Romosozumab in Postmenopausal Korean Women with Osteoporosis: A Randomized, Double-Blind, Placebo-Controlled Efficacy and Safety Study.

Background: This phase 3 study evaluated the efficacy and safety of 6-month treatment with romosozumab in Korean postmenopausal women with osteoporosis.

Methods: Sixty-seven postmenopausal women with osteoporosis (bone mineral density [BMD] T-scores ≤-2.5 at the lumbar spine, total hip, or femoral neck) were randomized (1:1) to receive monthly subcutaneous injections of romosozumab (210 mg; n=34) or placebo (n=33) for 6 months.

Determinants of Bone Mass and Insulin Resistance in Korean Postmenopausal Women: Muscle Area, Strength, or Composition?

Purpose: Muscle mass, strength, and composition determine muscle quantity and quality. However, data on muscle properties in relation to bone mass or insulin resistance are limited in Asian populations. This study aimed to investigate the relative importance of muscle measurements in regards to their relationship with lower bone mass and insulin resistance.

The novel myokine irisin: clinical implications and potential role as a biomarker for sarcopenia in postmenopausal women.

Purpose: To clarify the association of circulating irisin with muscle, liver and bone, and to evaluate irisin as a biomarker for sarcopenia in postmenopausal women.

Methods: Quadriceps cross-sectional area (QcCSA), bone mineral density (BMD), liver attenuation (measured in Hounsfield units (HU)) were assessed using quantitative computed tomography in 153 postmenopausal women, mean age of 72.20 ± 5.

The bone anabolic effects of irisin are through preferential stimulation of aerobic glycolysis.

Irisin, a recently identified hormone secreted by skeletal muscle in response to exercise, exhibits anabolic effects on the skeleton primarily through the stimulation of bone formation. However, the mechanism underlying the irisin-stimulated anabolic response remains largely unknown. To uncover the underlying mechanism, we biosynthesized recombinant irisin (r-irisin) using an Escherichia coli expression system and used it to treat several osteoblast cell types.

In silico discovery of quinoxaline derivatives as novel LRP5/6-sclerostin interaction inhibitors.

The Wnt/β-catenin signaling pathway is a key regulator of bone homeostasis. Sclerostin act as an extracellular inhibitor of canonical Wnt signaling through high-affinity binding to the Wnt co-receptor LRP5/6. Disruption of the interaction between LRP5/6 and sclerostin has been recognized as a therapeutic target for osteoporosis.

Effects of Single Vitamin D₃ Injection (200,000 Units) on Serum Fibroblast Growth Factor 23 and Sclerostin Levels in Subjects with Vitamin D Deficiency.

Background: Vitamin D deficiency remains common in all age groups and affects skeletal and non-skeletal health. Fibroblast growth factor 23 is a bone-derived hormone that regulates phosphate and 1,25-dihydroxyvitamin D homeostasis as a counter regulatory factor. 1,25-Dihydroxyvitamin D stimulates fibroblast growth factor 23 synthesis in bone, while fibroblast growth factor 23 suppresses 1,25-dihydroxyvitamin D production in the kidney.

Significant liver fibrosis assessed using liver transient elastography is independently associated with low bone mineral density in patients with non-alcoholic fatty liver disease.

Background: Metabolic bone disorders frequently occur in patients with chronic liver disease; however, the association between liver fibrosis and bone mineral density in patients with non-alcoholic fatty liver disease (NAFLD) is unclear.

Methods: This is a cross-sectional analysis of 231 asymptomatic subjects (160 women, 61.6 years old) from a university hospital setting, between February 2012 and December 2014.

Cyclized Oligopeptide Targeting LRP5/6-DKK1 Interaction Reduces the Growth of Tumor Burden in a Multiple Myeloma Mouse Model.

Purpose: Dickkopf 1 (DKK1) has been extensively investigated in mouse models of multiple myeloma, which results in osteolytic bone lesions. Elevated DKK1 levels in bone marrow plasma and serum inhibit the differentiation of osteoblast precursors. Present pharmaceutical approaches to target bone lesions are limited to antiresorptive agents.

