Genomic-, phenotypic-, and toxicity-based safety assessment and probiotic potency of Bacillus coagulans IDCC 1201 isolated from green malt.

Probiotics are beneficial microorganisms, and the evaluation of their safety for human use in the food industry has become critical. This study examines the safety of Bacillus coagulans IDCC 1201 isolated from green malt by analyzing its genomic and phenotypic characteristics and determining its toxicity. The presence of antibiotic resistance and toxigenic genes and gene transferability were investigated using whole-genome analysis. The strain's hemolytic and enzyme activities, minimum inhibitory concentrations of antibiotics, and biogenic amine and D-lactate production were also examined. Furthermore, the principal properties of B. coagulans IDCC 1201 as probiotics, such as resistance to abiotic stress and intestinal adhesion, were studied. The whole-genome analysis demonstrated that B. coagulans IDCC 1201 had no antibiotic resistance or toxigenic genes; the strain was susceptible to the nine antibiotics proposed by the European Food Safety Authority. Moreover, this strain lacked hemolytic and ß-glucuronidase activities. Additionally, it was confirmed that B. coagulans IDCC 1201 produced undesirable metabolites, including biogenic amines or D-lactate, at a safe level. Finally, the strain exhibited functional potential as a probiotic in terms of abiotic tolerance, such as bile tolerance and intestinal adhesion in in vitro experiments. In conclusion, B. coagulans IDCC 1201 can be considered as a safe probiotic with regard to human health.

Validation of an Operational Definition to Identify Distal Radius Fractures in a National Health Insurance Database.

PURPOSE: To develop and validate identification criteria for distal radius fractures (DRFs) and their treatment using a national health insurance database. METHODS: Patients who had at least 1 wrist radiograph taken in 2018 were recruited from a single academic referral hospital. After excluding patients who lacked immobilization code for wrist pathology, we collected data on the overall population. Because some patients might have undergone wrist radiography at another institution or had DRFs without an immobilization code, we additionally included patients who had a DRF diagnosis code at our institution. Reviews of medical records and wrist radiographs were considered for the diagnosis of DRF. We evaluated the sensitivity, specificity, and positive predictive value (PPV) of 3 operational definitions of fractures that were based on a single primary or secondary diagnosis code; all diagnosis codes, including primary and secondary codes; and all diagnosis and procedure codes. RESULTS: Among 768 patients included in the study, true DRFs were confirmed in 305. The sensitivity, specificity, and PPV for definition 1 were 91.5% (95% CI, 88.3%-94.6%), 97.5% (95% CI, 95.9%-99.1%), and 96.9% (95% CI, 94.9%-98.9%), respectively. Although the sensitivity of definition 2 was higher (92.1%; 95% CI, 89.1%-95.2%), its specificity and PPV were lower (96.4% [95% CI, 94.4%-98.3%] and 95.6% [95% CI, 93.2%-97.9%], respectively). The sensitivity of definition 3 was the lowest (88.2%; 95% CI, 84.6%-91.8%), but its specificity and PPV were the highest among the 3 definitions (98.6% [95% CI, 97.4%-98.8%] and 98.2% [95% CI, 96.6%-99.8%], respectively). CONCLUSIONS: Patients with DRFs can be identified from claims databases with high accuracy using an operational definition based on DRF diagnosis and procedure codes, including codes for surgical and nonoperative methods. CLINICAL RELEVANCE: Verified operational definitions will increase the consistency of results in future national health insurance database studies related to DRFs.

CPPF, A Novel Microtubule Targeting Anticancer Agent, Inhibits the Growth of a Wide Variety of Cancers.

