Serum Metalloproteinases 2 and 9 as Predictors of Gait Status,Pressure Ulcer and Mortality after Hip Fracture

Introduction

The aim of this study is to evaluate the serum activity of metalloproteinases (MMPs) -2 and -9 as predictors of pressure ulcer (PU), gait status and mortality 6 months after hip fracture.

Methods

Eighty-seven patients over the age of 65 admitted to the orthopedic unit from January to December 2010 with hip fracture were prospectively evaluated. Upon admission, patient demographic information, including age, gender and concomitant diseases, was recorded. Blood samples were taken for analysis of MMP -2 and -9 activity by gel zymography and for biochemical examination within the first 72 hours of the patient’s admission, after clinical stabilization. The fracture pattern (neck, trochanteric or subtrochanteric), time from admission to surgery, surgery duration and length of hospital stay were also recorded.

Results

Two patients were excluded due to the presence of pathological fractures (related to cancer), and three patients were excluded due to the presence of PU before admission. Eighty-two patients, with a mean age of 80.4 ± 7.3 years, were included in the analysis. Among these patients, 75.6% were female, 59.8% had PU, and 13.4% died 6 months after hip fracture. All patients underwent hip fracture repair. In a univariate analysis, there were no differences in serum MMP activity between hip fracture patients with or without PU. In addition, the multiple logistic regression analysis models, which were adjusted by age, gender, length of hospital stay and C-reactive protein, showed that the pro-MMP-9 complexed with neutrophil gelatinase-associated lipocalin form (130 kDa) was associated with gait status recovery 6 months after hip fracture.

Conclusions

In conclusion, serum pro-MMP-9 is a predictor of gait status recovery 6 months after hip fracture.     

Quantifying the Role of Adverse Events in the Mortality Difference between First and Second-Generation Antipsychotics in Older Adults: Systematic Review and Meta-Synthesis

Background

Observational studies have reported higher mortality among older adults treated with first-generation antipsychotics (FGAs) versus second-generation antipsychotics (SGAs). A few studies examined risk for medical events, including stroke, ventricular arrhythmia, venous thromboembolism, myocardial infarction, pneumonia, and hip fracture.

Objectives

1) Review robust epidemiologic evidence comparing mortality and medical event risk between FGAs and SGAs in older adults; 2) Quantify how much these medical events explain the observed mortality difference between FGAs and SGAs.

Data sources

Pubmed and Science Citation Index.

Study eligibility criteria, participants, and interventions

Studies of antipsychotic users that: 1) evaluated mortality or medical events specified above; 2) restricted to populations with a mean age of 65 years or older 3) compared FGAs to SGAs, or both to a non-user group; (4) employed a “new user” design; (5) adjusted for confounders assessed prior to antipsychotic initiation; (6) and did not require survival after antipsychotic initiation. A separate search was performed for mortality estimates associated with the specified medical events.

Study appraisal and synthesis methods

For each medical event, we used a non-parametric model to estimate lower and upper bounds for the proportion of the mortality difference—comparing FGAs to SGAs—mediated by their difference in risk for the medical event.

Results

We provide a brief, updated summary of the included studies and the biological plausibility of these mechanisms. Of the 1122 unique citations retrieved, we reviewed 20 observational cohort studies that reported 28 associations. We identified hip fracture, stroke, myocardial infarction, and ventricular arrhythmias as potential intermediaries on the causal pathway from antipsychotic type to death. However, these events did not appear to explain the entire mortality difference.

Conclusions

The current literature suggests that hip fracture, stroke, myocardial infarction, and ventricular arrhythmias partially explain the mortality difference between SGAs and FGAs.     

Age-Group-Specific Associations between the Severity of Obstructive Sleep Apnea and Relevant Risk Factors in Male and Female Patients

Aim

To seek accurate and credible correlation manner between gender, age, and obesity; and the severity of obstructive sleep apnea (OSA) in large-scale population.

Methods

Totals of 1,975 male and 378 female OSA patients were sequentially recruited. Centralized covariant tendencies between age, body mass index (BMI), and waist hip ratio (WHR); and OSA severity, were explored in a gender-specific manner via multiple statistical analyses. The accuracies of observed correlations were further evaluated by adaptive multiple linear regression.

