Efficacy of bisphosphonate therapy on postmenopausal osteoporotic women with and without diabetes: a prospective trial.

BACKGROUND: The co-occurrence of diabetes and osteoporosis is common in postmenopausal women. For the treatment of postmenopausal osteoporosis, current guidelines recommend initial treatment with bisphosphonates, but it is unclear whether bisphosphonates provide a similar degree of therapeutic efficacy in patients with diabetes. This study sought to compare the efficacy of monthly oral ibandronate for retaining bone mineral density (BMD) in diabetic and non-diabetic postmenopausal women with osteoporosis. METHODS: Postmenopausal osteoporotic women with or without diabetes were enrolled in this study from three hospitals in an open-label approach from 2018 to 2020. Each group of patients received oral ibandronate 150 mg once monthly for 1 year. BMD, trabecular bone score (TBS), serum C-terminal telopeptide of type I collagen (CTx) and procollagen type 1 N-terminal propeptide (P1NP) were evaluated prospectively. Treatment-emergent adverse events and changes in glucose metabolism during drug use were also monitored. RESULTS: Among the 120 study participants, 104 (86.7%) completed the study. Following 1 year of treatment, BMD increased by 3.41% vs. 3.71% in the lumbar spine, 1.30% vs. 1.18% in the femur neck, and 1.51% vs. 1.58% in the total hip in the non-diabetes and diabetes groups, respectively. There were no significant differences in BMD changes between the groups, and the differences in CTx or P1NP changes between groups were not significant. We did not observe any significant differences in baseline TBS values or the degree of change between before and after 1 year of ibandronate treatment in either group in this study. A total of 11 adverse events (9.2%) that recovered without sequelae occurred among the 120 included patients, and there was no significant difference in the frequency of adverse events between the groups (p = 0.862). The changes in fasting glucose and glycated hemoglobin levels between before and after treatment were not significant in the diabetic group. CONCLUSIONS: Bisphosphonate therapy showed similar increases in BMD and decreases in CTx and P1NP of postmenopausal women with and without diabetes. Monthly oral ibandronate can be a safe and effective therapeutic option in postmenopausal osteoporosis patients with type 2 diabetes. TRIAL REGISTRATION: NCT number: NCT05266261, Date of registration: 04 March 2022.

Association between the type of thyroid dysfunction induced by immune checkpoint inhibitors and prognosis in cancer patients.

BACKGROUND: Immune checkpoint inhibitors (ICIs) cause thyroid immune-related adverse effects (irAEs). However, associations between each type of thyroid immune-related adverse effect (irAE) and the anti-tumor effect of ICI remains unknown. This study aimed to determine the effects of each type of thyroid dysfunction on patient survival. METHODS: Patients who initiated ICI treatment from January 2015 to December 2019 in Seoul St. Mary's Hospital were retrospectively analyzed. Thyroid dysfunction was classified into four types: newly developed overt or subclinical hypothyroidism, thyrotoxicosis, worsened hypothyroidism, and subclinical hyperthyroidism. Patients were divided into two groups according to the presence or absence of thyroid dysfunction. RESULTS: Among the 191 patients, 64 (33.5%) developed thyroid irAEs. There was no significant difference in age, sex, or cancer type between the two groups. The overall survival in patients with thyroid irAEs was significantly higher than that in patients without thyroid irAEs (25 months vs. 18 months, respectively, p = 0.005). After adjusting for confounding factors, the hazard ratio for mortality in the thyroid irAE group compared to the no thyroid irAE group was 0.480 (p = 0.006). Newly developed overt or subclinical hypothyroidism patients showed a significantly lower hazard ratio for mortality of 0.324 (p = 0.002). Patients with thyrotoxicosis showed a worse hazard ratio for mortality than those without thyroid irAE, although the difference was not statistically significant. CONCLUSIONS: It was verified that ICI treatment-induced thyroid dysfunction was associated with better survival, even in the real-world practice. Thus, endocrinologists should cooperate with oncologists to monitor patients treated with ICIs.

Clinical outcomes of primary aldosteronism based on lateralization index and contralateral suppression index after adrenal venous sampling in real-world practice: a retrospective cohort study.

