BACKGROUND: The purpose of this study was to determine cut-off point of appendicular skeletal muscle mass (ASM) adjusted body mass index (BMI) for sarcopenia in the Korean women and evaluate the prevalence of sarcopenia in postmenopausal women. METHODS: This study was based on the data obtained from 2008 to 2011 Korean National Health and Nutrition Examination Survey (KNHANES) IV and V. A whole body dual energy X-ray absorptiometry (DXA) scan and measurement of BMI were performed on individuals of ≥10 years old. Five thousand, two hundred and fifteen women older than 50 years were included in the study. ASM was obtained by adding the muscle masses of the four limbs. To determine the young reference group, mean and standard deviation of ASM and ASM/BMI by ages was measured. We calculated the prevalence rate of sarcopenia by each age group according to the cut-off point based on ASM and ASM/BMI. RESULTS: In determining the cut-off values related ASM/BMI, using the value that is two standard deviations below mean values for young reference group (20's and 30's) thus recommends 0.50 m² in women. The overall prevalence among women older than 50 years was 15.6%. Among women older than 65 years prevalence of sarcopenia was 22.9%. CONCLUSIONS: The prevalence of sarcopenia among Korean women obtained in this study is within the proper range of value to research about sarcopenia. Furthermore, using 0.50 m² as the cut-off value can help compare various studies about sarcopenia in Korea.
Absorptiometry, Photon ; Body Mass Index* ; Extremities ; Female ; Humans ; Korea ; Muscle, Skeletal ; Nutrition Surveys ; Postmenopause ; Prevalence* ; Republic of Korea ; Sarcopenia*

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.
Asian Continental Ancestry Group* ; Bone Density ; Cohort Studies ; Genetic Markers ; Genome-Wide Association Study ; Hip Fractures ; Humans ; Osteoporosis ; Polymorphism, Single Nucleotide

BACKGROUND: Exposure to heavy metals from environmental and industrial sources remains a concern of serious public health risk. This study was conducted to analysis the relationship between heavy metal concentrations and bone density. METHODS: This study used data from a nation-based sample of Koreans (n=2,429) from 2008 to 2011 Korea National Health and Nutrition Examination Survey. We were obtained heavy metals (lead, mercury and cadmium), socioeconomic and demographic factors and bone mineral density (BMD) measured by T-score. RESULTS: Menopausal women, current smoker or the frequent alcohol drinking, low educational level and low family income were greater in the osteopenia or osteoporosis groups than normal group, and were associated with an increased blood heavy metal concentration levels. The highest quartile group in blood lead had a 1.47 times (95% confidence interval [CI] 1.16-1.87) risk of osteopenia or osteoporosis. In case of blood cadmium, the risk for osteopenia or osteoporosis increased 2.1 times (95% CI 1.64-2.68). CONCLUSIONS: We observed a significant association between blood heavy metals (lead and cadmium) levels and low BMD. Our findings suggest that heavy metal exposure may be a risk factor for osteoporosis.
Adult* ; Alcohol Drinking ; Bone Density* ; Bone Diseases, Metabolic ; Cadmium ; Demography ; Female ; Humans ; Korea ; Metals, Heavy ; Nutrition Surveys ; Osteoporosis ; Public Health ; Risk Factors

Adefovir dipivoxil (ADV) is a nucleotide used as long-term therapy of chronic hepatitis B. Many published reports have shown that long-term high-dose therapy with adefovir can be associated with proximal renal tubular dysfunction resulting in significant hypophosphatemia, renal insufficiency and osteomalacia. We have encountered two patients who developed evidence of hypophosphatemic osteomalacia while on long-term low-dose adefovir therapy for chronic hepatitis B. We report on its clinical features and its potential resolution with cessation of the drug and supplementation with phosphate. We also reviewed the other published cases associated with hypophosphatemic osteomalacia after low-dose adefovir therapy. The symptoms and the hypophosphatemia improved after cessation of the drug and supplementation with phosphate in most cases. Patients taking adefovir long-term should receive regular investigation of the phosphate level and renal function.
Fanconi Syndrome ; Hepatitis B, Chronic* ; Hepatitis, Chronic* ; Humans ; Hypophosphatemia ; Kidney Diseases ; Osteomalacia* ; Renal Insufficiency

