Background: There is an urgent need to limit the metabolic side-effects of glucocorticoid overexposure as these can lead to Cushing's syndrome, associated with high morbidity. We have explored the potential for metformin to ameliorate such effects whilst sparing the anti-inflammatory benefits of glucocorticoids. Methods: In this double-blind, phase 2 proof-of-concept trial, 53 patients without known diabetes established on mid-to-high doses of glucocorticoids, administered as treatment for a chronic inflammatory disease, were randomised to receive 2550mg/day metformin (n=26) or an identical placebo (n=27) for 12 weeks. The primary endpoint was the change in visceral to truncal subcutaneous fat ratio assessed by computed tomography; secondary endpoints involved metabolic, bone, cardiovascular and inflammatory parameters. Findings: Nineteen patients on metformin and 21 on placebo completed the study. The groups received equivalent cumulative dose of glucocorticoids (1860mg (IQR 1060 to 2810) vs. 1770mg (IQR 1020-2356) prednisolone equivalent; p=0.76). There was no change in the visceral-to-subcutaneous fat ratio (0.11 (95%CI-0.02 to 0.24); p=0.09) between the treatment groups but metformin-treated patients lost truncal subcutaneous fat (-3835mm 2 (95%CI-6781 to-888); p=0.01) compared to placebo. Improvements in markers of carbohydrate, lipid, liver and bone metabolism were observed on metformin. Additionally, metformin-treated patients had improved fibrinolysis, carotid intima-media thickness, inflammatory parameters and clinical markers of disease activity. The frequency of pneumonia (1 vs. 7 events; p=0.01), overall rate of moderate-to-severe infections (2 vs. 11; p=0.001), and all-cause hospital admissions due to adverse events (1 vs. 9; p=0.001) were lower in the metformin group compared with placebo. Metformin-treated patients experienced more diarrhoea initially. Interpretation: Metformin administration improved the metabolic profile of glucocorticoid-treated patients with inflammatory disease, favourably modifying cardiovascular risk surrogates, reducing inflammation and hospitalisation.

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Objectives:To evaluate the efficacy of orally-administered alendronate compared with intravenously-administered zoledronate.Methods:This prospective study was carried out at Barts Health HNS Trust between April 2010 and March 2012. This study compares changes in bone mineral density (BMD) in 234 patients treated with 2 bisphosphonates: alendronate taken orally, and zoledronate administered intravenously. One hundred and eighteen patients received alendronate at 70 mg/week, while 116 patients received zoledronate once annually. Dual energy x-ray absorptiometry was used to measure BMD of the left hip and anterior-posterior spine (lumbar L1-L4) skeletal sites at baseline, and at one-, and 2-years post-treatment.Results:This study provides evidence that lumbar spine BMD increased by 3.6% in patients receiving alendronate, and 5.7% in patients receiving zoledronate after 2 years compared with baseline values (p=0.0001 for both). Total hip BMD decreased in patients treated with alendronate by 0.4% but increased in patients receiving zoledronate by 0.8% (p=0.0001).Conclusion:This study provides evidence that zoledronate is more effective than alendronate in treating patients with osteoporosis and with no gastrointestinal (GI) serious side effects. Furthermore, zoledronate appears to have the added advantage of a better safety profile in patients suffering from GI intolerance of oral bisphosphonates.

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In this article, we present the elemental concentrations determined by INAA for 30 elements measured in some or all head hair samples of 100 Nigerian subjects and 20 elements in the fingernails of some of the same subjects. Measurements of the skewness of the distribution of each element in both tissues confirm previous reports that many tend toward a log-normal distribution. Thus, their concentrations in the tissues may not be under any homeostatic control. The ranges of elemental concentrations together with the medians, and the arithmetic and geometric means, with their respective standard deviations are presented and compared with literature values for other populations. Correlations between elements detected in hair are also sought.