In the past, several microtubule targeting agents (MTAs) have been developed into successful anticancer drugs. However, the usage of these drugs has been limited by the acquisition of drug resistance in many cancers. Therefore, there is a constant demand for the development of new therapeutic drugs. Here we report the discovery of 5-5 (3-cchlorophenyl)-N-(3-pyridinyl)-2-furamide (CPPF), a novel microtubule targeting anticancer agent. Using both 2D and 3D culture systems, we showed that CPPF was able to suppress the proliferation of diverse cancer cell lines. In addition, CPPF was able to inhibit the growth of multidrug-resistant cell lines that are resistant to other MTAs, such as paclitaxel and colchicine. Our results showed that CPPF inhibited growth by depolymerizing microtubules leading to mitotic arrest and apoptosis. We also confirmed CPPF anticancer effects in vivo using both a mouse xenograft and a two-step skin cancer mouse model. Using established zebrafish models, we showed that CPPF has low toxicity in vivo. Overall, our study proves that CPPF has the potential to become a successful anticancer chemotherapeutic drug.

The Pepper WPP Domain Protein, CaWDP1, Acts as a Novel Negative Regulator of Drought Stress via ABA Signaling.

Plants are constantly challenged by various environmental stresses, including high salinity and drought, and they have evolved defense mechanisms to counteract the deleterious effects of these stresses. The plant hormone ABA regulates plant growth and developmental processes and mediates abiotic stress responses. Here, we report the identification and characterization of a novel CaWDP1 (Capsicum annuum) protein. The expression of CaWDP1 in pepper leaves was induced by ABA, drought and NaCl treatments, suggesting its role in the abiotic stress response. CaWDP1 proteins show conserved sequence homology with other known WDP1 proteins, and they are localized in the nucleus and cytoplasm. We generated CaWDP1-silenced peppers via virus-induced gene silencing (VIGS). We evaluated the responses of these CaWDP1-silenced pepper plants and CaWDP1-overexpressing (OX) transgenic Arabidopsis plants to ABA and drought. CaWDP1-silenced pepper plants displayed enhanced tolerance to drought stress, and this was characterized by low levels of leaf water loss in the drought-treated leaves. In contrast to CaWDP1-silenced plants, CaWDP1-OX plants exhibited an ABA-hyposensitive and drought-susceptible phenotype, which was accompanied by high levels of leaf water loss, low leaf temperatures, increased stomatal pore size and low expression levels of stress-responsive genes. Our results indicate that CaWDP1, a novel pepper negative regulator of ABA, regulates the ABA-mediated defense response to drought stress.

The Pepper RING-Type E3 Ligase, CaAIP1, Functions as a Positive Regulator of Drought and High Salinity Stress Responses.

Plant adaptive responses to osmotic stress are co-ordinated by restriction of growth and developmental processes and by molecular and physiological activities. The phytohormone ABA is the primary regulator that induces and responds to osmotic stress, and its sensitivity markedly influences osmotic stress tolerance levels. Several E3 ubiquitin ligases act as positive or negative regulators of ABA, thereby mediating sensitivity to osmotic stress in higher plants. Here, we report that the C3H2C3-type RING finger E3 ligase, CaAIP1, regulates osmotic stress responses via ABA-mediated signaling. CaAIP1 contains a RING finger motif, which functions during attachment of ubiquitins to the target proteins. Expression of CaAIP1 was induced by ABA, drought and NaCl treatments, suggesting its role in the osmotic stress response. CaAIP1-silenced pepper plants displayed a drought-sensitive phenotype characterized by a high level of transpirational water loss in the drought-treated leaves. CaAIP1-overexpressing (OX) plants exhibited increased sensitivity to ABA, but an NaCl- and mannitol-tolerant phenotype during seed germination and seedling growth. CaAIP1-OX plants further displayed enhanced tolerance to drought stress, characterized by low levels of transpirational water loss via increased stomatal closure and leaf temperature. Our data indicate that CaAIP1 is a positive regulator of the osmotic stress tolerance mechanism.

Prevalence and predictors of non-steroidal anti-inflammatory drug/analgesic therapeutic duplication in the South Korean ambulatory care setting.