BACKGROUND: Sclerostin inhibits osteoblast functions, differentiations, and survival rates. As an endogenous inhibitor of the Wnt/beta-catenin pathway, the sclerostin should be related to decreased bone masses, although several studies indicate opposite results. In addition, it may be related to insulin resistances and carbohydrate metabolisms, a relation shared with other markers of bone metabolisms, such as osteocalcin. Hepatitis C virus (HCV) infected patients may present osteoporosis, and frequently show liver steatosis, which is a consequence of insulin resistance. The behaviour of sclerostin in these patients is yet unknown. The aim of this work is to analyse the relationships between serum sclerostin and osteocalcin levels and bone mineral density (BMD), liver functions, the intensity of liver steatosis and biochemical markers of bone homeostasis and insulin resistance in HCV-infected patients. METHODS: Forty HCV patients with 20 years of age and gender-matching controls were included in this study and underwent bone densitometry. Serum sclerostin, osteocalcin, collagen telopeptide, adiponectin, leptin, insulin, resistin, tumor necrosis factor (TNF)-alpha, and interleukin (IL)-6 were determined. Liver fat was histomorphometrically assessed. RESULTS: Sclerostin levels were slightly higher in patients than in controls, and were directly related to BMD at different parts of the skeleton, also to the serum telopeptide, and to the liver steatosis and TNF-alpha. On the contrary, osteocalcin showed a significant direct relationship with serum adiponectin, and an inverse one with IL-6. CONCLUSIONS: Serum sclerostin levels were within the normal range in HCV patients, and correlated directly with BMD and serum telopeptide. In addition, the relationships of sclerostin and osteocalcin with variables associated with insulin resistance suggested the role of bones for intermediary metabolisms.
Adiponectin ; Biomarkers ; Bone Density ; Collagen ; Densitometry ; Fatty Liver ; Hepacivirus* ; Hepatitis C* ; Hepatitis* ; Homeostasis ; Humans ; Insulin ; Insulin Resistance ; Interleukin-6 ; Interleukins ; Leptin ; Liver ; Osteoblasts ; Osteocalcin ; Osteoporosis ; Reference Values ; Resistin ; Skeleton ; Survival Rate ; Tumor Necrosis Factor-alpha

BACKGROUND: The relative importance of body composition, lifestyle factors, bone turnover and hormonal factors in determining bone mineral density (BMD) is unknown. We studied younger postmenopausal women to determine whether modifiable or nonmodifiable risk factors for osteoporosis have stronger associations with BMD. METHODS: In multivariable linear regression models, we tested associations between non-bone body composition measures, self-reported measures of physical activity and dietary intake, urinary N-telopeptide (NTx), sex hormone concentrations, and BMD in 109 postmenopausal women aged 50 to 64 years, adjusting for current hormone therapy use and clinical risk factors for low BMD. Lean mass, fat mass and areal BMD (aBMD) at the lumbar spine, femoral neck, total hip and distal radius were measured using dual energy X-ray absorptiometry. RESULTS: Higher body weight and self-reported nonwhite race were independently associated with higher aBMD at the lumbar spine, femoral neck, total hip and distal radius. Lean and fat mass were not independently associated with aBMD. Older age and higher urinary NTx were independently associated with lower aBMD at the distal radius but not at weight-bearing sites. Sensitivity analyses demonstrated lack of an independent association between total daily protein or calorie intake and BMD. CONCLUSIONS: BMD, weight and race were the most important determinants of aBMD at all sites. Older age and higher bone turnover were independently associated with lower aBMD at the distal radius. In a limited analysis, self-reported physical activity, dietary protein and calorie intake were not associated with aBMD after adjustment for the other variables.
Absorptiometry, Photon ; Body Composition* ; Body Weight ; Bone Density ; Continental Population Groups ; Dietary Proteins ; Female ; Femur Neck ; Hip ; Humans ; Life Style* ; Linear Models ; Menopause ; Motor Activity ; Osteoporosis ; Radius ; Risk Factors ; Spine ; Weight-Bearing

Osteocytes establish an extensive intracellular and extracellular communication system via gap junction-coupled cell processes and canaliculi, through which cell processes pass throughout bone, and the communication system is extended to osteoblasts on the bone surface. To examine the osteocyte function, several mouse models were established. To ablate osteocytes, osteocytes death was induced by diphtheria toxin. However, any types of osteocyte death result in necrosis, because dying osteocytes are not phagocytosed by scavengers. After the rupture of cytoplasmic membrane, immunostimulatory molecules are released from lacunae to bone surface through canaliculi, and stimulate macrophages. The stimulated macrophages produce interleukin (IL)-1, IL-6, and tumor necrosis factor-alpha (TNF-alpha), which are the most important proinflammatory cytokines triggering inflammatory bone loss. Therefore, the osteocyte ablation results in necrosis-induced severe osteoporosis. In conditional knockout mice of gap junction protein alpha-1 (GJA1), which encodes connexin 43 in Gap junction, using dentin matrix protein 1 (DMP1) Cre transgenic mice, osteocyte apoptosis and enhanced bone resorption occur, because extracellular communication is intact. Overexpression of Bcl-2 in osteoblasts using 2.3 kb collagen type I alpha1 (COL1A1) promoter causes osteocyte apoptosis due to the severe reduction in the number of osteocyte processes, resulting in the disruption of both intracellular and extracellular communication systems. This mouse model unraveled osteocyte functions. Osteocytes negatively regulate bone mass by stimulating osteoclastogenesis and inhibiting osteoblast function in physiological condition. Osteocytes are responsible for bone loss in unloaded condition, and osteocytes augment their functions by further stimulating osteoclastogenesis and further inhibiting osteoblast function, at least partly, through the upregulation of receptor activator of nuclear factor-kappa B ligand (RANKL) in osteoblasts and Sost in osteocytes in unloaded condition.
Animals ; Apoptosis ; Bone Resorption ; Cell Membrane ; Collagen Type I ; Connexin 43 ; Connexins ; Cytokines ; Dentin ; Diphtheria Toxin ; Gap Junctions ; Interleukin-6 ; Interleukins ; Macrophages ; Mice* ; Mice, Knockout ; Mice, Transgenic ; Necrosis ; Osteoblasts ; Osteocytes* ; Osteoporosis ; RANK Ligand ; Rupture ; Tumor Necrosis Factor-alpha ; Up-Regulation