BACKGROUND: We investigated whether the contralateral suppression index in aldosterone-producing adrenal adenoma could be used as a diagnostic criterion when catheterization in either right or left adrenal vein fails or when a discrepancy in the adrenal vein sampling (AVS) results and imaging findings occurs in the real-world practice. METHODS: We retrospectively reviewed 48 patients who had resistant hypertension (HTN) or hypokalemia with a biochemical diagnosis of primary aldosteronism and who underwent AVS from January 2009 to June 2017 at a tertiary referral hospital. Selection index (SI), lateralization index (LI), and contralateral suppression index (CSI) were calculated based on AVS results and the final clinical outcomes were evaluated. RESULTS: The catheterization of both adrenal veins was successful in 43 of 48 (89.6%) patients. The lateralization based only on LI was performed in 23 out of 43 (53.5%) patients. When CSI and LI were combined in decision making, the concordance between adrenal computed tomography scan and AVS for unilateral lesion improved from 59.3% (19/32) to 75.0% (24/32). CSI also correlated well with unilateral adrenal disease in the catheterization failure group. The final outcomes of HTN were better in the contralateral suppression group. CONCLUSION: CSI combined with LI could be a supplementary diagnostic tool in patients with non-lateralization or catheterization failure and predict the clinical outcomes of HTN in patients with primary aldosteronism.

Assessment of patient-reported outcomes (PROs): treatment satisfaction, medication adherence, and quality of life (QoL) and the associated factors in postmenopausal osteoporosis (PMO) patients in Korea.

Patient-reported outcomes (PROs) provide practical guides for treatment; however, studies that have evaluated PROs of women in Korea with postmenopausal osteoporosis (PMO) are lacking. This cross-sectional, multi-center (29 nationwide hospitals) study, performed from March 2013 to July 2014, aimed to assess PROs related to treatment satisfaction, medication adherence, and quality of life (QoL) in Korean PMO women using osteoporosis medication for prevention/treatment. Patient demographics, clinical characteristics, treatment patterns, PROs, and experience using medication were collected. The 14-item Treatment Satisfaction Questionnaire for Medication (TSQM) (score-range, 0-100; domains: effectiveness, side effects, convenience, global satisfaction), Osteoporosis-Specific Morisky Medication Adherence Scale (OS-MMAS) (score-range, 0-8), and EuroQol-5 dimensions questionnaire (index score range, - 0.22 to 1.0; EuroQol visual analog scale score range, 0-100) were used. To investigate factors associated with PROs, linear (treatment satisfaction/QoL) or logistic (medication adherence) regression analyses were conducted. A total of 1804 patients (age, 62 years) were investigated; 60.1% used bisphosphonate, with the majority (67.2%) using weekly medication, 27.8% used daily hormone replacement therapy, and 12.1% used daily selective estrogen receptor modulator. Several patients reported gastrointestinal (GI) events (31.6%) and dental visits due to problems (24.1%) while using medication. Factors associated with the highest OS-MMAS domain scores were convenience and global satisfaction. GI events were associated with non-adherence. TSQM scores for effectiveness, side effects, and GI risk factors were significantly associated with QoL. Our study elaborately assessed the factors associated with PROs of Korean PMO women. Based on our findings, appropriate treatment-related adjustments such as frequency/choice of medications and GI risk management may improve PROs.

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

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.

The Relationship of Serum Serotonin Levels to the Rate of Bone Loss and Fractures in Men.

Recent genetic studies in rodents have revealed that circulating serotonin plays a key role in regulating bone formation and skeletal mass. However, the reported effects of circulating serotonin on bone mass in humans have been conflicting. We determined whether circulating serotonin levels influenced the rate of bone loss and fractures in men. We assessed the effect of serum serotonin on bone loss rate in a population-based cohort of 202 ambulatory men aged 56-70 years who were followed up for a median duration of 3.7 years. Serum serotonin levels were assayed, and the Timed Up and Go Test (TUGT) was performed, at baseline. Dual-energy X-ray absorptiometry was performed both at baseline and during follow-up. Fracture prevalence was assessed using questionnaires. The serotonin levels were inversely associated with the lumbar spine bone mineral density (r = -0.174, p = 0.028) at baseline. No association was evident between the bone mineral densities of the femoral neck or total hip and serotonin level. The annual rates of bone loss from the lumbar spine, the femoral neck, and the total hip were 0.01%, 0.46%, and 0.46%, respectively. The baseline serum serotonin level did not predict the bone loss rate in any skeletal site. Lower limb disability evident upon TUGT at baseline predicted bone loss from the total hip. No significant difference of serotonin level was observed between subjects with and without fractures. The serum serotonin level was not associated with the rate of bone loss in elderly men. Thus, the circulating serotonin level does not reliably predict bone loss.

