Low-dose glucocorticoid increase the risk of fracture in postmenopausal women with low bone mass: a retrospective cohort study.

Long-term glucocorticoids (GCs) treatment is associated with osteoporosis and fractures. We investigated whether low-dose GC treatment also increased the risk of osteoporotic fractures, and the results showed that even low-dose GC treatment increased the risk of osteoporotic fractures, especially spine fractures. PURPOSE: The effect of low-dose glucocorticoid (GC) therapy on the fracture risk in postmenopausal women with low bone mass was investigated. METHODS: 119,790 66-year-old postmenopausal women with low bone mass based on bone mineral density (BMD) results were included. GC group consisted of patients who had been prescribed oral GCs within 6 months of BMD testing. In GC group, GCs dosage was calculated by a defined daily dose (DDD), and divided into five groups according to GC usage (Group 1[G1]; < 11.25 DDDs, G2; ≥ 11.25, < 22.5 DDDs, G3; ≥ 22.5, < 45 DDDs, G4; ≥ 45, < 90 DDDs, G5; ≥ 90 DDDs). The risk of major osteoporotic fractures (MOF) and non-MOF was analyzed and compared with that of the control group during the 1-year follow-up. RESULTS: The risk of total fracture was higher in G3-G5 than in the control group (G3, hazard ratio (HR) 1.25, 95% confidence interval [CI] 1.07-1.46; G4, 1.37 [1.13-1.66]; G5 1.45 [1.08-1.94]). The risk of MOF was higher in all groups except G2 than in the control group (G1, 1.23 [1.05-1.45]; G3, 1.37 [1.11-1.68]; G4, 1.41 [1.09-1.83]; G5, 1.66 [1.14-2.42]). The risk of spine fracture was significantly higher in all GC groups except G2 than in the control group. The risk of non-MOF was higher only in G4 than in the control group (G4, 1.48 [1.13-1.94]). CONCLUSION: Low-dose GC therapy can increase the risk of osteoporotic fractures, particularly spine fractures, in postmenopausal women with low bone mass.

Position Statement: Postmenopausal Osteoporosis Treatment Strategies in Korea.

Classifying patients with osteoporosis according to fracture risk and establishing adequate treatment strategies is crucial to effectively treat osteoporosis. The Korean Society for Bone and Mineral Research has issued a position statement regarding appropriate treatment strategies for postmenopausal osteoporosis. According to previous fragility fracture history, bone mineral density (BMD) test results, fracture risk assessment tool, and several clinical risk factors, fracture risk groups are classified into low, moderate, high, and very-high-risk groups. In high-risk groups, bisphosphonates (BPs) and denosumab are recommended as first-line therapies. Sequential BP treatment after denosumab discontinuation is required to prevent the rebound phenomenon. In the very high-risk group, anabolic drugs (teriparatide or romosozumab) are recommended as a first-line therapy; sequential therapy with antiresorptive agents is required to maintain BMD gain and reduce fracture risk. Fracture risk was reassessed annually, and the treatment plan was determined based on the results, according to the osteoporosis treatment algorithm for fracture risk.

Time-sequential fibroblast-to-myofibroblast transition in elastin-variable 3D hydrogel environments by collagen networks.

