Nutrition Examination Surveys.

Participants: A total of 1209 Koreans (586 men and 623 women) aged ≥50 years participated.

Main Outcome Measures: We calculated composite indices of FN strength, such as the compression strength index, bending strength index (BSI), and impact strength index, by combining BMD, body weight, and height with the femoral axis length and width, which were measured by dual-energy x-ray absorptiometry.

Results: Multiple regression analysis demonstrated that serum 25-hydroxyvitamin D [25(OH)D] levels were associated with compression strength index, BSI, and impact strength index in both genders. When women were categorized into four quartiles of 25(OH)D, FN BMD and composite indices (except for BSI) significantly increased from the lowest (Q1) to the highest quartile (Q4) (P for trend = .001-.004). In contrast, there is no significant association of quartiles with composite indices in men. When women were divided into two groups according to their serum 25(OH)D levels, the composite indices as well as the FN BMD were markedly higher in subjects with higher 25(OH)D levels (≥51.5 nmol/L).

Conclusion: These findings provide the first clinical evidence that high serum 25(OH)D levels exhibit higher composite indices of FN strength in a dose-dependent manner, especially in women.
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http://dx.doi.org/10.1210/jc.2014-4320DOI Listing
August 2015

The association between serum dehydroepiandrosterone Sulphate (DHEA-S) level and bone mineral density in Korean men.

Clin Endocrinol (Oxf) 2015 Aug 13;83(2):173-9. Epub 2015 Mar 13.

Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Context: Many lines of evidence indicate that dehydroepiandrosterone (DHEA) plays a distinct role in bone metabolism and that its sulphated form (DHEA-S), which is easily measured in blood, may be a potential biomarker of osteoporosis-related phenotypes. However, most previous epidemiologic studies focused on postmenopausal women and reported conflicting results.

Objective: We aimed to investigate the association between the serum DHEA-S level and bone mass in men.

Design And Methods: This large cross-sectional study included 1089 healthy Korean men who participated in a routine health screening examination. Bone mineral density (BMD) at the lumbar spine, total femur, femur neck, and trochanter and serum DHEA-S level were obtained in all subjects.

Results: After adjustment for age, body mass index, lifestyle factors and serum levels of calcium, phosphorus, testosterone, 25-OH-vitamin D3 and cortisol, higher serum DHEA-S concentrations were associated with higher BMD values at all skeletal sites. Consistently, compared to the subjects in the highest DHEA-S quartile (Q4), those in the lowest DHEA-S quartile (Q1) showed significantly lower BMD values. Multiple logistic regression analyses revealed that the odds ratios for the risk of lower BMD (T-score <-1) increased in a dose-dependent manner across decreasing DHEA-S quartiles and the odds for the risk of lower BMD were 2·59-fold higher in Q1 than in Q4.

Conclusion: These findings support previous evidences that DHEA-S has favourable effects on bone mass in men and suggest that a low serum DHEA-S level may be a potential risk factor for male osteoporosis.
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http://dx.doi.org/10.1111/cen.12755DOI Listing
August 2015

Higher plasma platelet-activating factor levels are associated with increased risk of vertebral fracture and lower bone mineral density in postmenopausal women.

J Bone Miner Metab 2015 Nov 14;33(6):701-7. Epub 2014 Dec 14.

Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, 388-1 Poongnap2-Dong, Songpa-Gu, Seoul, 138-736, Korea.

Despite experimental and animal evidence showing the detrimental effects of platelet-activating factor (PAF) on bone metabolism, there are no clinical studies relating PAF to osteoporosis-related phenotypes. This case-control study investigates the association between plasma PAF, osteoporotic vertebral fracture (VF), and bone mineral density (BMD) in postmenopausal Korean women. Among 474 eligible women not taking any drug or having any disease that could affect bone metabolism, we identified 73 cases defined as subjects with radiological VF. The controls were randomly selected from the remaining 401 subjects and matched 1:1 to cases in terms of both age and body mass index (BMI). Lateral thoracolumbar radiographs, BMD, and plasma PAF levels were determined for all subjects. Postmenopausal women with VF demonstrated 34.6 % higher plasma PAF levels than subjects without VF after adjusting for age, BMI, smoking habits, alcohol intake, regular exercise, and parental history of osteoporotic fractures (P = 0.021). Multiple logistic regression analyses revealed that the odds ratio for VF linearly increased across increasing PAF quartiles (P for trend = 0.040) and the odds for VF were 2.88-fold higher in subjects in the highest quartile in comparison with those in the lowest quartile (95 % CI 1.04-8.01). Plasma PAF levels were inversely correlated with BMD at various sites (γ = -0.253 to -0.176, P = 0.003-0.041). These findings suggest that plasma PAF may be a potential biomarker for predicting poor bone health in postmenopausal women.
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http://dx.doi.org/10.1007/s00774-014-0634-2DOI Listing
November 2015

