Development of a model to predict the age at breast cancer diagnosis in a global population.

Knowing the mean age at diagnosis of breast cancer (BC) in a country is important for setting up an efficient BC screening program. The aim of this study was to develop and validate a model to predict the mean age at diagnosis of BC at the country level. To develop the model, we used the CI5plus database from the IARC, which contains incidence data for 122 selected populations for a minimum of 15 consecutive years from 1993 to 2012 and data from the World Bank. The standard model was fitted with a generalized linear model with the age of the population, growth domestic product per capita (GDPPC) and fertility rate as fixed effects and continent as a random effect. The model was validated in registries of the Cancer Incidence in Five Continents that are not included in the CI5plus database (1st validation set: 1950-2012) and in the most recently released volume (2nd validation set: 2013-2017). The intercept of the model was 30.9 (27.8-34.1), and the regression coefficients for population age, GDPPC and fertility rate were 0.55 (95% CI: 0.53-0.58, p < 0.001), 0.46 (95% CI: 0.26-0.67, p < 0.001) and 1.62 (95% CI: 1.42-1.88, p < 0.001), respectively. The marginal R2 and conditional R2 were 0.22 and 0.81, respectively, suggesting that 81% percent of the variance in the mean age at diagnosis of BC was explained by the variance in population age, GDPPC and fertility rate through linear relationships. The model was highly accurate, as the correlations between the predicted age from the model and the observed mean age at diagnosis of BC were 0.64 and 0.89, respectively, and the mean relative error percentage errors were 5.2 and 3.1% for the 1st and 2nd validation sets, respectively. We developed a robust model based on population age and continent to predict the mean age at diagnosis of BC in populations. This tool could be used to implement BC screening in countries without prevention programs.

Patient-Derived Organoids Recapitulate Pathological Intrinsic and Phenotypic Features of Fibrous Dysplasia.

Fibrous dysplasia (FD) is a rare bone disorder characterized by the replacement of normal bone with benign fibro-osseous tissue. Developments in our understanding of the pathophysiology and treatment options are impeded by the lack of suitable research models. In this study, we developed an in vitro organotypic model capable of recapitulating key intrinsic and phenotypic properties of FD. Initially, transcriptomic profiling of individual cells isolated from patient lesional tissues unveiled intralesional molecular and cellular heterogeneity. Leveraging these insights, we established patient-derived organoids (PDOs) using primary cells obtained from patient FD lesions. Evaluation of PDOs demonstrated preservation of fibrosis-associated constituent cell types and transcriptional signatures observed in FD lesions. Additionally, PDOs retained distinct constellations of genomic and metabolic alterations characteristic of FD. Histological evaluation further corroborated the fidelity of PDOs in recapitulating important phenotypic features of FD that underscore their pathophysiological relevance. Our findings represent meaningful progress in the field, as they open up the possibility for in vitro modeling of rare bone lesions in a three-dimensional context and may signify the first step towards creating a personalized platform for research and therapeutic studies.

Vitamin D Attenuates Fibrotic Properties of Fibrous Dysplasia-Derived Cells for the Transit towards Osteocytic Phenotype.

Fibrous dysplasia (FD) poses a therapeutic challenge due to the dysregulated extracellular matrix (ECM) accumulation within affected bone tissues. In this study, we investigate the therapeutic potential of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in managing FD by examining its effects on FD-derived cells in vitro. Our findings demonstrate that 1,25(OH)2D3 treatment attenuates the pro-fibrotic phenotype of FD-derived cells by suppressing the expression of key pro-fibrotic markers and inhibiting cell proliferation and migration. Moreover, 1,25(OH)2D3 enhances mineralization by attenuating pre-osteoblastic cellular hyperactivity and promoting maturation towards an osteocytic phenotype. These results offer valuable insights into potential treatments for FD, highlighting the role of 1,25(OH)2D3 in modulating the pathological properties of FD-derived cells.

A Rare Skeletal Disorder, Fibrous Dysplasia: A Review of Its Pathogenesis and Therapeutic Prospects.

