Relationship between body mass index and fracture risk at different skeletal sites: a nationwide cohort study.

The association between obesity and fracture was skeletal site-specific with no gender difference. Obesity was associated with a higher risk of proximal humerus fractures but not for wrist or clinical vertebral fractures. PURPOSE: The association between body mass index (BMI) and the risk of clinical fractures at different sites is unclear. This study aimed to examine associations between BMI and fractures at different sites in Korean men and women. METHODS: This study analyzed 285,643 Korean adults (aged 50-80 years) who participated in health examinations from 2002 to 2003 and were followed up until 2015. The incidences of osteoporotic fractures were assessed using the International Classification of Diseases (10th revision; ICD-10) and procedure or radiographic codes. After adjusting for confounders, hazard ratios (HRs) were calculated using Cox proportional hazard models for fracture risk. RESULTS: Site-specific associations between BMI and fractures were found without gender difference. Specifically, an L-shaped association was found for clinical vertebral fractures, wherein the adjusted HRs per 5 kg/m2 increase were 0.80 (95% confidence interval [CI] = 0.76-0.83) in BMI groups < 25 kg/m2 and 0.97 (95% CI = 0.92-1.03) in BMI ≥ 25 kg/m2. A linear inverse correlation for wrist fractures was observed, wherein the HRs were 0.83 (95% CI = 0.81-0.86) per 5 kg/m2 increase. For proximal humerus fractures, a non-linear U-shape association was found, wherein the adjusted HRs per 5 kg/m2 increase were 0.66 (95% CI = 0.50-0.88) in BMI groups < 23 kg/m2 and 1.25 (95% CI = 1.08-1.45) in BMI ≥ 23 kg/m2. CONCLUSION: Low BMI was a risk factor for all tested fractures. Obesity was a risk factor for proximal humerus fracture, but it is a protective factor for wrist fracture.

Osteoporosis Pre-Screening Using Ensemble Machine Learning in Postmenopausal Korean Women.

As osteoporosis is a degenerative disease related to postmenopausal aging, early diagnosis is vital. This study used data from the Korea National Health and Nutrition Examination Surveys to predict a patient's risk of osteoporosis using machine learning algorithms. Data from 1431 postmenopausal women aged 40-69 years were used, including 20 features affecting osteoporosis, chosen by feature importance and recursive feature elimination. Random Forest (RF), AdaBoost, and Gradient Boosting (GBM) machine learning algorithms were each used to train three models: A, checkup features; B, survey features; and C, both checkup and survey features, respectively. Of the three models, Model C generated the best outcomes with an accuracy of 0.832 for RF, 0.849 for AdaBoost, and 0.829 for GBM. Its area under the receiver operating characteristic curve (AUROC) was 0.919 for RF, 0.921 for AdaBoost, and 0.908 for GBM. By utilizing multiple feature selection methods, the ensemble models of this study achieved excellent results with an AUROC score of 0.921 with AdaBoost, which is 0.1-0.2 higher than those of the best performing models from recent studies. Our model can be further improved as a practical medical tool for the early diagnosis of osteoporosis after menopause.

Age- and Sex-Specific Differences in Distribution of Cardiometabolic Diseases and Associations of Hand-Grip Strength Indices with Type 2 Diabetes in Korean Adults.