Site-Specific Difference of Bone Geometry Indices in Hypoparathyroid Patients.

Background: Hypoparathyroid patients often have a higher bone mineral density (BMD) than the general population. However, an increase in BMD does not necessarily correlate with a solid bone microstructure. This study aimed to evaluate the bone microstructure of hypoparathyroid patients by using hip structure analysis (HSA).

Efficacy and safety of vitamin D B.O.N intramuscular injection in Korean adults with vitamin D deficiency.

Objective: There has been no prospective study that examined intramuscular injection of high-dose vitamin D in Korean adults. The aim of this study was to assess the efficacy and safety of high-dose vitamin D after intramuscular injection in Korean adults with vitamin D deficiency.

Method: This study was a 24-week, prospective, multicenter, randomized, double-blind, placebo-controlled trial.

Z-score discordance and contributing factors in healthy premenopausal women with low bone mineral density: the Korean National Health and Nutrition Examination Survey 2008-9.

The premenopausal period is important for bone health and prevention of future fractures, but measuring bone mineral density (BMD) at only one site may not be sufficient to determine therapeutic strategies for low BMD in premenopausal women due to the presence of Z-score discordance. In this study, we investigated Z-score discordance in addition to contributing factors of idiopathic low BMD in healthy premenopausal Korean women. We studied 3003 premenopausal women aged 18-50 years, without secondary causes for low BMD and history of fragility fracture, who had participated in the Fourth Korean National Health and Nutrition Examination Surveys (2008-2009).

Low Dentin Matrix Protein 1 Is Associated With Incident Cardiovascular Events in Peritoneal Dialysis Patients.

Recent reports demonstrated that dentin matrix protein 1 (DMP1) acts as an inhibitor of vascular calcification and might be a potential biomarker for chronic kidney disease-mineral and bone disorder; however, no clinical investigations regarding DMP1 have been performed in dialysis patients. We investigated the prognostic value of DMP1 on cardiovascular outcomes in prevalent peritoneal dialysis patients. We recruited 223 prevalent peritoneal dialysis patients and divided them into high and low DMP1 groups according to log-transformed plasma DMP1 levels.

A Novel Human PTH Analog [Cys25]hPTH(1-34) Restores Bone Mass in Ovariectomized Mice.

Context: Recently, an arginine-to-cysteine homozygous mutation at position 25 in mature PTH was reported in a Korean patient with hypoparathyroidism.

Objective: To clarify whether the high bone mass phenotype observed in this patient was related to the hypoparathyroidism itself or to chronic elevation of mutant PTH.

Methods: A series of in vitro and in vivo experiments were performed in MC3T3E1, ROS 17/2.

The Role of Nuclear Factor-E2-Related Factor 1 in the Oxidative Stress Response in MC3T3-E1 Osteoblastic Cells.

Background: Reactive oxygen species (ROS) and antioxidants are associated with maintenance of cellular function and metabolism. Nuclear factor-E2-related factor 1 (NFE2L1, Nrf1) is known to regulate the expression of a number of genes involved in oxidative stress and inflammation. The purpose of this study was to examine the effects of NFE2L1 on the response to oxidative stress in osteoblastic MC3T3-E1 cells.

The systemic effects of sclerostin overexpression using ΦC31 integrase in mice.

Sclerostin, encoded by the Sost gene, is mainly produced by osteocytes in bone and antagonizes the Wnt/β-catenin signaling pathway, which is a requisite for bone formation. Currently, human anti-sclerostin antibodies are being tested in phase III clinical trials. In addition, serum sclerostin levels are reported to be associated with bone mineral density and fracture risk in normal individuals; however, the correlation between serum sclerostin and bone mass remains controversial.

Serum γ-Glutamyl Transferase Is Inversely Associated with Bone Mineral Density Independently of Alcohol Consumption.

Background: γ-Glutamyl transferase (GGT) is a well-known marker of chronic alcohol consumption or hepatobiliary diseases. A number of studies have demonstrated that serum levels of GGT are independently associated with cardiovascular and metabolic disorders. The purpose of this study was to test if serum GGT levels are associated with bone mineral density (BMD) in Korean adults.