Fibrous dysplasia (FD) is a rare, non-hereditary skeletal disorder characterized by its chronic course of non-neoplastic fibrous tissue buildup in place of healthy bone. A myriad of factors have been associated with its onset and progression. Perturbation of cell-cell signaling networks and response outputs leading to disrupted building blocks, incoherent multi-level organization, and loss of rigid structural motifs in mineralized tissues are factors that have been identified to participate in FD induction. In more recent years, novel insights into the unique biology of FD are transforming our understandings of its pathology, natural discourse of the disease, and treatment prospects. Herein, we built upon existing knowledge with recent findings to review clinical, etiologic, and histological features of FD and discussed known and potential mechanisms underlying FD manifestations. Subsequently, we ended on a note of optimism by highlighting emerging therapeutic approaches aimed at either halting or ameliorating disease progression.

Risk of Fractures in Thyroid Cancer Patients With Postoperative Hypoparathyroidism: A Nationwide Cohort Study in Korea.

Postoperative hypoparathyroidism (PO-hypoPT) is an uncommon complication of total thyroidectomy in thyroid cancer patients. Although long-term hypoPT causes characteristic changes in bone metabolism, the risk of fractures in hypoPT remains inconclusive. We investigated the risk of fractures in Korean thyroid cancer patients with PO-hypoPT. This was a retrospective cohort study using data from the Korea Central Cancer Registry and Korean National Health Insurance Service. We analyzed 115,821 thyroid cancer patients aged ≥18 years, who underwent total thyroidectomy between 2008 and 2016. The risk of any fractures, including vertebral, hip, humerus, and wrist fractures, according to parathyroid function after total thyroidectomy, was analyzed using the multivariable Cox proportional hazard model. The PO-hypoPT and preserved parathyroid function groups included 8789 (7.6%) and 107,032 (92.4%) patients, respectively. Over a mean follow-up duration of 4.8 years, 159 (1.8%) and 2390 (2.2%) fractures occurred in the PO-hypoPT and preserved parathyroid function groups, respectively. The risk of any fractures was significantly lower in the PO-hypoPT group than in the preserved parathyroid function group (hazard ratio [HR] = 0.83; 95% confidence interval [CI] 0.70-0.98; p = 0.037) after adjusting for confounders. Regarding the fracture site, only the risk of vertebral fractures was significantly lower in the PO-hypoPT group compared with the preserved parathyroid function group (HR = 0.67; 95% CI 0.47-0.96; p = 0.028) after adjusting for confounders. Subgroup analyses showed that bone mineral density measurements and calcium supplementation interacted with the relationship between PO-hypoPT and the risk of any fractures (p for interactions = 0.010 and 0.017, respectively). PO-hypoPT was associated with a lower risk of fractures in thyroid cancer patients, especially at the vertebra. The relatively low bone turnover caused by PO-hypoPT and appropriate management for PO-hypoPT with active vitamin D and calcium may prevent the deterioration of skeletal health in thyroid cancer patients who can easily be exposed to long-term overtreatment with levothyroxine. © 2023 American Society for Bone and Mineral Research (ASBMR).

Constitutive Expression of a Cytotoxic Anticancer Protein in Tumor-Colonizing Bacteria.

Bacterial cancer therapy is a promising next-generation modality to treat cancer that often uses tumor-colonizing bacteria to deliver cytotoxic anticancer proteins. However, the expression of cytotoxic anticancer proteins in bacteria that accumulate in the nontumoral reticuloendothelial system (RES), mainly the liver and spleen, is considered detrimental. This study examined the fate of the Escherichia coli strain MG1655 and an attenuated strain of Salmonella enterica serovar Gallinarum (S. Gallinarum) with defective ppGpp synthesis after intravenous injection into tumor-bearing mice (~108 colony forming units/animal). Approximately 10% of the injected bacteria were detected initially in the RES, whereas approximately 0.01% were in tumor tissues. The bacteria in the tumor tissue proliferated vigorously to up to 109 colony forming units/g tissue, whereas those in the RES died off. RNA analysis revealed that tumor-associated E. coli activated rrnB operon genes encoding the rRNA building block of ribosome needed most during the exponential stage of growth, whereas those in the RES expressed substantially decreased levels of this gene and were cleared soon presumably by innate immune systems. Based on this finding, we engineered ΔppGpp S. Gallinarum to express constitutively a recombinant immunotoxin comprising TGFα and the Pseudomonas exotoxin A (PE38) using a constitutive exponential phase promoter, the ribosomal RNA promoter rrnB P1. The construct exerted anticancer effects on mice grafted with mouse colon (CT26) or breast (4T1) tumor cells without any notable adverse effects, suggesting that constitutive expression of cytotoxic anticancer protein from rrnB P1 occurred only in tumor tissue.