PURPOSE: Therapeutic duplication (TD) in prescriptions is a common cause of inappropriate drug use. This study aimed to determine the prevalence of TD in the Korean ambulatory setting and to determine the patient and prescriber characteristics that were associated with TD of non-steroidal anti-inflammatory drugs (NSAIDs) and analgesics. METHODS: Ambulatory care cases with NSAID/analgesic prescriptions were extracted from the National Health Insurance database for January­March 2011. The Korean TD classification (64 ingredients) was used to define cases of TD. Multivariate logistic regression was used to determine the predictors of TD. The independent variables in the regression model included patient characteristics (sex, age, insurance type, comorbidity, diagnosis, and number of prescribed drugs) and prescriber characteristics (type of medical institution and specialty). RESULTS: Among 21 million patients, we identified 59,636,222 ambulatory care visits with NSAID/analgesic prescriptions; 13.3 % of these cases involved TD. The most frequent duplications were diclofenac/aceclofenac (12.4 % of TDs), diclofenac/talniflumate (11.2 %), and diclofenac/loxoprofen sodium (10.7 %). Male sex, older age, and a Charlson comorbidity index of ≥1 were associated with an increased likelihood of TD. Arthritis, injection administration (OR 3.676, 95 % CI 3.670­3.683), and the number of drugs per prescription were associated with an increased likelihood of TD. Orthopedic and pediatric specialties were associated with an increased likelihood of TD. CONCLUSIONS: This study is the first to determine the prevalence of NSAID TD and the factors that were associated with its occurrence in South Korea. These results may help prevent TD and improve appropriate medication use.

Incidence and Mortality after Distal Radius Fractures in Adults Aged 50 Years and Older in Korea.

The purpose of this study was to assess the incidence and mortality of distal radius fracture among patients 50 years of age and older with diagnosis code (ICD10; S52.5, S52.6) and treatment code using a nationwide claims database from 2008 to 2012. All patients were followed using patient identification code to identify deaths. Standardized mortality ratios (SMRs) of distal radius fracture were calculated based on age and gender-specific rates in the entire Korean population. The number of distal radius fractures increased by 54.2% over the 5-year study (48,145 in 2008 and 74,240 in 2012). The incidence of distal radius fracture increased from 367.4/100,000 in 2008 to 474.1/100,000 in 2012. The cumulative mortality rate over the first 12 months after distal radius fracture was decreased from 2.0% (968/48,145) in 2008 to 1.4% (1,045/74,240) in 2012. The mean year mortality over 5 years in men (2.6%, 1,279/50,128) over the first 12 months was 1.7-times higher than in women (1.5%, 3,952/257,045). The mean of SMR of distal radius fracture at 1 year post-fracture was 1.45 in men and 1.17 in women. This study using a nationwide database demonstrates that the distal radius fractures are increasing with a decreasing mortality in Korea.

Trends of Incidence, Mortality, and Future Projection of Spinal Fractures in Korea Using Nationwide Claims Data.

Spinal fractures have been recognized as a major health concern. Our purposes were to evaluate the trends in the incidence and mortality of spinal fractures between 2008 and 2012 and predict the number of spinal fractures that will occur in Korea up to 2025, using nationwide data from the National Health Insurance Service (NHIS). A nationwide data set was evaluated to identify all new visits to medical institutes for spinal fractures in men and women aged 50 years or older between 2008 and 2012. The incidence, mortality rates and estimates of the number of spinal fractures were calculated using Poisson regression. The number of spinal fractures increased over the time span studied. Men and women experienced 14,808 and 55,164 vertebral fractures in 2008 and 22,739 and 79,903 in 2012, respectively. This reflects an increase in the incidence of spinal fractures for both genders (men, 245.3/100,000 in 2008 and 312.5/100,000 in 2012; women, 780.6/100,000 in 2008 and 953.4/100,000 in 2012). The cumulative mortality rate in the first year after spinal fractures decreased from 8.51% (5,955/69,972) in 2008 to 7.0% (7,187/102,642) in 2012. The overall standardized mortality ratio (SMR) of spinal fractures at 1 year post-fracture was higher in men (7.76, 95% CI: 7.63-7.89) than in women (4.70, 95% CI: 4.63-4.76). The total number of spinal fractures is expected to reach 157,706 in 2025. The incidence of spinal fractures increased in Korea in the last 5 years, and the socioeconomic burden of spinal fractures will continue to increase in the near future.