Prognostic value of preoperative anti-thyroglobulin antibody in differentiated thyroid cancer.

CONTEXT: The coexistence of differentiated thyroid cancer (DTC) and thyroid autoimmune disease could represent a better or worse prognosis. This study investigated the prognostic importance of preoperative anti-thyroglobulin antibody (TgAb) in DTC patients. DESIGN AND PATIENTS: This retrospective hospital-cohort study enrolled 1171 consecutive DTC patients with preoperative TgAb data, who underwent total thyroidectomy between January 2006 and December 2011. Clinical parameters studied included demographics, primary tumour characteristics, radioiodine therapy, thyroid function tests, preoperative thyroglobulin (Tg) and TgAb levels, and cancer persistence/recurrence. RESULTS: A total of 254 (21.7%) patients were preoperatively TgAb positive. The percentage positive for thyroid peroxidase (TPO) antibody and lymphocytic thyroiditis was significantly higher in the TgAb-positive group. The TgAb-positive group had a significantly higher rate of lymphatic invasion and lymph node metastasis both overall and in patients without TPOAb and lymphocytic thyroiditis (non-HT group). The mean number of total and central lymph nodes dissected and rate of lateral lymph node dissection were significantly higher in the TgAb-positive group, both overall and in non-HT patients. In regression analysis, preoperative TgAb was an independent risk factor for lateral lymph node metastasis. Over 50.2±14.5 months of follow-up, disease persistence/recurrence was not significantly different between patients with and without TgAb, both overall and in non-HT patients. Preoperative TgAb showed no significant correlation with final disease status. CONCLUSION: Positive preoperative serum TgAb is associated with worse primary tumour characteristics but rarely showed poor prognosis, probably due to more aggressive treatment of these subjects.

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.

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.

Gender- and age-group-specific associations between physical performance and bone mineral density, falls, and osteoporotic fractures in Koreans: the Chungju Metabolic Disease Cohort study.

Several factors increase the risk of fragility fracture, including low bone mineral density, falls, and poor physical performance. The associations among these factors have been investigated; however, most of the subjects of previous studies were either elderly men or elderly women, and the associations were controversial. The aim of this study was to evaluate the associations between physical performance and bone mineral density, and the history of falls and fractures, stratified by gender and age group. We analyzed 5368 subjects who were aged 50 years or older, including 1288 younger men (younger than 70 years), 1615 younger women (younger than 70 years), 1087 older men (70 years or older), and 1378 older women (70 years or older). We used the one-leg standing time (OLST) for assessing static balance and the timed up-and-go test (TUGT) for assessing dynamic balance. The subjects in the worst performance quartile for the OLST were more likely to have osteoporosis than those in the best performance quartile. Additionally, women who had experienced a fracture during the past 2 years were 1.68 times more likely to be in the worst performance quartile for the OLST than women without a previous fracture. Although the TUGT time was not associated with either the incidence of osteoporosis or the fracture history, the odds ratios for falling were 1.51 and 1.28 as the TUGT time increased by one standard deviation in younger men and younger women, respectively. The findings of the present study show that the OLST was associated with the incidence of osteoporosis and previous fracture and that the TUGT time was associated with the incidence of falling.

Chronic Alcohol Consumption Results in Greater Damage to the Pancreas Than to the Liver in the Rats.

