Melissa Orlandin Premaor

Obesity and Fractures in Postmenopausal Women

Low body mass index (BMI) is a recognized risk factor for fragility fracture, whereas obesity is widely believed to be protective. As part of a clinical audit of guidance from the National Institute of Health and Clinical Excellence (NICE), we have documented the prevalence of obesity and morbid obesity in postmenopausal women younger than 75 years of age presenting to our Fracture Liaison Service (FLS). Between January 2006 and December 2007, 1005 postmenopausal women aged less than 75 years with a low‐trauma fracture were seen in the FLS. Of these women, 805 (80%) underwent assessment of bone mineral density (BMD) by dual energy X‐ray absorptiometry (DXA), and values for BMI were available in 799. The prevalence of obesity (BMI 30 to 34.9 kg/m2) and morbid obesity (BMI ≥ 35 kg/m2) in this cohort was 19.3% and 8.4%, respectively. Normal BMD was reported in 59.1% of obese and 73.1% of morbidly obese women, and only 11.7% and 4.5%, respectively, had osteoporosis (p < .0001). Multiple regression analysis revealed significant negative associations between hip T‐score and age (p < .0001) and significant positive associations with BMI (p < .0001) and previous fracture (p = .001). Our results demonstrate a surprisingly high prevalence of obesity in postmenopausal women presenting to the FLS with low‐trauma fracture. Most of these women had normal BMD, as measured by DXA. Our findings have important public heath implications in view of the rapidly rising increase in obesity in many populations and emphasize the need for further studies to establish the pathogenesis of fractures in obese individuals and to determine appropriate preventive strategies.

The association between fracture site and obesity in men: a population-based cohort study.

A site‐dependent association between obesity and fracture has been reported in postmenopausal women. In this study we investigated the relationship between body mass index (BMI) and fracture at different skeletal sites in older men (≥65 years). We carried out a population‐based cohort study using data from the Sistema d‘Informació per al Desenvolupament de l‘Investigació en Atenció Primària (SIDIAPQ) database. SIDIAPQ contains the primary care and hospital admission computerized medical records of >1300 general practitioners (GPs) in Catalonia (Northeast Spain), with information on a representative 30% of the population (>2 million people). In 2007, 186,171 men ≥65 years were eligible, of whom 139,419 (74.9%) had an available BMI measurement. For this analysis men were categorized as underweight/normal (BMI < 25 kg/m2, n = 26,298), overweight (25 ≤ BMI < 30 kg/m2, n = 70,851), and obese (BMI ≥ 30 kg/m2, n = 42,270). Incident fractures in the period 2007 to 2009 were ascertained using International Classification of Diseases, 10th edition (ICD‐10) codes. A statistically significant reduction in clinical spine and hip fractures was observed in obese (relative risk [RR], 0.65; 95% confidence interval [CI], 0.53–0.80 and RR, 0.63; 95% CI, 0.54–0.74, respectively), and overweight men (RR, 0.77; 95% CI, 0.64–0.92 and RR, 0.63; 95% CI 0.55–0.72, respectively) when compared with underweight/normal men. Additionally, obese men had significantly fewer wrist/forearm (RR, 0.77; 95% CI, 0.61–0.97) and pelvic (RR, 0.44; 95% CI, 0.28–0.70) fractures than underweight/normal men. Conversely, multiple rib fractures were more frequent in overweight (RR, 3.42; 95% CI, 1.03–11.37) and obese (RR, 3.96; 95% CI, 1.16–13.52) men. In this population‐based cohort of older men, obesity was associated with a reduced risk of clinical spine, hip, pelvis, and wrist/forearm fracture and increased risk of multiple rib fractures when compared to normal or underweight men. Further work is needed to identify the mechanisms underlying these associations.

