Bile acids, fibroblast growth factor-19, and glucagon-like peptide-1 levels in the long term after bariatric surgery.

OBJECTIVES: Glucagon-like peptide-1(GLP-1) is a hormone often measured in the short-term following Roux-en-Y gastric bypass (RYGB) due to its elevation and association with improvement of glucose metabolism. We examined the durability of this effect in patients with type 2 diabetes mellitus (DM) in the long term after RYGB. METHODS: Obese patients with type 2 DM who had received RYGB 10 years ago (n = 10) were enrolled and a meal tolerance test (MTT) was performed. A matched control group with type 2 DM (n = 5) underwent MTT. RESULTS: Glucose levels during the MTT did not differ between patients with RYGB and the nonsurgical group. Insulin, C-peptide and GLP-1 levels during MTT were significantly higher in patients with RYGB compared with the nonsurgical group (Area under the curve [AUC] of insulin; 57.4 ± 22.9 vs. 27.7 ± 11.1 mIU/L•hr, P = 0.008; AUC of total GLP-1; 189.4 ± 74.72 vs. 52.13 ± 10.23 pM •hr, P = 0.002), and in particular, peak insulin, C-peptide and GLP-1 levels observed 30-45 min after eating were markedly different from those in the nonsurgical group. Bile acids (BAs) and fibroblast growth factor 19 (FGF-19) levels during MTT were higher in patients with RYGB compared with the nonsurgical group. Peak BAs and FGF-19 levels tended to be higher in the RYGB. CONCLUSIONS: An enhanced GLP-1 response was noted 10 years after RYGB, strongly suggesting a durability of this effect. BAs and FGF-19 were increased in the RYGB group, but not as much as the pronounced increase in GLP-1 secretion.

Efficacy of a single 5 mg zoledronic acid infusion in preventing bone loss and fracture in postmenopausal women with breast cancer.

INTRODUCTION: Chemotherapy-induced bone loss (CTIBL) is common among breast cancer patients, requiring comprehensive assessment and intervention. Zoledronic acid, a strong inhibitor of bone resorption, is effective in CTIBL management, though information on dosing and intervals, particularly the efficacy of the 5 mg annual dose for osteoporosis in breast cancer patients, is limited. MATERIALS AND METHODS: In this 12-month prospective observational study, 85 breast cancer patients were divided into three groups: 17 received no treatment, 17 received tamoxifen, and 51 received anastrozole or letrozole (AI). Post-surgery, patients were administered a single 5 mg dose of zoledronic acid and monitored over 12 months for changes in bone mineral density (BMD), fracture rates, and biochemical markers. RESULTS: Initially, the AI group was the oldest, averaging 59.1 ± 8.7 years. At baseline, no significant differences in variables, except age, were observed. After 12 months, BMD increased in all groups following a single zoledronic acid dose, with the smallest increase in the AI group at the lumbar spine: no treatment (2.4% ± 6.1%), tamoxifen (2.6% ± 3.4%), AI (0.6% ± 14.5%) (p = 0.778). CTx and P1NP levels were consistently suppressed up to 12 months post-treatment, with smaller reductions in the AI group. There were no significant differences in fracture or bone metastasis rates among groups. CONCLUSION: A single infusion of 5 mg zoledronic acid was effective in increasing bone density in breast cancer patients. However, AI-treated patients showed less improvement in vertebral bone mineral density and biochemical markers. Further long-term studies with larger cohorts are needed.

Proposed Denosumab Biosimilar SB16 vs Reference Denosumab in Postmenopausal Osteoporosis: Phase 3 Results Up to Month 12.

