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      Risk factors for osteoporosis in Japan: is it associated with Helicobacter pylori?

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          A number of diseases and drugs may influence bone mineral density; however, there are few reports concerning the relationship between lifestyle-related diseases and osteoporosis in Japan as determined by multivariate analysis. The aim of this study was to investigate the risk factors for osteoporosis and whether infection by or eradication of Helicobacter pylori is associated with osteoporosis.


          Between February 2008 and November 2014, using a cross-sectional study design, we investigated patient profile (age, sex, BMI, alcohol, smoking), H. pylori infection status, comorbidities, internal medicine therapeutic agents (calcium channel blocker, HMG-CoA reductase inhibitors, proton pump inhibitor), serum parameters (Hb, calcium, γGTP), bone turn over markers (bone-specific alkaline phosphatase (BAP) and collagen type I cross-linked N telopeptide (NTX), findings on dual-energy x-ray absorptiometry (DEXA) and upper gastrointestinal endoscopy, and Frequency Scale for the Symptoms of GERD score in consecutive outpatients aged ≥50 years at our hospital. We divided the subjects into an osteoporosis group and a non-osteoporosis group and investigated risk factors for osteoporosis between the two groups by bivariate and multivariate analyses.


          Of the 255 eligible study subjects, 43 (16.9%) had osteoporosis. Bivariate analysis showed that advanced age, female sex, lower body mass index, lower cumulative alcohol intake, lower Brinkman index, H. pylori positivity, lower hemoglobin, bone-specific alkaline phosphatase, lower prevalence of hiatal hernia, and endoscopic gastric mucosal atrophy were related to osteoporosis. Multivariate analysis showed that advanced age (odds ratio [OR] 1.13, 95% confidence interval [CI] 1.07–1.19, P<0.001), female sex (OR 6.27, 95% CI 2.26–17.39, P<0.001), low BMI (OR 0.82, 95% CI 0.72–0.94, P=0.005), H. pylori positivity (OR 3.00, 95% CI 1.31–6.88, P=0.009), and BAP (OR 1.07, 95% CI 1.01–1.14, P=0.035) were related to osteoporosis.


          Advanced age, low BMI, BAP, and H. pylori positivity were risk factors for osteoporosis; however, the success of H. pylori eradication was not a risk factor for osteoporosis in Japan.

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          Most cited references 50

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          Systematic review of type 1 and type 2 diabetes mellitus and risk of fracture.

          The authors conducted a systematic review of published data on the association between diabetes mellitus and fracture. The authors searched MEDLINE through June 2006 and examined the reference lists of pertinent articles (limited to studies in humans). Summary relative risks and 95% confidence intervals were calculated with a random-effects model. The 16 eligible studies (two case-control studies and 14 cohort studies) included 836,941 participants and 139,531 incident cases of fracture. Type 2 diabetes was associated with an increased risk of hip fracture in both men (summary relative risk (RR) = 2.8, 95% confidence interval (CI): 1.2, 6.6) and women (summary RR = 2.1, 95% CI: 1.6, 2.7). Results were consistent between studies of men and women and between studies conducted in the United States and Europe. The association between type of diabetes and hip fracture incidence was stronger for type 1 diabetes (summary RR = 6.3, 95% CI: 2.6, 15.1) than for type 2 diabetes (summary RR = 1.7, 95% CI: 1.3, 2.2). Type 2 diabetes was weakly associated with fractures at other sites, and most effect estimates were not statistically significant. These findings strongly support an association between both type 1 and type 2 diabetes and increased risk of hip fracture in men and women.
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            Development and evaluation of FSSG: frequency scale for the symptoms of GERD.

            The aim of this study was to produce a simplified questionnaire for evaluation of the symptoms of gastroesophageal reflux disease (GERD). A total of 124 patients with an endoscopic diagnosis of GERD completed a 50-part questionnaire, requiring only "yes" or "no" answers, that covered various symptoms related to the upper gastrointestinal tract, as well as psychosomatic symptoms. The 12 questions to which patients most often answered "yes" were selected, and were assigned scores (never = 0; occasionally = 1; sometimes = 2; often = 3; and always = 4) to produce a frequency scale for symptoms of GERD (FSSG). Sensitivity, specificity, and accuracy of the FSSG questionnaire were evaluated in another group of patients with GERD and non-GERD. The usefulness of this questionnaire was evaluated in 26 other GERD patients who were treated with proton pump inhibitors for 8 weeks. When the cutoff score was set at 8 points, the FSSG showed a sensitivity of 62%, a specificity of 59%, and an accuracy of 60%, whereas a cutoff score of 10 points altered these values to 55%, 69%, and 63%. The score obtained using the questionnaire correlated well with the extent of endoscopic improvement in patients with mild or severe GERD. This new questionnaire is useful for the objective evaluation of symptoms in GERD patients.
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              Physiology and pathophysiology of bone remodeling.

              The skeleton is a metabolically active organ that undergoes continuous remodeling throughout life. This remodeling is necessary both to maintain the structural integrity of the skeleton and to subserve its metabolic functions as a storehouse of calcium and phosphorus. These dual functions often come into conflict under conditions of changing mechanical forces or metabolic and nutritional stress. The bone remodeling cycle involves a complex series of sequential steps that are highly regulated. The "activation" phase of remodeling is dependent on the effects of local and systemic factors on mesenchymal cells of the osteoblast lineage. These cells interact with hematopoietic precursors to form osteoclasts in the "resorption" phase. Subsequently, there is a "reversal" phase during which mononuclear cells are present on the bone surface. They may complete the resorption process and produce the signals that initiate formation. Finally, successive waves of mesenchymal cells differentiate into functional osteoblasts, which lay down matrix in the "formation" phase. The effects of calcium-regulating hormones on this remodeling cycle subserve the metabolic functions of the skeleton. Other systemic hormones control overall skeletal growth. The responses to changes in mechanical force and repair of microfractures, as well as the maintenance of the remodeling cycle, are determined locally by cytokines, prostaglandins, and growth factors. Interactions between systemic and local factors are important in the pathogenesis of osteoporosis as well as the skeletal changes in hyperparathyroidism and hyperthyroidism. Local factors are implicated in the pathogenesis of the skeletal changes associated with immobilization, inflammation, and Paget disease of bone.

                Author and article information

                Ther Clin Risk Manag
                Ther Clin Risk Manag
                Therapeutics and Clinical Risk Management
                Therapeutics and Clinical Risk Management
                Dove Medical Press
                06 March 2015
                : 11
                : 381-391
                Department of Gastroenterology, University of Juntendo, School of Medicine, Tokyo, Japan
                Author notes
                Correspondence: Daisuke Asaoka, Department of Gastroenterology, Juntendo University School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo 113-8421, Japan, Tel +813 3813 3111, Fax +813 3813 8862, Email daisuke@ 123456juntendo.ac.jp
                © 2015 Asaoka et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License

                The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

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