Scottish Intercollegiate Guidelines Network

Summary
A fracture risk assessment tool (FRAX™) is developed based on the use of clinical risk factors with or without bone mineral density tests applied to the UK.

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FRAX™ and the assessment of fracture probability in men and women from the UK

https://onlinelibrary.wiley.com/doi/pdf/10.1002/j.2051-5545.2011.tb00014.x

Physical illness in patients with severe mental disorders.I. Prevalence, impact of medications and disparities in health care

结节病易误诊,据王洪武等~([1])收集国内18篇关于此病误诊的文献,误诊率高达63.2%,当然有误诊就会有误治,如孙永昌等~([2])报道26例结节病在影像学检查诊断的第一印象中拟诊结核5例,其中就有2例完成规范的抗结核治疗,为此应引起临床对本病诊治的重视。

Sarcoidosis

Reports linking long-term use of bisphosphonates (BPs) with atypical fractures of the femur led the leadership of the American Society for Bone and Mineral Research (ASBMR) to appoint a task force to address key questions related to this problem. A multidisciplinary expert group reviewed pertinent published reports concerning atypical femur fractures, as well as preclinical studies that could provide insight into their pathogenesis. A case definition was developed so that subsequent studies report on the same condition. The task force defined major and minor features of complete and incomplete atypical femoral fractures and recommends that all major features, including their location in the subtrochanteric region and femoral shaft, transverse or short oblique orientation, minimal or no associated trauma, a medial spike when the fracture is complete, and absence of comminution, be present to designate a femoral fracture as atypical. Minor features include their association with cortical thickening, a periosteal reaction of the lateral cortex, prodromal pain, bilaterality, delayed healing, comorbid conditions, and concomitant drug exposures, including BPs, other antiresorptive agents, glucocorticoids, and proton pump inhibitors. Preclinical data evaluating the effects of BPs on collagen cross-linking and maturation, accumulation of microdamage and advanced glycation end products, mineralization, remodeling, vascularity, and angiogenesis lend biologic plausibility to a potential association with long-term BP use. Based on published and unpublished data and the widespread use of BPs, the incidence of atypical femoral fractures associated with BP therapy for osteoporosis appears to be very low, particularly compared with the number of vertebral, hip, and other fractures that are prevented by BPs. Moreover, a causal association between BPs and atypical fractures has not been established. However, recent observations suggest that the risk rises with increasing duration of exposure, and there is concern that lack of awareness and underreporting may mask the true incidence of the problem. Given the relative rarity of atypical femoral fractures, the task force recommends that specific diagnostic and procedural codes be created and that an international registry be established to facilitate studies of the clinical and genetic risk factors and optimal surgical and medical management of these fractures. Physicians and patients should be made aware of the possibility of atypical femoral fractures and of the potential for bilaterality through a change in labeling of BPs. Research directions should include development of animal models, increased surveillance, and additional epidemiologic and clinical data to establish the true incidence of and risk factors for this condition and to inform orthopedic and medical management. © 2010 American Society for Bone and Mineral Research.

https://asbmr.onlinelibrary.wiley.com/doi/pdf/10.1002/jbmr.416

Atypical subtrochanteric and diaphyseal femoral fractures: Report of a task force of the american society for bone and mineral Research

We studied the association between fractures and type 1 and type 2 diabetes mellitus. In this case-control study, all subjects diagnosed with a fracture (n=124,655) in Denmark served as cases, and for each case three control subjects (n=373,962) matched for sex and age were retrieved from the general population. Type 1 and type 2 diabetes were associated with an increased risk (1) of any fracture (odds ratio [OR]=1.3, 95% CI: 1.2–1.5 for type 1 diabetes and 1.2, 95% CI: 1.1–1.3 for type 2 diabetes after adjustment for confounders) and (2) of hip fractures (OR=1.7, 95% CI: 1.3–2.2 for type 1 diabetes, and 1.4, 95% CI: 1.2–1.6 for type 2 diabetes). Furthermore, type 2 diabetes was associated with a significant increase in forearm fractures (OR=1.2, 95% CI: 1.0–1.5), and type 1 diabetes was associated with an increased risk of spine fractures (OR=2.5, 95% CI: 1.3–4.6), whereas type 2 diabetes was not. Use of metformin and sulphonylureas was associated with a significantly decreased risk of any fracture, whereas a non-significant trend towards decreased risk of any fracture was associated with the use of insulin. Except for a decrease in hip fractures with use of sulphonylureas, no change in fracture risk in the hip, spine or forearm was associated with the use of insulin or oral antidiabetic drugs. Type 1 and type 2 diabetes are associated with an increased risk of any fracture and hip fractures. The use of drugs to control diabetes may reduce the association between diabetes and fractures.

