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High Dietary Sodium Intake Assessed by 24-hour Urine Specimen Increase Urinary Calcium Excretion and Bone Resorption Marker.

Sun Mi PARK ; Jaehwan JEE ; Ji Young JOUNG ; Yoon Young CHO ; Seo Young SOHN ; Sang Man JIN ; Kyu Yeon HUR ; Jae Hyeon KIM ; Sun Wook KIM ; Jae Hoon CHUNG ; Moon Kyu LEE ; Yong Ki MIN

Journal of Bone Metabolism.2014;21(3):189-194. doi:10.11005/jbm.2014.21.3.189

BACKGROUND: The average dietary sodium intake of Koreans is 2.6 times higher than the World Health Organization's recommended amount. The effect of a diet high in sodium on the skeletal system, especially osteoporosis, has not previously been examined in Korean postmenopausal women with low bone mass. We assessed the daily sodium intake, and determined the impact of sodium intake on urinary calcium excretion and bone resorption marker. METHODS: A retrospective review of medical records was performed for 86 postmenopausal subjects who were initially diagnosed with osteopenia or osteoporosis at the health promotion center. They were subsequently referred to the Division of Endocrinology and Metabolism between 2010 and 2013. All subjects completed a modified food frequency questionnaire. Twenty-four hour urine collection for sodium, calcium and creatinine excretion, and serum C-terminal telopeptides of type I collagen (CTX-I) were also obtained. RESULTS: The average amount of daily sodium and calcium intake were 3,466 mg and 813 mg, respectively. Average dietary sodium intake and 24-hour urinary sodium excretion showed significant positive linear correlation (r=0.29, P=0.006). There was also a significant positive linear correlation between 24-hour urine sodium and calcium excretion (r=0.42, P<0.001); CTX-I and 24-hour urinary calcium excretion (r=0.29, P=0.007). CONCLUSIONS: Excessive sodium intake assessed by 24-hour urine specimen is associated with high calcium excretion in urine. High calcium excretion is also related to increasing bone resorption marker.
Bone Diseases, Metabolic ; Bone Resorption* ; Calcium* ; Collagen Type I ; Creatinine ; Diet ; Endocrinology ; Female ; Health Promotion ; Humans ; Medical Records ; Metabolism ; Osteoporosis ; Retrospective Studies ; Sodium ; Sodium, Dietary* ; Urine Specimen Collection ; World Health ; World Health Organization ; Surveys and Questionnaires

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Microarray Analysis of Gene Expression Reveals that Cyclo-oxygenase-2 Gene Therapy Up-regulates Hematopoiesis and Down-regulates Inflammation During Endochondral Bone Fracture Healing.

K H William LAU ; Nicoleta L POPA ; Charles H RUNDLE

Journal of Bone Metabolism.2014;21(3):169-188. doi:10.11005/jbm.2014.21.3.169

BACKGROUND: Cyclo-oxygenase-2 (Cox-2) is an inflammatory mediator that is necessary for the tissue repair, including bone fracture healing. Although the application of Cox-2 gene therapy to a murine closed femoral fracture has accelerated bony union, but the beneficial effect was not observed until the endochondral stage of bone repair that is well after the inflammatory stage normally subsides. METHODS: To identify the molecular pathways through which Cox-2 regulates fracture healing, we examined gene expression profile in fracture tissues in response to Cox-2 gene therapy during the endochondral bone repair phase. Cox-2 gene therapy was applied to the closed murine femur fracture model. Microarray analysis was performed at 10 days post-fracture to examine global gene expression profile in the fracture tissues during the endochondral bone repair phase. The entire repertoire of significantly expressed genes was examined by gene set enrichment analysis, and the most up-regulated individual genes were evaluated further. RESULTS: The genes that normally promote inflammation were under-represented in the microarray analysis, and the expression of several inflammatory chemokines was significantly down-regulated. There was an up-regulation of two key transcription factor genes that regulate hematopoiesis and erythropoiesis. More surprisingly, there was no significant up-regulation in the genes that are normally involved in angiogenesis or bone formation. However, the expression of two tissue remodeling genes was up-regulated. CONCLUSIONS: The down-regulation of the inflammatory genes in response to Cox-2 gene therapy was unexpected, given the pro-inflammatory role of prostaglandins. Cox-2 gene therapy could promote bony union through hematopoietic precursor proliferation during endochondral bone repair and thereby enhances subsequently fracture callus remodeling that leads to bony union of the fracture gap.
Bony Callus ; Chemokines ; Cyclooxygenase 2 ; Down-Regulation ; Erythropoiesis ; Femoral Fractures ; Femur ; Fracture Healing ; Fractures, Bone* ; Gene Expression* ; Genetic Therapy* ; Hematopoiesis* ; Inflammation* ; Microarray Analysis* ; Osteogenesis ; Prostaglandins ; Transcription Factors ; Transcriptome ; Up-Regulation