Ginsenoside Re Promotes Osteoblast Differentiation in Mouse Osteoblast Precursor MC3T3-E1 Cells and a Zebrafish Model.

Bone homeostasis is tightly regulated to balance bone formation and bone resorption. Many anabolic drugs are used as bone-targeted therapeutic agents for the promotion of osteoblast-mediated bone formation or inhibition of osteoclast-mediated bone resorption. Previous studies showed that ginsenoside Re has the effect of the suppression of osteoclast differentiation in mouse bone-marrow derived macrophages and zebrafish. Herein, we investigated whether ginsenoside Re affects osteoblast differentiation and mineralization in in vitro and in vivo models. Mouse osteoblast precursor MC3T3-E1 cells were used to investigate cell viability, alkaline phosphatase (ALP) activity, and mineralization. In addition, we examined osteoblastic signaling pathways. Ginsenoside Re affected ALP activity without cytotoxicity, and we also observed the stimulation of osteoblast differentiation through the activation of osteoblast markers including runt-related transcription factor 2, type 1 collagen, ALP, and osteocalcin in MC3T3-E1 cells. Moreover, Alizarin red S staining indicated that ginsenoside Re increased osteoblast mineralization in MC3T3-E1 cells and zebrafish scales compared to controls. These results suggest that ginsenoside Re promotes osteoblast differentiation as well as inhibits osteoclast differentiation, and it could be a potential therapeutic agent for bone diseases.

RING Type E3 Ligase CaAIR1 in Pepper Acts in the Regulation of ABA Signaling and Drought Stress Response.

Several E3 ubiquitin ligases have been associated with the response to abiotic and biotic stresses in higher plants. Here, we report that the hot pepper (Capsicum annuum) ABA-Insensitive RING protein 1 gene (CaAIR1) is essential for a hypersensitive response to drought stress. CaAIR1 contains a C3HC4-type RING finger motif, which plays a role for attachment of ubiquitins to the target protein, and a putative transmembrane domain. The expression levels of CaAIR1 are up-regulated in pepper leaves by ABA treatments, drought and NaCl, suggesting its role in the response to abiotic stress. Our analysis showed that CaAIR1 displays self-ubiquitination and is localized in the nucleus. We generated CaAIR1-silenced peppers via virus-induced gene silencing (VIGS) and CaAIR1-overexpressing (OX) transgenic Arabidopsis plants to evaluate their responses to ABA and drought. VIGS of CaAIR1 in pepper plants conferred an enhanced tolerance to drought stress, which was accompanied by low levels of transpirational water loss in the drought-treated leaves. CaAIR1-OX plants displayed an impaired sensitivity to ABA during seed germination, seedling and adult stages. Moreover, these plants showed enhanced sensitivity to drought stress because of reduced stomatal closure and decreased expression of stress-responsive genes. Thus, our data indicate that CaAIR1 is a negative regulator of the ABA-mediated drought stress tolerance mechanism.

Eupafolin suppresses prostate cancer by targeting phosphatidylinositol 3-kinase-mediated Akt signaling.

Phosphatase and tensin homolog (PTEN) loss or mutation consistently activates the phosphatidylinositol 3-kinase (PI3-K)/Akt signaling pathway, which contributes to the progression and invasiveness of prostate cancer. Furthermore, the PTEN/PI3-K/Akt and Ras/MAPK pathways cooperate to promote the epithelial-mesenchymal transition (EMT) and metastasis initiated from prostate stem/progenitor cells. For these reasons, the PTEN/PI3-K/Akt pathway is considered as an attractive target for both chemoprevention and chemotherapy. Herein we report that eupafolin, a natural compound found in common sage, inhibited proliferation of prostate cancer cells. Protein content analysis indicated that phosphorylation of Akt and its downstream kinases was inhibited by eupafolin treatment. Pull-down assay and in vitro kinase assay results indicated that eupafolin could bind with PI3-K and attenuate its kinase activity. Eupafolin also exhibited tumor suppressive effects in vivo in an athymic nude mouse model. Overall, these results suggested that eupafolin exerts antitumor effects by targeting PI3-K.

