Skeletal Fragility in Type 2 Diabetes Mellitus

Type 2 diabetes (T2D) is associated with an increased risk of fracture, which has been reported in several epidemiological studies. However, bone mineral density in T2D is increased and underestimates the fracture risk. Common risk factors for fracture do not fully explain the increased fracture risk observed in patients with T2D. We propose that the pathogenesis of increased fracture risk in T2D is due to low bone turnover caused by osteocyte dysfunction resulting in bone microcracks and fractures. Increased levels of sclerostin may mediate the low bone turnover and may be a novel marker of increased fracture risk, although further research is needed. An impaired incretin response in T2D may also affect bone turnover. Accumulation of advanced glycosylation endproducts may also impair bone strength. Concerning antidiabetic medication, the glitazones are detrimental to bone health and associated with increased fracture risk, and the sulphonylureas may increase fracture risk by causing hypoglycemia. So far, the results on the effect of other antidiabetics are ambiguous. No specific guideline for the management of bone disease in T2D is available and current evidence on the effects of antiosteoporotic medication in T2D is sparse. The aim of this review is to collate current evidence of the pathogenesis, detection and treatment of diabetic bone disease

Diagnosis and management of primary hyperparathyroidism in Europe

Background: There is continued debate as to the optimal strategy for diagnosis and management of primary hyperparathyroidism (PHPT). Aim: To compare the strategies used for the diagnosis and management of PHPT by physicians in five European countries. Design: Questionnaire-based survey. Methods: Physicians in France, Germany, the UK, Italy and Spain were invited to participate in the survey which was conducted using a web-based interface and were included in the evaluation if they had treated a minimum of four patients suffering from PHPT in the past year. Results: A total of 421 physicians completed the survey. The majority of respondents were endocrinologists (68%) but other specialities included rheumatologists (10.9%), internists (11.8%) and urologists (9.2%). Diagnostic methods were similar across different countries and specialities but there were significant differences in the proportion of physicians who recommended parathyroidectomy in asymptomatic patients with indications for surgery according to the 2002 National Institutes of Health (NIH) consensus conference statement (χ(2 )= 26.1, P < 0.001). The proportion of patients referred for surgery ranged from 32% in Italy to 66% in Spain with intermediate values in Germany (64%), France (55%) and the UK (53%). Conversely, pharmacological therapy was used most frequently for these patients in Italy (32%) and least frequently in Spain (14%). Conclusion: Significant differences exist in the management of patients with asymptomatic PHPT in countries across Europe who have accepted indications for surgery according to the NIH consensus statement. Further research will be required to explore the reasons for this and to determine if these differences affect the clinical outcome of PHPT

Bone Density and Structure in Overweight Men With and Without Diabetes

OBJECTIVE: Metabolic syndrome (MetS), type 1 diabetes (T1D), and type 2 diabetes, are associated with an increased risk of fractures; however, the impact of obesity on bone deficits in diabetes is unknown. We aimed to compare markers of bone structure, bone density, and bone turnover in non-diabetic overweight men with MetS and overweight men with T1D or T2D. METHODS AND RESEARCH DESIGN: In this cross-sectional study we included participants from two previously described study cohorts consisting of participants with diabetes and participants with MetS. Participants underwent dual-energy X-ray absorptiometry measuring areal bone mineral density (aBMD) at the hip and lumbar spine, High Resolution peripheral Quantitative (HRpQCT) scan of the tibia and radius and measurement of circulating bone turnover markers. We compared groups with unpaired t test and performed multiple linear regression with adjustment for age, body mass index, and smoking. RESULTS: We included 33 participants with T1D, 25 participants with T2D, and 34 participants with MetS. Bone turnover markers levels were comparable between T1D and MetS. aBMD at the hip was lower in T1D compared to MetS, also after adjustment. P1NP and Osteocalcin levels were lower among individuals with T2D compared to MetS, whereas aBMD were similar between the groups after multiple adjustments. We observed no difference in volumetric BMD at the tibia or radius between MetS and T1D and T2D, respectively. Participants with T2D had a higher trabecular number and lower trabecular separation compared to individuals with MetS at the tibia, which remained signficant after multiple adjustments. CONCLUSION: In conclusion, we observed no clinically important differences in bone density or structure between men with T2D, T1D, or MetS. However, men with T2D displayed lower bone turnover compared to MetS highlighting that T2D per se and not obesity, is associated with low bone turnover