Results

All of age, BMI, WHR, smoking, drinking, and OSA severity differed between males and females. BMI and WHR were positively and (approximately) linearly associated with OSA severity in both males and females. Restricted cubic spline analysis was more effective than was the Pearson correlation approach in correlating age with AHI, and provided age crossover points allowing further piecewise linear modeling for both males and females. Multiple linear regression showed that increasing age was associated with OSA exacerbation in males aged ≤40 years and in females aged 45–53 years. BMI, WHR, and diabetes were independently associated with OSA severity in males with age-group-specific pattern. In females, only BMI was associated with OSA severity at all ages.

Conclusions

In male patients, BMI and WHR are prominent risk factors for OSA exacerbation. Age and diabetes are associated with OSA severity in males of particular ages. In females, BMI is also a prominent risk factor for severe OSA, and OSA severity increased with age in the range 45–53 years.     

An Osteoprotegerin Gene Polymorphism Is Associated with an Increased Risk of Hip Fracture in Japanese Patients with Rheumatoid Arthritis: Results from the IORRA Observational Cohort Study

Introduction

Patients with rheumatoid arthritis (RA) have a higher prevalence of osteoporosis and hip fracture than healthy individuals. Multiple genetic loci for osteoporotic fracture were identified in recent genome-wide association studies. The purpose of this study was to identify genetic variants associated with the occurrence of hip fracture in Japanese patients with RA.

Methods

DNA samples from 2,282 Japanese patients with RA were obtained from the DNA collection of the Institute of Rheumatology Rheumatoid Arthritis cohort (IORRA) study. Six single nucleotide polymorphisms (SNPs) that have been reported to be associated with fractures in recent studies were selected and genotyped. Forty hip fractures were identified with a maximum follow-up of 10 years. The genetic risk for hip fracture was examined using a multivariate Cox proportional hazards regression model.

Results

The risk analyses revealed that patients who are homozygous for the major allele of SNP rs6993813, in the OPG locus, have a higher risk for hip fracture (hazard ratio [95% CI]  = 2.53 [1.29–4.95], P  = 0.0067). No association was found for the other SNPs.

Conclusions

Our results indicate that an OPG allele is associated with increased risk for hip fracture in Japanese patients with RA.     

Rheumatoid arthritis patients are not at increased risk for 30-day cardiovascular events,infections, or mortality after total joint arthroplasty

Introduction

Serious infection, cardiovascular disease, and mortality are increased in rheumatoid arthritis (RA). Whether RA affects the risk for these complications after total joint arthroplasty (TJA) is unknown, we hypothesize that it does. We compared the occurrence of 30-day postoperative complications and mortality in a large cohort of RA and osteoarthritis (OA) patients undergoing hip or knee TJA.

Methods

Analyses included 7-year data from the Veterans Affairs Surgical Quality Improvement Program. The 30-day complications were compared by diagnosis by using logistic regression, and long-term mortality was examined by using Cox proportional hazards regression. All analyses were adjusted for age, sex, and clustering by surgical site. Additional covariates included sociodemographics, comorbidities, health behaviors, and operative risk factors.

Results

The 34,524 patients (839 RA, 33,685 OA) underwent knee (65.9%) or hip TJA. Patients were 95.7% men with a mean (SD) age of 64.4 (10.7) years and had 3,764 deaths over a mean follow-up of 3.7 (2.3) years. Compared with OA patients, those with RA were significantly more likely to require a return to the operating room (odds ratio (OR), 1.45 (95% CI, 1.08 to 1.94), but had similar rates of 30-day postoperative infection, OR 1.02 (0.72 to 1.47), cardiovascular events, OR 0.69 (0.37 to 1.28), and mortality, OR 0.94 (0.38 to 2.33). RA was associated with a significantly higher long-term mortality; hazard ratio (HR), 1.22 (1.00 to 1.49).

Conclusion

In this study of US veterans, RA patients were not at an increased risk for short-term mortality or other major complications after TJA, although they returned to the operating room more often and had increased long-term mortality.     

Prevalence of Sarcopenia and Its Relationship with Sites of Fragility Fractures in Elderly Chinese Men and Women

Objective

Sarcopenia might be associated with bone fragility in elderly individuals. This study aimed to investigate the prevalence of sarcopenia and its association with fragility fracture sites in elderly Chinese patients.

Methods

Patients (322 men and 435 women) aged 65–94 years and with a history of fragility fractures in the ankle, wrist, vertebrae or hip, and healthy men (n = 1263) and women (n = 1057) aged 65–92 years without a history of fractures were enrolled. Whole-body dual energy X-ray absorptiometry was used to analyze skeletal muscle mass index (SMI), fat mass and bone mineral density. Sarcopenia was defined as SMI less than two standard deviations below the mean of a young reference group.

