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.

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.

Site-specific impairment of perivascular adipose tissue on advanced atherosclerotic plaques using multimodal nonlinear optical imaging.

Perivascular adipose tissue (PVAT), as a mechanical support, has been reported to systemically regulate vascular physiology by secreting adipokines and cytokines. How PVAT spatially and locally changes as atherosclerosis progresses is not known, however. We aimed to reveal the molecular changes in PVAT in advanced atherosclerosis based on multimodal nonlinear optical (MNLO) imaging. First, using an atherogenic apolipoprotein E knockout mouse model, we precisely assessed the browning level of thoracic PVAT via a correlative analysis between the size and number of lipid droplets (LDs) of label-free MNLO images. We also biochemically demonstrated the increased level of brown fat markers in the PVAT of atherosclerosis. In the initial stage of atherosclerosis, the PVAT showed a highly activated brown fat feature due to the increased energy expenditure; however, in the advanced stage, only the PVAT in the regions of the atherosclerotic plaques, not that in the nonplaque regions, showed site-specific changes. We found that p-smad2/3 and TGF-ß signaling enhanced the increase in collagen to penetrate the PVAT and the agglomeration of LDs only at the sites of atherosclerotic plaques. Moreover, atherosclerotic thoracic PVAT (tPVAT) was an increased inflammatory response. Taken together, our findings show that PVAT changes differentially from the initial stages to advanced stages of atherosclerosis and undergoes spatial impairment focused on atherosclerotic plaques. Our study may provide insight into the local control of PVAT as a therapeutic target.

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.

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.

Higher cholesterol levels, not statin use, are associated with a lower risk of hepatocellular carcinoma.

We aimed to examine whether statin users have a lower risk of hepatocellular carcinoma (HCC) after careful consideration of prevalent statin use and cholesterol levels. During a mean prospective follow-up of 8.4 years in 400,318 Koreans, 1686 individuals were diagnosed with HCC. When prevalent users were included, HCC risk was reduced by >50% in statin users, regardless of adjustment for total cholesterol (TC). When prevalent users were excluded, new users who initiated statins within 6 months after baseline had a 40% lower risk of HCC (hazard ratio [HR] = 0.59) in a TC-unadjusted analysis. However, this relationship disappeared (HR = 1.16, 95% CI = 0.80-1.69) after adjusting for TC levels measured within 6 months before statin initiation. TC levels had strong inverse associations with HCC in each model. High cholesterol levels at statin initiation, not statin use, were associated with reduced risk of HCC. Our study suggests no protective effect of statins against HCC.

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.

Clinical Manifestations and Factors Associated with Osteosarcopenic Obesity Syndrome: A Cross-Sectional Study in Koreans with Obesity.

Demonstrating the clinical consequences of osteosarcopenic obesity (OSO) is complex. This study evaluated clinical manifestations and factors associated with bone and muscle loss in Koreans with obesity. This cross-sectional observational study enrolled Koreans with obesity aged ≥ 50 years from the Korea National Health and Nutrition Examination Survey. Clinical manifestations were compared among four groups: obesity (O), sarcopenic obesity (SO), osteopenic obesity (OO), and OSO. Factors associated with appendicular skeletal muscle mass (ASM) or bone mineral density (BMD) were evaluated. OSO increases with age in both sexes. Men with SO and OSO had increased cardiometabolic diseases and markers, percentages of body fat (BF %), and trunk fat (TF %), and decreased limb fat percentage (LF %). Women with SO and OSO had increased metabolic markers, BF %, and TF % but those with OSO had increased cardiometabolic diseases and lower LF %. Both sexes with OSO had decreased ASM and vitamin D, and higher vitamin D deficiency. BF % was negatively associated with ASM and femur BMD in both sexes. TF % was negatively and LF % was positively associated with ASM in both sexes and with femur BMD in women. Vitamin D was positively associated with femur BMD in men and with ASM and BMD at all sites in women. ASM and BMD were positively associated with each other. Appendicular muscle loss is metabolically significant regardless of bone loss in men; however, appendicular muscle loss with bone loss is metabolically more significant in women. Regional body composition, fat distribution, and vitamin D deficiency were associated with OSO phenotype in both sexes.