Assessment of gene-by-sex interaction effect on bone mineral density

To access publisher's full text version of this article. Please click on the hyperlink in Additional Links field.Sexual dimorphism in various bone phenotypes, including bone mineral density (BMD), is widely observed; however, the extent to which genes explain these sex differences is unclear. To identify variants with different effects by sex, we examined gene-by-sex autosomal interactions genome-wide, and performed expression quantitative trait loci (eQTL) analysis and bioinformatics network analysis. We conducted an autosomal genome-wide meta-analysis of gene-by-sex interaction on lumbar spine (LS) and femoral neck (FN) BMD in 25,353 individuals from 8 cohorts. In a second stage, we followed up the 12 top single-nucleotide polymorphisms (SNPs; p < 1 × 10(-5) ) in an additional set of 24,763 individuals. Gene-by-sex interaction and sex-specific effects were examined in these 12 SNPs. We detected one novel genome-wide significant interaction associated with LS-BMD at the Chr3p26.1-p25.1 locus, near the GRM7 gene (male effect = 0.02 and p = 3.0 × 10(-5) ; female effect = -0.007 and p = 3.3 × 10(-2) ), and 11 suggestive loci associated with either FN- or LS-BMD in discovery cohorts. However, there was no evidence for genome-wide significant (p < 5 × 10(-8) ) gene-by-sex interaction in the joint analysis of discovery and replication cohorts. Despite the large collaborative effort, no genome-wide significant evidence for gene-by-sex interaction was found to influence BMD variation in this screen of autosomal markers. If they exist, gene-by-sex interactions for BMD probably have weak effects, accounting for less than 0.08% of the variation in these traits per implicated SNP. © 2012 American Society for Bone and Mineral Research.Medtronic NIH R01 AG18728 R01HL088119 R01AR046838 U01 HL084756 R01 AR43351 P01-HL45522 R01-MH-078111 R01-MH-083824 Nutrition and Obesity Research Center of Maryland P30DK072488 NIAMS/NIH F32AR059469 Instituto de Salud Carlos III-FIS (Spanish Health Ministry) PI 06/0034 PI08/0183 Canadian Institutes of Health Research (CIHR) NHLBI HHSN268201200036C N01-HC-85239 N01-HC-85079 N01-HC-85086 N01-HC-35129 N01 HC15103 N01 HC-55222 N01-HC-75150 N01-HC-45133 HL080295 HL087652 HL105756 NIA AG-023629 AG-15928 AG-20098 AG-027058 N01AG62101 N01AG62103 N01AG62106 1R01AG032098-01A1 National Center of Advancing Translational Technologies CTSI UL1TR000124 National Institute of Diabetes and Digestive and Kidney Diseases DK063491 EUROSPAN (European Special Populations Research Network) European Commission FP6 STRP grant 018947 LSHG-CT-2006-01947 Netherlands Organisation for Scientific Research Erasmus MC Centre for Medical Systems Biology (CMSB) Netherlands Brain Foundation (HersenStichting Nederland) US National Institute for Arthritis, Musculoskeletal and Skin Diseases National Institute on Aging R01 AR/AG41398 R01 AR050066 R21 AR056405 National Heart, Lung, and Blood Institute's Framingham Heart Study N01-HC-25195 Affymetrix, Inc. N02-HL-6-4278 Canadian Institutes of Health Research from Institute of Aging 165446 Institute of Genetics 179433 Institute of Musculoskeletal health 221765 Intramural Research Program of the NIH, National Institute on Aging National Institutes of Health HHSN268200782096C Hong Kong Research Grant Council HKU 768610M Bone Health Fund of HKU Foundation KC Wong Education Foundation Small Project Funding 201007176237 Matching Grant CRCG Grant Osteoporosis and Endocrine Research Fund Genomics Strategic Research Theme of The University of Hong Kong Netherlands Organisation of Scientific Research NWO Investments 175.010.2005.011 911-03-012 Research Institute for Diseases in the Elderly 014-93-015 Netherlands Genomics Initiative (NGI)/Netherlands Consortium for Healthy Aging (NCHA) 050-060-810 Erasmus Medical Center and Erasmus University, Rotterdam Netherlands Organization for the Health Research and Development (ZonMw) Research Institute for Diseases in the Elderly (RIDE) Ministry of Education, Culture and Science Ministry for Health, Welfare and Sports European Commission (DG XII) Municipality of Rotterdam German Bundesministerium fur Forschung und Technology 01 AK 803 A-H 01 IG 07015