Results

Sarcopenia occurrence varied with fracture location. Sarcopenia was more common in females with vertebral and hip fractures and in men with hip and ankle fractures than in the non-fracture group). Sarcopenia was significantly more prevalent in men with wrist, hip and ankle fractures than in women. SMI was correlated with BMD in different fracture groups. Logistic regression analyses revealed that lower SMI was associated with an increased risk of hip fracture both in men and women and ankle fracture in men.

Discussion

Sarcopenia may be an independent risk factor for hip and ankle fractures in men, and for hip fractures in women.     

The Epidemic of Hip Fractures: Are We on the Right Track?

Background

Hip fractures are a public health problem, leading to hospitalization, long-term rehabilitation, reduced quality of life, large healthcare expenses, and a high 1-year mortality. Especially older adults are at greater risk of fractures than the general population, due to the combination of an increased fall risk and osteoporosis. The aim of this study was to determine time trends in numbers and incidence rates of hip fracture-related hospitalizations and admission duration in the older Dutch population.

Methods and Findings

Secular trend analysis of all hospitalizations in the older Dutch population (≥65 years) from 1981 throughout 2008, using the National Hospital Discharge Registry. Numbers, age-specific and age-adjusted incidence rates (per 10,000 persons) of hospital admissions and hospital days due to a hip fracture were used as outcome measures in each year of the study. Between 1981 and 2008, the absolute number of hip fractures doubled in the older Dutch population. Incidence rates of hip fracture-related hospital admissions increased with age, and were higher in women than in men. The age-adjusted incidence rate increased from 52.0 to 67.6 per 10,000 older persons. However, since 1994 the incidence rate decreased (percentage annual change −0.5%, 95% CI: −0.7; −0.3), compared with the period 1981–1993 (percentage annual change 2.3%, 95% CI: 2.0; 2.7). The total number of hospital days was reduced by a fifth, due to a reduced admission duration in all age groups. A possible limitation was that data were obtained from a linked administrative database, which did not include information on medication use or co-morbidities.

Conclusions

A trend break in the incidence rates of hip fracture-related hospitalizations was observed in the Netherlands around 1994, possibly as a first result of efforts to prevent falls and fractures. However, the true cause of the observation is unknown.     

Timing Matters in Hip Fracture Surgery: Patients Operated within 48 Hours Have Better Outcomes. A Meta-Analysis and Meta-Regression of over 190,000 Patients

Background

To assess the relationship between surgical delay and mortality in elderly patients with hip fracture. Systematic review and meta-analysis of retrospective and prospective studies published from 1948 to 2011. Medline (from 1948), Embase (from 1974) and CINAHL (from 1982), and the Cochrane Library. Odds ratios (OR) and 95% confidence intervals for each study were extracted and pooled with a random effects model. Heterogeneity, publication bias, Bayesian analysis, and meta-regression analyses were done. Criteria for inclusion were retro- and prospective elderly population studies, patients with operated hip fractures, indication of timing of surgery and survival status.

Methodology/Principal Findings

There were 35 independent studies, with 191,873 participants and 34,448 deaths. The majority considered a cut-off between 24 and 48 hours. Early hip surgery was associated with a lower risk of death (pooled odds ratio (OR) 0.74, 95% confidence interval (CI) 0.67 to 0.81; P<0.000) and pressure sores (0.48, 95% CI 0.38 to 0.60; P<0.000). Meta-analysis of the adjusted prospective studies gave similar results. The Bayesian probability predicted that about 20% of future studies might find that early surgery is not beneficial for decreasing mortality. None of the confounders (e.g. age, sex, data source, baseline risk, cut-off points, study location, quality and year) explained the differences between studies.

Conclusions/Significance

Surgical delay is associated with a significant increase in the risk of death and pressure sores. Conservative timing strategies should be avoided. Orthopaedic surgery services should ensure the majority of patients are operated within one or two days.     

Increased risk of fragility fractures among HIV infected compared to uninfected male veterans

Background

HIV infection has been associated with an increased risk of fragility fracture. We explored whether or not this increased risk persisted in HIV infected and uninfected men when controlling for traditional fragility fracture risk factors.