Background: To evaluate age- and sex-specific differences in the distribution of cardiometabolic diseases and associations of hand-grip strength (HGS) indices with type 2 diabetes (T2D). Methods: This cross-sectional observational study enrolled participants from the Korea National Health and Nutrition Examination Survey (n = 16,126, age ≥19 years). Information on cardiometabolic diseases was obtained through surveys or proper criteria applied for undiagnosed participants. Absolute and body size-adjusted HGS indices were evaluated. Clinical manifestations were compared, and associations of HGS indices with T2D were estimated by using odd ratio (OR). Results: Prevalence of T2D in all, younger, and older groups were 13.1%, 4.2%, and 21.4%, respectively. Proportions of cardiometabolic diseases were all higher in those with than without T2D in sex-stratified age groups, whereas obesity (OB) and nonalcoholic fatty liver disease (NAFLD) were higher in younger T2D, and hypertension (HTN) was higher in older T2D in both sexes. Adjusted HGS significantly correlated with cardiometabolic parameters, and thus, high ORs for T2D in low tertiles of adjusted HGS were shown in all groups, whereas high ORs for T2D in low tertiles of absolute HGS were observed only in older men. Conclusions: Among highly prevalent cardiometabolic diseases associated with T2D, OB and NAFLD were more prevalent in younger T2D, but HTN was more prevalent in older T2D in both sexes. Low adjusted HGS was associated with higher T2D risk in all groups, whereas low absolute HGS was associated with higher T2D risk in older men. Thus, adjusted HGS might be useful in screening especially younger or obese T2D.

Association between relative hand-grip strength and chronic cardiometabolic and musculoskeletal diseases in Koreans: A cross-sectional study.

OBJECTIVES: This study evaluated clinical and cardiometabolic markers associated with relative hand-grip strength (HGS), and investigated odds ratios (ORs) for chronic cardiometabolic and musculoskeletal diseases according to relative HGS. METHODS: This cross-sectional observational study enrolled subjects from the Korea National Health and Nutrition Examination Survey who were 50 years and older (N = 2451). Information on chronic diseases was taken by individual surveys and other proper criteria were applied for undiagnosed subjects. Absolute HGS was calculated from the maximal bilateral HGS (kg) as measured by a dynamometer and relative HGS was calculated by dividing absolute HGS by body mass index (BMI). Associated clinical and cardiometabolic markers to relative HGS were investigated and ORs for chronic diseases according to relative HGS tertiles were estimated from multivariate linear or logistic regression analyses. RESULTS: The mean relative HGS (kg/BMI) was 3.1 ± 0.6 for men and 1.9 ± 0.5 for women. Insulin-resistance parameters and high-sensitivity C-reactive protein were negatively and high-density lipoprotein cholesterol was positively related with relative HGS in both sexes adjusting for age and lifestyle factors, while systolic blood pressure showed negative relationship in women. High ORs for various chronic diseases were observed in the lowest relative HGS tertile of both sexes, but high OR for hyperlipidemia was observed only in women. CONCLUSIONS: Relative HGS is a convenient measure for overall muscle strength according to body size and may have an influence on chronic disease development or aggravation. Thus, relative HGS might be a cost-effective and useful tool to screen for prevalent chronic diseases in elderly population.

Prevalence and complications of nonsurgical hypoparathyroidism in Korea: A nationwide cohort study.

OBJECTIVE: The risk of complications of nonsurgical hypoparathyroidism in Asia is unclear. We estimated the prevalence and risk of complications in patients with nonsurgical hypoparathyroidism. METHODS: We performed a retrospective cohort study using a nationwide claims database from 2005 to 2016. Among the entire Korean population, we identified 897 patients diagnosed with nonsurgical hypoparathyroidism during 2005-2015. We selected 210 patients with nonsurgical hypoparathyroidism during 2005-2008 who had no complications at baseline and followed them to 2016. Control subjects (n = 2075) were matched using propensity scores based on age, sex, and comorbid disease with a 1:10 ratio and monitored until 2016. RESULTS: The age-standardized prevalence of nonsurgical hypoparathyroidism was 0.2 cases per 100,000 persons in 2005. During a mean follow-up period of 9.5 years, patients with nonsurgical hypoparathyroidism had a higher risk of cardiovascular disease, especially arrhythmia (hazard ratio [HR], 2.03; 95% confidence interval [CI], 1.11-3.70) and heart failure (HR, 2.43; 95% CI, 1.22-4.83). The risk of vertebral fracture was higher in patients than in controls (HR, 2.27; 95% CI, 1.09-4.72). Patients had a significantly increased risk of renal disease (HR, 2.57; 95% CI, 1.56-4.21), seizure (HR, 5.74; 95% CI, 3.34-9.86), depression and bipolar disease (HR, 1.82; 95% CI, 1.30-2.56), and cataract (HR, 1.90; 95% CI, 1.30-2.79) compared with controls. CONCLUSIONS: The prevalence of nonsurgical hypoparathyroidism was very low in Korea but was associated with a higher risk of incident cardiovascular disease and vertebral fracture as well as known complications including renal disease, seizure, and cataract.