Design and synthesis of novel 2,4-diaryl-5H-indeno[1,2-b]pyridine derivatives, and their evaluation of topoisomerase inhibitory activity and cytotoxicity.

For the development of potential anticancer agents, we designed and synthesized 30 new 2,4-diaryl-5H-indeno[1,2-b]pyridine derivatives containing aryl moiety such as furyl, thienyl, pyridyl, and phenyl at 2- and 4-position of 5H-indeno[1,2-b]pyridine. They were evaluated for topoisomerase I and II inhibitory activity, and cytotoxicity against several human cancer cell lines. Among prepared 30 compounds, 7, 8, 9, 10, 12, 14, 16, 19, 20, 22, and 23 with 2- or 3-furyl and/or 2- or 3-thienyl either at 2- or 4-position of central pyridine showed the significant or moderate topoisomerase II inhibitory activity. Compounds 7, 8, 11, 12, 13, and 22 with 2-furyl, 2-thienyl or 3-thienyl at 2-position of central pyridine showed the significant or moderate topoisomerase I inhibitory activity. Especially, compound 12 with strong topoisomerase II inhibitory activity at 100 µM and 20 µM, and moderate topoisomerase I inhibitory activity displayed strong cytotoxicity against several human cancer cell lines.

Design and synthesis of conformationally constrained hydroxylated 4-phenyl-2-aryl chromenopyridines as novel and selective topoisomerase II-targeted antiproliferative agents.

To develop novel selective topoisomerase II inhibitors, we designed and synthesized a series of conformationally constrained hydroxylated 4-phenyl-2-aryl chromenopyridines and evaluated their topoisomerase inhibitory activity and cytotoxicity against three human cancer cell lines (DU145, HCT15, and T47D) and a normal cell line (MCF10A). All of the prepared compounds displayed stronger or similar topoisomerase II inhibitory activity as well as cytotoxicity against three human cancer cell lines compared to etoposide. Compounds 10a, 10g, 11a, 11f, 11g, 12a, 12f, and 12g especially showed stronger topoisomerase II inhibitory activity as compared to etoposide at both 100 µM and 20 µM. A structure-activity relationship study revealed that hydroxyphenyl moiety at 4-position of pyridine and ortho-hydroxyphenyl or thienyl moiety at 2-position of pyridine has an important role in displaying selective topoisomerase II inhibition. The compound 12b with para-hydroxyphenyl and meta-hydroxyphenyl at 4- and 2-position of pyridine, respectively, showed the most significant cytotoxicity against all three cancer cell lines, whereas less cytotoxicity to a normal cell line as compared to adriamycin.

A chrysin derivative suppresses skin cancer growth by inhibiting cyclin-dependent kinases.

