Adenosine washing improves the retention rate of fat grafts under conditions of obesity

Background@#Fat grafting is a commonly employed aesthetic procedure for contour enhancement. However, outcome prediction is challenging due to the complex regeneration and remodeling processes involved. We investigated whether adenosine improves engraftment and fat graft survival under conditions of obesity. @*Methods@#Fat was harvested from mice fed a high-fat diet. This fat was washed with either Krebs-Ringer bicarbonate HEPES buffer (the vehicle group) or a buffer containing 500 nM adenosine (the adenosine wash group). Subsequently, the fat was transplanted into normal mice at 0.2 mL per mouse. In both groups, 50% of the mice were sacrificed at 1 week and the remainder at 4 weeks post-transplantation. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis was conducted during week 1. In week 4, micro-computed tomography, immunofluorescence staining, and RT-qPCR were performed. A sample of the initially harvested fat was set aside for lipolysis assay. @*Results@#Adenosine washing improved fat graft retention volumes by up to 50%. One week post-transplantation, the expression of adipogenic and angiogenic genes was found to be upregulated in the adenosine wash group. After 4 weeks, immunofluorescence staining revealed greater adipocyte integrity and an increased number of vessels. Furthermore, adenosine appeared to modulate inflammation by stabilizing the lipolysis rate. @*Conclusions@#Adenosine washing increased the fat graft survival rate under conditions of obesity. Clinically, this suggests a simple, cost-effective adjuvant method for improving fat graft survival in individuals with obesity. Further research is warranted to elucidate the underlying mechanisms and explore the applicability of this technique for autologous transplantation.

Impact of COVID-19 on the Incidence of Fragility Fracture in South Korea

Background@#The coronavirus disease 2019 (COVID-19) pandemic and the consequent social distancing period are thought to have influenced the incidence of osteoporotic fracture in various ways, but the exact changes have not yet been well elucidated. The purpose of this study was to investigate the impact of the COVID-19 pandemic on the incidence of osteoporotic fracture using a nationwide cohort. @*Methods@#The monthly incidence rates of vertebral; hip; and non-vertebral, non-hip fractures were collected from a nationwide database of the Korean National Health Insurance Review and Assessment from July 2016 to June 2021. Segmented regression models were used to assess the change in levels and trends in the monthly incidence of osteoporotic fractures. @*Results@#There was a step decrease in the incidence of vertebral fractures for both males (6.181 per 100,000, P=0.002) and females (19.299 per 100,000, P=0.006). However, there was a negative trend in the incidence of hip fracture among both males (-0.023 per 100,000 per month, P=0.023) and females (-0.032 per 100,000 per month, P=0.019). No impact of COVID-19-related social distancing was noted. @*Conclusions@#In conclusion, during the early days of the COVID-19 pandemic, vertebral fracture incidence considerably decreased with the implementation of social distancing measures.

Higher Plasma Stromal Cell-Derived Factor 1 Is Associated with Lower Risk for Sarcopenia in Older Asian Adults

Background@#Despite the protective effects of stromal cell-derived factor 1 (SDF-1) in stimulating muscle regeneration shown in experimental research, there is a lack of clinical studies linking circulating SDF-1 concentrations with muscle phenotypes. In order to elucidate the role of SDF-1 as a potential biomarker reflecting human muscle health, we investigated the association of plasma SDF-1 levels with sarcopenia in older adults. @*Methods@#This cross-sectional study included 97 community-dwelling participants who underwent a comprehensive geriatric assessment at a tertiary hospital in South Korea. Sarcopenia was defined by specific cutoff values applicable to the Asian population, whereas plasma SDF-1 levels were determined using an enzyme immunoassay. @*Results@#After accounting for sex, age, and body mass index, participants with sarcopenia and low muscle mass exhibited plasma SDF-1 levels that were 21.8% and 18.3% lower than those without these conditions, respectively (P=0.008 and P=0.009, respectively). Consistently, higher plasma SDF-1 levels exhibited a significant correlation with higher skeletal muscle mass index (SMI) and gait speed (both P=0.043), and the risk of sarcopenia and low muscle mass decreased by 58% and 55% per standard deviation increase in plasma SDF-1 levels, respectively (P=0.045 and P=0.030, respectively). Furthermore, participants in the highest SDF-1 tertile exhibited significantly higher SMI compared to those in the lowest tertile (P=0.012). @*Conclusion@#These findings clinically corroborate earlier experimental discoveries highlighting the muscle anabolic effects of SDF- 1 and support the potential role of circulating SDF-1 as a biomarker reflecting human muscle health in older adults.