The Effects of a High Fat Diet Containing Diacylglycerol on Bone in C57BL/6J Mice.

Purpose: In epidemiologic and animal studies, a high fat diet (HFD) has been shown to be associated with lower bone mineral density (BMD) and a higher risk of osteoporotic fractures. Meanwhile, consuming a HFD containing diacylglycerol (DAG) instead of triacylglycerol (TAG) is known to offer metabolically beneficial effects of reductions in body weight and abdominal fat. The purpose of this study was to investigate the effects of a HFD containing DAG (HFD-DAG) on bone in mice.

Increased sclerostin levels after further ablation of remnant estrogen by aromatase inhibitors.

Background: Sclerostin is a secreted Wnt inhibitor produced almost exclusively by osteocytes, which inhibits bone formation. Aromatase inhibitors (AIs), which reduce the conversion of steroids to estrogen, are used to treat endocrine-responsive breast cancer. As AIs lower estrogen levels, they increase bone turnover and lower bone mass.

Concurrent bisphosphonate-related bilateral atypical subtrochanteric fractures and osteonecrosis of the jaw on bone scintigraphy.

An 82-year-old woman presented with bilateral thigh pain. She had pain in her right thigh operated for a low-trauma fracture 2 years earlier and newly developed pain in her left thigh without trauma. A whole-body bone scan revealed increased tracer uptake in her bilateral subtrochanteric femoral shafts and in the right mandible without evidence of metastatic bone disease.

Comparison of Buckling Ratio and Finite Element Analysis of Femoral Necks in Post-menopausal Women.

Objectives: Osteoporosis is a prevalent problem amongst the elderly. Bone mineral density (BMD) obtained from dual X-ray absorptiometry (DXA) is the gold standard in diagnosing osteopenia (-1.0 < t < -2.

The effect of renal dysfunction on circulating sclerostin level in patients with type 2 diabetes.

Objective. Sclerostin is a Wnt inhibitor produced specifically by osteocytes. However, it is not currently clear whether renal dysfunction has an effect on circulating sclerostin level in patients with type 2 diabetes.

Role of miRNAs in bone and their potential as therapeutic targets.

MicroRNAs (miRNAs) are noncoding, single-stranded RNAs that regulate the expression of target genes by binding their 3'-untranslated region. miRNAs are important regulators of various biological processes, including cellular differentiation, proliferation, apoptosis, and tissue development. Furthermore, aberrant miRNA expression has emerged as an important pathomechanism in various human diseases, including osteoporosis.

The combination of vitamin D deficiency and mild to moderate chronic kidney disease is associated with low bone mineral density and deteriorated femoral microarchitecture: results from the KNHANES 2008-2011.

Context: Although mild to moderate chronic kidney disease (CKD) and vitamin D deficiency are prevalent in the elderly population worldwide and are associated with sarcopenia, their influence on bone mineral density (BMD) has not been determined.

Objective: The objective of the study was to determine the combined effects of vitamin D deficiency and CKD on BMD in the elderly population and their relationships with sarcopenia and PTH levels.

Design, Setting, And Subjects: This was a cross-sectional study with nationally representative samples of 6949 subjects aged 55 years or older from the Korea National Health and Nutrition Examination Surveys conducted between 2008 and 2011.

Efficacy and safety of weekly alendronate plus vitamin D₃ 5600 IU versus weekly alendronate alone in Korean osteoporotic women: 16-week randomized trial.

Vitamin D (vit-D) is essential for bone health, although many osteoporosis patients have low levels of 25-hydroxy-vit-D [25(OH)D]. This randomized, open-label study compared the effects of once weekly alendronate 70 mg containing 5600 IU vit-D₃ (ALN/D5600) to alendronate 70 mg without additional vit-D (ALN) on the percent of patients with vit-D insufficiency [25(OH)D <15 ng/mL, primary endpoint] and serum parathyroid hormone (PTH, secondary endpoint) levels in postmenopausal, osteoporotic Korean women. Neuromuscular function was also measured.

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.