BACKGROUND: Epidemiology studies suggest that oral bisphosphonate may increase the risk of esophageal cancer. The present study aimed to investigate the association between exposure of oral bisphosphonate and risk of esophageal cancer. METHODS: Using the nationwide medical claim database in South Korea, 2,167,955 subjects, who initiated osteoporosis treatment (oral bisphosphonate, intravenous bisphosphonate or raloxifene) or performed dual energy X-ray absorptiometry (DXA) between 2008 and 2012, were analyzed. Diagnosis of esophageal cancer was estimated from medical claim database. Standardized incidence ratio (SIR) was estimated by comparing with incidence in the general population. Cox proportional hazards modeling was used to investigate age-adjusted hazard ratio (aHR) of esophageal cancer. RESULTS: The present study included oral bisphosphonate group (N=1,435,846), comparator group 1 (intravenous bisphosphonate or raloxifene, N=78,363) and comparator group 2 (DXA, N=653,746). Mean age was 65.6+/-8.8 years and mean observation duration was 30.9+/-17.7 months. During 5,503,688 patient-years, 205 esophageal cancer incidences were observed. The annual incidence of esophageal cancer was 3.88, 4.21, and 3.30 for oral bisphosphonate group, comparator group 1 and comparator group 2, respectively. SIR of esophageal cancer was 1.24, 1.38, and 1.40 for oral bisphosphonate group, comparator group 1 and comparator group 2, respectively. Esophageal cancer risk of oral bisphosphonate group was not significantly different from comparator group 1 and comparator group 2 (aHR 0.87; 95% confidence interval [CI] 0.39-1.98 and aHR 0.94; 95% CI 0.68-1.30, respectively). CONCLUSIONS: The use of oral bisphosphonate was not associated with increased risk of esophageal cancer in real clinical practice using large scale nationwide database.
Absorptiometry, Photon ; Diagnosis ; Epidemiology ; Esophageal Neoplasms* ; Incidence ; Korea ; Osteoporosis ; Proportional Hazards Models ; Raloxifene Hydrochloride

BACKGROUND: Sarcopenia is considering important disease entity in elderly. Several study groups define the sum of the muscle masses of the four limbs as appendicular skeletal mass (ASM) to calculate skeletal muscle index (SMI). The purpose of this study was to determine cut point of SMI for sarcopenia in Korean women. METHODS: This study was based on data obtained from the 2008 to 2011 Korean National Health and Nutrition Examination Survey (KNHANES) IV and V. A whole body dual energy X-ray absorptiometry scan were performed on individuals of > or =10 years old from July 2008 to May 2011. In the analysis, 11,633 women were included. ASM was calculated and SMI was obtained as ASM/height2. Cutoff value was defined two standard deviations below mean values for young reference group. RESULTS: Of 11,633 women aged 10 to 97 years, mean and standard deviation of year was 46.73+/-18.54 years. The highest level of height was noted in 20's and the highest total sum of skeletal mass was seen 14.87 kg in 40's. The highest value of SMI was noted in 60's in Korean women. Cutoff value as mean value of young women was decided with SMI of 30's and 40's that have peak ASM. Mean and standard deviation of SMI in those ages was 5.9+/-0.7 kg/m2. A SMI of two standard deviations below the mean SMI of reference groups was 4.4 kg/m2 as cutoff value. CONCLUSIONS: This study shows that 4.4 kg/m2 of SMI in Korean women was cutoff value of sarcopenia. Further study is clearly required to decide cutoff value of SMI for sarcopenia, especially for Korean women.
Absorptiometry, Photon ; Aged ; Diagnosis ; Extremities ; Female ; Humans ; Korea ; Muscle, Skeletal* ; Nutrition Surveys ; Reference Values* ; Sarcopenia*