Chrysin (5,7-dihydroxyflavone), a natural flavonoid widely distributed in plants, reportedly has chemopreventive properties against various cancers. However, the anticancer activity of chrysin observed in in vivo studies has been disappointing. Here, we report that a chrysin derivative, referred to as compound 69407, more strongly inhibited EGF-induced neoplastic transformation of JB6 P(+) cells compared with chrysin. It attenuated cell cycle progression of EGF-stimulated cells at the G1 phase and inhibited the G1/S transition. It caused loss of retinoblastoma phosphorylation at both Ser-795 and Ser-807/811, the preferred sites phosphorylated by Cdk4/6 and Cdk2, respectively. It also suppressed anchorage-dependent and -independent growth of A431 human epidermoid carcinoma cells. Compound 69407 reduced tumor growth in the A431 mouse xenograft model and retinoblastoma phosphorylation at Ser-795 and Ser-807/811. Immunoprecipitation kinase assay results showed that compound 69407 attenuated endogenous Cdk4 and Cdk2 kinase activities in EGF-stimulated JB6 P(+) cells. Pulldown and in vitro kinase assay results indicated that compound 69407 directly binds with Cdk2 and Cdk4 in an ATP-independent manner and inhibited their kinase activities. A binding model between compound 69407 and a crystal structure of Cdk2 predicted that compound 69407 was located inside the Cdk2 allosteric binding site. The binding was further verified by a point mutation binding assay. Overall results indicated that compound 69407 is an ATP-noncompetitive cyclin-dependent kinase inhibitor with anti-tumor effects, which acts by binding inside the Cdk2 allosteric pocket. This study provides new insights for creating a general pharmacophore model to design and develop novel ATP-noncompetitive agents with chemopreventive or chemotherapeutic potency.

Effective policy initiatives to constrain lipid-lowering drug expenditure growth in South Korea.

BACKGROUND: The rapid growth of prescription drug expenditures is a major problem in South Korea. Accordingly, the South Korean government introduced a positive listing system in 2006. They also adopted various price reduction policies. Nevertheless, the total expenditure for lipid-lowering drugs have steadily increased throughout South Korea. The present study explores the factors that have influenced the increased expenditures of lipid-lowering drugs with a particular focus on the effects of statins in this process. METHODS: This paper investigates the National Health Insurance claims data for prescribed lipid-lowering drugs collected between January 1, 2005 and December 31, 2009. We specifically focused on statins and assessed the yearly variation of statin expenditure by calculating the increased rate of paired pharmaceutical expenditures over a 2 year period. Our study classified statins into three categories: new entrants, core medicines and exiting medicines. For core medicines, we further examined influencing factors such as price, amount of drugs consumed by volume, and prescription changes (substitutes for other drug). RESULTS: Statin expenditure showed an average annual increase of 25.7% between 2005 and 2009. Among the different statins, the expenditure of atorvastatin showed a 36.6% annual increase rate, which was the most dramatic among all statins. Also we divided expenditure for core medicines by the price factor, volume factor, and prescription change. The result showed that annual weighted average prices of individual drug decreased each year, which clearly showed that price influenced statin expenditure in a negative direction. The use of generic drugs containing the same active ingredient as name-brand drugs increased and negatively affected statin expenditure (Generic Mix effect). However, the use of relatively expensive ingredients within statin increase, Ingredient Mix effect contributed to increased statin expenditure (Ingredient Mix effect). In particular, the volume effect was found to be critical for increasing statin expenditure as the amount of statin consumed increased steadily throughout the study period. CONCLUSIONS: The recent rapid increase in statin expenditure can largely be attributed to an increase in consumption volume. In order to check drug expenditures effectively in our current situation, in which chronic diseases remain steadily on the rise, it is necessary to not only have supply-side initiatives such as price reduction, but also demand-side initiatives that could control drug consumption volume, for example: educational programs for rational prescription, generic drug promotional policies, and policies providing prescription targets.

Trends of surgical treatment in femoral neck fracture: a nationwide study based on claim registry.

We evaluated current trends of surgical treatment, such as internal fixation and hip arthroplasty, in femoral neck fracture. We assessed annual proportion of the each procedure in patients aged 50 years or more from 2006 to 2011, using the data of Health Insurance Review and Assessment Service (HIRA), which is a national claim registry. The proportion of hip arthroplasty increased while that of internal fixation decreased annually during the 5 years. The proportion of total hip arthroplasty increased in patients aged ≤ 65 years, and that of hemiarthroplasty increased in patients aged ≥ 65 years. The proportional increase of hip arthroplasty seemed to conform to the recent evidence regarding the outcomes of surgical treatments for the femoral neck fracture.

Aloe-emodin suppresses prostate cancer by targeting the mTOR complex 2.