Chronic Kidney Disease Increases the Risk of Hip Fracture: A Prospective Cohort Study in Korean Adults.

This study was conducted to examine the association between renal function and hip fracture. We followed up 352,624 Korean adults, who participated in health examinations during 2009-2010 until 2013. Kidney function was assessed by creatinine-based estimated glomerular filtration rate (eGFR) and albuminuria using urine reagent strip results. The incidence of hip fracture was examined by hospital discharge records. Hazard ratios (HRs) for hip fracture were calculated using Cox proportional hazard models after adjusting for multiple confounders. During a mean follow-up of 4.0 years, 1177 participants suffered a hip fracture. Lower eGFR and more severe albuminuria were associated with a higher risk of hip fracture. The HRs for hip fracture were 1.89 (95% confidence interval [CI] 1.47-2.43) and 3.75 (95% CI 2.30-6.11) among participants with eGFRs of 30 to 44 and 15 to 29 mL/min/1.73m2 relative to those with an eGFR ≥60 mL/min/1.73m2 , respectively. The HRs were 1.30 (95% CI 1.02-1.65) for moderate albuminuria and 1.58 (95% CI 1.07-2.35) for severe albuminuria (p for trend = 0.002). Participants with albuminuria had a higher risk of hip fracture than those without albuminuria, even when they belonged to the same eGFR category (HR = 1.75 versus 3.30 for an eGFR of 30 to 44 mL/min/1.73m2 ; HR = 2.72 versus 7.84 for an eGFR of 15 to 29 mL/min/1.73m2 ). The effects of each 10 mL/min/1.73m2 decrease in eGFR were stronger with advancing albuminuria severity (pinteraction = 0.016). In conclusion, both low eGFR and albuminuria were risk factors for incident hip fracture in Korean adults. Moreover, these factors exerted a synergistic effect on the risk of hip fracture. © 2020 American Society for Bone and Mineral Research.

Predictive costs in medical care for Koreans with metabolic syndrome from 2009 to 2013 based on the National Health Insurance claims dataset.

BACKGROUND/AIMS: Although metabolic syndrome has been associated with increasing medical costs worldwide, there have been no studies using a nationwide and longitudinal South Korean dataset. We investigated trends in subsidized medical costs among Korean adults with metabolic syndrome. METHODS: This study was based on the National Sample Cohort database of South Korea. We used data of national health checkups in 2009 as well as data of subsidized prescription drugs and the Korean Classification of Disease diagnosis codes from claims in 2007 to 2008 to identify underlying diseases. We calculated the direct medical costs, which were subsidized by the Korean National Health Insurance, among 204,768 individuals older than 20 years from 2009 to 2013. RESULTS: The proportion of subjects with metabolic syndrome was 27.2%. Direct medical costs for 5 years differed by a magnitude of 2.16 between subjects with and without metabolic syndrome. The costs increased by approximately 41.8% in the metabolic syndrome group in 5 years. Direct medical costs increased with every additional risk factor, even if a subject had less than three risk factors of metabolic syndrome. Metabolic syndrome per se and all of its components, except low serum high-density lipoprotein cholesterol level, resulted in a significant increase in medical costs. CONCLUSION: The medical costs of subjects with metabolic syndrome were higher than that of those without metabolic syndrome and it increased with the number of risk factors. Further research using cumulative data of more than 10 years, including unsubsidized and indirect costs, is needed in the future.