Alcohol consumption increases the risk of type 2 diabetes. However, its effects on prediabetes or early diabetes have not been studied. We investigated endoplasmic reticulum (ER) stress in the pancreas and liver resulting from chronic alcohol consumption in the prediabetes and early stages of diabetes. We separated Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a type-2 diabetic animal model, into two groups based on diabetic stage: prediabetes and early diabetes were defined as occurrence between the ages of 11 to 16 weeks and 17 to 22 weeks, respectively. The experimental group received an ethanol-containing liquid diet for 6 weeks. An intraperitoneal glucose tolerance test was conducted after 16 and 22 weeks for the prediabetic and early diabetes groups, respectively. There were no significant differences in body weight between the control and ethanol groups. Fasting and 120-min glucose levels were lower and higher, respectively, in the ethanol group than in the control group. In prediabetes rats, alcohol induced significant expression of ER stress markers in the pancreas; however, alcohol did not affect the liver. In early diabetes rats, alcohol significantly increased most ER stress-marker levels in both the pancreas and liver. These results indicate that chronic alcohol consumption increased the risk of diabetes in prediabetic and early diabetic OLETF rats; the pancreas was more susceptible to damage than was the liver in the early diabetic stages, and the adaptive and proapoptotic pathway of ER stress may play key roles in the development and progression of diabetes affected by chronic alcohol ingestion.

Meta-analysis identifies a MECOM gene as a novel predisposing factor of osteoporotic fracture.

BACKGROUND: Osteoporotic fracture (OF) as a clinical endpoint is a major complication of osteoporosis. To screen for OF susceptibility genes, we performed a genome-wide association study and carried out de novo replication analysis of an East Asian population. METHODS: Association was tested using a logistic regression analysis. A meta-analysis was performed on the combined results using effect size and standard errors estimated for each study. RESULTS: In a combined meta-analysis of a discovery cohort (288 cases and 1139 controls), three hospital based sets in replication stage I (462 cases and 1745 controls), and an independent ethnic group in replication stage II (369 cases and 560 for controls), we identified a new locus associated with OF (rs784288 in the MECOM gene) that showed genome-wide significance (p=3.59×10(-8); OR 1.39). RNA interference revealed that a MECOM knockdown suppresses osteoclastogenesis. CONCLUSIONS: Our findings provide new insights into the genetic architecture underlying OF in East Asians.

Association of osteoporosis susceptibility genes with bone mineral density and bone metabolism related markers in Koreans: the Chungju Metabolic Disease Cohort (CMC) study.

In this study, we evaluated the association between bone mineral density (BMD) and 10 single-nucleotide polymorphisms (SNPs) within eight osteoporosis susceptibility genes that were previously identified in genome-wide association studies (GWASs). A total of 494 men and 493 postmenopausal women participating in the Chungju Metabolic Disease cohort study in Korea were included. The following 10 SNPs were genotyped: ZBTB40 rs6426749, MEF2C rs1366594, ESR1 rs2941740, TNFRSF11B rs3134070, TNFRSF11B rs2073617, SOX6 rs711785, LRP5 rs599083, TNFSF11 rs227438, TNFSF11 rs9594782, and FOXL1 rs10048146; and the association between these SNPs and bone metabolism-related markers was assessed. Two SNPs, TNFSF11 rs2277438 and FOXL1 rs1004816, were associated with lumbar spine BMD. TNFSF11 rs2277438 in men and SOX6 rs7117858 and FOXL1 rs10048146 in postmenopausal women were found to be associated with lumbar BMD. ZBTB40 rs6426749, MEF2C rs1366594, and LRP5 rs599083 showed significant associations with femur neck BMD. These three SNPs in men and MEF2C rs1366594 and ESR1 rs2941740 in postmenopausal women were associated with femur neck BMD. A significant association between MEF2C rs1366594 and serum calcium levels was observed in men. Serum phosphorus levels were related to SOX6 rs7117858. Serum PTH levels were significantly associated with TNFRSF11B rs3134070 in men, and SOX6 rs711858 in postmenopausal women. In conclusion, our study independently confirmed associations between several SNPs: ZBTB40, MEF2C, ESR1, SOX6, LRP5, TNFSF11, and FOXL1 and bone marrow density in the Korean population.

Endocrinopathies in transfusion-associated iron overload.