CONTEXT: SB16 is a proposed biosimilar to reference denosumab (DEN; brand name: Prolia). OBJECTIVE: This phase 3 randomized, double-blind, multicenter study evaluated the biosimilarity of SB16 to DEN in women with postmenopausal osteoporosis (PMO; NCT04664959). DESIGN: The study included 457 PMO patients who had a lumbar spine or total hip T-score between -2.5 and -4. Patients were randomized in a 1:1 ratio to receive either 60 mg of SB16 or DEN subcutaneously at Month 0 and Month 6. At Month 12, patients were re-randomized to continue with the assigned treatment or switch from DEN to SB16 up to Month 18. This report includes results up to Month 12. METHODS: The primary endpoint was the percent change from baseline in lumbar spine bone mineral density (BMD) at Month 12. Secondary endpoints including the percent change from baseline in BMD of the lumbar spine (except for Month 12), total hip and femoral neck; pharmacokinetic, pharmacodynamic (serum C-telopeptide of type I collagen [CTX] and procollagen type I N-terminal propeptide [P1NP]), safety, and immunogenicity profiles were measured up to Month 12. RESULTS: The least-squares mean differences in percent change from baseline in lumbar spine BMD at Month 12 were 0.33% (90% confidence interval [CI]: -0.25, 0.91) in the full analysis set and 0.39% (95% CI: -0.36, 1.13) in the per-protocol set; both within the pre-defined equivalence margin. The secondary endpoints were comparable between the two treatment groups. CONCLUSION: The reported efficacy, PK, PD, safety, and immunogenicity data support the biosimilarity of SB16 to DEN.

Beyond breast cancer: role of selective estrogen receptor modulators in reducing systemic malignancies: evidence from population-based data.

BACKGROUND: Raloxifene and bazedoxifene are selective estrogen receptor modulators (SERMs) used to prevent and treat osteoporosis in postmenopausal women. Raloxifene is also known for its preventive effect against invasive breast cancer; however, its effect on other cancer types is unclear. This study investigated the incidence of various cancers in osteoporosis patients receiving SERM therapy to determine its association with the risk of developing specific cancer types. METHODS: This retrospective cohort study examined the association between SERM use and the incidence of cervical, endometrial, ovarian, and colorectal cancers in postmenopausal women using data from the Korean National Health Insurance Service. Propensity score matching ensured group comparability by analyzing 95,513 participants. Cox proportional hazard models were used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) to assess the cancer risk associated with SERM therapy, differentiating between the effects of raloxifene and bazedoxifene. RESULTS: SERM therapy was associated with a reduced risk of cervical (adjusted HR = 0.47, 95% CI = 0.31-0.71), ovarian (adjusted HR = 0.61, 95% CI = 0.42-0.88), and colorectal cancer (adjusted HR = 0.49, 95% CI = 0.42-0.57). No significant risk reduction was observed for endometrial cancer (adjusted HR = 1.05, 95% CI = 0.70-1.59). A comparison between raloxifene and bazedoxifene revealed no significant differences in their cancer prevention effects. CONCLUSION: SERM therapy administration is associated with a decreased incidence of cervical, ovarian, and colorectal cancers. Notably, the effects of raloxifene and bazedoxifene were consistent. Further investigations are crucial to elucidate the mechanisms underlying these observations and their clinical implications.

Effects of Endocrine-Disrupting Chemicals on Bone Health.

This comprehensive review critically examines the detrimental impacts of endocrine-disrupting chemicals (EDCs) on bone health, with a specific focus on substances such as bisphenol A (BPA), per- and polyfluoroalkyl substances (PFASs), phthalates, and dioxins. These EDCs, by interfering with the endocrine system's normal functioning, pose a significant risk to bone metabolism, potentially leading to a heightened susceptibility to bone-related disorders and diseases. Notably, BPA has been shown to inhibit the differentiation of osteoblasts and promote the apoptosis of osteoblasts, which results in altered bone turnover status. PFASs, known for their environmental persistence and ability to bioaccumulate in the human body, have been linked to an increased osteoporosis risk. Similarly, phthalates, which are widely used in the production of plastics, have been associated with adverse bone health outcomes, showing an inverse relationship between phthalate exposure and bone mineral density. Dioxins present a more complex picture, with research findings suggesting both potential benefits and adverse effects on bone structure and density, depending on factors such as the timing and level of exposure. This review underscores the urgent need for further research to better understand the specific pathways through which EDCs affect bone health and to develop targeted strategies for mitigating their potentially harmful impacts.