Predictive value of FRAX® for fracture in obese older women

Recent studies indicate that obesity is not protective against fracture in postmenopausal women and increases the risk of fracture at some sites. Risk factors for fracture in obese women may differ from those in the nonobese. We aimed to compare the ability of FRAX with and without bone mineral density (BMD) to predict fractures in obese and nonobese older postmenopausal women who were participants in the Study of Osteoporotic Fractures. Data for FRAX clinical risk factors and femoral neck BMD were available in 6049 women, of whom 18.5% were obese. Hip fractures, major osteoporotic fractures, and any clinical fractures were ascertained during a mean follow‐up period of 9.03 years. Receiving operator curve (ROC) analysis, model calibration, and decision curve analysis were used to compare fracture prediction in obese and nonobese women. ROC analysis revealed no significant differences between obese and nonobese women in fracture prediction by FRAX, with or without BMD. Predicted hip fracture risk was lower than observed risk in both groups of women, particularly when FRAX + BMD was used, but there was good calibration for FRAX + BMD in prediction of major osteoporotic fracture in both groups. Decision curve analysis demonstrated that both FRAX models were useful for hip fracture prediction in obese and nonobese women for threshold 10‐year fracture probabilities in the range of 4% to 10%, although in obese women FRAX + BMD was superior to FRAX alone. For major osteoporotic fracture, both FRAX models were useful in both groups of women for threshold probabilities in the range of 10% to 30%. For all clinical fractures, the FRAX models were not useful at threshold probabilities below 30%. We conclude that FRAX is of value in predicting hip and major osteoporotic fractures in obese postmenopausal women, particularly when used with BMD.

Urinary kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin as indicators of tubular damage in normoalbuminuric patients with type 2 diabetes.

OBJECTIVES Renal dysfunction has been reported in normoalbuminuric patients, demonstrating the necessity to improve the diagnostic and prognostic tools for diabetic kidney disease (DKD) investigation. Therefore, the aim of this study was to investigate whether the urinary levels of neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) are increased in type 2 diabetes mellitus (DM) patients with normal or mildly increased albuminuria. DESIGN AND METHODS In this study, 117 type 2 DM patients classified into three groups according to urinary albumin/creatinine ratio (uACR): uACR<10mg/g creatinine, uACR 10-30mg/g creatinine and uACR>30mg/g creatinine were enrolled. Urinary concentrations of KIM-1 (uKIM-1) and NGAL (uNGAL) were measured. RESULTS uKIM-1 levels increased progressively from uACR<10mg/g creatinine (69.0±20.8pg/ml) to uACR 10-30mg/g creatinine (106.1±41.2pg/ml) and to uACR>30mg/g creatinine (166.0±31.9pg/ml) (P<0.001). In addition, uNGAL levels increased progressively from uACR<10mg/g creatinine (29.5±8.8ng/ml) to uACR 10-30mg/g creatinine (51.7±10.9ng/ml) and to uACR>30mg/g creatinine (71.0±9.6ng/ml) (P<0.001) patients. Similarly, both uKIM-1 and uNGAL adjusted by urinary creatinine were increased in patients with uACR 10-30mg/g creatinine. Significant and positive correlations were observed between uACR, uKIM-1 and uNGAL. CONCLUSIONS uKIM-1 and uNGAL were increased in type 2 DM patients with normal or mildly increased albuminuria, which indicates that tubular and glomerular injuries may be occurring even at the earliest stage of DKD.

Obesity and fractures

Until recently obesity was believed to be protective against fractures. However, a report from a Fracture Liaison Clinic in the UK (2010) reported a surprisingly high proportion of obese postmenopausal women attending the clinic with fractures, and in the GLOW study (2011), a similar prevalence and incidence of fractures in obese and non-obese postmenopausal women was observed. Subsequently, other studies have demonstrated the importance of obesity in the epidemiology of fractures. Obese women are at increased risk of fracture in ankle, leg, humerus, and vertebral column and at lower risk of wrist, hip and pelvis fracture when compared to non-obese women. In men, it has been reported that multiple rib fractures are associated with obesity. Furthermore, falls appear to play an important role in the pathogenesis of fractures in obese subjects. Regarding hip fracture and major fractures, the FRAX algorithm has proven to be a useful predictor in obese individuals. Obese people are less likely to receive bone protective treatment; they have a longer hospital stay and a lower quality of life both before and after fracture. Moreover, the efficacy of antiresorptive therapies is not well established in obese people. The latter is a field for future research.