BACKGROUND: Fibrosis plays an important role in both normal physiological and pathological phenomena as fibroblasts differentiate to myofibroblasts. The activation of fibroblasts is determined through interactions with the surrounding extracellular matrix (ECM). However, how this fibroblast-to-myofibroblast transition (FMT) is regulated and affected by elastin concentration in a three-dimensional (3D) microenvironment has not been investigated. METHODS: We developed an insoluble elastin-gradient 3D hydrogel system for long-lasting cell culture and studied the molecular mechanisms of the FMT in embedded cells by nanoflow LC-MS/MS analysis along with validation through real-time PCR and immunofluorescence staining. RESULTS: By optimizing pH and temperature, four 3D hydrogels containing fibroblasts were successfully fabricated having elastin concentrations of 0, 20, 50, and 80% in collagen. At the low elastin level (20%), fibroblast proliferation was significantly increased compared to others, and in particular, the FMT was clearly observed in this condition. Moreover, through mass spectrometry of the hydrogel environment, it was confirmed that differentiation proceeded in two stages. In the early stage, calcium-dependent proteins including calmodulin and S100A4 were highly associated. On the other hand, in the late stage after several passages of cells, distinct markers of myofibroblasts were presented such as morphological changes, increased production of ECM, and increased α-SMA expression. We also demonstrated that the low level of elastin concentration induced some cancer-associated fibroblast (CAF) markers, including PDGFR-ß, and fibrosis-related disease markers, including THY-1. CONCLUSION: Using our developed 3D elastin-gradient hydrogel system, we evaluated the effect of different elastin concentrations on the FMT. The FMT was induced even at a low concentration of elastin with increasing CAF level via calcium signaling. With this system, we were able to analyze varying protein expressions in the overall FMT process over several cellular passages. Our results suggest that the elastin-gradient system employing nonlinear optics imaging provides a good platform to study activated fibroblasts interacting with the microenvironment, where the ECM plays a pivotal role.

Accelerated tibia fracture healing in traumatic brain injury in accordance with increased hematoma formation.

BACKGROUND: Traumatic brain injury (TBI) has been known to accelerate bone healing. Many cells and molecules have been investigated but the exact mechanism is still unknown. The neuroinflammatory state of TBI has been reported recently. We aimed to investigate the effect of TBI on fracture healing in patients with tibia fractures and assess whether the factors associated with hematoma formation changed more significantly in the laboratory tests in the fractures accompanied with TBI. METHODS: We retrospectively investigated patients who were surgically treated for tibia fractures and who showed secondary bone healing. Patients with and without TBI were divided for comparative analyses. Radiological parameters were time to callus formation and the largest callus ratio during follow-up. Preoperative levels of complete blood count and chemical battery on admission were measured in all patients. Subgroup division regarding age, gender, open fracture, concomitant fracture and severity of TBI were compared. RESULTS: We included 48 patients with a mean age of 44.9 (range, 17-78), of whom 35 patients (72.9%) were male. There were 12 patients with TBI (Group 1) and 36 patients without TBI (Group 2). Group 1 showed shorter time to callus formation (P <  0.001), thicker callus ratio (P = 0.015), leukocytosis and lymphocytosis (P ≤ 0.028), and lower red blood cell counts (RBCs), hemoglobin, and hematocrit (P <  0.001). Aging and severity of TBI were correlated with time to callus formation and callus ratio (P ≤ 0.003) while gender, open fracture, and concomitant fracture were unremarkable. CONCLUSION: Tibia fractures with TBI showed accelerated bone healing and superior measurements associated with hematoma formation (lymphocytes, RBCs, hemoglobin, hematocrit). Promoted fracture healing in TBI was correlated with the enhanced proinflammatory state. LEVEL OF EVIDENCE: III, case control study.

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.

Particulate Matter Promotes Melanin Production through Endoplasmic Reticulum Stress‒Mediated IRE1α Signaling.

Particulate matter (PM) is believed to be related to cardiovascular and respiratory diseases. The skin is also known to be affected by PM exposure as a result of skin barrier dysfunction, cutaneous inflammation, and apoptotic cell death. Epidemiological studies have suggested that PM is related to pigment spots. Recently, diesel exhaust particles are reported to cause a tanning response mediated by oxidative stress. However, the direct effects of PM on melanogenesis and the related mechanisms have not yet been clarified. Our study showed that PM can increase melanin production in melanocyte, mouse skin, and human skin models. RNA-sequencing analyses of melanocytes revealed that the expressions of unfolded protein response molecules were increased after PM exposure. In particular, IRE1α signaling pathway, which was consistently upregulated, was related to PM-triggered melanogenesis. In addition, PM-induced melanogenesis was abrogated by an IRE1α inhibitor. Therefore, our findings corroborate previous findings in melanocytes and in mouse and human models and also illuminate the involvement of the IRE1α pathway as a mechanism of PM-induced melanogenesis.