Bisphosphonates Use and Risk of Subtrochanteric and Diaphyseal Femur Fractures in Korea: Results from the National Claim Registry.

Although Asian with bisphosphonate has been considered to have higher risk of subtrochanteric and diaphyseal femur (ST/DF) fractures, the occurrence of those fractures has been still unclear in Asia. The purpose of this study was to investigate the incidence rate of ST/DF fractures among bisphosphonate users from nationwide database in South Korea. Using national health insurance claim database, we only included the bisphosphonate users who took bisphosphonate for the first time in 2008 and evaluated the incidence rate of ST/DF fracture from 2008 to 2013. Non-user controls were matched to bisphosphonate users by propensity score matching with age and gender. Cox regression models were used to calculate hazard ratios of ST/DF fracture with and without adjustment for comorbidity. A total of 682 ST/DF fractures were observed among 348,311 bisphosphonate users. The incidence rate of ST/DF fracture among bisphosphonate users (37.75/100,000 person years, 95% CI 35.02-40.70) was higher compared with non-users (24.41/100,000 person years, 95% CI 22.31-26.71). The risk of ST/DF fracture was greater in bisphosphonate users compared with non-users (hazard ratio 1.541, 1.370-1.734; p < 0.001). The incidence rate of ST/DF fracture after bisphosphonate use could be determined in Korean patients, which can provide basal information for further studies on risk and benefit of continuing bisphosphonate.

A novel PI3K/mTOR dual inhibitor, CMG002, overcomes the chemoresistance in ovarian cancer.

OBJECTIVE: Ovarian cancer is the leading cause of gynecologic-related mortality worldwide. Despite successful initial treatment, overall survival rates are very low because tumors develop resistance to chemotherapeutic drugs. The PI3K/mTOR pathway is a key signaling pathway involved in drug resistance of ovarian cancer cells. The aim of this study was to examine the effect of a newly developed PI3K/mTOR dual inhibitor, CMG002, on chemoresistant ovarian cancer cells. METHODS: We examined the effects of CMG002, and its synergistic effects when combined with paclitaxel or cisplatin, on cell viability, cell cycle arrest, and apoptosis of PTX-resistant SKpac17 or cisplatin-resistant A2780cis ovarian cancer cells in vitro. Western blot analysis was performed to assess expression of PI3K, p-mTOR, p-Akt, p-S6, Bim, and caspase-3. In vivo studies were carried out in a xenograft mouse model, followed by TUNEL and immunohistochemical staining of excised tumor tissue. RESULTS: CMG002 showed marked toxicity against chemoresistant ovarian cancer cells and re-sensitized these cells to chemotherapeutic agents by suppressing cell proliferation and inducing G1 cell cycle arrest and apoptosis. In vivo xenograft studies revealed that treatment with CMG002, either alone or in combination with paclitaxel or cisplatin, led to a marked reduction in tumor growth. CMG002 caused marked suppression of mTOR (Ser2448), Akt (Ser473), Akt (Thr308), and S6 (Ser235/236) phosphorylation, both in vitro and in vivo. CONCLUSION: Taken together, CMG002, a very potent PI3K/mTOR dual inhibitor, induced cytotoxicity in chemoresistant ovarian cancer cells, suggesting that this novel inhibitor might be a new therapeutic strategy for chemoresistant ovarian cancer.

Dehydroabietic Acid Induces Regeneration of Collagen Fibers in Ultraviolet B-Irradiated Human Dermal Fibroblasts and Skin Equivalents.

BACKGROUND/AIMS: Dehydroabietic acid (DAA) is a natural phytochemical found in red pine trees and herbal plants. While DAA and its derivatives are known for improving diabetes and hyperlipidemia, the antiaging effect and its underlying mechanisms of DAA on skin have not been fully examined. Here, we assessed the antiaging effects of DAA on human dermal fibroblasts and skin equivalents. METHODS: We investigated the effect of DAA on the secretion of type I procollagen and matrix metalloproteinase-1 (MMP-1) in ultraviolet B (UVB)-irradiated neonatal normal human dermal fibroblasts (NHDFn). Using nonlinear optical imaging techniques, we visualized quantitative and qualitative changes of collagen fibers by DAA treatment in human skin equivalent models. RESULTS: DAA induces increases in type I procollagen secretion when treated on UVB-irradiated NHDFn. DAA also downregulates secretion of MMP-1 through the inhibition of the JNK signaling pathway. In human skin equivalent models, we successfully visualized the spatial distribution of collagen fibers in the dermis and found that quantity, diameter, and arrangement of collagen fibers in the dermis were significantly improved by DAA treatment. CONCLUSION: Our results suggest that DAA could be a useful agent for improving skin photoaging through the protection and regeneration of collagen fibers in skin.