Predicting fragility fractures based on frailty and bone mineral density among rural community-dwelling older adults.

OBJECTIVE: We aim to investigate the association between bone mineral density (BMD) measurement and fragility fractures and assess the predictive value of combining BMD measurement and frailty for fracture risk assessment. METHODS: This retrospective cohort study analyzed data from 5126 rural Koreans in the Chungju Metabolic Disease Cohort study. Frailty was defined using Fried's frailty phenotype. Fractures were assessed via structured medical interviews. Adjusted odds ratios (ORs) were calculated considering age, sex, body mass index, behavior, BMD, handgrip strength, medications, and comorbidities. RESULTS: The study cohort consisted of 5126 participants comprising 1955 (38.1%) males and 3171 (61.9%) females. Osteoporosis significantly increased the fracture risk across all types, except vertebral fracture, with adjusted OR (95% CI) of 1.89 (1.23-3.47) for any fracture, 2.05 (1.37-2.98) for hip fracture, 2.18 (1.06-4.50) for other fracture, and 1.71 (1.03-3.63) for major osteoporotic fracture (MOF). Frail individuals exhibited significantly increased risk for any fracture (OR 2.12; 95% CI, 1.21-3.71), vertebral fracture (2.48; 1.84-3.61), hip fracture (2.52; 1.09-3.21), other fracture (2.82; 1.19-8.53), and MOF (1.87; 1.01-3.47). The combination of frailty and BMD further increased the risks, with frail individuals demonstrating elevated ORs across BMD categories. In subgroup analyses, men showed a significant association between frailty with osteoporosis in hip fracture and MOF. Frail women with osteoporosis exhibited the highest risks for all fractures, particularly vertebral (OR 5.12; 95% CI, 2.07-9.68) and MOF (OR 5.19; 95% CI, 2.07-6.61). Age-specific analysis revealed that individuals aged 70 and older exhibited markedly higher fracture risks compared with those under 70. The combination of frailty and low BMD further elevated the fracture risk. Frailty was applied with BMD and demonstrated superior risk prediction for MOF compared with that with either score alone (area under the curve 0.825; P = .000). CONCLUSIONS: Combining frailty with BMD provides a more accurate fracture risk assessment for individuals over 50 years.

Effect of Pravastatin on Kidney Function in Patients with Dyslipidemia and Type 2 Diabetes Mellitus: A Multicenter Prospective Observational Study.

INTRODUCTION: Several studies have reported that pravastatin can mitigate the progression of kidney disease, but limited evidence exists regarding its effects on kidney function in Asian patients. This multicenter prospective observational study aimed to assess the effect of pravastatin on kidney function in Korean patients with dyslipidemia and type 2 diabetes mellitus (T2DM) in clinical practice. METHODS: This 48-week prospective multicenter study included 2604 of 2997 eligible patients with dyslipidemia and T2DM who had available estimated glomerular filtration rate (eGFR) measurements. The primary endpoint was eGFR percent change at week 24 from baseline. We also assessed secondary endpoints, which included percent changes in eGFR at weeks 12 and 48 from baseline, as well as changes in eGFR, metabolic profiles (lipid and glycemic levels) at 12, 24, and 48 weeks from baseline, and safety. RESULTS: We noted a significant improvement in eGFR, with mean percent changes of 2.5%, 2.5%, and 3.0% at 12, 24, and 48 weeks, respectively (all adjusted p < 0.05). The eGFR percent changes significantly increased in subgroups with baseline eGFR 30-90 mL/min/1.73 m2, glycated hemoglobin (HbA1c) ≥ 7 at baseline, no hypertension history, T2DM duration > 5 years, or previous statin therapy. Lipid profiles were improved and remained stable throughout the study, and interestingly, fasting glucose and HbA1c were improved at 24 weeks. CONCLUSION: Our findings suggest that pravastatin may have potential benefits for improving eGFR in Korean patients with dyslipidemia and T2DM. This could make it a preferable treatment option for patients with reduced kidney function. TRIAL REGISTRATION NUMBER: NCT05107063 submitted October 27, 2021.