Evaluation of the relationship of subclinical hypothyroidism with metabolic syndrome and its components in adolescents: a population-based study.

PURPOSE: This study investigated the association of subclinical hypothyroidism (SCH) with metabolic syndrome (MetS) and its components in adolescents. METHODS: The study population included 1006 adolescents (aged 10-18 years) from the Korea National Health and Nutrition Examination Surveys; SCH subjects were compared with euthyroid subjects. MetS was defined using the International Diabetes Federation criteria. The risks of MetS and its components in SCH and euthyroid subjects were calculated using binary logistic regression analyses. RESULTS: Study subjects had a mean age of 14.2 ± 2.5 years, and 53% were male. The prevalence of MetS was 2.5% in the overall study population (3.2% of males and 1.7% of females). Among the 1006 subjects, 143 (14.2%) had SCH. The risk of MetS was not higher in SCH subjects than in euthyroid subjects (odds ratio [OR], 1.50; 95% confidence interval [CI], 0.54-4.11); however, among the components of MetS, the risk of abdominal obesity was higher in SCH subjects than in euthyroid subjects (OR, 2.08; 95% CI, 1.04-4.15) after adjusting for age, sex, and body mass index (BMI). Although not statistically significant, a trend toward increased risk of elevated blood pressure (BP) was observed in SCH subjects relative to euthyroid subjects after further adjusting for age, sex, and BMI (OR, 2.01; 95% CI, 0.89-4.52). Furthermore, non-obese SCH subjects had higher systolic BP compared with non-obese euthyroid subjects after adjusting for age, sex, and BMI (P = 0.014). CONCLUSIONS: SCH was not associated with the presence of MetS. However, SCH may be associated with abdominal obesity and possibly elevated BP in adolescents.

Clinical Manifestations and Factors Associated with Osteosarcopenic Obesity Syndrome: A Cross-Sectional Study in Koreans with Obesity.

Demonstrating the clinical consequences of osteosarcopenic obesity (OSO) is complex. This study evaluated clinical manifestations and factors associated with bone and muscle loss in Koreans with obesity. This cross-sectional observational study enrolled Koreans with obesity aged ≥ 50 years from the Korea National Health and Nutrition Examination Survey. Clinical manifestations were compared among four groups: obesity (O), sarcopenic obesity (SO), osteopenic obesity (OO), and OSO. Factors associated with appendicular skeletal muscle mass (ASM) or bone mineral density (BMD) were evaluated. OSO increases with age in both sexes. Men with SO and OSO had increased cardiometabolic diseases and markers, percentages of body fat (BF %), and trunk fat (TF %), and decreased limb fat percentage (LF %). Women with SO and OSO had increased metabolic markers, BF %, and TF % but those with OSO had increased cardiometabolic diseases and lower LF %. Both sexes with OSO had decreased ASM and vitamin D, and higher vitamin D deficiency. BF % was negatively associated with ASM and femur BMD in both sexes. TF % was negatively and LF % was positively associated with ASM in both sexes and with femur BMD in women. Vitamin D was positively associated with femur BMD in men and with ASM and BMD at all sites in women. ASM and BMD were positively associated with each other. Appendicular muscle loss is metabolically significant regardless of bone loss in men; however, appendicular muscle loss with bone loss is metabolically more significant in women. Regional body composition, fat distribution, and vitamin D deficiency were associated with OSO phenotype in both sexes.

Association Between Body Mass Index and the Risk of Hip Fracture by Sex and Age: A Prospective Cohort Study.