Investigation of cell signalings and therapeutic targets in PTPRK-RSPO3 fusion-positive colorectal cancer.

INTRODUCTION: Colorectal cancer (CRC) is one of the most deadly and common diseases in the world, accounting for over 881,000 casualties in 2018. The PTPRK-RSPO3 (P:R) fusion is a structural variation in CRC and well known for its ability to activate WNT signaling and tumorigenesis. However, till now, therapeutic targets and actionable drugs are limited in this subtype of cancer. MATERIALS AND METHOD: The purpose of this study is to identify key genes and cancer-related pathways specific for P:R fusion-positive CRC. In addition, we also inferred the actionable drugs in bioinformatics analysis using the Cancer Genome Atlas (TCGA) data. RESULTS: 2,505 genes were altered in RNA expression specific for P:R fusion-positive CRC. By pathway analysis based on the altered genes, ten major cancer-related signaling pathways (Apoptosis, Direct p53, EGFR, ErbB, JAK-STAT, tyrosine kinases, Pathways in Cancer, SCF-KIT, VEGFR, and WNT-related Pathway) were significantly altered in P:R fusion-positive CRC. Among these pathways, the most altered cancer genes (ALK, ACSL3, AXIN, MYC, TP53, GNAQ, ACVR2A, and FAS) specific for P:R fusion and involved in multiple cancer pathways were considered to have a key role in P:R fusion-positive CRC. Based on the drug-target network analysis, crizotinib, alectinib, lorlatinib, brigatinib, ceritinib, erdafitinib, infigratinib and pemigatinib were selected as putative therapeutic candidates, since they were already used in routine clinical practice in other cancer types and target genes of the drugs were involved in multiple cancer-pathways.

Lipocalin2 as a potential antibacterial drug against Acinetobacter baumannii infection.

Available antibiotics to treat Acinetobacter baumannii infection is limited due to increasing resistance and the emergence of multiple drug-resistant strains. Hence, discovering effective agents against A. baumannii to reduce the number of infection-related deaths is imperative. In search of novel and alternative antibiotics, the antibacterial function of lipocalin2 (Lcn2) was investigated to treat systemic infections of A. baumannii using a mouse neutropenia model. We observed a significant increase in serum Lcn2 levels upon bacterial injection into the mouse, and the administration of recombinant Lcn2 (rmLcn2) extended their survival. Such protective effects were also observed in rmLcn2-pretreated macrophages, where rmLcn2 reduced the survival of the pathogen inside the macrophages. The underlying molecular mechanism of Lcn2 protection was also investigated. We observed that pretreatment of the Raw-264.7 macrophages with rmLcn2 markedly altered the expression of tonB3, which encodes a component of the transporter for ferrisiderophores in A. baumannii. However, the expression of katG, the gene encoding catalase, remained unaffected. These indicate that Lcn2-mediated defense against the pathogen is related to nutritional immunity rather than reactive oxygen species (ROS) production. Furthermore, the addition of rmLcn2 in infected mice diminished bacterial burden in multiple organs and enhanced the expression of tonB3 in the liver, spleen, and lungs of the infected mice. Increased survival rate due to rmLcn2 treatment declined when the infection model was established using lcn2-defective (lcn2-/-) mice, which indicated the necessity of endogenous Lcn2. Therefore, the antibacterial function of Lcn2 can be exploited to develop an alternative therapeutic agent against A. baumannii.

Medication Related Osteonecrosis of the Jaw: 2021 Position Statement of the Korean Society for Bone and Mineral Research and the Korean Association of Oral and Maxillofacial Surgeons.

Antiresorptives are the most widely prescribed drugs for the treatment of osteoporosis. They are also used in malignant bone metastases, multiple myeloma, and Paget's disease, and provide therapeutic efficacy on those diseases. However, it was reported that the occurrence of osteonecrosis of the jaw (ONJ) could be related to antiresorptive exposures, and there have been many cases regarding this issue. Therefore, a clearer definition and treatment guidelines were needed for this disease. The American Society for Bone and Mineral Research and the Amnerican Association of Oral and Maxillofacial Surgeons reported statements on bisphosphonate-related ONJ (BRONJ), and a revised version was recently presented. In the revised edition, the diagnosis BRONJ was changed to medication-related ONJ (MRONJ), which reflects consideration of the fact that ONJ also occurs for denosumab, a bone resorption inhibitor of the receptor activator of the nuclear factor-κB ligand antibody family, and bevacizumab, an anti-angiogenesis inhibitor. The Korean Society for Bone and Mineral Research and the Korean Association of Oral and Maxillofacial Surgeons had collectively formed a task force for the preparation of an official statement on MRONJ based on a previous position paper in 2015. The task force reviewed current knowledge and coordinated dental and medical opinions to propose the guideline customized for the local Korean situation.