Major cardiovascular events in long-term multiple myeloma survivors: a Korean case-control study (the CAREMM-2105 study).

PURPOSE: Despite improvements in multiple myeloma (MM) survival rates, data on cardiovascular outcomes in long-term survivors remain lacking. METHODS: This retrospective case-control study utilized the Korean National Health Insurance Service database (2009-2020) to compare the incidence of cardiovascular disease (CVD) between patients with MM and a matched control group, focusing on long-term (> 5 years) survivors. A preliminary case cohort (n = 15,402 patients with MM) and a matched control cohort (n = 123,216 patients without MM) were established based on birth year and sex. Following 1:1 propensity score matching, the final matched cohorts each comprised 15,402 participants. RESULTS: The case and control cohorts were comparable in mean age (66.2 ± 11.5 years vs. 66.1 ± 11.3 years), sex, age distribution, and comorbidities. By the 8-year follow-up, the cumulative incidence of CV events (12.5% vs. 22.1%) and CVD risk were significantly lower in the case cohort. The 5-year landmark analysis revealed significant differences in CVD incidence between the cohorts (7.8% [case cohort] vs. 9.8% [control cohort]), with variations across age groups and sex, highlighting a significantly higher CVD risk among patients aged < 50 years in the case cohort (P < 0.001). CONCLUSIONS: These findings underscore the need for vigilant CVD monitoring in MM long-term survivors, particularly those aged < 50 years at first diagnosis. IMPLICATION FOR CANCER SURVIVORS: This study highlights the importance of integrating cardiovascular monitoring and risk management into long-term care for MM survivors, with a focus on younger patients and personalized interventions.

Bone Loss after Solid Organ Transplantation: A Review of Organ-Specific Considerations.

This review article investigates solid organ transplantation-induced osteoporosis, a critical yet often overlooked issue, emphasizing its significance in post-transplant care. The initial sections provide a comprehensive understanding of the prevalence and multifactorial pathogenesis of transplantation osteoporosis, including factors such as deteriorating post-transplantation health, hormonal changes, and the impact of immunosuppressive medications. Furthermore, the review is dedicated to organ-specific considerations in transplantation osteoporosis, with separate analyses for kidney, liver, heart, and lung transplantations. Each section elucidates the unique challenges and management strategies pertinent to transplantation osteoporosis in relation to each organ type, highlighting the necessity of an organ-specific approach to fully understand the diverse manifestations and implications of transplantation osteoporosis. This review underscores the importance of this topic in transplant medicine, aiming to enhance awareness and knowledge among clinicians and researchers. By comprehensively examining transplantation osteoporosis, this study contributes to the development of improved management and care strategies, ultimately leading to improved patient outcomes in this vulnerable group. This detailed review serves as an essential resource for those involved in the complex multidisciplinary care of transplant recipients.

Cardiorenal outcomes and mortality after sodium-glucose cotransporter-2 inhibitor initiation in type 2 diabetes patients with percutaneous coronary intervention history.