The association between body mass index (BMI) and hip fracture may differ by ethnic group. We examined the association between BMI and hip fracture according to sex and age and to identify BMI ranges associated with the lowest risk in Korean men and women. We followed up 288,068 Korean adults (aged 50 to 80 years), who underwent health examinations in 2002-03 to 2013; we examined national hospital discharge records. Hazard ratios (HRs) were calculated using Cox proportional hazard models after adjusting for confounders. During a mean follow-up period of 10.5 years, 1502 men and 2432 women suffered a hip fracture. Nonlinear associations were observed between BMI and hip fracture: a U-curve for women and a reverse J-curve for men. Men with BMIs of 27.5 to 29.9 kg/m2 and women with BMIs of 25 to 27.4 kg/m2 showed the lowest incidence of hip fracture. The multivariate-adjusted HRs for hip fracture per 5 kg/m2 decrease in BMI were 2.09 (95% confidence interval [CI] 1.83-2.38) and 1.34 (95% CI 1.19-1.51) in men and women with BMI <25 kg/m2 . The HRs were generally highest in the age group of 50 to 59 years (HR = 3.42 in men and 2.27 in women) and thereafter decreased with age. Among participants with BMI ≥25 kg/m2 , the HRs for hip fracture per 5 kg/m2 increase in BMI were 1.26 (95% CI 1.08-1.47) in women and 0.91 (95% CI 0.62-1.33) in men. In conclusion, the overweight range of BMI was associated with the lowest risk of hip fracture. Lower BMI was a risk factor for hip fracture, whereas obesity was associated with an increased risk of hip fracture, particularly in women. Overweight may be protective against hip fracture in Asian adults but not obesity. © 2018 American Society for Bone and Mineral Research.

Clinical and Body Compositional Factors Associated with Metabolic Syndrome in Obese Koreans: A Cross-Sectional Study.

BACKGROUND: Obesity and metabolic syndrome (MetS) are increasing rapidly worldwide, but metabolically healthy population exists. Thus, this study evaluated the proportion of obesity and MetS and investigated clinical and body compositional factors associated with MetS in obese Koreans. METHODS: This cross-sectional observational study enrolled subjects from the Korea National Health and Nutrition Examination Survey (n = 15,408). Obesity was defined by body mass index (BMI) cutoff points of 25 and 27.5 kg/m2. Clinical and laboratory parameters were compared by MetS presence and factors associated with insulin resistance or MetS in obese subjects were evaluated by multivariate or logistic regression analyses. RESULTS: The proportion of obesity was 29.7% at a BMI cutoff point of 25 kg/m2 and 10.4% at 27.5 kg/m2. The proportion of MetS was greater in obese population and increased with higher obesity cutoff point, where men were more prevalent than women. The subjects with MetS showed higher age, glycated hemoglobin, insulin resistance, liver enzymes, and ferritin compared with metabolically healthy population in both obese genders. Factors associated with insulin level or presence of MetS were high trunk fat percentage, trunk-to-limb fat ratio, and trunk-to-leg fat ratio, but low limb fat percentage and leg fat percentage. Among body composition indices, trunk-to-limb fat ratio and trunk-to-leg fat ratio showed significantly high odds ratios for MetS in both obese genders regardless of BMI cutoff points. CONCLUSIONS: MetS in obese population concurrently increased with higher obesity cutoff point. Higher age, insulin resistance, liver enzymes, ferritin, and higher proportion of truncal fat mass-to-limb or leg fat mass significantly contribute to MetS, where trunk-to-limb fat ratio and trunk-to-leg fat ratio could be helpful in identifying and preventing MetS in the obese Korean population.

Increased risk of hip fractures in Korean patients with type 2 diabetes: a 6-year nationwide population-based study.