Changes in bone mineral density and bone turnover markers during treatment with teriparatide in pregnancy- and lactation-associated osteoporosis.

CONTEXT: Teriparatide (TPTD) therapy has been proposed as a potential treatment strategy in severe cases of pregnancy- and lactation-associated osteoporosis (PLO) characterized by the occurrence of fragility fractures in the third trimester or early postpartum. OBJECTIVE: To investigate the changes in bone mineral density (BMD) and bone turnover markers in patients with PLO with and without TPTD treatment. DESIGN: Retrospective cohort study. PATIENTS: Thirty-two patients with PLO who presented with multiple vertebral fractures to a tertiary institution between 2007 and 2015 were included. MEASUREMENTS: Changes in BMD at the lumbar spine (LSBMD) and proximal femur after 12 months of daily subcutaneous injections of 20 µg TPTD (n = 27) were assessed. Subjects who rejected the TPTD treatment were used as controls (n = 5). RESULTS: LSBMD increased in both subjects treated with TPTD and controls, with greater increases in the TPTD group (15.5 ± 6.6% vs 7.5 ± 7.1%, P = .020) after adjustment for age and baseline LSBMD. During follow-up, serum levels of osteocalcin (OCN) and C-telopeptide of type I collagen (CTX) increased significantly in the TPTD group. In multivariate linear regression models, TPTD treatment (adjusted ß = 7.92, P = .032) and younger age (adjusted ß = 1.06, P = .046), but not baseline LSBMD, body mass index, serum OCN level and CTX level, were independently associated with greater increases in LSBMD. CONCLUSIONS: In patients with PLO, LSBMD at 12 months increased in both the TPTD-treated and control groups. TPTD treatment and younger age were associated with greater increases in LSMBD irrespective of baseline LSBMD.

Increased risk of hip fractures in Korean patients with type 2 diabetes: a 6-year nationwide population-based study.

We compared the incidence and risk of hip fractures in Korean patients with type 2 diabetes and non-diabetic subjects in a nationwide population-based study. The study included 17,110 patients diagnosed with type 2 diabetes in 2004 and 34,220 randomly selected age- and sex-matched control subjects drawn from the Korean National Health Insurance Research database. Fracture events occurring between 2004 and 2010 were identified from medical claims data. The adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for fractures associated with diabetes were calculated. A total of 3855 fractures of any type (3029 in females and 826 in males) and 493 hip fractures (353 in females and 140 in males) were observed in 51,330 subjects over a 6-year follow-up period. The risk of hip fractures was significantly higher in female (HR 1.73; 95% CI 1.38-2.16) and male (HR 1.84; 95% CI 1.29-2.63) diabetics than in non-diabetic controls after adjusting for multiple confounders. Stratification by age revealed that the adjusted HR for hip fractures was highest in diabetic patients aged 50-64 years (HR 2.54 in females and 2.70 in males) and decreased with increasing age. The risk of other fractures did not differ between the groups. Korean males and females with type 2 diabetes are at an increased risk of hip fractures compared with non-diabetic individuals. Osteoporosis assessments and fracture prevention strategies are necessary for Koreans with type 2 diabetes.

Antimelanogenic Efficacy of Melasolv (3,4,5-Trimethoxycinnamate Thymol Ester) in Melanocytes and Three-Dimensional Human Skin Equivalent.