/pdf/relative-fracture-risk-in-patients-with-diabetes-mellitus-29huk3sf3f.pdf

Relative fracture risk in patients with diabetes mellitus, and the impact of insulin and oral antidiabetic medication on relative fracture risk

Obesity, diabetes, hypertension, and hyperlipidemia constitute risk factors for morbidity and premature mortality. Based on animal and in vitro studies, resveratrol reverts these risk factors via stimulation of silent mating type information regulation 2 homolog 1 (SIRT1), but data in human subjects are scarce. The objective of this study was to examine the metabolic effects of high-dose resveratrol in obese human subjects. In a randomized, placebo-controlled, double-blinded, and parallel-group design, 24 obese but otherwise healthy men were randomly assigned to 4 weeks of resveratrol or placebo treatment. Extensive metabolic examinations including assessment of glucose turnover and insulin sensitivity (hyperinsulinemic euglycemic clamp) were performed before and after the treatment. Insulin sensitivity, the primary outcome measure, deteriorated insignificantly in both groups. Endogenous glucose production and the turnover and oxidation rates of glucose remained unchanged. Resveratrol supplementation also had no effect on blood pressure; resting energy expenditure; oxidation rates of lipid; ectopic or visceral fat content; or inflammatory and metabolic biomarkers. The lack of effect disagrees with persuasive data obtained from rodent models and raises doubt about the justification of resveratrol as a human nutritional supplement in metabolic disorders.

https://diabetes.diabetesjournals.org/content/diabetes/62/4/1186.full.pdf

High-Dose Resveratrol Supplementation in Obese Men: An Investigator-Initiated, Randomized, Placebo-Controlled Clinical Trial of Substrate Metabolism, Insulin Sensitivity, and Body Composition

Summary We performed a meta-analysis of cross-sectional studies on serum 25(OH)D status globally. Serum 25(OH)D levels on average were 54 nmol/l, were higher in women than men, and higher in Caucasians than in non-Caucasians. There was no trend in serum 25(OH)D level with latitude. Vitamin D deficiency was widespread.

/pdf/global-vitamin-d-levels-in-relation-to-age-gender-skin-2n8zoj4apu.pdf

Global vitamin D levels in relation to age, gender, skin pigmentation and latitude: an ecologic meta-regression analysis.

We studied the effect of proton pump inhibitors, histamine H(2) receptor antagonists, and other types of antacid drugs on fracture risk. All cases were subjects with any fracture sustained during the year 2000 (n = 124,655). For each case, three controls (n = 373,962) matched on age and gender were randomly drawn from the background population. The primary exposure variables were use of proton pump inhibitors, histamine H(2) antagonists, and other antacid drugs. Adjustments were made for several confounders, including diagnosis of an ulcer, nonsteroidal anti-inflammatory drug use, use of histamine H(1) antagonists, stomach resection, previous fracture, and use of corticosteroids. The effect of dose was examined by stratifying for cumulated dose (defined daily dose). Use of proton pump inhibitors was associated with an increase in fracture risk for use within the last year [odds ratio (OR) = 1.18, 95% confidence interval (CI) 1.12-1.43 for overall fracture risk; OR = 1.45, 95% CI 1.28-1.65 for hip fractures; and OR = 1.60, 95% CI 1.25-2.04 for spine fractures). Histamine H(2) antagonists were associated with a decreased fracture risk if they had been used within the last year (OR = 0.88, 95% CI 0.82-0.95 for any fracture, OR = 0.69, 95% CI 0.57-0.84 for hip fractures). Other antacids were not associated with overall fracture risk but were associated with hip and spine fractures. Proton pump inhibitors appeared to be associated with a limited increase in fracture risk, in contrast to histamine H( 2 ) antagonists, which seemed to be associated with a small decrease in fracture risk. In all cases, the changes in risk estimates were small and the clinical significance was limited.

Proton pump inhibitors, histamine H2 receptor antagonists, and other antacid medications and the risk of fracture.

In a cohort of 169,145 patients with a hip fracture and 524,010 controls we observed an excess mortality among patients compared to controls for as long as 20 years after the hip fracture. The main reason for the excess mortality was linked to the trauma that caused the hip fracture. Patients with a hip fracture have a significant excess mortality. However, it remains unclear if the mortality is linked to the pre-morbid conditions or to complications to the fracture. All subjects with a hip fracture in Denmark between 1977 and 2001 were compared with three age- and gender-matched subjects from the general population. A total of 169,145 fracture cases were compared to 524,010 controls. The cases had a much higher prevalence of co-morbidity than the controls. The mortality rate was twice as high in fracture cases compared with controls (HR = 2.26, 95% CI: 2.24–2.27). Adjustments for confounders only changed the excess mortality risk little. The mortality after the hip fracture was divided into two categories: an excess mortality of 19% within the first year following the fracture (relative survival = 0.81 compared to controls), and an excess mortality of 1.8% per year (relative survival 0.982) for every additional year following the fracture. The major causes of the excess mortality were due to complications to the fracture event (70.8% within the first 30 days). Patients with a hip fracture have a pronounced excess mortality risk. The major cause was linked to the fracture event and not to pre-existing co-morbidity.

P. Vestergaard

Papers

Relative fracture risk in patients with diabetes mellitus, and the impact of insulin and oral antidiabetic medication on relative fracture risk

High-Dose Resveratrol Supplementation in Obese Men: An Investigator-Initiated, Randomized, Placebo-Controlled Clinical Trial of Substrate Metabolism, Insulin Sensitivity, and Body Composition

Global vitamin D levels in relation to age, gender, skin pigmentation and latitude: an ecologic meta-regression analysis.

Proton pump inhibitors, histamine H2 receptor antagonists, and other antacid medications and the risk of fracture.

Increased mortality in patients with a hip fracture-effect of pre-morbid conditions and post-fracture complications.