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.

Molecule-Resolved Visualization of Particulate Matter on Human Skin Using Multimodal Nonlinear Optical Imaging.

Precise measurement of particulate matter (PM) on skin is important for managing and preventing PM-related skin diseases. This study aims to directly visualize the deposition and penetration of PM into human skin using a multimodal nonlinear optical (MNLO) imaging system. We successfully obtained PM particle signals by merging two different sources, C-C vibrational frequency and autofluorescence, while simultaneously visualizing the anatomical features of the skin via keratin, collagen, and elastin. As a result, we found morphologically dependent PM deposition, as well as increased deposition following disruption of the skin barrier via tape-stripping. Furthermore, PM penetrated more and deeper into the skin with an increase in the number of tape-strippings, causing a significant increase in the secretion of pro-inflammatory cytokines. Our results suggest that MNLO imaging could be a useful technique for visualizing and quantifying the spatial distribution of PM in ex vivo human skin tissues.

Length difference of multi-walled carbon nanotubes generates differential cytotoxic responses.

Carbon nanotubes have recently been rated as an effective biomaterial owing to their functionalization ability. However, the safety of multi-walled carbon nanotubes (MWCNTs) has yet to be clearly understood. To investigate how cells differentially react to minor geometric differences, we prepared well-dispersed and stable long and short MWCNTs showing an approximately 100-nm length difference in an in vitro system. Through an optimal combination of bovine serum albumin (BSA) and fetal bovine serum (FBS) biosurfactants and ultrasonication, we first confirmed that the MWCNTs were maintained without aggregation throughout the experiments. Internalized MWCNTs in human coronary artery smooth muscle cells were then quantified in a label-free manner using coherent anti-Stokes Raman scattering, followed by an analysis of their localization via two-photon excitation fluorescence. Intracellular MWCNTs were found to primarily localize in mitochondria with abnormal morphologies. Mitochondrial dysfunction, which was found to result from early stages of oxidative stress that consequently lead to cell death, was then proved via decreasing mitochondrial membrane potentials, with short MWCNTs showing significantly greater cytotoxicity than long MWCNTs. Our results suggest that even small length differences of MWCNTs may lead to differential responses in cells.

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.

Incidence of and risk for osteonecrosis of the jaw in Korean osteoporosis patients treated with bisphosphonates: A nationwide cohort-study.

PURPOSE: To estimate the incidence of osteonecrosis of the jaw (ONJ) in patients treated with bisphosphonates (BPs) and to identify clinical risk factors that increase the risk for ONJ in Korean osteoporosis patients. METHODS: We used data acquired from the Korean National Health Insurance Service. Among 2,140,149 participants with osteoporosis in 2012, we selected 164,926 new BP users and 164,926 age- and sex-matched control subjects. The control group included only patients with no prescriptions for BPs between January 1, 2011, and December 31, 2016. Participants were followed for 4 years. RESULTS: Over the 4-year follow-up period, the cumulative incidence rates of ONJ were 20.9 and 6.9 per 100,000 person-years in the BP and control groups, respectively. The BP group had an increased risk for ONJ compared to the control group after adjusting for multiple variables (hazard ratio [HR] 3.72, 95% CI 2.70-5.11). Advanced age (≥70 years), comorbid diseases such as diabetes, hypertension, and rheumatoid arthritis (RA) were independent risk factors for the development of ONJ. In addition, tooth extraction (HR 9.85), gingivitis, and periodontal disease (HR 4.78) were strongly associated with ONJ. CONCLUSIONS: ONJ incidence was 21 per 100,000 person-years in osteoporosis patients receiving bisphosphonates. Clinical factors including advanced age, diabetes, RA, dental disease, as well as BP use were significantly associated with ONJ.