We compared the incidence and risk of hip fractures in Korean patients with type 2 diabetes and non-diabetic subjects in a nationwide population-based study. The study included 17,110 patients diagnosed with type 2 diabetes in 2004 and 34,220 randomly selected age- and sex-matched control subjects drawn from the Korean National Health Insurance Research database. Fracture events occurring between 2004 and 2010 were identified from medical claims data. The adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for fractures associated with diabetes were calculated. A total of 3855 fractures of any type (3029 in females and 826 in males) and 493 hip fractures (353 in females and 140 in males) were observed in 51,330 subjects over a 6-year follow-up period. The risk of hip fractures was significantly higher in female (HR 1.73; 95% CI 1.38-2.16) and male (HR 1.84; 95% CI 1.29-2.63) diabetics than in non-diabetic controls after adjusting for multiple confounders. Stratification by age revealed that the adjusted HR for hip fractures was highest in diabetic patients aged 50-64 years (HR 2.54 in females and 2.70 in males) and decreased with increasing age. The risk of other fractures did not differ between the groups. Korean males and females with type 2 diabetes are at an increased risk of hip fractures compared with non-diabetic individuals. Osteoporosis assessments and fracture prevention strategies are necessary for Koreans with type 2 diabetes.

Medical treatment of severe osteoporosis including new concept of advanced severe osteoporosis.

Osteoporosis is a metabolic bone disease characterized by decreased bone strength, leading to an increased risk of fracture. The World Health Organization (WHO) defines osteoporosis as a bone mineral density (BMD) of 2.5 standard deviations below that of a young adults (T-score of -2.5 or lower). Severe osteoporosis is differentiated from osteoporosis by the presence of one or more fragility fractures in addition to this T-score. However, the current WHO definition may be insufficient to reflect the diverse spectrum of osteoporosis or severe osteoporosis, which can encompass various number and severity of prevalent fractures. To overcome these shortcomings of the WHO definition of osteoporosis, we propose a concept of 'advanced severe osteoporosis', which is defined by the presence of proximal femur fragility fracture or two or more fragility fractures in addition to BMD T-score of -2.5 or less. Based on the previous clinical trials and post-hoc analyses, we recommend selective estrogen receptor modulators, bisphosphonates, receptor activator of nuclear factor kappa-B ligand (RANKL) monoclonal antibody, and parathyroid hormone for the medical treatment of severe osteoporosis. In cases of advanced severe osteoporosis or osteoporosis that does not respond to previous anti-osteoporotic treatments, we also recommend parathyroid hormone, bisphosphonates, and RANKL monoclonal antibody. In conclusion, we need more precise assessment of osteoporosis and further stratification of the disease by number of prevalent fractures in addition to BMD. More aggressive managements should be provided for those with advanced severe osteoporosis.

Modifications of T-scores by quantitative ultrasonography for the diagnosis of osteoporosis in koreans.

To identify a proper T-score threshold for the diagnosis of osteoporosis in Koreans using quantitative ultrasonography (QUS), normative data from 240 females and 238 males (ages 20-29 yr) were newly generated. Then, the osteoporosis prevalence estimate for men and women over 50 yr of age was analyzed using previous World Health Organization (WHO) methods and heel QUS. T-scores were calculated from the normative data. There were definite negative correlations between age and all of the QUS parameters, such as speed of sound (SOS), broadband ultrasound attenuation (BUA), and estimated heel bone mineral density (BMD) (p<0.0001). After applying the recently determined prevalence of incident vertebral fracture in Koreans over 50 yr of age (11.6% and 9.1%, female vs male, respectively) to the diagnosis of osteoporosis by T-scores from heel BMD as measured by QUS, it was revealed that applicable T-scores for women and men were -2.25 and -1.85, respectively. These data suggest that simply using a T-score of -2.5, the classical WHO threshold for osteoporosis, underestimates the true prevalence when using peripheral QUS. Further prospective study of the power of QUS in predicting the absolute risk of fracture is needed.

Angiogenesis inhibitor attenuates parathyroid hormone-induced anabolic effect.