BACKGROUND: The purpose of this study is to investigate 1) whether equol has the direct modulation on vascular tone of endothelium-denuded human uterine artery, and 2) if present, whether this equol-induced modulation of vascular tone is mediated by intracellular calcium modulation through Ca2+ & K+ channels on vascular smooth muscle cell membrane. METHODS: The uterine arteries were obtained at the time of hysterectomy from 15 women. The uterine smooth muscles were pretreated with phenylephrine, 10(-5) M & high KCl solution 70 mM. The equol at 6 different concentrations from 10(-11) to 10(-6) M were used for the evaluation of modulatory action of equol on precontracted vascular smooth. The cumulative concentration-response for equol were determined on phenylephrine-induced contractions and compared with the results without pretreatment. RESULTS: Equol 10(-11) to 10(-6) M in concentration showed relaxation effect on vascular smooth muscle contraction which was induced by phenylephrine 10(-5) M. This relaxation effect of equol was dose-dependent. Equol in same concentrations showed no significant effects on vascular smooth muscle contraction induced by high KCI solution. Phenylephrine-induced contraction was markedly reduced from 10(-7) to 10(-4) M in concentration by pretreatment of equol, but high KCI-induced contraction was not affected by pretreatment of equol. CONCLUSIONS: This vasodilatation effect of equol may be induced by calcium antagonistic action, which was mediated through antagonistic action for receptor-dependent Ca2+ channel, but not for voltage-dependent Ca2+ channel. As far as we know, this is the first report of phytoestrogen equol on vascular reactivity of human vessels.
Calcium ; Cell Membrane ; Equol ; Female ; Humans ; Hysterectomy ; Muscle, Smooth ; Muscle, Smooth, Vascular ; Phenylephrine ; Phytoestrogens ; Relaxation ; Uterine Artery* ; Vasodilation*

BACKGROUND: Many histone deacetylase (HDAC) inhibitors are well recognized as potential anti-cancer drugs. Inhibition of HDACs induces temporal transcription or epigenetic control, thus regulating many different biological responses. Here, we investigated the osteogenic effect of the HDAC inhibitor suberoylanilide hydroxamic acid (SAHA; vorinostat). METHODS: The effects of SAHA on osteoblast differentiation were examined in the 6XOSE-Luc reporter assay for determination of runt-related transcription factor 2 (Runx2) activity and alkaline phosphatase (ALP) activity and in an immunoprecipitation assay to determine the Runx2 acetylation state. The osteogenic activity of SAHA in vivo was studied in and receptor activator of nuclear factor-kappa B ligand (RANKL)-induced osteoporotic mouse model. RESULTS: SAHA increased the transcriptional activity of Runx2 in a dose-dependent manner in the 6XOSE-Luc reporter assay. SAHA by itself was unable to induce ALP activity; however, SAHA enhanced ALP activity induced by bone morphogenetic protein-2 (BMP-2). The degree of acetylation of Runx2 was increased with SAHA treatment, which suggests that the increase in Runx2 transcriptional activity might be dependent on stabilization by acetylation. Also, SAHA successfully reversed soluble RANKL-induced osteoporotic bone loss. CONCLUSIONS: Our study shows an intriguing osteogenic potential of SAHA in a BMP-2-dependent manner and suggests that SAHA could be used at lower doses along with BMP-2 to treat osteoporosis.
Acetylation ; Alkaline Phosphatase ; Animals ; Bone Morphogenetic Protein 2 ; Epigenomics ; Histone Deacetylase Inhibitors ; Histone Deacetylases ; Hydroxamic Acids* ; Immunoprecipitation ; Mice ; Osteoblasts ; Osteogenesis ; Osteoporosis ; RANK Ligand ; Transcription Factors

BACKGROUND: Although dual energy X-ray absorptiometry (DXA) is known to standard equipment for bone mineral density (BMD) measurements. Different results of BMD measurement using a number of different types of devices are difficult to use clinical practice. The purpose of this study was to evaluate discrepancy and standardizations of DXA devices from three manufactures using a European Spine Phantom (ESP). METHODS: We calculated the accuracy and precision of 36 DXA devices from three manufacturers (10 Hologic, 16 Lunar, and 10 Osteosys) using a ESP (semi-anthropomorphic). The ESP was measured 5 times on each equipment without repositioning. Accuracy was assessed by comparing BMD (g/cm2) values measured on each device with the actual value of the phantom. Precision was assessed by the coefficient of variation (CVsd). RESULTS: Lunar devices were, on average, 22%, 8.3%, and 5% overestimation for low (L1) BMD values, medium (L2), and high (L3) BMD values. Hologic devices were, on average, 6% overestimation for L1 BMD, and 5% and 6.2% underestimation for L2 and L3 BMD values. Osteosys devices was, on average, 12.7% (0.063 g/cm2), 6.3% (0.062 g/cm2), and 5% (0.075 g/cm2) underestimation for L1, L2, and L3, respectively. The mean CVsd for L1-L3 BMD were 0.01%, 0.78%, and 2.46% for Lunar, Hologic, and Osteosys devices respectively. CONCLUSIONS: The BMD comparison in this study demonstrates that BMD result of three different devices are significant different between three devices. Differences of BMD between three devices are necessary to BMD standardization.
Absorptiometry, Photon ; Bone Density ; Densitometry* ; Lumbar Vertebrae ; Spine*