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Factors and Mechanisms Involved in the Coupling from Bone Resorption to Formation: How Osteoclasts Talk to Osteoblasts.

Kyoji IKEDA ; Sunao TAKESHITA

Journal of Bone Metabolism.2014;21(3):163-167. doi:10.11005/jbm.2014.21.3.163

Bone remodeling is the fundamental means by which the quality as well as quantity of the skeleton is maintained throughout adult life. When bone remodeling goes awry, a metabolic bone disease such as osteoporosis ensues. Among multiple phases of the complex remodeling process, we focus in this review on factors and mechanisms that are involved in the coupling of bone formation to preceding resorption.
Adult ; Bone Diseases, Metabolic ; Bone Remodeling ; Bone Resorption* ; Humans ; Osteoblasts* ; Osteoclasts* ; Osteogenesis ; Osteoporosis ; Skeleton

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A Latent Autoimmune Diabetes in Adults Patient Manifesting Severe Musculoskeletal Complications.

In Ho YANG ; Sun Hee LEE ; Sang Ouk CHIN ; Suk CHON

Journal of Bone Metabolism.2014;21(4):283-289. doi:10.11005/jbm.2014.21.4.283

Patients with diabetes have many different kinds of complications involving multiple organs, but those involving the musculoskeletal system are relatively uncommon. Diabetic muscle infarction (DMI) is a rare, painful, and potentially serious condition in patients with poorly controlled diabetes mellitus. A 35-year-old man diagnosed with type 2 diabetes eight years ago, visited with severe muscle pain in the right anteromedial thigh without any event of trauma. He had been treated with metformin, but his glycemic control was very poor with a glycated hemoglobin of 14.5%. Evaluation of his painful thigh lesion did not reveal any evidence of infection or vasculitis, but the magnetic resonance imaging and bone scan showed findings of DMI at vastus medialis muscle and an insufficiency fracture at the right medial tibial condyle. He was diagnosed with retinopathy, neuropathy and microalbuminuria but not macrovascular complications. We also diagnosed his diabetes as latent autoimmune diabetes in adults (LADA) based on his low C-peptide level, positive anti-glutamic acid decarboxylase (GAD) antibody and early onset diabetes. Instead of antibiotics, bed rest, analgesics and strict blood glucose control with multiple daily insulin injections led to symptom improvement. This is an unusual case of a young man with LADA experiencing severe musculoskeletal complication of DMI and insufficiency fracture. If a poorly controlled diabetic patient appears to have unaccounted soft tissue pain, musculoskeletal complications such as DMI associated with hyperglycemia should be considered.
Adult* ; Analgesics ; Anti-Bacterial Agents ; Bed Rest ; Blood Glucose ; C-Peptide ; Diabetes Mellitus ; Diabetes Mellitus, Type 1* ; Fractures, Stress ; Hemoglobin A, Glycosylated ; Humans ; Hyperglycemia ; Infarction ; Insulin ; Magnetic Resonance Imaging ; Metformin ; Musculoskeletal System ; Myalgia ; Nociceptive Pain ; Quadriceps Muscle ; Thigh ; Vasculitis

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Mutiple Spontaneous Rib Fractures in Patient with Cushing's Syndrome.