Decreased Serum Level of Sclerostin in Older Adults with Sarcopenia

Background@#Although muscles and bones interact with each other through various secretory factors, the role of sclerostin, an osteocyte-secreted factor, on muscle metabolism has not been well studied. We investigated the levels of serum sclerostin in Korean older adults with sarcopenia. @*Methods@#Blood samples were collected from 129 participants who underwent evaluation of muscle mass and function in an outpatient geriatric clinic of a teaching hospital. Sarcopenia and related parameters were determined using cutoff values for the Asian population. Serum sclerostin levels were measured using an enzyme-linked immunosorbent assay. @*Results@#The mean age of the participants was 69.6 years, and 20 participants (15.5%) were classified as having sarcopenia. After adjusting for age, sex, and body mass index, serum sclerostin levels were significantly lower in participants with sarcopenia, low muscle mass, or weak muscle strength (P=0.003 to 0.045). Serum sclerostin levels were positively associated with skeletal muscle index and grip strength after adjusting for confounders (P=0.001 and P=0.003), whereas sarcopenic phenotype score showed a negative association (P=0.006). These increases in muscle mass and strength were also dose dependent as serum sclerostin levels increased (P for trends=0.003 and P for trends=0.015). Higher serum sclerostin levels were associated with lower odds ratio (ORs) for sarcopenia, low muscle mass, and weak muscle strength after adjusting for confounders (OR, 0.27 to 0.50; P<0.001 to 0.025). @*Conclusion@#Higher serum sclerostin levels were associated with a lower risk of sarcopenia, low muscle mass, and weak muscle strength in Korean older adults.

Benefits of lumican on human bone health: clinical evidence using bone marrow aspirates

Background/Aims@#Lumican, a small leucine-rich proteoglycan, has shown osteoprotective effects by synchronously stimulating bone formation and suppressing bone resorption. To clarify the role of lumican in human bone metabolism, the association between lumican concentrations and osteoporosis-related phenotypes was evaluated using bone marrow (BM) samples directly reflecting local microenvironments. @*Methods@#BM aspirates were obtained from 77 patients during hip surgery for either fragility hip fractures (HF) (n = 29) or osteoarthritis (n = 48) and centrifuged. Concentrations of lumican and biochemical bone markers in BM supernatants were measured using enzyme linked immunosorbent assays. @*Results@#After considering confounders, lumican concentrations in BM supernatants were 16.9% lower in patients with HF than in controls, with each increase in the standard deviation of lumican concentration being associated with a 61% lower likelihood of HF. The odds ratios for HF decreased linearly with increasing lumican tertiles in BM, with the odds of having fragility HF markedly lower in participants in the highest than in the lowest lumican tertile. Higher lumican level correlated significantly with higher femur neck bone mineral density and higher bone-specific alkaline phosphatase levels, but not with tartrate-resistant acid phosphatase 5b concentrations, in BM supernatants. @*Conclusions@#These data clinically validate previous in vitro and animal experiments showing the beneficial roles of lumican for bone homeostasis and suggest that lumican may contribute to a reduction in fracture risk in humans mainly through its stimulation of bone formation.

Effect of CCL11 on In Vitro Myogenesis and Its Clinical Relevance for Sarcopenia in Older Adults