Methodology/Principal Findings

Cox regression models were used to assess the association of HIV infection with the risk for incident hip, vertebral, or upper arm fracture in male Veterans enrolled in the Veterans Aging Cohort Study Virtual Cohort (VACS-VC). We calculated adjusted hazard ratios comparing HIV status and controlling for demographics and other established risk factors. The sample consisted of 119,318 men, 33% of whom were HIV infected (34% aged 50 years or older at baseline, and 55% black or Hispanic). Median body mass index (BMI) was lower in HIV infected compared with uninfected men (25 vs. 28 kg/m²; p<0.0001). Unadjusted risk for fracture was higher among HIV infected compared with uninfected men [HR: 1.32 (95% CI: 1.20, 1.47)]. After adjusting for demographics, comorbid disease, smoking and alcohol abuse, HIV infection remained associated with an increased fracture risk [HR: 1.24 (95% CI: 1.11, 1.39)]. However, adjusting for BMI attenuated this association [HR: 1.10 (95% CI: 0.97, 1.25)]. The only HIV-specific factor associated with fragility fracture was current protease inhibitor use [HR: 1.41 (95% CI: 1.16, 1.70)].

Conclusions/Significance

HIV infection is associated with fragility fracture risk. This risk is attenuated by BMI.     

Assortative mating in fallow deer reduces the strength of sexual selection

Background

Assortative mating can help explain how genetic variation for male quality is maintained even in highly polygynous species. Here, we present a longitudinal study examining how female and male ages, as well as male social dominance, affect assortative mating in fallow deer (Dama dama) over 10 years. Assortative mating could help explain the substantial proportion of females that do not mate with prime-aged, high ranking males, despite very high mating skew. We investigated the temporal pattern of female and male matings, and the relationship between female age and the age and dominance of their mates.

Results

The peak of yearling female matings was four days later than the peak for older females. Younger females, and especially yearlings, mated with younger and lower-ranking males than older females. Similarly, young males and lower-ranking males mated with younger females than older males and higher-ranking males. Furthermore, the timing of matings by young males coincided with the peak of yearling female matings, whereas the timing of older male matings (irrespective of rank) coincided with the peak of older female matings.

Conclusions

Assortative mating, through a combination of indirect and/or direct female mate choice, can help explain the persistence of genetic variation for male traits associated with reproductive success.     

Association of Abdominal Obesity with Lumbar Disc Degeneration – A Magnetic Resonance Imaging Study

Purpose

To evaluate whether midsagittal (abdominal) obesity in magnetic resonance imaging (MRI), waist circumference (WC) and body fat percentage are associated with lumbar disc degeneration in early adulthood.

Methods

We obtained the lumbar MRI (1.5-T scanner) of 325 females and 233 males at a mean age of 21 years. Lumbar disc degeneration was evaluated using Pfirrmann classification. We analysed the associations of MRI measures of obesity (abdominal diameter (AD), sagittal diameter (SAD), ventral subcutaneous thickness (VST), and dorsal subcutaneous thickness (DST)), WC and body fat percentage with disc degeneration sum scores using ordinal logistic regression.

Results

A total of 155 (48%) females and 147 (63%) males had disc degeneration. AD and SAD were associated with a disc degeneration sum score of ≥3 compared to disc degeneration sum score of 0–2 (OR 1.67; 95% confidence interval (CI) 1.20–2.33 and OR 1.40; 95% CI 1.12–1.75, respectively) among males, but we found no association among females. WC was also associated with disc degeneration among males (OR 1.03 per one cm; 95% CI 1.00–1.05), but not among females.

Conclusion

Measures of abdominal obesity in MRI and waist circumference were associated with disc degeneration among 21-year-old males.     

Adjunctive steroid in HIV-negative patients with severe Pneumocystis pneumonia

Background

High-dose steroid therapy has been proven effective in AIDS-related Pneumocystis pneumonia (PCP) but not in non-AIDS-related cases. We evaluated the effects on survival of steroids in HIV-negative patients with PCP.

Methods

Retrospective study patients admitted to the ICU with hypoxemic PCP. We compared patients receiving HDS (≥1 mg/Kg/day prednisone equivalent), low-dose steroids (LDS group, <1 mg/Kg/day prednisone equivalent), and no steroids (NS group). Variables independently associated with ICU mortality were identified.