Hyun Jung LEE ; Ji Hye JE ; Ji Hye SEO ; Young Ju NA ; Hye Jin YOO

Journal of Bone Metabolism.2014;21(4):277-282. doi:10.11005/jbm.2014.21.4.277

Glucocorticoid (GC) excess, including Cushing's syndrome, is a common cause of secondary osteoporosis. Thirty to fifty percent of Cushing's syndrome patients experience non-traumatic fractures, which is often the presenting manifestation of Cushing's syndrome. However, there have been rare cases of Cushing's syndrome diagnosed only based upon bone manifestations. We describe a case of Cushing's syndrome that was diagnosed in a 44-year-old woman who initially visited our hospital due to multiple non-traumatic rib fractures. She did not exhibit any other manifestations of Cushing's syndrome such as moon face, buffalo hump or abdominal striae. Initially, we evaluated her for bone metastases from a cancer of unknown origin, but there was no evidence of metastatic cancer. Instead, we found a left adrenal incidentaloma. As a result of the hormone study, she was diagnosed as having Cushing's syndrome. Interestingly, her bony manifestation of Cushing's syndrome, which was evident in the bone scan and bone mineral densitometry, completely recovered after a left adrenalectomy. Therefore, the possibility of Cushing's syndrome as a cause of secondary osteoporosis should be considered in young patients with non-traumatic multiple fractures, with or without any other typical features of Cushing's syndrome.
Adrenalectomy ; Adult ; Buffaloes ; Cushing Syndrome* ; Densitometry ; Female ; Humans ; Neoplasm Metastasis ; Osteoporosis ; Rib Fractures*

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Methanol Extract of Croton Pycnanthus Benth. Inhibits Osteoclast Differentiation by Suppressing the MAPK and NF-kappaB Signaling Pathways.

Jiyeon LEE ; Hong Hee KIM

Journal of Bone Metabolism.2014;21(4):269-275. doi:10.11005/jbm.2014.21.4.269

BACKGROUND: Osteoclasts are differentiated from monocytes/macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor-kappa B (NF-kappaB) ligand (RANKL). Croton pycnanthus Benth. (CPB) is a herbal plant that belongs to Euphorbiaceae family. The aim of this study was to investigate the effects of CPB on osteoclastogenesis and RANKL-dependent signaling pathways. METHODS: Methanol extract of CPB was obtained from International Biological Material Research Center. Osteoclast differentiation was achieved by culturing mouse bone marrow-derived macrophages (BMMs) with M-CSF and RANKL. Osteoclast numbers were evaluated by counting multinuclear cells positive for tartrate-resistant acid phosphatase (TRAP). mRNA and protein levels were analyzed by real-time polymerase chain reaction (PCR) and Western blotting, respectively. The activation of signaling molecules were assessed after acute stimulation of cells with high dose of RANKL by Western blotting with phospho-specific antibodies. RESULTS: CPB reduced the generation of TRAP-positive multinucleated cells and the activation of mitogen-activated protein kinase (MAPK) and NF-kappaB signaling pathways. The induction of the expression of c-Fos, nuclear factor-activated T cells c1 (NFATc1) and dendritic cell-specific transmembrane protein (DC-STAMP) by RANKL was also suppressed. CONCLUSIONS: CPB exerts negative effects on osteoclast differentiation in response to the RANKL. The inhibitory mechanism involves the suppression of MAPK and NF-kappaB signaling pathways and subsequently the down-regulation of c-Fos and NFATc1 transcription factors.
Acid Phosphatase ; Animals ; Antibodies, Phospho-Specific ; Blotting, Western ; Cell Differentiation ; Colony-Stimulating Factors ; Croton* ; Down-Regulation ; Euphorbiaceae ; Humans ; Macrophage Colony-Stimulating Factor ; Macrophages ; Methanol* ; Mice ; NF-kappa B* ; NFATC Transcription Factors ; Osteoclasts* ; Plants ; Protein Kinases ; RANK Ligand ; Real-Time Polymerase Chain Reaction ; Receptor Activator of Nuclear Factor-kappa B ; RNA, Messenger ; T-Lymphocytes

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Multiple Fractures in Patient with Graves' Disease Accompanied by Isolated Hypogonadotropic Hypogonadism.