The effect of a single dose versus a daily dose of cholecalciferol on the serum 25-hydroxycholecalciferol and parathyroid hormone levels in the elderly with secondary hyperparathyroidism living in a low-income housing unit

We designed a randomized, double-blind, controlled clinical trial to compare the effect of two regimens for administering cholecalciferol on the serum 25-hydroxycholecalciferol [25(OH)D] levels and in the reversion of secondary hyperparathyroidism in the elderly living in a low-income housing unit in the city of Porto Alegre, southern Brazil. We studied 28 individuals ranging in age from 65 to 102 years with serum parathyroid hormone (PTH) levels greater than 48 pg/ml and normal or reduced serum calcium levels. Subjects were randomized to receive oral cholecalciferol, as a single dose of 300 000 IU (group 1) or 800 IU (group 2) daily for 9 months. Both groups received 1250 mg calcium carbonate per day. Serum 25(OH)D and PTH levels were measured at baseline and after 1, 2, 3, 6, and 9 months. Serum 25(OH)D levels in group 1 were significantly higher than in group 2 during the study (P < 0.001). After 1 (P < 0.001) and 2 (P < 0.04) months of treatment, mean serum 25(OH)D levels were higher in group 1. The number of subjects who reached serum 25(OH)D levels ≥20 ng/dl was higher in group 1, after the first (P < 0.001) and third (P = 0.008) months. In the short term, a single 300 000 IU oral dose of vitamin D3 was more effective than 800 IU per day to increase serum 25(OH)D levels in elderly persons, living in a low-income housing unit, who were taking 500 mg elementary calcium supplement per day.

Oxidative DNA damage is associated with inflammatory response, insulin resistance and microvascular complications in type 2 diabetes

Urinary markers of nucleic acid oxidation may be useful biomarkers in diabetes. It has been demonstrated that T2DM patients have an increased level of oxidative DNA damage; however, it is unclear whether increased DNA damage may be related to a greater degree of inflammation and insulin resistance. Thus, the aim of this present study was to investigate the relation of the impact of oxidative DNA damage, assessed by urinary 8-OHdG, on the levels of inflammatory cytokines, as well as insulin resistance. In addition, we also investigated the diagnostic ability of urinary 8-OHdG in the identification of microvascular complications in T2DM.A case-control study, enrolling 22 healthy controls and 54 subjects with T2DM, was performed to evaluate the relation between oxidative DNA damage and interleukin-6 (IL-6), IL-1,tumor necrosis factor-alpha (TNF-α), IL-10, and Homeostasis Model Assessment (HOMA-IR) index. T2DM patients presented higher urinary 8-OHdG, IL-6, IL-1, TNF-α levels and HOMA-IR, and lower IL-10 levels than control subjects. Moreover, urinary 8-OHdG levels were significantly higher in the group T2DM with microvascular complications when compared to the without complications. The areas under the curve for urinary 8-OHdG and urinary albumin were, respectively, 0.836 (P<0.001) and 0.786 (P=0.002). Thus, urinary 8-OHdG has a slightly higher ability to discriminate microvascular complications in T2DM compared with urinary albumin. It was also demonstrated that T2DM patients with higher median of urinary 8-OHdG had significantly elevated levels of IL-6, TNF-α and HOMA-IR, and decreased IL-10 levels. Our findings showed that T2DM patients with higher urinary 8-OHdG levels showed a greater inflammatory degree and higher insulin resistance. It is possible to speculate that T2DM patients present a cascade of events as increasing metabolic abnormalities such as insulin resistance and inflammatory activation, as well as increased ROS generation factors that may contribute directly to greater oxidative DNA damage.