Background@#The C-C motif chemokine ligand 11 (CCL11) has been receiving attention as a potential pro-aging factor. Accordingly, it may be involved in muscle metabolism and sarcopenia, a key component of aging phenotypes. To clarify this potential, we investigated the effects of CCL11 on in vitro muscle biology and its clinical relevance for sarcopenia parameters in older adults. @*Methods@#Myogenesis was induced in mouse C2C12 myoblasts with 2% horse serum. Human blood samples were collected from 79 participants who underwent a functional assessment. Thereafter, CCL11 level was measured using a quantikine ELISA kit. Sarcopenia was defined using the Asian-specific guideline. @*Results@#Recombinant CCL11 treatment significantly stimulated myogenesis in a dose-dependent manner, and consistently increased the expression of myogenic differentiation markers. Among the C-C chemokine receptors (CCRs), CCR5, not CCR2 and CCR3, was predominantly expressed in muscle cells. Further, the CCR5 inhibitor blocked recombinant CCL11-stimulated myogenesis. In a clinical study, serum CCL11 level was not significantly different according to the status of sarcopenia, low muscle mass, weak muscle strength, and poor physical performance, and was not associated with skeletal muscle index, grip strength, short physical performance battery score, gait speed, and time to complete 5 chair stands, after adjusting for sex, age, and body mass index. @*Conclusion@#Contrary to expectations, CCL11 exerted beneficial effects on muscle metabolism at least in vitro system. However, its impact on human muscle health was not evident, suggesting that circulating CCL11 may not be a useful biomarker for sarcopenia risk assessment in older adults.

Aldosterone Inhibits In Vitro Myogenesis by Increasing Intracellular Oxidative Stress via Mineralocorticoid Receptor

Background@#Despite clinical evidence indicating poor muscle health in subjects with primary aldosteronism (PA), it is still unclear whether the role of aldosterone in muscle metabolism is direct or mediated indirectly via factors, such as electrolyte imbalance or impaired glucose uptake. As one approach to clarify this issue, we investigated the effect of aldosterone on in vitro myogenesis and the potential mechanism explaining it. @*Methods@#Myogenesis was induced in mouse C2C12 myoblasts with 2% horse serum. Immunofluorescence, quantitative reversetranscription polymerase chain reaction, Western blot, viability, and migration analyses were performed for experimental research. @*Results@#Recombinant aldosterone treatment suppressed muscle differentiation from mouse C2C12 myoblasts in a dose-dependent manner, and consistently reduced the expression of myogenic differentiation markers. Furthermore, aldosterone significantly increased intracellular reactive oxygen species (ROS) levels in myotubes, and treatment with N-acetyl cysteine, a potent biological thiol antioxidant, reversed the decrease of myotube area, myotube area per myotube, nucleus number per myotube, and fusion index due to aldosterone through decreasing oxidative stress. A binding enzyme-linked immunosorbent assay confirmed that mineralocorticoid receptor (MR) interacted with aldosterone in C2C12 myoblasts, while eplerenone, an MR inhibitor, blocked aldosterone-stimulated intracellular ROS generation during myogenesis and markedly attenuated the suppression of in vitro myogenesis by aldosterone. @*Conclusion@#These findings support the hypothesis that hypersecretion of aldosterone, like PA, directly contributes to muscular deterioration and suggest that antioxidants and/or MR antagonists could be effective therapeutic options to reduce the risk of sarcopenia in these patients.

Effect of CCL11 on In Vitro Myogenesis and Its Clinical Relevance for Sarcopenia in Older Adults

Background@#The C-C motif chemokine ligand 11 (CCL11) has been receiving attention as a potential pro-aging factor. Accordingly, it may be involved in muscle metabolism and sarcopenia, a key component of aging phenotypes. To clarify this potential, we investigated the effects of CCL11 on in vitro muscle biology and its clinical relevance for sarcopenia parameters in older adults. @*Methods@#Myogenesis was induced in mouse C2C12 myoblasts with 2% horse serum. Human blood samples were collected from 79 participants who underwent a functional assessment. Thereafter, CCL11 level was measured using a quantikine ELISA kit. Sarcopenia was defined using the Asian-specific guideline. @*Results@#Recombinant CCL11 treatment significantly stimulated myogenesis in a dose-dependent manner, and consistently increased the expression of myogenic differentiation markers. Among the C-C chemokine receptors (CCRs), CCR5, not CCR2 and CCR3, was predominantly expressed in muscle cells. Further, the CCR5 inhibitor blocked recombinant CCL11-stimulated myogenesis. In a clinical study, serum CCL11 level was not significantly different according to the status of sarcopenia, low muscle mass, weak muscle strength, and poor physical performance, and was not associated with skeletal muscle index, grip strength, short physical performance battery score, gait speed, and time to complete 5 chair stands, after adjusting for sex, age, and body mass index. @*Conclusion@#Contrary to expectations, CCL11 exerted beneficial effects on muscle metabolism at least in vitro system. However, its impact on human muscle health was not evident, suggesting that circulating CCL11 may not be a useful biomarker for sarcopenia risk assessment in older adults.