BACKGROUND/AIMS: Excessive melanogenesis often causes unaesthetic hyperpigmentation. In a previous report, our group introduced a newly synthesized depigmentary agent, Melasolv™ (3,4,5-trimethoxycinnamate thymol ester). In this study, we demonstrated the significant whitening efficacy of Melasolv using various melanocytes and human skin equivalents as in vitro experimental systems. METHODS: The depigmentary effect of Melasolv was tested in melan-a cells (immortalized normal murine melanocytes), α-melanocyte-stimulating hormone (α-MSH)-stimulated B16 murine melanoma cells, primary normal human melanocytes (NHMs), and human skin equivalent (MelanoDerm). The whitening efficacy of Melasolv was further demonstrated by photography, time-lapse microscopy, Fontana-Masson (F&M) staining, and 2-photon microscopy. RESULTS: Melasolv significantly inhibited melanogenesis in the melan-a and α-MSH-stimulated B16 cells. In human systems, Melasolv also clearly showed a whitening effect in NHMs and human skin equivalent, reflecting a decrease in melanin content. F&M staining and 2-photon microscopy revealed that Melasolv suppressed melanin transfer into multiple epidermal layers from melanocytes as well as melanin synthesis in human skin equivalent. CONCLUSION: Our study showed that Melasolv clearly exerts a whitening effect on various melanocytes and human skin equivalent. These results suggest the possibility that Melasolv can be used as a depigmentary agent to treat pigmentary disorders as well as an active ingredient in cosmetics to increase whitening efficacy.

Ultrasound-Guided Cervical Nerve Root Block: Does Volume Affect the Spreading Pattern?

OBJECTIVE: Ultrasound-guided cervical nerve root block (US-CRB) is considered a safe and effective method for the treatment of radicular pain. However, previous studies on the spreading pattern of injected solution in US-CRB have reported conflicting results. The aim of this study was to investigate the spreading pattern in relation to injection volume. DESIGN: An institutional, prospective case series. SETTING: A university hospital. SUBJECTS: Fifty-three patients diagnosed with mono-radiculopathy in C5, 6, or 7. METHODS: US-CRB with fluoroscopic confirmation was performed. After the cervical roots were identified in ultrasound imaging, a needle was gently introduced toward the posterior edge of the root using an in-plane approach. The spread of 1 mL and 4 mL contrast medium, each injected in the same needle position, was examined with anteroposterior and lateral fluoroscopic views. After contrast injection, a mixture of local anesthetic and corticosteroid was injected. Clinical outcome was assessed using a numeric rating scale before and 2 weeks after the procedure. RESULTS: Contrast medium did not spread into the epidural space in any patients with 1 mL contrast medium injection, but it did spread into the intraforaminal epidural space in 13 patients (24.5%) with 4 mL. Pain improved in all patients. There was no significant difference in pain relief according to the spreading pattern. CONCLUSION: The spreading pattern of injected solution in US-CRB could be partially affected by the injectant volume. However, further studies are needed to assess the importance of other factors, such as needle position and physiological effects.

Effect of liver dysfunction on circulating sclerostin.

Sclerostin is a Wnt inhibitor produced specifically by osteocytes. It decreases bone formation by repressing osteoblast differentiation and proliferation. Whether circulating sclerostin level is affected by liver function is not currently clear. The aim of the study was to evaluate this relationship. Our cross-sectional study included 47 patients with liver cirrhosis and 50 healthy controls. Serum sclerostin level was analyzed by ELISA. Serum sclerostin levels were significantly higher in patients with cirrhosis than in controls (50.8 ± 38.2 vs. 35.1 ± 8.8 pmol/L, p = 0.008). After further adjustment for age, sex, body mass index, serum creatinine, and presence of diabetes, cirrhosis patients had higher sclerostin than controls. Subgroup analysis found that patients with Child-Pugh class B or C had higher sclerostin levels than patients with class A or controls after adjusting for multiple confounding factors. Multiple regression analysis showed that gender (p = 0.022), presence of diabetes (p < 0.001), albumin (p = 0.010), and serum creatinine (p = 0.037) were independent factors for circulating sclerostin level. Circulating sclerostin was higher in patients with advanced liver cirrhosis than in healthy controls or patients with early liver cirrhosis. The elevated sclerostin levels clearly correlated with markers of liver dysfunction such as albumin. The relationship between circulating sclerostin and liver function indicates a possible role of the liver in sclerostin metabolism.

Effect of high parathyroid hormone level on bone mineral density in a vitamin D-sufficient population: Korea National Health and Nutrition Examination Survey 2008-2010.

