Vertebral fracture risk with long-term corticosteroid therapy: prevalence and relation to age, bone density, and corticosteroid use

BACKGROUND: Few data are available regarding vertebral fracture risk in patients treated with oral corticosteroids. The aim of this study was to determine the prevalence and the role of risk factors such as age, bone mineral density (BMD), and corticosteroid use for vertebral deformity in patients receiving long-term corticosteroid therapy. METHODS: Thoracolumbar x-ray films, BMD, and details on corticosteroid use were obtained on 229 consecutive patients treated with long-term corticosteroid regimens (> or = 6 months of prednisone, > or = 5mg/d or equivalent) seen at 4 referral centers. Comparisons were made with a population control group of 286 male and female controls not taking corticosteroids (aged > or = 60 years). RESULTS: Sixty-five patients (28%) had at least 1 vertebral deformity and 25 (11%) had 2 or more vertebral deformities. Older age, independent of BMD, was a significant risk factor for deformity. Patients aged 70 to 79 years had a 5-fold increased risk of deformity compared with patients younger than 60 years (odds ratio, 5.13; 95% confidence interval, 2.03-13.0). Compared with the population controls, the prevalence of deformities increased to a greater extent with each decade of age in the corticosteroid group (P =.005). Mean lumbar spine and femoral neck BMD Z scores were lower in the steroid-treated patients with deformities compared with the nonsteroid control group with deformities. When the effects of age, sex, body mass index, and duration of corticosteroid use were adjusted for in logistic regression analysis, low BMD was a modest predictor of deformity (for a 1-SD decrease in lumbar spine BMD: odds ratio, 1.31; 95% confidence interval, 1.02-1.68) and for a 1-SD decrease in femoral neck BMD: odds ratio, 1.77; 95% confidence interval, 1.07-2.94). CONCLUSIONS: The combination of increasing age and corticosteroid use is associated with a marked increase in the risk of vertebral deformity. Elderly patients commencing long-term corticosteroid therapy should be considered for antiosteoporotic therapy independently of their BMD. Arch Intern Med. 2000;160:2917-2922     

Reproductive Hormones and Longitudinal Change in Bone Mineral Density and Incident Fracture Risk in Older Men: The Concord Health and Aging in Men Project

The objectives of this study were to examine relationships between baseline levels of reproductive hormones in older men and (1) change in bone mineral density (BMD) over 5 years and (2) incident fractures over an average of 6 years' follow‐up. A total of 1705 men aged 70 years and older from the Concord Health and Ageing in Men Project (CHAMP) study were assessed at baseline (2005–2007), 2 years follow‐up (2007–2009), and 5 years follow‐up (2010–2013). At baseline, testosterone (T), dihydrotestosterone (DHT), estradiol (E2), and estrone (E1) were measured by liquid chromatography–tandem mass spectrometry (LC‐MS/MS), and sex hormone–binding globulin (SHBG), luteinizing hormone (LH), and follicle‐stimulating hormone (FSH) by immunoassay. Hip BMD was measured by dual X‐ray absorptiometry (DXA) at all three time‐points. Fracture data were collected at 4‐monthly phone calls and verified radiographically. Statistical modeling was by general estimating equations and Cox model regression. Univariate analyses revealed inverse associations for serum SHBG, FSH, and LH and positive association for E1 but not DHT or E2 with BMD loss at the hip across the three time points. Serum levels of SHBG (β = –0.071), FSH (β = –0.085), LH (β = –0.070), and E1 (β = 0.107) remained significantly associated with BMD loss in multivariate‐adjusted models; however, we were unable to identify any thresholds for accelerated BMD loss according to reproductive steroids. Incident fractures (all, n = 171; hip, n = 44; and nonvertebral, n = 139) were all significantly associated with serum SHBG, FSH, and LH levels in univariate models but none remained significantly associated in multivariate‐adjusted model. Serum T, DHT, E2, and E1 levels were not associated with incident fractures in univariate or multivariate‐adjusted analyses. In older men, lower serum SHBG, FSH, and LH and higher E1 levels protected against loss of BMD without increasing fracture rate. This means these reproductive variables may be considered as novel biomarkers of bone health during male aging. © 2015 American Society for Bone and Mineral Research.     