Results

139 HIV-negative patients with PCP were included. Median age was 48 [40–60] years. The main underlying conditions were hematological malignancies (n=55, 39.6%), cancer (n=11, 7.9%), and solid organ transplantation (n=73, 52.2%). ICU mortality was 26% (36 deaths). The HDS group had 72 (51.8%) patients, the LDS group 35 (25%) patients, and the NS group 32 (23%) patients. Independent predictors of ICU mortality were SAPS II at ICU admission (odds ratio [OR], 1.04/point; [95%CI], 1.01-1.08, P=0.01), non-hematological disease (OR, 4.06; [95%CI], 1.19-13.09, P=0.03), vasopressor use (OR, 20.31; 95%CI, 6.45-63.9, P<0.001), and HDS (OR, 9.33; 95%CI, 1.97-44.3, P=0.02). HDS was not associated with the rate of ICU-acquired infections.

Conclusions

HDS were associated with increased mortality in HIV-negative patients with PCP via a mechanism independent from an increased risk of infection.     

Treatment of rheumatoid arthritis in the Medicare Current Beneficiary Survey

Introduction

Numerous studies across different health systems have documented that many patients with rheumatoid arthritis (RA) do not receive disease-modifying anti-rheumatic drugs (DMARDs). Relatively little is known about correlates of DMARD use and whether there are socioeconomic and demographic disparities. We examined DMARD use during 2001 to 2006 in the Medicare Current Beneficiary Survey (MCBS), a longitudinal US survey of randomly selected Medicare beneficiaries.

Methods

Participants in MCBS with RA were included in the analyses, and DMARD use was based on an in-home assessment of all medications. Variables included as potential correlates of DMARD use in weighted regression models included race/ethnicity, insurance, income, education, rheumatology visit, region, age, gender, comorbidity index, and calendar year.

Results

The cohort consisted of 509 MCBS participants with a diagnosis code for RA. Their median age was 70 years, 72% were female, and 24% saw a rheumatologist. Rates of DMARD use ranged from 37% among those <75 years of age to 25% of those age 75 to 84 and 4% of those age 85 and older. The multivariable adjusted predictors of DMARD use include: visit with a rheumatologist in the prior year (odds ratio, OR, 7.74, 95% CI, 5.37, 11.1) and older patient age (compared with <75 years, ages 75 to 84, OR 0.58, 95% CI 0.37, 0.92, and 85 and over, OR 0.09, 95% CI 0.02, 0.31). In those without a rheumatology visit, lower income and older age were associated with a significantly reduced probability of DMARD use; no association of DMARD use with income or age was observed for subjects seen by rheumatologists. Race and ethnicity were not significantly associated with receipt of DMARDs.

Conclusions

Among individuals not seeing rheumatologists, lower income and older age were associated with a reduced probability of DMARD use.     

Aging, transition, and estimating the global burden of disease

Background

The World Health Organization''s Global Burden of Disease (GBD) reports are an important tool for global health policy makers, however the accuracy of estimates for countries undergoing an epidemiologic transition is unclear. We attempted to validate the life table model used to generate estimates for all-cause mortality in developing countries.

Methods and Results

Data were obtained for males and females from the Human Mortality Database for all countries with available data every ten years from 1900 to 2000. These provided inputs for the GBD life table model and served as comparison observed data. Above age sixty model estimates of survival for both sexes differed substantially from those observed. Prior to the year 1960 for males and 1930 for females, estimated survival tended to be greater than observed; following 1960 for both males and females estimated survival tended to be less than observed. Viewing observed and estimated survival separately, observed survival past sixty increased over the years considered. For males, the increase was from a mean (sd) probability of 0.22 (0.06) to 0.46 (0.1). For females, the increase was from 0.26 (0.06) to 0.65 (0.08). By contrast, estimated survival past sixty decreased over the same period. Among males, estimated survival probability declined from 0.54 (0.2) to 0.09 (0.06). Among females, the decline was from 0.36 (0.12) to 0.15 (0.08).

Conclusions

These results show that the GBD mortality model did not accurately estimate survival at older ages as developed countries transitioned in the twentieth century and may be similarly flawed in developing countries now undergoing transition. Estimates of the size of older-age populations and their attributable disease burden should be reconsidered.     

Serum Creatinine Modifies Associations between Body Mass Index and Mortality and Morbidity in Prevalent Hemodialysis Patients

Background

High body mass index (BMI) is paradoxically associated with better outcomes in hemodialysis (HD) patients. This study aimed to examine whether serum creatinine (Cr), a marker of muscle mass, could modify the association between BMI, and mortality and morbidity in prevalent HD patients.