The detrimental effect of high parathyroid hormone (PTH) on bone has not been adequately evaluated in vitamin D-sufficient Koreans. The aim of this study was to investigate the effect of high PTH on bone mineral density (BMD) in such a population. A total of 5,403 subjects (2,644 men and 2,759 postmenopausal women; ≥50 years old) were selected from the 2008-2010 Korea National Health and Nutrition Examination Survey (KNHANES). Subjects were divided into four groups according to vitamin D status (<20 and ≥20 ng/mL) and PTH levels (≤65 and >65 pg/mL). Total hip and spine BMD were evaluated in each group. High PTH level was found in 50% of vitamin D-deficient subjects and 35% of vitamin D-sufficient subjects. In the vitamin D-deficient group, subjects with normal PTH level had higher total hip and spine BMD than those with high PTH after adjusting for multiple confounding factors, regardless of gender. In the vitamin D-sufficient group, only women with high PTH showed lower total hip and spine BMD than those with normal PTH. Multivariable linear regression analysis found that PTH level was independently associated with total hip BMD in vitamin D-sufficient women as well as vitamin D-insufficient women, but no association was found in men. In conclusion, high serum PTH level has an additive detrimental effect on BMD in postmenopausal women even though they had sufficient vitamin D levels.

Five novel mutations of GALNS in Korean patients with mucopolysaccharidosis IVA.

Mucopolysaccharidosis IVA (MPS IVA; OMIM #253000) is caused by the deficiency of N-acetylgalactosamine-6-sulfate sulfatase (GALNS), a lysosomal enzyme involved in the catabolism of keratan and chondroitin sulfate. In this study, we examined biochemical and genetic data from 6 Korean patients presenting with classic MPS IVA by measuring GALNS activity in peripheral blood leukocytes and skin fibroblasts. We initially identified Korean patients with MPS IVA by clinical, biochemical, and genetic analyses. We performed PCR-direct sequencing to identify molecular defects of the GALNS gene in patients and assessed the mutational statuses of family members as well as 50 healthy unrelated subjects. In silico analyses were performed to check for novel mutations. The mean age of the six female patients was 8.0 ± 5.2 years (range: 2-17 years), and were all found to have severe reductions of GALNS enzyme. A total of 12 mutant alleles were identified, corresponding to 7 different mutations. Five novel mutations were c.218A>G (p.Y73C), c.451C>A (p.P151T), c.725C>G (p.S242C), c.752G>A (p.R251Q), and c.1000C>T (p.Q334X). Two other mutations were c.1156C>T (p.R386C) and c.1243-1G>A. Two mutations, c.451C>A and c.1000C>T, accounted for 58% of all mutations in this sample.

The association of serum 25-hydroxyvitamin D and vertebral fractures in patients with type 2 diabetes.

Vitamin D is an important regulator of bone health. Previous studies examining the association between vitamin D deficiency and osteoporotic fractures have reported conflicting results. The relationship between vitamin D status and risk of vertebral fractures in diabetic patients is unknown. The objective of this study was to examine whether low serum 25-hydroxyvitamin D [25(OH)D] levels were associated with vertebral fractures in patients with type 2 diabetes. This cross-sectional study was conducted among 161 postmenopausal women and 180 men with type 2 diabetes. Serum concentrations of 25(OH)D were measured and the presence of vertebral fracture was assessed using lateral plain radiographs of the thoracolumbar spine. Women had lower 25(OH)D levels than men (31.3 ± 17.7 vs. 41.3 ± 26.5 ng/mL, p<0.001). Vertebral fractures were found in 16% of patients. Men with a serum 25(OH)D concentration greater than 30 ng/mL showed a lower prevalence of vertebral fractures compared to those with 20-29.9 ng/mL or those with less than 20 ng/mL (9.4% vs. 17.9% vs. 21.7%, p for trend=0.036). However, there was no significant association between vitamin D status and the prevalence of vertebral fractures in women (14.4% vs. 19.2% vs. 26.6%, p for trend=0.111). After adjusting for multiple confounding factors, men with a serum 25(OH)D concentration of less than 20 ng/mL were associated with an increased risk of vertebral fractures (OR 7.87; 95% CI 1.69-36.71), but not women. In conclusion, serum 25(OH)D levels below 20 ng/mL were associated with an increased vertebral fracture risk in men with type 2 diabetes.