Aldosterone Inhibits In Vitro Myogenesis by Increasing Intracellular Oxidative Stress via Mineralocorticoid Receptor

Background@#Despite clinical evidence indicating poor muscle health in subjects with primary aldosteronism (PA), it is still unclear whether the role of aldosterone in muscle metabolism is direct or mediated indirectly via factors, such as electrolyte imbalance or impaired glucose uptake. As one approach to clarify this issue, we investigated the effect of aldosterone on in vitro myogenesis and the potential mechanism explaining it. @*Methods@#Myogenesis was induced in mouse C2C12 myoblasts with 2% horse serum. Immunofluorescence, quantitative reversetranscription polymerase chain reaction, Western blot, viability, and migration analyses were performed for experimental research. @*Results@#Recombinant aldosterone treatment suppressed muscle differentiation from mouse C2C12 myoblasts in a dose-dependent manner, and consistently reduced the expression of myogenic differentiation markers. Furthermore, aldosterone significantly increased intracellular reactive oxygen species (ROS) levels in myotubes, and treatment with N-acetyl cysteine, a potent biological thiol antioxidant, reversed the decrease of myotube area, myotube area per myotube, nucleus number per myotube, and fusion index due to aldosterone through decreasing oxidative stress. A binding enzyme-linked immunosorbent assay confirmed that mineralocorticoid receptor (MR) interacted with aldosterone in C2C12 myoblasts, while eplerenone, an MR inhibitor, blocked aldosterone-stimulated intracellular ROS generation during myogenesis and markedly attenuated the suppression of in vitro myogenesis by aldosterone. @*Conclusion@#These findings support the hypothesis that hypersecretion of aldosterone, like PA, directly contributes to muscular deterioration and suggest that antioxidants and/or MR antagonists could be effective therapeutic options to reduce the risk of sarcopenia in these patients.

Potential Biomarkers to Improve the Prediction of Osteoporotic Fractures

Osteoporotic fracture (OF) is associated with high disability and morbidity rates. The burden of OF may be reduced by early identification of subjects who are vulnerable to fracture. Although the current fracture risk assessment model includes clinical risk factors (CRFs) and bone mineral density (BMD), its overall ability to identify individuals at high risk for fracture remains suboptimal. Efforts have therefore been made to identify potential biomarkers that can predict the risk of OF, independent of or combined with CRFs and BMD. This review highlights the emerging biomarkers of bone metabolism, including sphongosine-1-phosphate, leucine-rich repeat-containing 17, macrophage migration inhibitory factor, sclerostin, receptor activator of nuclear factor-κB ligand, and periostin, and the importance of biomarker risk score, generated by combining these markers, in enhancing the accuracy of fracture prediction.

Long-term Prognosis of Patients with Alopecia Areata Treated with Diphenylcyclopropenone / 대한피부과학회지

No abstract available.

Hereditary Papulotranslucent Acrokeratoderma: Prominent Clinical Presentation after Water Exposure

No abstract available.

Quality of Life with Alopecia Areata versus Androgenetic Alopecia Assessed Using Hair Specific Skindex-29

No abstract available.

Characteristics of Adrenal Incidentalomas in a Large, Prospective Computed Tomography-Based Multicenter Study: The COAR Study in Korea