Methods

A retrospective study was conducted using a nationwide database from the registry of the Japanese Society for Dialysis Therapy. A total of 119,099 patients were selected (age: 65±12 years; median time on HD: 5.6 years; male: 62%), and we examined the association of basal BMI with mortality and morbidity after a 1-year period. Patients were stratified either by BMI into 4 groups or by serum Cr levels into 3 tertiles. Odds ratio (OR) [95% confidence interval] was calculated by multivariate logistic regression analysis.

Results

Higher BMI did not predict a higher 1-year total mortality. However, when we stratified the patients by serum Cr levels, the risk of cardiac death became significantly higher in obese patients with the lowest Cr levels, in both males (OR 2.82 [1.51–5.27], p<0.01) and females (OR 2.00 [1.03–3.90], p<0.05). The risk of new cerebral infarction was also higher in obese male patients within the lowest Cr tertile. In contrast, there was a significantly lower risk of cardiac, cerebrovascular, and infection-related death in non-obese patients with higher levels of Cr. Higher serum Cr was also related to a lower risk of cardiovascular events and hip fracture in non-obese HD patients.

Conclusions

The obesity paradox was found to be present in HD patients only when obesity was defined by BMI. Decreased serum Cr levels were found to be positively associated with clinical poor outcomes in all BMI groups. Thus, irrespective of BMI, the evaluation of serum Cr levels is important to predict mortality and morbidity in patients receiving regular HD.     

Multifaceted intervention to improve diagnosis and treatment of osteoporosis in patients with recent wrist fracture: a randomized controlled trial

Background

Older patients who experience a fragility fracture are at high risk of future fractures but are rarely tested or treated for osteoporosis. We developed a multifaceted intervention directed at older patients with wrist fractures (in the form of telephone-based education) and their physicians (in the form of guidelines endorsed by opinion leaders, supported by reminders) to improve the quality of osteoporosis care.

Methods

In a randomized controlled trial with blinded ascertainment of outcomes, we compared our intervention with usual care (provision of printed educational materials to patients). Eligible patients were those older than 50 years of age who had experienced a wrist fracture and were seen in emergency departments and fracture clinics; we excluded those who were already being treated for osteoporosis. The primary outcome was bisphosphonate treatment within 6 months after the fracture. Secondary outcomes included bone mineral density testing, “appropriate care” (consisting of bone mineral density testing with treatment if bone mass was low) and quality of life.

Results

We screened 795 patients for eligibility and randomly assigned 272 to the intervention (137 patients) or control (135 patients) group. The median age was 60 years; 210 (77%) of the subjects were women, and 130 (48%) reported a previous fracture as an adult. Six months after the fracture, 30 (22%) of the intervention patients, as compared with 10 (7%) of the control patients, were receiving bisphosphonate therapy for osteoporosis (adjusted relative risk [RR] 2.6, 95% confidence interval [CI] 1.3–5.1, p = 0.008). Intervention patients were more likely than control patients to undergo bone mineral density testing (71/137 [52%] v. 24/135 [18%]; adjusted RR 2.8, 95% CI 1.9–4.2, p < 0.001) and to receive appropriate care (52/137 [38%] v. 15/135 [11%]; adjusted RR 3.1, 95% CI 1.8–5.3, p < 0.001). There were no differences between the groups in other outcomes. One patient died, and 4 others experienced recurrent fracture.

Interpretation

A multifaceted intervention directed at high-risk patients and their physicians substantially increased rates of testing and treatment for osteoporosis. Nevertheless, more than half of the patients in the intervention group were not receiving appropriate care 6 months after their fracture, which suggests that additional strategies should be explored. (ClinicalTrials.gov trial register no. NCT00152321.)Osteoporosis is a common, chronic and costly condition affecting at least 25% of women and 12% of men over 50 years of age.^1–3 Without better prevention strategies, the incidence of and costs related to osteoporotic fractures are expected to increase by 50% over the next 2 decades.³ Case-finding and secondary prevention (e.g., by identifying patients who have experienced a fragility fracture, ensuring that their bone mineral density is tested and offering efficacious osteoporosis treatments to those with low bone mass) constitute the most cost-effective strategy for reducing future fractures.^4–6An obvious target group for case-finding consists of older patients who experience a wrist fracture. Wrist fracture is the most common symptomatic fracture related to osteoporosis; its occurrence is a powerful forecaster of future fractures, and these fractures typically occur 10–20 years before the more devastating osteoporosis-related fractures of the spine or the hip.⁷ Unfortunately, although most older patients with wrist fractures have low bone mass and are eligible for treatment,^4,7 less than about 10% to 20% are tested or treated for osteoporosis in the 6 to 12 months after a wrist fracture.^4–9We previously reported a nonrandomized study of an intervention that incorporated patient education, physician reminders and treatment guidelines endorsed by opinion leaders, to improve osteoporosis treatment in patients with wrist fractures; in that study, which involved 102 patients, the rate of treatment was 40% in the intervention group but only 10% in the group receiving usual care.⁷ Several concerns were raised about the internal and external validity of that small study, so we conducted a randomized controlled trial of the intervention, which is reported here.     