In vivo osteogenic responses to anabolic stimuli are expected to be accompanied by angiogenesis as well as in the process of remodeling of bone. Consequently, angiogenesis might play an important role in mediating bone forming stimulating effect of parathyroid hormone (PTH). To investigate this relationship, we used actively growing young Sprague-Dawley rats and CKD-732, one of the angiogenesis inhibitor (AI) to reveal the relationship of angiogenesis in the effect of PTH. The groups were divided as (1) vehicle [VEH group], (2) PTH(1-84) [PTH group], (3) AI alone [AI group], (4) PTH(1-84)+AI concomitance [PTH-AI group] and were treated for 6 weeks. The bone mineral density (BMD) of PTH group was higher than VEH group and the gain of bone mass was attenuated in PTH-AI group. The maximal failure load in PTH group was higher than VEH group, but it was definitely attenuated by concurrent use of AI. Moreover, the toughness showed similar significant deterioration in PTH-AI group. General bone turnover was also significantly decreased in PTH-AI group as shown by the absence of increase in osteocalcin and beta-crosslaps and by decrease in metaphyseal length. The BMD or the biomechanic data of AI only group were similar to the VEH group, suggesting the minimal effect of AI itself on the normal modeling phase of the growing rats. In conclusion, the angiogenesis seemed to contribute to completing the anabolic effect of PTH especially for bone strength.

Assessment of clinical risk factors to validate the probability of osteoporosis and subsequent fractures in Korean women.

This cross-sectional, observational study was designed to identify clinical risk factors of osteoporosis and fractures in Korean women to validate the probability of osteoporosis and subsequent fractures. A total of 1541 Korean women were recruited nationally. Fracture history of any site, risk factors of osteoporosis, and fall-related risk factors were surveyed and physical performance tests were conducted. Peripheral dual-energy X-ray absorptiometry was used to measure calcaneus bone mineral density (BMD). The number of positive responses on the modified 1-min osteoporosis risk test was related to the risk of osteoporosis. The frequency of osteoporosis was higher in those with a height reduction of >4 cm and a reduced body mass index (BMI). Multivariate analysis showed that older age and lower BMI were related to higher relative risk of osteoporosis. Time required to stand up from a chair and questions related to fall injury were significantly related to clinical fracture history of any site. Multivariate analysis showed that the relative risk of fractures at any site was higher in older subjects with a lower T-score and parental hip fracture history. This study shows that age and BMI are the most significant clinical risk factors for osteoporosis and that age, BMD, and parental history of hip fracture are highly applicable risk factors for validating the probability of osteoporotic fractures in Korean women.

Echogenic carotid artery plaques are associated with vertebral fractures in postmenopausal women with low bone mass.

Although low bone mass has been associated with atherosclerosis even after adjustment for age, little is known about the association between vertebral fractures and calcified atherosclerotic plaques. Our objective was to investigate whether osteoporotic vertebral fractures are independently related to the prevalence of atherosclerotic carotid plaques in postmenopausal women with low bone mass. We enrolled 195 postmenopausal women with osteopenia or osteoporosis. Bone mineral density and the presence of vertebral fractures were assessed. Intima media thickness and atherosclerotic plaques of the carotid artery were assessed using ultrasonography. Of the 195 subjects in the study, 84 had no plaques and 111 had at least one. The percentage of women with vertebral fractures was significantly higher in subjects with echogenic carotid plaques than in those without (27% vs. 11%, respectively; P < 0.05). However, there was no difference in the prevalence of vertebral fractures between women with echolucent plaques and those without (10.9% vs. 10.7%, respectively; P = nonsignificant). By logistic regression analysis with multivariate adjustment, age (P < 0.01), dyslipidemia (P < 0.05), and the presence of vertebral fracture (P < 0.05) were independent risk factors for echogenic carotid plaques. Osteoporotic vertebral fractures are associated with an increased risk of echogenic atherosclerotic plaques in postmenopausal women with low bone mass. It appears that the high association of echogenic atherosclerotic plaques and vertebral fractures could partially explain why osteoporotic vertebral fractures are linked to increased mortality.