Phosphatidylinositol 3-kinase (PI3-K) amplification and phosphatase and tensin homolog (PTEN) deletion-caused Akt activation contribute to the development of prostate cancer. Mammalian target of rapamycin complex 2 (mTORC2) is a kinase complex comprised of mTOR, Rictor, mSin1, mLST8/GßL and PRR5 and functions in the phosphorylation of Akt at Ser473. Herein, we report that mTORC2 plays an important role in PC3 androgen refractory prostate cell proliferation and anchorage-independent growth. Aloe-emodin, a natural compound found in aloe, inhibited both proliferation and anchorage-independent growth of PC3 cells. Protein content analysis suggested that activation of the downstream substrates of mTORC2, Akt and PKCα, was inhibited by aloe-emodin treatment. Pull-down assay and in vitro kinase assay results indicated that aloe-emodin could bind with mTORC2 in cells and inhibit its kinase activity. Aloe-emodin also exhibited tumor suppression effects in vivo in an athymic nude mouse model. Collectively, our data suggest that mTORC2 plays an important role in prostate cancer development and aloe-emodin suppresses prostate cancer progression by targeting mTORC2.

Burden of osteoporosis in adults in Korea: a national health insurance database study.

We evaluated the number of osteoporosis patients under treatment and secular trends in 2005-2008 in South Korea. We investigated nationwide data regarding the number of osteoporosis patients under treatment in South Korea using data from the Health Insurance Review and Assesment Service (HIRA), which includes nationwide information [corrected]. Reimbursement records from the HIRA database between 1 January 2004 and 31 December 2008 were investigated. Patients aged ≥30 years old with osteoporosis were identified based on a study-defined algorithm using prescription data and diagnostic codes. During the study periods, the number of patients receiving medical treatment related to osteoporosis increased from 1,034,399 to 1,392,189 for women and from 120,496 to 171,902 for men. The calculated proportion of osteoporosis patients under treatment in the general population over 50 years of age was 6.1% for men and 33.3% for women, and in the general population over 30 years of age was 2.7% for men and 16.6% for woman. More than 40% of patients (59.1% for women; 41.2% for men) were treated with medication indicated only for osteoporosis. About 4-7% of osteoporosis patients had a past medical history suggesting a secondary cause of osteoporosis. More than 80% of all osteoporosis patients were women older than 50 years, reflecting the pronounced burden of osteoporosis among postmenopausal women. This study demonstrated a substantial increasing trend in medical claims related to osteoporosis in 2005-2008 among adults in Korea and a pronounced burden of osteoporosis among postmenopausal women.

The incidence and residual lifetime risk of osteoporosis-related fractures in Korea.

Although the Korean population does not have high risk for osteoporosis, the numbers of osteoporosis-related fractures represent a considerable economic burden to society. The purpose of this study was to determine the incidence and residual lifetime risk of osteoporosis-related fractures in Korea, using data from the Health Insurance Review and Assessment Service (HIRA), which includes nationwide information compiled by the Korean government. All new visits or admissions to Korean clinics or hospitals for fractures were recorded prospectively in a nationwide cohort by the Korean HIRA using the International Classification of Diseases, 10th revision, codes and procedure codes. These data were retrospectively evaluated to determine the incidence and residual lifetime risk of osteoporosis-related fractures (hip, spine, distal radius, and humerus fractures), in men and women aged 50 years or more between 2005 and 2008. The annual incidences of osteoporosis-related fractures were 1,661, 1,646, 1,623, and 1,614 per 100,000 person-years in men and women aged 50 years or more from the year 2005 to 2008. The annual incidence of osteoporosis-related fracture in women was three times that of men. The incidence of osteoporosis-related fractures increased with advancing age. In Korea, at the age of 50 years, the residual lifetime probabilities of osteoporosis-related fractures are 59.5% for women and 23.8% for men. This study presents the baseline data for treatment and research on osteoporosis and provides an estimate of osteoporosis-related fractures in Korea.