AIMS: To evaluate the effects of initiating sodium-glucose cotransporter-2 (SGLT2) inhibitors on cardiorenal outcomes and mortality compared to dipeptidyl peptidase-4 (DPP-4) inhibitors as active comparators in patients diagnosed with type 2 diabetes with a history of percutaneous coronary intervention (PCI). MATERIALS AND METHODS: We used an active-comparator, new-user design and nationwide data from the National Health Insurance Service in South Korea from 2014 to 2019. Of the 56 392 patients who underwent PCI, 4610 new SGLT2 inhibitor users were paired 1:1 with DPP-4 inhibitor users for analysis using propensity-score matching. RESULTS: During 13 708.59 person-years of follow-up, the initiation of SGLT2 inhibitors, compared with the initiation of DPP-4 inhibitors, was associated with a significantly lower risk of composite repeat revascularization, myocardial infarction, stroke, heart failure (HF), all-cause death and end-stage renal disease (ESRD). The beneficial effects of SGLT2 inhibitor use were consistent with the components of stroke, HF, all-cause death and ESRD. In the cohort that included health examination data, including anthropometric and metabolic factors, new use of SGLT2 inhibitors was associated with a significantly lower risk of HF (hazard ratio [HR] 0.574, 95% confidence interval [CI] 0.36-0.915), all-cause death (HR 0.731, 95% CI 0.567-0.942), and ESRD (HR 0.076, 95% CI 0.018-0.319). The effects of SGLT2 inhibitor use were consistent regardless of the timing of the previous PCI. CONCLUSIONS: The initiation of SGLT2 inhibitors in patients with type 2 diabetes and a history of PCI was significantly associated with a reduced risk of cardiorenal consequences and mortality, irrespective of time since the last PCI.

Cost-consequence analysis of continuous denosumab therapy for osteoporosis treatment in South Korea.

BACKGROUND: Insurance reimbursement provisions in South Korea limit osteoporosis medication availability for patients with T-scores exceeding - 2.5. This study aimed to evaluate the financial impact and fracture prevention of continuous denosumab therapy until a T-score>-2.0 (Dmab-C strategy), versus discontinuation of denosumab after reaching T-score>-2.5 (Dmab-D strategy) in osteoporosis patients. METHODS: A cost-consequence analysis from a Korean healthcare system perspective was performed using a newly developed Markov model. The incidence of vertebral and non-vertebral fracture, fracture-related deaths, drug costs, and fracture-treatment costs were estimated and compared between Dmab-C and Dmab-D strategy over a lifetime in eligible patients aged 55 years. RESULTS: Base-case analysis revealed that Dmab-C prevented 32.21 vertebral fracture (VF) and 12.43 non-VF events per 100 patients over a lifetime, while reducing 1.29 fracture-related deaths. Lifetime direct healthcare cost saving per patient was KRW 1,354,655 if Dmab-C replaces Dmab-D. When productivity losses were considered, Dmab-C saved KRW 29,025,949 per patient compared to Dmab-D. The additional treatment costs of Dmab-C could be offset by the higher subsequent treatment costs and fracture treatment costs of Dmab-D. The sensitivity analysis showed consistent patterns with results of the base-case analysis. CONCLUSION: Continuous treatment using denosumab until osteoporosis patients achieve and maintain a T-score of -2.0 would provide greater clinical and economic benefits in terms of fracture prevention and reduced mortality risks compared to outcomes from discontinuing treatment at a T-score of -2.5 or above. This new treatment strategy would effectively lower the risk of fractures and fracture-related mortality, ultimately leading to lower medical expenses.

Weight change in patients with new-onset type 2 diabetes mellitus and its association with remission: Comprehensive real-world data.

AIMS: We aimed to investigate weight change in patients with new-onset type 2 diabetes mellitus and the association of weight loss on diabetes remission in Korean adults. MATERIALS AND METHODS: We used the health examination database of the Korean National Health Insurance Service. Patients diagnosed with type 2 diabetes mellitus from 2009 to 2012 were enrolled and followed to 2017. The baseline body weight was measured at the health examination closest to the time the patient was enrolled, and the change was calculated by examining the weight measured at the subsequent examination within 2 years. Remission was defined as fasting blood glucose less than 126 mg/dl at two or more consecutive health examinations after stopping medication. RESULTS: In total, 114, 874 patients with new-onset type 2 diabetes mellitus were analysed. Of these, 23 156 (20.2%) lost more than 5% of their body weight, and 2429 (2.1%) achieved remission. The adjusted odds ratio for remission in the weight loss group was 2.56 (95% confidence interval 2.35-2.79) compared with the group with stable body weight. Sensitivity analysis according to the degree of weight change showed that the greater weight loss, the higher the likelihood of remission. In the subgroup analysis, the effects of weight loss on remission were significantly greater in subgroups of age <65 years, male sex and body mass index >25. CONCLUSION: Weight loss within the first 2 years of treating type 2 diabetes mellitus was associated with diabetes remission. Physicians should pay more attention to weight management in new-onset type 2 diabetes mellitus, particularly for young and obese individuals.