Incidence and Risk of Venous Thromboembolism in Bisphosphonates and Selective Estrogen Receptor Modulators Treatment in Korea.

BACKGROUND: Selective estrogen receptor modulators (SERMs) were associated with an increased risk of venous thromboembolism (VTE) due to the estrogen effect. In this study, we investigated the effect of SERMs on VTE compared to bisphosphonates (BPs) using the Korean National Health Insurance claims database. METHODS: This was a retrospective cohort study. Women over 50 years old who were first prescribed BPs or SERMs for osteoporosis treatment in 2012 were included. The difference in VTE incidence between the SERMs and BP groups was compared. Both groups were followed up for VTE or PE occurrence, death, or until December 2016. The study population was analyzed by 3:1 matching according to age using a multivariate Cox model. RESULTS: The hazard ratio (HR) for VTE was 0.72 (95% confidence interval [CI], 0.40-1.28) in the SERMs group compared to BP group. Older age (60-69 vs. 50-59 years: HR, 3.77; 95% CI, 2.07-6.86 and 70-79 vs. 50-59 years: HR, 5.88; 95% CI, 3.14-11.02), major osteoporotic fracture (HR, 1.77; 95% CI, 1.16- 2.70), atrial fibrillation (HR, 3.31; 95% CI, 1.35-8.11), and estrogen replacement (HR, 3.40; 95% CI, 2.01-5.73) all increased VTE risk. In subgroup analysis of the SERMs group, past hospitalization (HR, 2.24; 95% CI, 1.02-4.92), estrogen replacement (HR, 5.75; 95% CI, 2.29-14.39), and glucocorticoid replacement (HR, 2.71; 95% CI, 1.05-7.0) increased VTE risk. CONCLUSION: SERMs did not increase the risk of VTE compared to BPs in Koreans with osteoporosis. However, old age and estrogen replacement both increased VTE risk.

Elucidation of Novel Therapeutic Targets for Breast Cancer with ESR1-CCDC170 Fusion.

Among the various types of breast cancer, the luminal B subtype is the most common in young women, and ESR1-CCDC170 (E:C) fusion is the most frequent oncogenic fusion driver of the luminal B subtype. Nevertheless, treatments targeting E:C fusion has not been well established yet. Hence, the aim of this study is to investigate potential therapies targeting E:C fusion based on systematic bioinformatical analysis of the Cancer Genome Atlas (TCGA) data. One thousand related genes were extracted using transcriptome analysis, and major signaling pathways associated with breast cancer were identified with over-representation analysis. Then, we conducted drug-target network analysis based on the OncoKB and CIViC databases, and finally selected potentially applicable drug candidates. Six major cancer-related signaling pathways (p53, ATR/ATM, FOXM1, hedgehog, cell cycle, and Aurora B) were significantly altered in E:C fusion-positive cases of breast cancer. Further investigation revealed that nine genes (AURKB, HDAC2, PLK1, CENPA, CHEK1, CHEK2, RB1, CCNA2, and MDM2) in coordination with E:C fusion were found to be common denominators in three or more of these pathways, thereby making them promising gene biomarkers for target therapy. Among the 21 putative actionable drugs inferred by drug-target network analysis, palbociclib, alpelisib, ribociclib, dexamethasone, checkpoint kinase inhibitor AXD 7762, irinotecan, milademetan tosylate, R05045337, cisplatin, prexasertib, and olaparib were considered promising drug candidates targeting genes involved in at least two E:C fusion-related pathways.

Is implant surgery a risk factor for osteonecrosis of the jaw in older adult patients with osteoporosis? A national cohort propensity score-matched study.