PURPOSE: Previous studies on adrenal incidentalomas (AIs) are limited by their retrospective design, small numbers of patients, Western populations, or use of an outdated imaging technique. We investigated the characteristics of AIs in Korean patients and compared them with those reported in the largest retrospective study in Italy to discover the effects of improved imaging techniques and ethnicity differences. MATERIALS AND METHODS: This was a prospective, multicenter, cross-sectional observational study including 1005 Korean patients. Levels of plasma adrenocorticotrophic hormone, 24-h urinary free cortisol (UFC), serum cortisol after a 1 mg-dexamethasone suppression test, 24-h urinary fractionated metanephrine, and plasma aldosterone and plasma renin activity were measured. All AIs were characterized using computed tomography (CT). RESULTS: Compared with the results of the Italian study, AIs in Korean patients were observed more frequently in men and predominantly on the left side. Korean patients with AIs were slightly younger, and fewer patients underwent surgery. Most AIs were nonfunctional in both studies, while fewer subclinical hypercortisolism and more primary aldosteronism (PA) cases were detected in Korean patients. In our study, high UFC levels showed very low sensitivity, compared to those in the Italian study. In pheochromocytoma or PA cases, there were no hormonal differences between the studies. AIs in Korean patients were smaller, such that a lower cutoff size for detecting adrenocortical carcinoma (ACC) could be warranted. CONCLUSION: Recent advances in CT technology were leveraged to provide accurate characteristics of AIs and to detect smaller ACCs.

Bone Health in Adrenal Disorders

Secondary osteoporosis resulting from specific clinical disorders may be potentially reversible, and thus continuous efforts to find and adequately treat the secondary causes of skeletal fragility are critical to ameliorate fracture risk and to avoid unnecessary treatment with anti-osteoporotic drugs. Among the hyperfunctional adrenal masses, Cushing's syndrome, pheochromocytoma, and primary aldosteronism are receiving particularly great attention due to their high morbidity and mortality mainly by increasing cardiovascular risk. Interestingly, there is accumulating experimental and clinical evidence that adrenal hormones may have direct detrimental effects on bone metabolism as well. Thus, the present review discusses the possibility of adrenal disorders, especially focusing on pheochromocytoma and primary aldosteronism, as secondary causes of osteoporosis.

Korean Society for Bone and Mineral Research Task Force Report: Perspectives on Intermittent High-dose Vitamin D Supplementation

An adequate supply of vitamin D is considered necessary for osteoporosis management and fracture prevention. Intermittent high-dose vitamin D supplementation is an effective and convenient way to achieve and maintain sufficient vitamin D status. However, the long-term effectiveness of supplementation for preventing falls and fractures is unclear, and some deleterious effects of such treatments have been reported. Concerning these issues, the Korean Society for Bone and Mineral Research task force team reviewed previous clinical trials and provided the following perspectives based on current evidence: 1) An adequate supply of vitamin D is necessary for preventing falls and fractures in postmenopausal women and men older than 50 years. An oral intake of 800 to 1,000 IU/day of vitamin D is generally recommended. 2) Care should be taken concerning the routine use of intermittent high-dose vitamin D, as large-scale clinical trials showed increased risk of falls or fractures after high-dose vitamin D administration. Intermittent high-dose vitamin D supplementation is recommendable only in cases of malabsorption or when oral administration is not suitable. 3) Monitoring of the serum level of 25-hydroxy-vitamin D (25[OH]D) is advisable, especially when intermittent high-dose vitamin D is used for supplementation. The task force team suggests that a serum 25(OH)D level of >20 ng/mL is generally appropriate for the prevention of osteoporosis, and that a serum 25(OH)D level of >30 ng/mL is probably helpful both for the management of osteoporosis and the prevention of fractures and falls. However, serum 25(OH)D level >50 ng/mL (this value can vary depending on the measurement method used) is unnecessary and may be undesirable. These perspectives are relevant for the management of osteoporosis, falls, or fractures. Other metabolic bone diseases or non-skeletal disorders are not within the scope of these perspectives.

The Association of Higher Plasma Macrophage Migration Inhibitory Factor Levels with Lower Bone Mineral Density and Higher Bone Turnover Rate in Postmenopausal Women