Assessment of the anti-obesity effects of the TNP-470 analog, CKD-732.

The systemic treatment with angiogenesis inhibitor has been shown to result in weight reduction and adipose tissue loss in various models of obesity. To verify the mechanism of CKD-732 (TNP-470 analog) against obesity, we evaluated CKD-732's peripheral and central anti-obesity effects. CKD-732 was injected subcutaneously (s.c.) for 7 days in various animal models and intracerebroventricularly (i.c.v.) in arcuate nucleus (ARC) lesion mice, ob/ob mice, and normal littermates. Modulation of the hypothalamic neuropeptide mRNAs after i.c.v. injection was evaluated in ARC lesion mice and normal littermates. A conditioned taste aversion (CTA) was performed using lithium chloride (LiCl) as a positive control agent in Long-Evans Tokushima Otsuka and Otsuka Long-Evans Tokushima fatty (OLETF) rats. As a result, 7 days of CKD-732 s.c. injection reduced the cumulative food intake and the body weight significantly in both treated obese (e.g. 114.8 +/- 13.4 g vs 170.7 +/- 20.6 g, 7.9 +/- 0.5% decrease vs 0.3 +/- 2.2% decrease; in treated OLETF rat versus control OLETF rat, P < 0.01 respectively) and non-obese models. Epididymal and mesenteric fat pads, and the size of adipocytes were significantly decreased in treated rats. A single i.c.v. injection decreased food intake and body weight in ARC lesion mice and ob/ob mice but not in normal littermates. Unexpectedly, the hypothalamic neuropeptide mRNAs were not altered by single i.c.v. injection. CKD-732 also induced a dose-dependent CTA comparable with LiCl injection, which is a commonly used agent to produce a CTA. In conclusion, CKD-732 causes significant body weight and appetite reduction, possibly by decreasing adiposity directly and inducing central anorexia, which is partly explained by a CTA. These results should be carefully verified to assess the utility of CKD-732 as an anti-obesity drug.

Predictive clinical parameters for therapeutic efficacy of rosiglitazone in Korean type 2 diabetes mellitus.

This study evaluated the efficacy of rosiglitazone in non-obese and obese Korean type 2 diabetic patients of long duration. A total of 125 patients (M:F=44:81, mean age: 58.4+/-9.1 years, BMI: 24.2+/-2.7 kg/m2, duration of diabetes: 11.0+/-6.4 years) were randomly allocated to 12 weeks of rosiglitazone treatment (4 mg per day) or a control group. Responders were defined as patients who experienced fasting plasma glucose (FPG) reduction of >20% or HbA1c reduction of >1 (%). Rosiglitazone significantly improved glycemic control by reducing FPG and HbA1c (-3.4 mmol/l and -1.1%, P<0.001, respectively). It also significantly increased HOMA(beta-cell function) (+9.7, P<0.01) and QUICKI (+0.029, P<0.001), and decreased HOMA(IR) (-1.73, P<0.001). Females and those with higher waist-hip ratio made up a greater portion of rosiglitazone-responders. Responders (45 patients, 75%) also showed significantly higher FPG, HbA1c, systolic blood pressures, fasting insulin levels and HOMA(IR), and lower QUICKI than nonresponders. Among these parameters of responders, waist-hip ratio of non-obese subgroup, initial glycemic control of obese subgroup, and systolic blood pressure of both subgroups lost their significance after subdivision analysis. However, the baseline HOMA(IR) and QUICKI were significantly correlated with the response rate to rosiglitazone. Moreover, in multiple logistic regression analysis, HOMA(IR) and QUICKI retained their significance as the independent predictors. Even in Korean type 2 diabetic patients of long duration but with relatively preserved beta-cell function, rosiglitazone improved glycemic control, insulin sensitivity, and beta-cell function. In this ethnic group, female gender, central obesity, and especially severe insulin resistance were identified as predictive clinical parameters of rosiglitazone-responders.