Bisphosphonate is notable for the treatment of osteoporosis in the world. But recently if Bisphosphonate is taken for a long time, it causes an insufficiency fracture by suppression of bone turn-over and it is reported rarely on femur neck. Here we report a case of insufficiency fracture on ipsilateral femur neck in woman treated with long term Bisphosphonate therapy.
Female ; Femur ; Femur Neck ; Fractures, Stress ; Humans ; Osteoporosis

Cushing's syndrome is characterized by central obesity, fatigability, weakness, amenorrhea, hirsutism, edema, hypertension, impaired glucose tolerance, and osteoporosis due to excessive production of steroids. Cushing's syndrome is an important cause of secondary osteoporosis. Patients with Cushing's syndrome have a high incidence of osteoporotic fractures. At least, 30-50% of patients with Cushing's syndrome experience fractures, particularly in the vertebral body. And it is consistent with the 50% prevalence of osteoporosis in patients with Cushing's syndrome. However, reports of multiple pathological fractures in young patients with Cushing's syndrome are rare. Thus, we describe the case of a 26-year-old woman with Cushing's syndrome accompanied with recurrent multiple osteoporotic fractures and being treated by parathyroid hormone. Careful consideration for the possibility of Cushing's syndrome will be necessary in case of young patients with a spontaneous multiple compression fractures in spine.
Adult ; Amenorrhea ; Cushing Syndrome ; Edema ; Female ; Fractures, Compression ; Fractures, Spontaneous ; Glucose ; Hirsutism ; Humans ; Hypertension ; Incidence ; Obesity, Abdominal ; Osteoporosis ; Osteoporotic Fractures ; Parathyroid Hormone ; Prevalence ; Spine ; Steroids

As a result of aging population, the incidence of pelvic insufficiency fracture has been increasing. Pain-related immobility caused by pelvic insufficiency fractures may result in a serious dependency and high mortality with preexisting comorbidities. We present two cases of pelvic insufficiency fracture in elderly patients which had good clinical outcome by parathyroid hormone 1-34(teriparatide) treatment as well as a literature review.
Aged ; Aging ; Comorbidity ; Dependency (Psychology) ; Fractures, Stress ; Humans ; Incidence ; Osteoporosis ; Parathyroid Hormone ; Pelvis

Bisphosphonate generally seems to be safe, but hypocalcemia may occasionally develop in the course of bisphosphonate treatment. Hypocalcemia induced by bisphosphonate is usually mild and asymptomatic, but unrecognized or poorly treated hypocalcemia can lead to life-threatening state. A 78-year-old woman who had a history of hip arthroplasty and intravenous zoledronate treatment for femur neck fracture was presented to emergency department with altered mental status. It turned out that her symptom was due to severe hypocalcemia which was caused by intravenous zoledronate treatment. She also had renal dysfunction. She was treated by intravenous calcium gluconate and calcitriol administration. This case supports the need for evaluation of renal dysfunction, vitamin D deficiency and parathyroid gland dysfunction before bisphosphonate treatment and accurate monitoring of plasma calcium and creatinine levels. In addition, vitamin D and calcium supply during treatment with bisphosphonate is mandatory.
Aged ; Arthroplasty ; Calcitriol ; Calcium ; Calcium Gluconate ; Creatinine ; Diphosphonates ; Emergencies ; Female ; Femoral Neck Fractures ; Gluconates ; Hip ; Humans ; Hypocalcemia ; Imidazoles ; Osteoporosis ; Parathyroid Glands ; Plasma ; Vitamin D ; Vitamin D Deficiency

Steroid-induced osteoporosis is the most common cause of secondary osteoporosis and accounts for one-fifth of all osteoporosis cases. The fracture incidence under steroid may be as high as 50%. However, many patients do not undergo appropriate risk assessment and treatment before and after steroid exposure. We described a 56-year-old male patient with multiple punched-out lesions in skull unusually as well as vertebral, fibular, rib and humeral fractures during steroid use without proper management.
Humans ; Humeral Fractures ; Incidence ; Male ; Middle Aged ; Osteoporosis ; Ribs ; Risk Assessment ; Skull