Secondary Hyperparathyroidism Is Associated with Increased Risk of Hospitalization or Death in Elderly Adults Living in a Geriatric Institution

Background: The presence of secondary hyperparathyroidism is very frequent in the elderly population living in geriatric institutions. It has been associated with an increased mortality rate in previous studies. Objectives: To evaluate the association of secondary hyperparathyroidism with mortality or hospitalization or both (combined outcome) during a 6-month period in individuals living in geriatric institutions. Methods: A cohort of 100 individuals aged between 65 and 102 years living in geriatric institutions in the city of Porto Alegre, Brazil, was prospectively studied. Serum levels of 25-hydroxyvitamin D [25(OH)D], parathyroid hormone (PTH), albumin, total calcium, phosphorus, magnesium, creatinine and alkaline phosphatase were measured. The glomerular filtration rate (GFR) was calculated using the Cockcroft-Gault equation. Secondary hyperparathyroidism was defined as serum PTH levels higher than 48 pg/ml and normal or reduced serum calcium levels. The deaths were verified by means of death certificates and hospitalization by the discharge summaries provided by the Brazilian health system hospitals. Results: Fifty-eight percent of the individuals had secondary hyperparathyroidism, defined as serum PTH >48 pg/ml and normal or low serum calcium. Mean serum 25(OH)D levels were 12.5 ± 8 ng/ml. The odds ratio of an individual with secondary hyperparathyroidism to die, to be hospitalized or to have the combined outcome within 6 months was 6.6 [confidence interval (CI) 95% 0.8–54.6; p = 0.07], 10.7 (CI 95% 1.3–85.9; p = 0.007) and 5.20 (CI 95% 1.10–27.7; p = 0.04), respectively. Secondary hyperparathyroidism and body mass index were independently associated with the combined outcome, after correction for the GFR and 25(OH)D. Conclusion: Secondary hyperparathyroidism could be an important prognostic factor for individuals living in geriatric institutions.

Butyrylcholinesterase and γ-Glutamyltransferase Activities and Oxidative Stress Markers Are Altered in Metabolic Syndrome, But Are Not Affected by Body Mass Index

Metabolic syndrome (MetS) leads to changes in enzymatic activities, oxidative and inflammatory parameters. Adenosine deaminase (ADA), dipeptidyl peptidase IV (DPP-IV), butyrylcholinesterase (BuChE) and γ-glutamyltransferase (γ-GT) activities, C-reactive protein (hsCRP) and nitric oxide levels (NOx), as well as oxidative stress markers were analyzed in 39 subjects with MetS and 48 controls. Also, the influence of body mass index (BMI) and anthropometric measurements were evaluated. Disturbances in antioxidant defenses and higher γ-GT and BuChE activities, NOx and hsCRP levels were observed in subjects with MetS. These findings remained associated with MetS after adjustment for BMI, except for hsCRP. ADA was correlated with age, insulin levels and HOMA-IR index in MetS. DPP-IV and total cholesterol (TC), BuChE activity and TC, and VIT C and hsCRP levels also were correlated. The analyzed parameters may reflect the inflammatory state of the MetS, and could contribute to prevention and control of various aspects of this syndrome.

Predictors of hip fracture mortality at a general hospital in South Brazil: an unacceptable surgical delay

OBJECTIVE: Hip fractures have been associated with increased mortality in the elderly. Several risk factors such as the time between the insult and the surgical repair have been associated with hip fracture mortality. Nevertheless, the risk of delayed surgical repair remains controversial. Few studies have examined this issue in Brazil. The aim of this study was to study the risk factors for death one year after hip fracture and in-hospital stay at a tertiary hospital in South Brazil. METHODS: A prospective cohort study was carried out from April 2005 to April 2011 at a tertiary university hospital at Santa Maria, Brazil. Subjects admitted for hip fracture who were 65 years of age or older were followed for one year. Information about fracture type, age, gender, clinical comorbidities, time to surgery, discharge, and American Society of Anesthesiologists score were recorded. Death was evaluated during the hospital stay and at one year. RESULTS: Four hundred and eighteen subjects were included in the final analysis. Of these, 4.3% died in-hospital and 15.3% were dead at one year. Time to surgery, American Society of Anesthesiologists score, Ischemic Heart Disease, and in-hospital stay were associated with death at one year in the univariate analysis. The American Society of Anesthesiologists score and time to surgery were one-year mortality predictors in the final regression model. In-hospital death was associated with American Society of Anesthesiologists score and age. CONCLUSION: Time to surgery is worryingly high at the South Brazil tertiary public health center studied here. Surgical delay is a risk factor that has the potential to be modified to improve mortality.