OBJECTIVES: This study aimed to investigate the association between dental implant therapy and osteonecrosis of the jaw (ONJ) in osteoporotic patients and the relationship between tooth extraction, dental implantation, and ONJ. MATERIAL AND METHODS: This retrospective cohort study used the Customized Health Information Data from the National Health Insurance Corporation in South Korea. The study population included patients older than 70 years with a history of osteoporosis; the cases included patients who had undergone dental implant surgery between July 2014 and July 2016 with specific procedure codes. The case and control cohorts were stratified by tooth extraction because it was the strongest risk factor to consider in this study. Each group of patients was matched using the propensity score. To investigate the relationship between dental implants and ONJ, a Cox proportional hazard model was applied to socio-economic factors, comorbidities, and bisphosphonates (BPs). All analyses were conducted using SAS statistical software. RESULTS: Based on the fully adjusted model, the propensity score-matched osteoporosis patients with dental implants had a 0.51 times hazard ratio of osteonecrosis. On the contrary, tooth extraction was associated with a higher risk of ONJ (HR = 5.89). The patients with rheumatoid arthritis (RA) and those using BPs had a higher HR, respectively, 6.80 and 4.09 HR (p < .001). CONCLUSIONS: Dental implantation was not a risk factor and patients with implants show rather lower ratios. However, older osteoporotic Korean patients who had undergone tooth extraction had higher risks of ONJ. A significantly higher risk of ONJ was associated with RA and BPs as well.

Osteoporotic Fractures of the Spine, Hip, and Other Locations after Adjuvant Endocrine Therapy with Aromatase Inhibitors in Breast Cancer Patients: a Meta-analysis.

BACKGROUND: Aromatase inhibitors (AIs) play an important role in the endocrine therapy of postmenopausal breast cancer patients, with a recent tendency to extend the duration of their use. However, AIs may increase the risk of osteoporotic bone fractures. This meta-analysis evaluated the risk of osteoporotic fractures of the hip, spine, and other locations in breast cancer patients using AIs. METHODS: We performed a systematic search to identify randomized controlled clinical trials that investigated osteoporotic fractures in breast cancer patients on AI therapy. The main outcomes were the incidence and risk of osteoporotic fractures in general and of hip, vertebral, and non-vertebral fractures in AI users and controls. RESULTS: The systematic review found a total of 30 randomized controlled trials including 117,974 participants. The meta-analysis showed a higher incidence of osteoporotic fracture in AI users: The crude risk ratio for all osteoporotic fractures was 1.35 (95% confidence interval [CI], 1.29-1.42; P < 0.001), for hip fractures 1.18 (95% CI, 1.02-1.35; P < 0.001), for vertebral fractures 1.84 (95% CI, 1.36-2.49; P < 0.001), and for non-vertebral fractures 1.18 (95% CI, 1.02-1.35; P < 0.001), respectively, compared to the controls. CONCLUSION: Our meta-analysis suggested an increased risk of osteoporotic fractures for AI therapy in patients with breast cancer that was most expressed for vertebral fractures. Breast cancer patients on AIs need to be monitored for osteoporosis and osteoporotic fractures, and active prevention measures should be implemented.

Risk factors for subsequent hip fractures and fatality after an initial hip fracture in Korea: using nationwide claims data.

In this study, the risk of fatality after hip fracture but not the risk of subsequent hip fractures was higher among men. INTRODUCTION: The purpose of this study was to analyze the risk factors for subsequent hip fractures and fatality after an initial hip fracture among Koreans older than 50 years of age using information in the national claims database. METHODS: Our study was conducted using data from the Korean National Health Insurance Service database from 2007 to 2016. A total of 16,915 Korean patients aged ≥ 50 years with a first hip fracture in 2012 were followed for 4 years. Data on fracture, comorbidity, and prescription variables were retrieved from the national registry. The Cox proportional hazards model was used to identify the risk factors affecting subsequent hip fractures and fatality after the initial hip fracture. RESULTS: A total of 952 patients had subsequent hip fractures, and 6793 patients died. The cumulative incidence rates were 1.3% after 1 year and 5.6% after 4 years. Old age, renal disease, dementia, and Parkinson's disease were associated with a higher risk of subsequent hip fractures. The fatality rate after the initial hip fracture was 1.6 times higher among men than among women. Certain risk factors for fatality, such as pneumonia after fracture, cerebrovascular disease, mild liver disease, renal disease, and malignancy, were more prevalent among men. CONCLUSION: During the study period, the risk of fatality after hip fracture but not the risk of subsequent hip fractures was higher among men. The gender difference in fatality might be explained by the larger burden of comorbid diseases among men.

