Ethanol reduces bone formation and may cause osteoporosis

INTRODUCTION: The etiology of ethanol-associated osteopenia is not fully understood. In order to define the role of ethanol in the pathogenesis of hepatic osteodystrophy, we compared two groups of alcoholic patients with histologically established alcoholic liver disease. PATIENTS AND METHODS: Twenty-eight patients currently drinking ethanol ("drinkers") and 12 claiming not to have consumed any ethanol for at least six months ("abstainers") were enrolled in the study. In addition, 35 non-alcoholic control subjects without clinical or biochemical evidence of liver disease were also studied. Bone mineral density and various biochemical and hormonal values were measured in each subject; iliac crest biopsies were taken under local anesthesia in the patients and under general anesthesia in the control subjects. RESULTS: Forearm bone mineral densities, spinal bone mineral densities, and iliac crest cancellous bone areas were significantly lower in the alcoholic patients compared with control subjects (p less than 0.01 for all measurements), but these values did not differ between the drinkers and the abstainers. The drinkers, however, had significantly less osteoblastic activity than the abstainers, as assessed by dynamic bone histomorphometry (p less than 0.001). Serum bone Gla-protein concentrations were higher in the abstainers than in the drinkers (p less than 0.001). No differences were seen relating to histologic parameters of bone resorption, although the alcoholic patients who had lower serum free testosterone concentrations than the control subjects also had higher urinary hydroxyproline excretion rates. CONCLUSION: These data suggest that ethanol may be responsible for osteoblastic dysfunction resulting in diminished bone formation and reduced bone mineralization.     

The renin-angiotensin-aldosterone system in fulminant hepatic failure

The relationship of the renin-angiotensin-aldosterone system to blood pressure and sodium homeostasis and to renal function was investigated serially in 12 patients with fulminant hepatic failure. The plasma concentrations of renin, angiotensin II, and aldosterone were, in most instances, markedly increased. Systolic blood pressure, which was often very low, showed a significant inverse relationship to the plasma renin concentration, suggesting that the marked stimulation of the system is a homeostatic response to hypotension. However, the plasma renin substrate concentration was markedly decreased, and the conversion of angiotensin II to inactive peptides increased, both of which may have severely limited the full 'expression' of the stimulated system. Renin and angiotensin II levels were both related to creatinine clearance, which was often reduced, but it is not clear as to which was cause and which effect. No relationship between the plasma aldosterone concentration and renal sodium excretion could be detected.     

Use of high resolution dual‐energy x‐ray absorptiometry‐region free analysis (DXA‐RFA) to detect local periprosthetic bone remodeling events

Dual‐energy x‐ray absorptiometry (DXA) is the gold standard method for measuring periprosthetic bone remodeling, but relies on a region of interest (ROI) analysis approach. While this addresses issues of anatomic variability, it is insensitive to bone remodeling events at the sub‐ROI level. We have validated a high‐spatial resolution tool, termed DXA‐region free analysis (DXA‐RFA) that uses advanced image processing approaches to allow quantitation of bone mineral density (BMD) at the individual pixel (data‐point) level. Here we compared the resolution of bone remodeling measurements made around a stemless femoral prosthesis in 18 subjects over 24 months using ROI‐based analysis versus that made using DXA‐RFA. Using the ROI approach the regional pattern of BMD change varied by region, with greatest loss in ROI5 (20%, p < 0.001), and largest gain in ROI4 (6%, p < 0.05). Analysis using DXA‐RFA showed a focal zone of increased BMD localized to the prosthesis–bone interface (30–40%, p < 0.001) that was not resolved using conventional DXA analysis. The 20% bone loss observed in ROI5 with conventional DXA was resolved to a focal area adjacent to the cut surface of the infero‐medial femoral neck (up to 40%, p < 0.0001). DXA‐RFA enables high resolution analysis of DXA datasets without the limitations incurred using ROI‐based approaches. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:712–716, 2015.     

A Synthetic Influenza Virus Vaccine Induces a Cellular Immune Response That Correlates with Reduction in Symptomatology and Virus Shedding in a Randomized Phase Ib Live-Virus Challenge in Humans

Current influenza vaccines elicit primarily antibody-based immunity. They require yearly revaccination and cannot be manufactured until the identification of the circulating viral strain(s). These issues remain to be addressed. Here we report a phase Ib trial of a vaccine candidate (FLU-v) eliciting cellular immunity. Thirty-two males seronegative for the challenge virus by hemagglutination inhibition assay participated in this single-center, randomized, double-blind study. Volunteers received one dose of either the adjuvant alone (placebo, n = 16) or FLU-v (500 μg) and the adjuvant (n = 16), both in saline. Twenty-one days later, FLU-v (n = 15) and placebo (n = 13) volunteers were challenged with influenza virus A/Wisconsin/67/2005 (H3N2) and monitored for 7 days. Safety, tolerability, and cellular responses were assessed pre- and postvaccination. Virus shedding and clinical signs were assessed postchallenge. FLU-v was safe and well tolerated. No difference in the prevaccination FLU-v-specific gamma interferon (IFN-γ) response was seen between groups (average ± the standard error of the mean [SEM] for the placebo and FLU-v, respectively, 1.4-fold ± 0.2-fold and 1.6-fold ± 0.5-fold higher than the negative-control value). Nineteen days postvaccination, the FLU-v group, but not the placebo group, developed FLU-v-specific IFN-γ responses (8.2-fold ± 3.9-fold versus 1.3-fold ± 0.1-fold higher than the negative-control value [average ± SEM] for FLU-v versus the placebo [P = 0.0005]). FLU-v-specific cellular responses also correlated with reductions in both viral titers (P = 0.01) and symptom scores (P = 0.02) postchallenge. Increased cellular immunity specific to FLU-v correlates with reductions in both symptom scores and virus loads. (This study has been registered at ClinicalTrials.gov under registration no. {"type":"clinical-trial","attrs":{"text":"NCT01226758","term_id":"NCT01226758"}}NCT01226758 and at hra.nhs.uk under EudraCT no. 2009-014716-35.)