Hyon Seung YI ; Ji Min KIM ; Sang Hyeon JU ; Younghak LEE ; Hyun Jin KIM ; Koon Soon KIM

Journal of Bone Metabolism.2016;23(1):40-44. doi:10.11005/jbm.2016.23.1.40

Isolated hypogonadotropic hypogonadism (IHH) is known to decrease bone mineral density due to deficiency of sex steroid hormone. Graves' disease is also an important cause of secondary osteoporosis. However, IHH does not preclude the development of primary hyperthyroidism caused by Graves' disease, leading to more severe osteoporosis rapidly. Here, we describe the first case of 35-year-old Asian female patient with IHH accompanied by Graves' disease and osteoporosis-induced multiple fractures. Endocrine laboratory findings revealed preserved anterior pituitary functions except for secretion of gonadotropins and showed primary hyperthyroidism with positive autoantibodies. Sella magnetic resonance imaging showed slightly small sized pituitary gland without mass lesion. Dual energy X-ray absorptiometry revealed severe osteoporosis in lumbar spine and femur neck of the patient. Plain film radiography of the pelvis and shoulder revealed a displaced and nondisplaced fracture, respectively. After surgical fixation with screws for the femoral fracture, the patient was treated with antithyroid medication, calcium, and vitamin D until now and has been recovering fairly well. We report a patient of IHH with Graves' disease and multiple fractures that is a first case in Korea.
Absorptiometry, Photon ; Adult ; Asian Continental Ancestry Group ; Autoantibodies ; Bone Density ; Calcium ; Female ; Femoral Fractures ; Femur Neck ; Gonadotropins ; Graves Disease* ; Humans ; Hyperthyroidism ; Hypogonadism* ; Korea ; Magnetic Resonance Imaging ; Osteoporosis ; Pelvis ; Pituitary Gland ; Radiography ; Shoulder ; Spine ; Vitamin D

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Osteoporotic Fracture Risk Assessment Using Bone Mineral Density in Korean: A Community-based Cohort Study.

Eun Jin JANG ; Young Kyun LEE ; Hyung Jin CHOI ; Yong Chan HA ; Sunmee JANG ; Chan Soo SHIN ; Nam Han CHO

Journal of Bone Metabolism.2016;23(1):34-39. doi:10.11005/jbm.2016.23.1.34

BACKGROUND: Fracture-risk assessment tool (FRAX) using just clinical risk factors of osteoporosis has been developed to estimate individual risk of osteoporotic fractures. We developed prediction model of fracture risk using bone mineral density (BMD) as well as clinical risk factors in Korean, and assessed the validity of the final model. METHODS: To develop and validate an osteoporotic FRAX, a total of 768 Korean men and women aged 50 to 90 years were followed for 7 years in a community-based cohort study. BMD as well as clinical risk factors for osteoporotic fracture including age, sex, body mass index, history of fragility fracture, family history of fracture, smoking status, alcohol intake, use of oral glucocorticoid, rheumatoid arthritis, and other causes of secondary osteoporosis were assessed biannually. RESULTS: During the follow-up period, 86 osteoporotic fractures identified (36 in men and 50 in women). The developed prediction models showed high discriminatory power and had goodness of fit. CONCLUSIONS: The developed a Korean specific prediction model for osteoporotic fractures can be easily used as a screening tool to identify individual with high risk of osteoporotic fracture. Further studies for validation are required to confirm the clinical feasibility in general Korean population.
Arthritis, Rheumatoid ; Body Mass Index ; Bone Density* ; Cohort Studies* ; Female ; Follow-Up Studies ; Humans ; Korea ; Male ; Mass Screening ; Osteoporosis ; Osteoporotic Fractures* ; Risk Assessment* ; Risk Factors ; Smoke ; Smoking

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Relationship between Serum Inflammatory Marker and Bone Mineral Density in Healthy Adults.