Incidence and mortality of subsequent vertebral fractures: analysis of claims data of the Korea National Health Insurance Service from 2007 to 2016.

BACKGROUND CONTEXT: Vertebral fracture is related to an increased risk for subsequent and recurrent osteoporotic fracture as well as increased mortality. However, no study has investigated the exact incidence and mortality of subsequent vertebral fractures. OBJECTIVE: The purpose of our study was to determine trends in the incidence and mortality of subsequent vertebral fractures after first-time vertebral fracture in Koreans older than 50 years using the national claims database. STUDY DESIGN: Retrospective cohort study. PATIENT SAMPLE: Data from the Korea National Health Insurance Service database from 2007 to 2016. OUTCOME MEASURES: The incidence of subsequent vertebral fracture during a 4-year follow-up period. The mortality and standardized mortality ratio (SMR) after subsequent vertebral fractures during the 1-year period after fracture were also determined. Analysis was restricted to patients older than 50 years. METHODS: The national claims data set was analyzed to find all new visits and revisits after 6 months from the last claim to a hospital or clinic for vertebral fractures and revisits in men and women aged 50 years or older between 2007 and 2016. The number of first-time vertebral fractures in 2012 was investigated to determine subsequent vertebral fractures. The incidence, mortality rates, and SMR of subsequent vertebral fractures were calculated. There were no sources of funding and no conflicts of interest associated with this study. RESULTS: During the 4-year follow-up period, the overall cumulative incidence of subsequent vertebral fractures were 27.53%. According to sex, the cumulative incidence of subsequent vertebral fractures was 20.09% in men and 29.98% in women. The cumulative mortality rate over the first year after subsequent vertebral fractures was 5%. The mortality rates over 1 year were 10.04% for men and 3.81% for women. The overall SMR at the 1-year follow-up after subsequent vertebral fractures was 10.58 (95% confidence interval: 9.29-12.05) in men and 3.88 (95% confidence interval: 3.5-4.3) in women. CONCLUSIONS: Our study showed that subsequent vertebral fractures were more common in women, with an incidence rate of 29.98% over 4 years. However, the mortality rate was higher in men, reaching 10.04% in 1 year. Subsequent vertebral fractures occurred in large numbers, and the mortality rates were relatively high. Thus, first vertebral fracture may be considered as an early warning of high risk for future subsequent vertebral fractures, especially in women.

Causative agents and epidemiology of diarrhea in Korean native calves.

Calf diarrhea caused by infectious agents is associated with economic losses in the cattle industry. The purpose of this study was to identify the causative agents and epidemiological characteristics of diarrhea in Korean native calves (KNC). In total, 207 diarrheal KNC aged less than 7 months were investigated. Fecal samples collected from the rectum were examined for causative agents using polymerase chain reaction (PCR) or real-time PCR and the number of oocysts were counted. Fourteen causative agents were detected from 164 of the 207 diarrheal KNC. Rotavirus was the most common agent (34.8%), followed by Eimeria spp. (31.7%), Escherichia coli (22.0%), Giardia spp. (14.0%), Clostridium difficile (9.8%), bovine viral diarrhea virus (8.5%), coronavirus (7.9%), Cryptosporidium spp. (7.3%), torovirus (6.7%), parvovirus (5.5%), norovirus (4.9%), kobuvirus (1.8%), adenovirus (1.2%), and Salmonella spp. (0.6%). About 95 (57.9%) of 164 calves were infected with a single causative agent and 42.1% were infected by multiple agents. No significant difference was observed in mortality between calves infected with a single agent and multiple agents. The occurrence of diarrhea caused by rotavirus, Eimeria spp., kobuvirus, and Giardia spp. was significantly different based on onset age, and the prevalence of diarrhea caused by rotavirus or C. difficile was significantly different between seasons. This study help the understanding of KNC diarrhea for the development of an effective strategy for disease prevention and control, especially in Eastern provinces of South Korea.

Medical Treatment with Somatostatin Analogues in Acromegaly: Position Statement.

The Korean Endocrine Society (KES) published clinical practice guidelines for the treatment of acromegaly in 2011. Since then, the number of acromegaly cases, publications on studies addressing medical treatment of acromegaly, and demands for improvements in insurance coverage have been dramatically increasing. In 2017, the KES Committee of Health Insurance decided to publish a position statement regarding the use of somatostatin analogues in acromegaly. Accordingly, consensus opinions for the position statement were collected after intensive review of the relevant literature and discussions among experts affiliated with the KES, and the Korean Neuroendocrine Study Group. This position statement includes the characteristics, indications, dose, interval (including extended dose interval in case of lanreotide autogel), switching and preoperative use of somatostatin analogues in medical treatment of acromegaly. The recommended approach is based on the expert opinions in case of insufficient clinical evidence, and where discrepancies among the expert opinions were found, the experts voted to determine the recommended approach.