Osteoporosis and Osteoporotic Fracture Fact Sheet in Korea.

BACKGROUND: The socioeconomic burdens of osteoporosis and related fractures have increased in parallel with population aging. The Korea Society of Bone and Mineral Research published fact sheets on these topics in 2017, 2018, and 2019. This study provides complied epidemiological data based on these fact sheets for understanding current status of osteoporosis in Korea. METHODS: Data from the Korea National Health and Nutrition Examination Survey (2008-2011) performed by the Korea Centers for Disease Control and Prevention and from National Health Information database (2008-2016) by National Health Insurance Service of Korea was used for analyzing the prevalence and incidence of osteoporosis and related fractures, respectively, fatality rates after fractures, and prescription status of anti-osteoporotic medications (AOMs). RESULTS: Among Korean adults aged ≥50 years, 22.4% and 47.9% had osteopenia or osteoporosis, respectively. Incidences of osteoporotic hip, vertebral, humerus, and distal radius fractures plateaued in 2013. The cumulative incidence of subsequent fractures gradually increased over 4 years of follow-up once an osteoporotic fracture occurred. Crude fatality rates in the first 12 months after hip fracture were 14.0% for women and 21.0% for men. Only 33.5% of patients with osteoporosis took AOMs, and even after an osteoporotic fracture, only 41.9% of patients took AOMs within the following 12 months. Despite a steady increase in AOM prescriptions of ~6% per annum, only 33.2% of patients were medication compliant (medication possession ratio ≥80%) at 12 months after treatment initiation. CONCLUSIONS: Continuous efforts are required to diagnose patients at high risk of fracture and ensure proper management in Korea.

Diagnosis and Treatment of Growth Hormone Deficiency: A Position Statement from Korean Endocrine Society and Korean Society of Pediatric Endocrinology.

Growth hormone (GH) deficiency is caused by congenital or acquired causes and occurs in childhood or adulthood. GH replacement therapy brings benefits to body composition, exercise capacity, skeletal health, cardiovascular outcomes, and quality of life. Before initiating GH replacement, GH deficiency should be confirmed through proper stimulation tests, and in cases with proven genetic causes or structural lesions, repeated GH stimulation testing is not necessary. The dosing regimen of GH replacement therapy should be individualized, with the goal of minimizing side effects and maximizing clinical improvements. The Korean Endocrine Society and the Korean Society of Pediatric Endocrinology have developed a position statement on the diagnosis and treatment of GH deficiency. This position statement is based on a systematic review of evidence and expert opinions.

Synthetic Retinoid Seletinoid G Improves Skin Barrier Function through Wound Healing and Collagen Realignment in Human Skin Equivalents.

The outer epidermal skin is a primary barrier that protects the body from extrinsic factors, such as ultraviolet (UV) radiation, chemicals and pollutants. The complete epithelialization of a wound by keratinocytes is essential for restoring the barrier function of the skin. However, age-related alterations predispose the elderly to impaired wound healing. Therefore, wound-healing efficacy could be also considered as a potent function of an anti-aging reagent. Here, we examine the epidermal wound-healing efficacy of the fourth-generation retinoid, seletinoid G, using HaCaT keratinocytes and skin tissues. We found that seletinoid G promoted the proliferation and migration of keratinocytes in scratch assays and time-lapse imaging. It also increased the gene expression levels of several keratinocyte proliferation-regulating factors. In human skin equivalents, seletinoid G accelerated epidermal wound closure, as assessed using optical coherence tomography (OCT) imaging. Moreover, second harmonic generation (SHG) imaging revealed that seletinoid G recovered the reduced dermal collagen deposition seen in ultraviolet B (UVB)-irradiated human skin equivalents. Taken together, these results indicate that seletinoid G protects the skin barrier by accelerating wound healing in the epidermis and by repairing collagen deficiency in the dermis. Thus, seletinoid G could be a potent anti-aging agent for protecting the skin barrier.

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.