Repeated detection of non-alcoholic fatty liver disease increases the incidence risk of type 2 diabetes in young adults.

AIM: This study aimed to investigate the effects of repeated detection of non-alcoholic fatty liver disease (NAFLD) on the incidence risk of type 2 diabetes in young adults. MATERIALS AND METHODS: In this nationwide population-based observational study using data from the Korean National Health Insurance Service, approximately 1 125 015 young adults aged 20-39 years who underwent health screening four times between 2009 and 2013 were included. NAFLD was defined as a fatty liver index (FLI) of ≥60. Repeated detection of NAFLD scores was defined as the number of times the participants met the criteria for NAFLD (0-4). To account for the degree of repeated detection of NAFLD, weighted repeated NAFLD scores were scaled as a sum by assigning points (0 points for FLI <30, 1 point for 30 ≤ FLI < 60, and 2 points for FLI ≥60) ranging from 0 to 8 points. RESULTS: The multivariable-adjusted hazard ratios of type 2 diabetes associated with repeated detection of NAFLD scores of 1, 2, 3 and 4 were 2.74 (95% confidence interval 2.57-2.921), 3.45 (3.221-3.694), 4.588 (4.303-4.892) and 6.126 (5.77-6.504), respectively. The incidence risk of type 2 diabetes increased significantly with repeated detection of the NAFLD score. In the analysis of the weighted repeated NAFLD score, the hazard ratios for the incidence of type 2 diabetes showed a significant continuous positive linear association with increasing scores. CONCLUSIONS: Repeated detection of NAFLD influenced the incidence risk of type 2 diabetes in young adults, and a higher degree of repeated detection of NAFLD was independently associated with the risk of type 2 diabetes in young adults.

Associations between body composition and the risk of fracture according to bone mineral density in postmenopausal women: a population-based database cohort study.

OBJECTIVE: We aimed to investigate the associations of body composition and the risk of fracture in postmenopausal women, stratified based on bone mineral density. METHODS: A population-based cohort study using the database of the National Screening Program for Transitional Ages with women aged 66 years was performed. Bone mineral density was categorized as normal, osteopenia, and osteoporosis. The following body mass index (BMI) categories for general obesity were used: underweight (<18.5), normal (18.5-22.9), overweight (23-24.9), obese (25-29.9), and severely obese (≥30 kg/m2). Waist circumference (WC) used for central obesity assessment was categorized into 5 groups. Newly diagnosed fracture during the follow-up period defined based on ICD-10 codes was the primary outcome. RESULTS: During 7.7 ± 1.4 years of follow-up, 41 672 (17.9%) participants experienced any fracture, 20 326 (8.7%) experienced vertebral fractures (VFs), and 2883 (1.2%) experienced hip fractures (HFs). The adjusted hazard ratios (aHRs) for any fracture showed a progressive increase with higher BMI and WC categories in individual with osteopenia and osteoporosis. Regarding VF, aHR was highest in severely obese individuals with osteoporosis (aHR [95% CI], 3.45 [2.99-3.97]) and in individuals with WC ≥ 95 cm with osteoporosis (4.79 [4.09-5.60]). The aHR [95% CI] for HF was highest in the underweight group with osteopenia (1.94 [1.16-3.27]) and osteoporosis (2.96 [2.15-4.10]). In central obesity individuals with WC ≥ 95 cm, aHR [95% CI] for HF was 2.80 [1.91-4.91]. CONCLUSIONS: General obesity and central obesity are not protective against any fracture, VF and HF in postmenopausal women with osteopenia or osteoporosis.