Efficacy and Safety of Oral and Transdermal Opioid Analgesics for Musculoskeletal Pain in Older Adults: A Systematic Review of Randomized,Placebo-Controlled Trials

This systematic review with meta-analysis was performed to evaluate the efficacy and safety of using opioid analgesics in older adults with musculoskeletal pain. We searched Cochrane Library, MEDLINE, EMBASE, Web of Science, AMED, CINAHL, and LILACS for randomized controlled trials with mean population age of 60 years or older, comparing the efficacy and safety of opioid analgesics with placebo for musculoskeletal pain conditions. Reviewers extracted data, assessed risk of bias, and evaluated the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation approach. Random effects models were used to calculate standardized mean differences (when different scales were used across trials), mean differences and odds ratios with respective 95% confidence intervals (CIs). Meta-regressions were carried out to assess the influence of opioid analgesic daily dose and treatment duration on our main outcomes. We included 23 randomized placebo-controlled trials in the meta-analysis. Opioid analgesics had a small effect on decreasing pain intensity (standardized mean difference = ?.27; 95% CI = ?.33 to ?.20) and improving function (standardized mean difference = ?.27, 95% CI = ?.36 to ?.18), which was not associated with daily dose or treatment duration. The odds of adverse events were 3 times higher (odds ratio = 2.94; 95% CI = 2.33–3.72) and the odds of treatment discontinuation due to adverse events 4 times higher (odds ratio = 4.04; 95% CI = 3.10–5.25) in patients treated with opioid analgesics. The results show that in older adults suffering from musculoskeletal pain, using opioid analgesics had only a small effect on pain and function at the cost of a higher odds of adverse events and treatment discontinuation. For this specific population, the opioid-related risks may outweigh the benefits.

Role of macrophage inflammatory protein-2 in aspiration-induced lung injury

OBJECTIVE: To determine the role of the chemokine, macrophage inflammatory protein (MIP)-2, in the pathogenesis of aspiration-induced lung injury in the rat. DESIGN: Prospective, randomized, controlled animal study. SETTING: University research laboratories. SUBJECTS: Adult, male Long-Evans rats. INTERVENTIONS: Anesthetized rats underwent induction of lung injury by well-described models of aspiration triggered by intra-tracheal delivery of acid alone, gastric particles alone, or the combination. After injury, induction of MIP-2 messenger RNA in whole lungs and immunoreactive MIP-2 in bronchoalveolar lavage (BAL) fluids was determined. The contribution of MIP-2 to BAL fluid chemotactic activity was defined by using an in vitro chemotaxis assay. The in vivo effect of blocking MIP-2 on pulmonary vascular leak, BAL fluid neutrophils, PaO2/FIO2 ratio, and alveolar-arterial oxygen tension gradient in acid-induced lung injury was determined. MEASUREMENTS AND MAIN RESULTS: Induction of MIP-2 messenger RNA and protein over time was observed in response to all three stimuli. A significant portion (25% to 41%) of the chemotactic activity in BAL fluids from injured rats was inhibited by anti-MIP-2 antibody. After acid injury, blocking of MIP-2 was associated with a 53% decrease in BAL fluid neutrophils and a 33% decrease in pulmonary vascular leak. Although acid injury both impaired oxygenation and increased venous admixture, in vivo blocking of MIP-2 was associated with improved oxygenation as well as decreased venous admixture. CONCLUSIONS: MIP-2 was up-regulated during the development of aspiration-induced lung injury in rats. MIP-2 contributed to lung accumulation of neutrophils via a chemotactic mechanism. Although oxygenation and venous admixture are worsened by acid-induced lung injury in vivo, blocking of MIP-2 at the onset of injury improved these physiologic alterations. Because the aspiration event often is witnessed, chemokines may be valid therapeutic targets for inhibiting the subsequent inflammatory response.     

Some operational factors influencing the utility of culture examination in the diagnosis of pulmonary tuberculosis

Culture examination is technically superior to direct microscopy in the diagnosis of pulmonary tuberculosis, but its practicability and relative importance in various phases of national tuberculosis control programmes in developing countries must be studied before culture facilities are provided on a large scale.