BACKGROUND: Transfusional iron overload primarily results in reticuloendothelial iron accumulation, which is considered to be less harmful than parenchymal iron accumulation. However, systematic and comprehensive data on endocrine function in transfusion-associated haemochromatosis are limited. METHODS: We examined 25 aplastic anaemia patients (11 men and 14 women) diagnosed with transfusion-associated haemochromatosis at a single institution. Pituitary function was determined with a combined pituitary function test. On a different day, a 75-g oral glucose tolerance test was performed. The bone mineral density (BMD) of the lumbar spine and total hip was assessed with dual-energy X-ray absorptiometry. RESULTS: Twenty-two (88%) of these 25 patients had at least one endocrine abnormality, and 12 had more than one abnormality. The most common pituitary hormonal deficiency involved the pituitary-gonadal axis; 54% of the total subjects had hypogonadotropic hypogonadism. Two patients had an insufficient cortisol response to corticotrophin-releasing hormone stimulation. No patient had a deficiency of growth hormone or thyroid-stimulating hormone. Twelve (48%) had diabetes mellitus, and these patients tended to have higher concentrations of ferritin, alanine aminotransferase and γ-glutamyl transferase. Osteoporosis (T-score <-2·5 SD) was observed in 48% of patients. The reduction in BMD was more pronounced in the lumbar spine than in the total hip. The patients with osteoporosis were accompanied by hypogonadism, which predominantly affected the trabecular bone. CONCLUSIONS: Our observations suggest that endocrinopathies are common in transfusion-associated haemochromatosis.

Serum alkaline phosphatase, body composition, and risk of metabolic syndrome in middle-aged Korean.

Some papers have suggested that alkaline phosphatase (ALP) level is a predictor of the metabolic syndrome (MetS) in the general population. However, the association is still controversial, and the mechanisms underlying an association between ALP level and the MetS have not been elucidated. We analyzed the association between serum ALP level and the development of the MetS over a 4-year period. A total of 14,224 subjects who visited the Health Promotion Center for a medical examination in 2005 were followed up after 4 years. Serum ALP level correlated positively with body fat mass and visceral fat mass. The adjusted geometric mean ALP levels were higher in subjects with elevated C-reactive protein level or greater fat mass (P < 0.001). None of the subjects had the MetS at baseline, but 1,179 exhibited the MetS at the 4-year follow-up. After multiple adjustments, the odds ratio (OR) was substantially higher for development of the MetS (OR 1.56, 95% confidence intervals, 1.21-2.01) in subjects in the highest ALP quintile compared with those in the lowest quintile. After adjusting for various covariates, we found significant associations between the quintile of serum ALP level and abdominal obesity, low high-density lipoprotein cholesterol level, and high triglyceride level. Higher serum ALP level was a significant predictor of the MetS in middle-aged Koreans. Serum ALP level correlated positively with body fat mass and independently with a more atherogenic lipid profile in the general population in Korea.

The association between daily calcium intake and sarcopenia in older, non-obese Korean adults: the fourth Korea National Health and Nutrition Examination Survey (KNHANES IV) 2009.

Recent data suggest that variations in calcium intake may influence body weight and composition; however, the relationship between daily calcium intake and muscle mass has not been well established. The objective of this study was to assess the relationship between daily calcium intake and sarcopenia. We analyzed data for older adults (over 60 years) from the fourth Korea National Health and Nutrition Examination Survey (KNHANES) conducted in 2009. A total of 1339 Non-Obese (BMI between 18.5 and 25 kg/m²), older adults (592 men and 707 women) were enrolled. Dietary variables were assessed using a nutrition survey that used a 24-hour recall method. Daily calcium intake based on the consumption of each food item was calculated. Sarcopenia was defined as an appendicular skeletal muscle mass divided by body weight less than 2 SD below the sex-specific mean for young adults. We found that daily calcium intake was negatively correlated with total body fat percentage and positively correlated with appendicular skeletal mass (p<0.001). Participants with sarcopenia appear to have significantly lower daily calcium intakes than participants without sarcopenia (p<0.001). The unadjusted prevalence of sarcopenia according to daily calcium intake tertiles were 6.3%, 4.3%, and 2.7% in tertiles 1, 2, and 3, respectively. After adjustment for age, sex, BMI, total energy intake, and lifestyle factors, compared with those in the lowest tertile of daily calcium intake, participants in the highest tertile had an odds ratio for sarcopenia of 0.295 (95% confidence interval, 0.087-0.768; p for trend = 0.014). We found that daily calcium intake, corrected for total energy intake and serum 25(OH)D status, was significantly lower in subjects with sarcopenia than in those without. Our results suggest a strong inverse association between daily calcium intake and sarcopenia in non-obese, older Korean adults.