Association of vitamin D status with arterial blood pressure and hypertension risk : a mendelian randomisation study

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New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

The Impact of Multifaceted Osteoporosis Group Education on Patients’ Decision-Making regarding Treatment Options and Lifestyle Changes

Introduction. Patients with chronic diseases like osteoporosis constantly have to make decisions related to their disease. Multifaceted osteoporosis group education (GE) may support patients’ decision-making. This study investigated multifaceted osteoporosis GE focusing on the impact of GE on patients’ decision-making related to treatment options and lifestyle. Material and Methods. An interpretive description design using ethnographic methods was utilized with 14 women and three men diagnosed with osteoporosis who attended multifaceted GE. Data consisted of participant observation during GE and individual interviews. Results. Attending GE had an impact on the patients’ decision-making in all educational themes. Patients decided on new ways to manage osteoporosis and made decisions regarding bone health and how to implement a lifestyle ensuring bone health. During GE, teachers and patients shared evidence-based knowledge and personal experiences and preferences, respectively, leading to a two-way exchange of information and deliberation about recommendations. Though teachers and patients explored the implications of the decisions and shared their preferences, teachers stressed that the patients ultimately had to make the decision. Teachers therefore refrained from participating in the final step of the decision-making process. Conclusion. Attending GE has an impact on the patients’ decision-making as it can initiate patient reflection and support decision-making

Can bone loss be reversed by antithyroid drug therapy in premenopausal women with Graves' disease?

CONTEXT: Hyperthyroidism can lead to reduced bone mineral density (BMD) and increased fracture risk particularly in postmenopausal women, but the mechanism behind is still unclear. OBJECTIVE: Prospective examination of the influence of thyroid hormones and/or thyroid autoantibodies on BMD in premenopause. DESIGN: We have examined 32 premenopausal women with untreated active Graves' disease from time of diagnosis, during 18 months of antithyroid drug therapy (ATD) and additionally 18 months after discontinuing ATD. Variables of thyroid metabolism, calcium homeostasis and body composition were measured every 3 months. BMD of lumbar spine and femoral neck were measured at baseline, 18 ± 3 and 36 ± 3 months. Data were compared to base line, a sex- and age matched control group and a group of patients with Hashimoto's thyroiditis treated with non-suppressive doses of levothyroxine. RESULTS: The study showed significantly (p < 0.002) lower BMD in the thyrotoxic state compared to the control group with subsequent significant improvement during 18 ± 3 months of ATD compared to baseline (p < 0.001). However, during the following 18 months after stopping ATD femoral neck BMD decreased again unrelated to age (more than 0.4% per year, p < 0,002). The wellestablished effect of thyrotoxicosis on calcium homeostasis was confirmed. The positive predictor for best BMD was TSH receptor antibodies (TRAb) while free T4 correlated negatively in the thyrotoxic female Graves' patients (p < 0.02 and p < 0.003). In healthy controls and patients with treated Graves' disease both TSH and T4 correlated negatively to the bone mass (BMC) (p < 0.003). CONCLUSION: The results indicated a clinically relevant impact of thyroid function on bone modulation also in premenopausal women with Graves' disease, and further indicated the possibility for a direct action of TRAb on bones