Effect of Denosumab on Bone Density in Postmenopausal Osteoporosis: A Comparison with and without Calcium Supplementation in Patients on Standard Diets in Korea.

The side effects and safety issues tied to calcium supplementation raise questions about its necessity in osteoporosis treatment. We retrospectively evaluated 189 postmenopausal osteoporosis patients treated with denosumab for 12 months. Patients exhibited neither renal dysfunction nor compromised general dietary intake. Patients were divided into three groups as follows: group A, weekly vitamin D 7000 IU; group B, daily vitamin D 1000 IU with elemental calcium 100 mg; and group C, daily vitamin D 1000 IU with elemental calcium 500 mg. All groups showed significant increases in bone density: +6.4 ± 4.7% for the lumbar spine, +2.2 ± 3.5% for the femoral neck, and +2.4 ± 3.8% for the total hip in group A; +7.0 ± 10.9% for the lumbar spine, +2.3 ± 5.2% for the femoral neck, and +2.4 ± 3.8% for the total hip in group B; and + 6.7 ± 8.7% for the lumbar spine, +2.5 ± 8.4% for the femoral neck, and +2.3 ± 4.0% for the total hip in group C. Serum calcium levels increased over time in all three groups with no significant difference. Changes in CTX and P1NP levels did not differ between the groups (all p > 0.05). With regular dietary intake, calcium supplementation levels showed no significant effect on bone density, bone marker changes, or hypocalcemia incidence during denosumab treatment.

Bone-modifying agents for non-small-cell lung cancer patients with bone metastases during the era of immune checkpoint inhibitors: A narrative review.

During the course of lung cancer progression, bone metastases occur in about 40% of patients. Common complications associated with bone metastases in lung cancer patients include musculoskeletal pain, pathologic fractures, spinal cord compression, and hypercalcemia. We discuss the efficacy of bone-modifying agents (BMAs) in reducing skeletal-related events (SREs) and improving cancer-related outcomes, particularly in patients with stage IV non-small-cell lung cancer with bone metastases. In addition, the combined effects of BMAs with radiotherapy or immunotherapy in reducing SREs in patients with lung cancer and bone metastases are explored.

Physical activity and reduced risk of fracture in thyroid cancer patients after thyroidectomy - a nationwide cohort study.

Objectives: Levothyroxine suppressive therapy following thyroidectomy for thyroid cancer patients is considered as a risk factor for osteoporosis and fragility fractures. We evaluated the association of regular exercise and exercise habit change with fracture risk in adults older than 40 years who underwent thyroidectomy for thyroid cancer. Methods: We enrolled the patients who underwent thyroidectomy for thyroid cancer older than 40 years between 2010 and 2016 from the Korean National Health Insurance Service data, and they were followed through 2019. Based on the questionnaire of health examination within 2 years before and after surgery, whether regular exercise once a week was evaluated. The reference group for the statistical analysis was the continuing lack of physical activity group that did not exercise before or after surgery. For fractures newly diagnosed during the follow-up period, univariate and multivariate Cox regression analyses were performed for risk evaluation. Results: We evaluated 74,774 subjects, of whom 2,924 (3.9%) experienced any fractures during a median follow-up of 4.5 years. Compared with the group consistently lack of physical activity, the group that exercised before and after surgery showed a significant decrease in the risk of any fracture, vertebral fracture, and hip fracture: adjusted hazard ratio 0.848 (95% Confidence Interval 0.771-0.932), 0.703 (0.591-0.836), and 0.405 (0.224-0.732), respectively. For vertebral fracture, a significant reduction in fracture risk was confirmed even in patients who started their regular exercise after surgery: adjusted hazard ratio 0.779 (0.648-0.936). The risk reduction for vertebral fractures upon the initiation of exercise was found to be significant in the high-risk groups of patients: women and total thyroidectomy patients. Conclusion: We suggest that maintaining or starting regular exercise after surgery may help prevent fractures in thyroid cancer patients older than 40 years who have undergone thyroidectomy.