High serum vitamin D levels reduce the risk for nonalcoholic fatty liver disease in healthy men independent of metabolic syndrome.

Recent studies suggest an association of vitamin D with obesity, diabetes and cardiovascular diseases. We analyzed the association of serum vitamin D level assessed by 25-hydroxyvitamin D3 {25(OH)D3 } with nonalcoholic fatty liver disease (NAFLD) in apparently healthy men. We performed a cross-sectional study of 6,567 Korean men who participated in a health screening program, evaluating the association of serum 25(OH)D3 levels with the risk of NAFLD assessed by abdominal ultrasonogram. Of the participants, 43.6% had NAFLD and 21.1% had metabolic syndrome. Age, serum calcium, and aspartate aminotransferase levels showed weak but significant positive correlations with 25(OH)D3 level; total cholesterol, triglycerides, low-density lipoprotein cholesterol and fasting insulin level showed weak but significant negative correlations with 25(OH)D3 level. The mean 25(OH)D3 level was significantly lower in participants with NAFLD than in those without (38.7 ± 9.0 vs. 39.7 ± 9.7 nmol/L, p < 0.001). When participants were divided into tertiles based on mean 25(OH)D3 level, the proportion with NAFLD significantly increased as mean 25(OH)D3 level decreased (40.0, 45.0 and 45.9%, p for linear trend < 0.001). Multiple logistic regression analyses with NAFLD as the dependent variable showed that the tertiles with lower 25(OH)D3 levels had a significantly increased risk for NAFLD compared with the highest tertile, even after adjusting for body mass index and metabolic syndrome (OR 1.247 and 1.408 vs. the highest tertile, p < 0.001). Thus, participants with higher serum 25(OH)D3 showed a significantly reduced risk for NAFLD compared with the low 25(OH)D3 groups, independent of obesity and metabolic syndrome.

Persistence with Denosumab in Male Osteoporosis Patients: A Real-World, Non-Interventional Multicenter Study.

BACKGRUOUND: Persistence with denosumab in male patients has not been adequately investigated, although poor denosumab persistence is associated with a significant risk of rebound vertebral fractures. METHODS: We retrospectively evaluated 294 Korean male osteoporosis patients treated with denosumab at three medical centers and examined their persistence with four doses of denosumab injection over 24 months of treatment. Persistence was defined as the extent to which a patient adhered to denosumab treatment in terms of the prescribed interval and dose, with a permissible gap of 8 weeks. For patients who missed their scheduled treatment appointment(s) during the follow-up period (i.e., no-shows), Cox proportional regression analysis was conducted to explore the factors associated with poor adherence. Several factors were considered, such as age, prior anti-osteoporotic drug use, the treatment provider's medical specialty, the proximity to the medical center, and financial burdens of treatment. RESULTS: Out of 294 male patients, 77 (26.2%) completed all four sequential rounds of the denosumab treatment. Out of 217 patients who did not complete the denosumab treatment, 138 (63.6%) missed the scheduled treatment(s). Missing treatment was significantly associated with age (odds ratio [OR], 1.03), prior bisphosphonate use (OR, 0.76), and prescription by non-endocrinologists (OR, 2.24). Denosumab was stopped in 44 (20.3%) patients due to medical errors, in 24 (11.1%) patients due to a T-score improvement over -2.5, and in five (2.3%) patients due to expected dental procedures. CONCLUSION: Our study showed that only one-fourth of Korean male osteoporosis patients were fully adherent to 24 months of denosumab treatment.

Impact of common type 2 diabetes risk gene variants on future type 2 diabetes in the non-diabetic population in Korea.