Different relationships between body compositions and bone mineral density according to gender and age in Korean populations (KNHANES 2008-2010).

J Clin Endocrinol Metab 2014 Oct 24;99(10):3811-20. Epub 2014 Jun 24.

Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736, Republic of Korea.

Context: Fat and muscle are linked to bone metabolism.

Objective: The objective of the study was to investigate the association of fat mass (FM) and lean mass (LM) with bone mineral density (BMD) according to gender and age.

Design And Setting: This was a population-based, cross-sectional study from Korea National Health and Nutrition Examination Surveys.

Participants: 15,036 Koreans (6692 men and 8344 women) aged 10-95 years.

Main Outcome Measures: BMD and body compositions were measured using dual-energy X-ray absorptiometry. BMD was determined at the femoral neck, total hip, and lumbar spine. Body compositions included total FM (TFM), percentage FM (PFM), truncal FM (TrFM), total LM (TLM), and appendicular skeletal muscle mass/weight (ASM/Wt).

Results: We categorized each man and woman into one of three age groups, based on changes in age-related BMD and the hormonal status. In all gender and age groups, TFM, PFM, and TrFM associated inversely with BMD (P < .001-.034), whereas TLM and ASM/Wt associated positively (P < .001-.037) after adjusting for confounders. The negative contribution of FM (P < .001-.034), and the positive contribution of LM (P < .001-.035) on BMD were significantly stronger in men than in women. The associations were strongest in men of growing age (P = .003-.040). When we subdivided the subjects into four groups based on the median values of PFM and TLM, FM had a greater effect than LM on BMD in men (P < .001-.006).

Conclusion: These results demonstrate that the effects of FM and LM on BMD may be based on gender and age.
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http://dx.doi.org/10.1210/jc.2014-1564DOI Listing
October 2014

Independent associations of circulating 25-hydroxyvitamin D and parathyroid hormone concentrations with blood pressure among Koreans: The Korea National Health and Nutrition Examination Survey (KNHANES), 2009-2010.

Calcif Tissue Int 2013 Dec 11;93(6):549-55. Epub 2013 Oct 11.

Department of Internal Medicine, Veterans Health Service Medical Center, 53 Jinhwangdo-ro 61-Gil, Gangdong-gu, Seoul, Korea.

Although lower vitamin D and higher parathyroid hormone (PTH) concentrations have been associated with hypertension, their independent contribution to blood pressure (BP) is unclear. The independent associations of serum 25-hydroxyvitamin D (25[OH]D) and PTH levels with BP were therefore investigated. This is a population-based cross-sectional study from the Korea National Health and Nutrition Examination Surveys, which includes a total of 4,513 participants (2,019 men and 2,494 women) aged ≥ 50 years. 25(OH)D and PTH were measured by radioimmunoassays, and BP was determined with a sphygmomanometer. Hypertensive subjects had significantly lower 25(OH)D (p = 0.023) and significantly higher PTH (p < 0.001) concentrations than normotensives. In subjects not taking antihypertensive medications, 25(OH)D showed reverse correlations with systolic and diastolic BP, both in men (p = 0.038-0.061 and p = 0.011-0.038, respectively) and in women (p = 0.006-0.018 and p = 0.001-0.011, respectively), while serum PTH concentrations showed positive correlations with systolic and diastolic BP in men (p = 0.001-0.014 and p < 0.001, respectively) and women (p < 0.001-0.008 and p = 0.001-0.040, respectively). When 25(OH)D and PTH were included in the same model, both remained independently associated with BP in men and women. In conclusion, both lower 25(OH)D and higher PTH may be independent factors for the development of hypertension.
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http://dx.doi.org/10.1007/s00223-013-9789-4DOI Listing
December 2013
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