Malignant Lymphatic and Hematopoietic Neoplasms Mortality in Serbia, 1991–2010: A Joinpoint Regression Analysis

Background

Limited data on mortality from malignant lymphatic and hematopoietic neoplasms have been published for Serbia.

Methods

The study covered population of Serbia during the 1991–2010 period. Mortality trends were assessed using the joinpoint regression analysis.

Results

Trend for overall death rates from malignant lymphoid and haematopoietic neoplasms significantly decreased: by −2.16% per year from 1991 through 1998, and then significantly increased by +2.20% per year for the 1998–2010 period. The growth during the entire period was on average +0.8% per year (95% CI 0.3 to 1.3). Mortality was higher among males than among females in all age groups. According to the comparability test, mortality trends from malignant lymphoid and haematopoietic neoplasms in men and women were parallel (final selected model failed to reject parallelism, P = 0.232). Among younger Serbian population (0–44 years old) in both sexes: trends significantly declined in males for the entire period, while in females 15–44 years of age mortality rates significantly declined only from 2003 onwards. Mortality trend significantly increased in elderly in both genders (by +1.7% in males and +1.5% in females in the 60–69 age group, and +3.8% in males and +3.6% in females in the 70+ age group). According to the comparability test, mortality trend for Hodgkin''s lymphoma differed significantly from mortality trends for all other types of malignant lymphoid and haematopoietic neoplasms (P<0.05).

Conclusion

Unfavourable mortality trend in Serbia requires targeted intervention for risk factors control, early diagnosis and modern therapy.     

A GC polymorphism associated with serum 25-hydroxyvitamin D level is a risk factor for hip fracture in Japanese patients with rheumatoid arthritis: 10-year follow-up of the Institute of Rheumatology,Rheumatoid Arthritis cohort study

Introduction

Vitamin D deficiency has been reported to be common in patients with rheumatoid arthritis (RA) who have a higher prevalence of osteoporosis and hip fracture than healthy individuals. Genetic variants affecting serum 25-hydroxyvitamin D (25(OH)D) concentration, an indicator of vitamin D status, were recently identified by genome-wide association studies of Caucasian populations. The purpose of this study was to validate the association and to test whether the serum 25(OH)D-linked genetic variants were associated with the occurrence of hip fracture in Japanese RA patients.

Methods

DNA samples of 1,957 Japanese RA patients were obtained from the Institute of Rheumatology, Rheumatoid Arthritis (IORRA) cohort DNA collection. First, five single nucleotide polymorphisms (SNPs) that were reported to be associated with serum 25(OH)D concentration by genome-wide association studies were genotyped. The SNPs that showed a significant association with serum 25(OH)D level in the cross-sectional study were used in the longitudinal analysis of hip fracture risk. The genetic risk for hip fracture was determined by a multivariate Cox proportional hazards model in 1,957 patients with a maximum follow-up of 10 years (median, 8 years).

Results

Multivariate linear regression analyses showed that rs2282679 in GC (the gene encoding group-specific component (vitamin D binding protein)) locus was significantly associated with lower serum 25(OH)D concentration (P = 8.1 × 10^-5). A Cox proportional hazards model indicated that rs2282679 in GC was significantly associated with the occurrence of hip fracture in a recessive model (hazard ratio (95% confidence interval) = 2.52 (1.05-6.05), P = 0.039).

Conclusions

A two-staged analysis demonstrated that rs2282679 in GC was associated with serum 25(OH)D concentration and could be a risk factor for hip fracture in Japanese RA patients.