We prospectively examined the association between type 2 diabetes mellitus (T2DM) progression and common T2DM-risk gene variants in 870 non-diabetic participants in a Chungju Metabolic Disease Cohort Study in Korea. We genotyped the following six single nucleotide polymorphisms (SNPs): KCNQ1 (potassium voltage-gated channel, KQT-like subfamily member 1) rs2237892, CDKAL1 (regulatory subunit-associated protein 1-like 1) rs7554840, CDKN2A/B (cyclin-dependent kinase inhibitor 2A/B) rs1081161, SCL30A8 (solute carrier family 30 member 8 gene) rs13266634, TCF7L2 (transcription factor 7-like 2) rs7903146, and PPARG (peroxisome proliferator activated receptor gamma) rs1801282. Anthropometric data and metabolic parameters were obtained at baseline and year 4. Pancreatic ß cell function was assessed by the homeostasis model assessment index of ß cells (HOMA-ß). After 4 years, 137 subjects developed T2DM (15.7%). A significant association was found in the variant of KCNQ1 rs2237892, whereas the SNPs of CDKAL1, CDKN2A/B, SCL30A8, TCF7L2 and PPARG were not associated. The C-allele carriers of KCNQ1 conferred a significantly increased risk for T2DM compared with the T/T genotype, independently of clinical risk factors (odds ratio=2.61, 95% confidence intervals=1.02-6.69, P=0.04). Although no differences were observed at baseline among the KCNQ1 variants, HOMA-ß levels by year 4 were significantly lower in the C-allele carriers after controlling for metabolic parameters. The genetic variations in KCNQ1 are associated with future development of T2DM in Koreans, which might be mediated by differences in insulin secretory function.

Osteoporosis Patient Treatment Satisfaction Questionnaire in postmenopausal women intermittently treated with oral bisphosphonates: the BRAVO study.

The Osteoporosis Patient Treatment Satisfaction Questionnaire (OPSAT-Q) is a psychometric measure of patient satisfaction with bisphosphonate treatment for osteoporosis. The study was a multicenter, nationwide, cross-sectional, patient-reported outcome study conducted to evaluate treatment satisfaction and quality of life using the OPSAT-Q in patients receiving oral bisphosphonate therapy. This study enrolled postmenopausal women from 43 hospitals and 112 clinics who had intermittently taken oral bisphosphonates for treatment of osteoporosis. 4,220 postmenopausal Korean women with a mean age of 65.3 years and a mean body mass index of 22.9 kg/m(2) participated in the study. All items within each subscale domain were more highly correlated with their hypothesized subscale domain relative to the other subscale domains, and all 16 items were significantly correlated with an overall composite satisfaction score (CSS). All scores showed acceptable internal consistency reliability (Cronbach's alpha >0.70, range 0.88-0.91). Comparisons of OPSAT-Q scores were made between selective subgroups of participants: monthly versus weekly administration, years of taking bisphosphonates, smoking habitus, acid-related medication and comorbid conditions. Mean OPSAT-Q subscale domains and CSS were higher for users of monthly bisphosphonates, with shorter duration, non-smokers, and non-users of acid-related medication. Mean OPSAT-Q subscale domain scores of side-effects were high for absence of comorbid conditions. The OPSAT-Q demonstrated acceptable measurement properties, including validity and reliability of subscale domains and CSS, in oriental women with postmenopausal osteoporosis. Postmenopausal women intermittently using oral bisphosphonate therapy reported increased satisfaction with monthly administration, with shorter duration, non-smokers, non-users of acid-related medication, and an absence of comorbid conditions.

Relationship between vitamin D, parathyroid hormone, and bone mineral density in elderly Koreans.

There is controversy regarding definition of vitamin D inadequacy. We analyzed threshold 25-hydroxyvitamin D (25[OH]D) below which intact parathyroid hormone (iPTH) increases, and examined age- and sex-specific changes of 25(OH)D and iPTH, and association of 25(OH)D and iPTH with bone mineral density (BMD) in elderly Koreans. Anthropometric parameters, serum 25(OH)D and iPTH, lumbar spine and femur BMD by dual-energy radiography absorptiometry (DXA) were measured in 441 men and 598 postmenopausal women. iPTH increased below serum 25(OH) of 36.7 ng/mL in men, but failed to reach plateau in women. Femur neck BMD above and below threshold differed when threshold 25(OH)D concentrations were set at 15-27.5 ng/mL in men, and 12.5-20 ng/mL in postmenopausal women. Vitamin D-inadequate individuals older than 75 yr had higher iPTH than those aged ≤ 65 yr. In winter, age-associated iPTH increase in women was steeper than in summer. In conclusion, vitamin D inadequacy threshold cannot be estimated based on iPTH alone, and but other factors concerning bone health should also be considered. Older people seemingly need higher 25(OH)D levels to offset age-associated hyperparathyroidism. Elderly vitamin D-inadequate women in the winter are most vulnerable to age-associated hyperparathyroidism.