Hee Sook LIM ; Yoon Hyung PARK ; Soon Kyung KIM

Journal of Bone Metabolism.2016;23(1):27-33. doi:10.11005/jbm.2016.23.1.27

BACKGROUND: Inflammatory markers have been shown to play an important role in bone remodeling. The purpose of this study was to investigate the relationship among serum C-reactive protein (CRP), adiponectin, tumor necrosis factor-alpha (TNF-alpha) and bone health in healthy adults. METHODS: We measured serum levels of CRP, adiponectin, TNF-alpha as well as lumbar spine and femoral neck bone mineral density (BMD) in 76 adults. Anthropometric measurements and nutrient intake survey of participants were carried out. The participants were divided into two groups (normal BMD group=40; 52.6%, decreased BMD group=36; 47.4%). RESULTS: The CRP concentration was significantly higher in the decreased BMD group. The adiponectin concentration was lower in the decreased BMD group but the difference was not significant. The TNF-alpha concentration was higher in the decreased BMD group, the difference was not significant. The participants in the decreased BMD group were found to have lower calcium intakes. The sodium intake of the decreased BMD group was significantly higher. The BMD in the decreased BMD group showed inverse correlations with CRP and dietary sodium intake. CONCLUSIONS: Serum CRP and dietary sodium intake is associated with BMD. Further research is needed to confirm the potential role of inflammatory marker to modulate the effects on bone.
Adiponectin ; Adult* ; Bone Density* ; Bone Remodeling ; C-Reactive Protein ; Calcium ; Femur Neck ; Humans ; Nutritional Status ; Sodium ; Sodium, Dietary ; Spine ; Tumor Necrosis Factor-alpha

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Prevalence of Sarcopenia in the Korean Woman Based on the Korean National Health and Nutritional Examination Surveys.

Hyoung Joon KWON ; Yong Chan HA ; Hyoung Moo PARK

Journal of Bone Metabolism.2016;23(1):23-26. doi:10.11005/jbm.2016.23.1.23

BACKGROUND: The criteria for defining sarcopenia vary among studies and confusion has arisen when defining the cutoff value. As a result, the prevalence of sarcopenia differs markedly depending on the definition. This study used the Asian Working Group for Sarcopenia (AWGS) definition to determine the prevalence of sarcopenia among Korean women. METHODS: This study was based on data obtained from the 2008 to 2011 Korean National Health and Nutrition Examination Surveys IV and V. We used the AWGS recommended cutoff value of 5.4 kg/m2 to determine the prevalence of sarcopenia in Korean women. RESULTS: The prevalence rates of sarcopenia using a cutoff value of 5.4 kg/m2 were 385 (19.5%) in women in their 50s, 286 (16.6%) in women in their 60s, 293 (23.7%) in women in their 70s, and 91 (30.8%) in women > or =80 years. The prevalence rates of sarcopenia were 307 (19.0%) in women 65 to 74 years, 194 (27.4%) in women 75 to 84 years, and 32 (40.5%) in women > or =85 years. The overall prevalence among women >50 years was 20.2%. The prevalence of sarcopenia in women >65 years was 22.1%. CONCLUSIONS: The prevalence of sarcopenia among Korean women was within the range of values of previous research about sarcopenia. Furthermore, using 5.4 kg/m2 as the cutoff value was useful to compare various studies about sarcopenia in Koreans.
Asian Continental Ancestry Group ; Female ; Humans ; Korea ; Prevalence* ; Sarcopenia*

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