The osteocyte has long been considered to be the primary mechanosensory cell in the bone. Recent evidence has emerged that the osteocyte is also a key regulator of various bone and mineral metabolism and that its regulatory effects are in part mediated through locally produced osteocyte-derived factors, such as sclerostin, receptor activator of nuclear factor-kappa B ligand (RANKL), and fibroblast growth factor (FGF)-23. Osteocytes secrete large amounts of insulin-like growth factor (IGF)-I in bone. Although IGF-I produced locally by other bone cells, such as osteoblasts and chondrocytes, has been shown to play important regulatory roles in bone turnover and developmental bone growth, the functional role of osteocyte-derived IGF-I in the bone and mineral metabolism has not been investigated and remains unclear. However, results of recent studies in osteocyte Igf1 conditional knockout transgenic mice have suggested potential regulatory roles of osteocyte-derived IGF-I in various aspects of bone and mineral metabolism. In this review, evidence supporting a regulatory role for osteocyte-derived IGF-I in the osteogenic response to mechanical loading, the developmental bone growth, the bone response to dietary calcium depletion and repletion, and in fracture repair is discussed. A potential coordinated regulatory relationship between the effect of osteocyte-derived IGF-I on bone size and the internal organ size is also proposed.
Animals ; Bone Development ; Bone Regeneration ; Bone Remodeling ; Calcium, Dietary ; Chondrocytes ; Fibroblast Growth Factors ; Fracture Healing ; Insulin-Like Growth Factor I* ; Metabolism ; Mice ; Mice, Transgenic ; Organ Size ; Osteoblasts ; Osteocytes ; RANK Ligand ; Regeneration*

The clinical significance of sarcopenia and osteoporosis has increased with the increase in the population of older people. Sarcopenia is defined by decreased muscle mass and impaired muscle function, which is related to osteoporosis independently and dependently. Numerous lines of clinical evidence suggest that lean body mass is positively related to bone mass, which leads to reduced fracture risk. Genetic, endocrine and mechanical factors affect both muscle and bone simultaneously. Vitamin D, the growth hormone/insulin-like growth factor I axis and testosterone are physiologically and pathologically important as endocrine factors. These findings suggest the presence of interactions between muscle and bone, which might be very important for understanding the physiology and pathophysiology of sarcopenia and osteoporosis. Muscle/bone relationships include two factors: local control of muscle to bone and systemic humoral interactions between muscle and bone. As a putative local inducer of muscle ossification, we found Tmem119, a parathyroid hormone-responsive osteoblast differentiation factor. Moreover, osteoglycin might be one of the muscle-derived humoral bone anabolic factors. This issue may be important for the development of novel drugs and biomarkers for osteoporosis and sarcopenia. Further research will be necessary to clarify the details of the linkage of muscle and bone.
Axis, Cervical Vertebra ; Biomarkers ; Bone and Bones ; Fibrinogen ; Muscles* ; Osteoblasts ; Osteoporosis ; Physiology ; Sarcopenia ; Testosterone ; Vitamin D

Advocacy for the use of calcium supplements arose at a time when there were no other effective interventions for the prevention of osteoporosis. Their promotion was based on the belief that increasing calcium intake would increase bone formation. Our current understandings of the biology of bone suggest that this does not occur, though calcium does act as a weak antiresorptive. Thus, it slows postmenopausal bone loss but, despite this, recent meta-analyses suggest no significant prevention of fractures. In sum, there is little substantive evidence of benefit to bone health from the use of calcium supplements. Against this needs to be balanced the likelihood that calcium supplement use increases cardiovascular events, kidney stones, gastrointestinal symptoms, and admissions to hospital with acute gastrointestinal problems. Thus, the balance of risk and benefit seems to be consistently negative. As a result, current recommendations are to obtain calcium from the diet in preference to supplements. Dietary calcium intake has not been associated with the adverse effects associated with supplements, probably because calcium is provided in smaller boluses, which are absorbed more slowly since they come together with quantities of protein and fat, resulting in a slower gastric transit time. These findings suggest that calcium supplements have little role to play in the modern therapeutics of osteoporosis, which is based around the targeting of safe and effective anti-resorptive drugs to individuals demonstrated to be at increased risk of future fractures.
Biology ; Calcium* ; Calcium, Dietary ; Diet ; Female ; Humans ; Kidney Calculi ; Myocardial Infarction ; Osteogenesis ; Osteoporosis* ; Osteoporosis, Postmenopausal