Genotoxicity Study of Glycopeptide (G-7%NANA).

Glycomacropeptide (GMP), a whey protein of milk, has functions including differentiation and development of nervous system, and anticancer and antiviral effects. To develop new functions, N-acetylneuraminic acid (NANA) containing 7% sialic acid was separated from GMP to produce G-7%NANA. N-glycolylneuraminic acid (Neu5Gc) is another type of sialic acid separated from GMP, which has been linked to immune disorders and chronic inflammation-mediated diseases. Therefore, safety was a concern in the use of G-7%NANA in functional foods. To ensure safety, in this study, three genetic toxicity tests on G-7%NANA were conducted. In the reverse mutation test using Salmonella typhimurium TA98, TA100, TA1535, TA1537, and Escherichia coli WP2uvrA, and in the chromosome aberration test using CHO-K1 cells, no significant differences from negative control were found at all dose levels. Similarly, no dose-related differences were evident compared to negative control in the micronucleus test using ICR mice. There was no evidence of G-7%NANA-related genetic toxicity.

Utilization of Osteoporosis-Related Health Services: Use of Data from the Korean National Health Insurance Database 2008-2012.

BACKGROUND: Osteoporosis and its related fractures are increasingly being recognized as major health problems because of the rapidly increasing elderly population. In this study, we investigated the annual trend of osteoporosis-related health services utilization. METHODS: Participants aged over 50 years were identified from the Korean National Health Insurance Service database between 2008 and 2012. Health service utilization rate and treatment rate were calculated through the operational definition. RESULTS: In this period, the number of osteoporosis patients, aged over 50 years, using the medical service, increased by 33.2%. This increase was higher in males than in females. Moreover, the number of newly diagnosed osteoporosis patients increased by 4.3% in women and 20.4% in men. To estimate the proportion of osteoporosis patients who utilize medical services, we analyzed prevalence data from the Korea National Health and Nutrition Examination Survey from 2008 to 2010. Less than 60% of patients with osteoporosis were estimated to have utilized medical services because of osteoporosis. Drug treatment rates were 34.1%, 31.1%, and 33.5% in 2008, 2009, and 2010, respectively. CONCLUSION: This study demonstrated an increasing trend in the utilization of the osteoporosis-related health services from 2008 to 2012 in Korea. The proportion of newly diagnosed osteoporosis patients and the prevalence of access to medical services increased more in men than in women. Therefore, an increasing need for prevention and treatment of male osteoporosis was observed. The osteoporosis treatment rate was lower than that for other chronic diseases; more efforts are needed to improve awareness regarding osteoporosis treatment.

Preventive effects of tonsil-derived mesenchymal stem cells on osteoradionecrosis in a rat model.

BACKGROUND: The purpose of this study was to investigate the effects of tonsil-derived mesenchymal stem cells (MSCs) on osteoradionecrosis (ORN). METHOD: We generated a mandibular ORN rat model using a combination of 20-Gy single-dose irradiation and tooth extraction. Study groups were negative control (tooth extraction only), ORN group (irradiation, tooth extraction), Matrigel-1 group (Matrigel; BD Biosciences, San Jose, CA; irradiation, Matrigel application immediately after tooth extraction), tonsil-derived MSC-1 group (irradiation, tonsil-derived MSC application immediately after tooth extraction), Matrigel-4 group (irradiation, Matrigel application 4 weeks after tooth extraction), and tonsil-derived MSC-4 group (irradiation, tonsil-derived MSC application 4 weeks after tooth extraction). RESULT: Bone mineral density was significantly lower in the ORN group than in the negative control group. The tonsil-derived MSC-1 group showed significantly higher bone mineral density than did the ORN and tonsil-derived MSC-4 groups. CONCLUSION: A single 20-Gy dose of irradiation combined with tooth extraction successfully generated ORN in the rat model. The tonsil-derived MSCs can be effective for bone regeneration in ORN, particularly when applied immediately after dentoalveolar trauma or surgery.