BACKGROUND: Despite evidence from animal and clinical studies showing the detrimental effects of macrophage migration inhibitory factor (MIF) on bone metabolism, there are no clinical studies relating circulating MIF levels to osteoporosis-related phenotypes. This cross-sectional study investigated the association of plasma MIF with bone mineral density (BMD), bone turnover markers (BTMs), and prevalence of osteoporosis in postmenopausal Korean women. METHODS: A total of 246 women not taking any medications or diagnosed with any diseases that could affect bone metabolism were enrolled. BMD values at the lumbar spine, femoral neck, and total femur, and blood levels of MIF and BTMs were measured in all subjects. Osteoporosis was defined by World Health Organization criteria. RESULTS: Before and after adjustment for confounding variables, higher MIF levels were significantly associated with lower BMD values at all measured sites and higher levels of all BTMs. All BMD values and BTMs significantly changed in a dose-dependent fashion across increasing MIF quartile. When participants were divided into two groups according to osteoporosis status, postmenopausal women with osteoporosis demonstrated 24.2% higher plasma MIF levels than those without osteoporosis (P=0.041). The odds ratio per each standard deviation increment of MIF levels for prevalent osteoporosis was 1.32 (95% confidence interval, 1.01 to 1.73). CONCLUSION: This study provides the first epidemiological evidence that higher plasma MIF may be associated with higher risk of osteoporosis resulting from lower bone mass and higher bone turnover rate, and thus it could be a potential biomarker of poor bone health outcomes in postmenopausal women.

Replication of Caucasian Loci Associated with Osteoporosis-related Traits in East Asians

BACKGROUND: Most reported genome-wide association studies (GWAS) seeking to identify the loci of osteoporosis-related traits have involved Caucasian populations. We aimed to identify the single nucleotide polymorphisms (SNPs) of osteoporosis-related traits among East Asian populations from the bone mineral density (BMD)-related loci of an earlier GWAS meta-analysis. METHODS: A total of 95 SNPs, identified at the discovery stage of the largest GWAS meta-analysis of BMD, were tested to determine associations with osteoporosis-related traits (BMD, osteoporosis, or fracture) in Korean subjects (n=1,269). The identified SNPs of osteoporosis-related traits in Korean subjects were included in the replication analysis using Chinese (n=2,327) and Japanese (n=768) cohorts. RESULTS: A total of 17 SNPs were associated with low BMD in Korean subjects. Specifically, 9, 6, 9, and 5 SNPs were associated with the presence of osteoporosis, non-vertebral fractures, vertebral fractures, and any fracture, respectively. Collectively, 35 of the 95 SNPs (36.8%) were associated with one or more osteoporosis-related trait in Korean subjects. Of the 35 SNPs, 19 SNPs (54.3%) were also associated with one or more osteoporosis-related traits in East Asian populations. Twelve SNPs were associated with low BMD in the Chinese and Japanese cohorts. Specifically, 3, 4, and 2 SNPs were associated with the presence of hip fractures, vertebral fractures, and any fracture, respectively. CONCLUSIONS: Our results identified the common SNPs of osteoporosis-related traits in both Caucasian and East Asian populations. These SNPs should be further investigated to assess whether they are true genetic markers of osteoporosis.

Association of Bone Marrow Sphingosine 1-phosphate Levels with Osteoporotic Hip Fractures

BACKGROUND: Sphingosine 1-phosphate (S1P) has been discovered to be a critical regulator of bone metabolism. Very recently, we found that higher circulating S1P levels were associated with higher rate of prevalent osteoporotic fracture in human. METHODS: This was a cross-sectional study of 16 patients who underwent hip replacement surgeries. Bone marrow fluids were obtained during hip surgeries, and the S1P levels were measured using a competitive enzyme-linked immunosorbent assay (ELISA) assay. Bone mineral densities (BMDs) at various skeletal sites were obtained using dual energy X-ray absorptiometry. RESULTS: Among 16 patients, 4 patients were undergone operations due to hip fractures, and the others were done by any other causes. Bone marrow S1P levels were significantly lower in patients with hip fractures than in those without, before and after adjusting for confounding factors (P=0.047 and 0.025, respectively). We failed to demonstrate significant associations between bone marrow S1P levels and any BMD values (gamma=0.026-0.482, P=0.171-0.944). CONCLUSIONS: In conjunction with our previous findings, these suggest that the effects of gradient between peripheral blood and bone marrow, but not S1P itself, may be the most critical on bone metabolism.

Response: The Effects of Combination Therapy of Cathepsin K Inhibitor and PTH on Change in Bone Mineral Density in an Animal Model of Osteoporosis

No abstract available.