Optimal LDL cholesterol levels in young and old patients with type 2 diabetes for secondary prevention of cardiovascular diseases are different.

Objective: Real-world-based population data about the optimal low-density lipoprotein cholesterol (LDL-C) level for preventing cardiovascular disease in very high-risk populations is scarce. Methods: From 2009 to 2012, 26,922 people aged ≥ 40 years with type 2 diabetes mellitus (T2DM) who had a history of percutaneous coronary intervention (PCI) were analyzed. Data from the Korean National Health Insurance System were used. They were followed up to the date of a cardiovascular event or the time to death, or until December 31, 2018. Endpoints were recurrent PCI, newly stroke or heart failure, cardiovascular death, and all-cause death. Participants were divided into the following categories according to LDL-C level: <55 mg/dL, 55-69 mg/dL, 70-99 mg/dL, 100-129 mg/dL, 130-159 mg/dL, and ≥ 160 mg/dL. Results: Compared to LDL-C < 55 mg/dL, the hazard ratios (HR) for re-PCI and stroke increased linearly with increasing LDL-C level in the population < 65 years. However, in ≥ 65 years old, HRs for re-PCI and stroke in LDL-C = 55-69 mg/dL were 0.97 (95% CI: 0.85-1.11) and 0.96 (95% CI: 0.79-2.23), respectively. The optimal range with the lowest HR for heart failure and all-cause mortality were LDL-C = 70-99 mg/dL and LDL-C = 55-69 mg/dL, respectively, in all age groups (HR: 0.99, 95% CI: 0.91-1.08 and HR: 0.91, 95% CI: 0.81-1.01). Conclusion: LDL-C level below 55 mg/dL appears to be optimal in T2DM patients with established cardiovascular disease aged < 65 years, while an LDL-C level of 55-69 mg/dL may be optimal for preventing recurrent PCI and stroke in patients over 65 years old.

Effects of Bazedoxifene/Vitamin D Combination Therapy on Serum Vitamin D Levels and Bone Turnover Markers in Postmenopausal Women with Osteopenia: A Randomized Controlled Trial.

BACKGROUND: This study aimed to evaluate the effectiveness of bazedoxifene/vitamin D combination therapy in preventing osteoporosis in postmenopausal women with osteopenia. METHODS: This was an open-label, multicenter randomized-controlled, phase 4 clinical trial. Women between ages of 55 and 70 years in 9 medical tertiary centers in Korea were enrolled and assigned into 2 groups: an experiment group and a control group. The experimental group received bazedoxifene 20 mg/vitamin D 800 IU tablets for 6 months, and the control group received calcium 100 mg/vitamin D 1,000 IU tablets for 6 months. RESULTS: A total of 142 patients (70 in the experimental group and 72 in the control group) were included. The least-square mean±standard error of change in propeptide of type I collagen after 3 months was -6.87±2.56% in the experimental group and 1.22±2.54% in the control group. After 6 months, it was -21.07±2.75% in the experimental group and 1.26±2.71% in the control group. The difference between the 2 groups was -22.33% (p<0.01). The change of C-terminal telopeptide was -12.55±4.05% in the experimental group and 11.02±4.03% in the control group after 3 months. It was -22.0±3.95% and 10.20±3.89, respectively, after 6 months. The difference between the 2 groups was -32.21% (p<0.01) after 6 months. There was no significant difference in adverse events between the 2 groups. CONCLUSIONS: The osteoporosis preventive effect and safety of administering bazedoxifene/vitamin D combination pill were confirmed in postmenopausal women who needed osteoporosis prevention.